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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241614EnglishN2014July22HealthcareEFFECT OF SLEEP DEPRIVATION ON MEMORY IN RATS
English0106Damel LakshmiEnglish KayalvizhiEnglish ChandrasekharEnglish PriyadarshiniEnglishObjective: To study the effect of sleep deprivation on memory in rats. Methods: The experiment was done at Department of Physiology, Meenakshi Medical College and Research Institute, Enathur, Kanchipuram. Ethical clearance was obtained from CPCSEA. 12 male Wistar albino rats were used in the study, control group (6) and study group (6). Sleep deprivation was performed by using single platform method (Flower pot method). Study group was exposed to 5 hours of sleep deprivation for 5 days. Behavior, learning and memory was assessed using T maze and radial arm maze. Results: Rats subjected to sleep deprivation showed alteration in behavior and memory impairment. In T maze, there was significant increase in time spent in left arm, number of fecal bolus count with significant decrease in number of rearing, grooming and number of urination were decreased when compared with control group. In Radial arm maze impairment in memory was observed when compared with the control group. Conclusion: Rats showed memory impairment after subjected to sleep deprivation, which was assessed by standardized T maze and Radial arm maze.
EnglishSingle platform method, T Maze, Radial arm Maze.INTRODUCTION
Sleep is a naturally or artificially induced state of sensory and motor activity1 . Sleep occupies approximately one-third of a person’s life19 . Normal adult have 8 – 9 hours of sleep in a day. Sleep has two phases; Non-rapid eye movement sleep (NREM) and rapid eye movement sleep (REM). Sleep includes 5-6 cycles / day. Each cycle has NREM sleep for 70 minutes and REM sleep for 20 minutes12. NREM sleep is generated by pre optic region of hypothalamus and its adjacent basal forebrain. REM sleep is generated by pons and adjacent portions of midbrain10. Suprachiasmatic nucleus (SCN) maintains the circadian cycle in the mammalian body. One of the most prominent circadian rhythm is the cycle of sleep and wakefulness. All physiologic and behavioral functions are generated by a circadian pacemaker of SCN located in the anterior hypothalamus11. Sleep plays a major role in wound healing, basal metabolic rate, energy conservation, development of brain, learning and memory processing, cognitive functions, dreaming22 . Sleep deprivation is the condition of not having enough sleep. It is considered as an extreme case of sleep reduction, in that the organism is simply awake for a prolonged period of time2 . Deprived sleep may occur due to various reasons like physiological stress, a poor sleep environment and an inconsistent sleep schedule. Common physiological effects of deprived sleep are headache, malaise, increased blood pressure, increased stress hormone levels, irritability, confusion, memory lapses, and depression21 . Recalling of learned events at conscious or sub conscious level is called memory, which includes non-declarative (procedural) memory and declarative memory constituting short term (working) memory and long term memory9 . Memory consolidation is a slow process which converts learned events into a more permanent or enhanced form by uniting the medial temporal lobes and neocortical areas7 . Paradoxical sleep (PS) has a major role in the development of nervous system and neural plasticity; it is also assumed that immediate or short term memory storage takes place during PS4 . Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, which plays important roles in the survival, maintenance, and growth of neurons. It supports the growth of many neurons, complexity of dentrites in the cerebral cortex. It also enhances synaptic transmission and long term potentiation which is considered to be a potent cellular mechanism in learning and memory. The purpose of this experiment is to study the effect of paradoxical sleep deprivation on memory in rats.
MATERIALS AND METHOD
The experiment was carried out in the Department of Physiology, Meenakshi Medical College hospital and Research Institute, Enathur, Kanchipuram. Proper ethical clearance was obtained from Institutional Animal Ethical Committee. 12 male Wistar albino rats weighing 800 to 900g were used for the study. The animals were grouped into 2 groups with 6 animals in each; Control group (6) and study group (6). The animals were adapted to the laboratory environment 7 days prior to the initiation of the experiment and 12 hours dark/light cycle was maintained (4). Study group rats were subjected to sleep deprivation by single platform method. Control group rats were left free in home cage with free access to food and water in the same environment were sleep deprivation is performed during the period of experiment. Single platform method: This apparatus consists of a small platform (6.5 cm in diameter and 10 cm high) inside the chamber (22 x 22 x 35 cm) (Fig:1). The platform was submerged in water until 1-2 cm below its surface (Jouvet et. al. 1964)16 . Rats were placed over the small platform for 5 hours for 5 days between 9.00 am to 2.00 pm for sleep deprivation. After 5 days of sleep deprivation the rats were allowed to explore in T maze and radial arm maze. T maze: It is used to assess rodent behavior with reference and working memory. A wooden T maze apparatus was made which has a stem (50x16 cm), right arm and left arm (50x10 cm). The side walls are raised to 30 cm height4 (Fig: 2). Rats were exposed to T maze for 10 minutes then observed for side preference.
Radial arm maze: It is used to evaluate working memory. It consists of eight equally spaced arms from octagonal central platform. Each arm measures 50x12 cm extends from octagonal shaped central hub of 30 cm diameter. The platform is elevated 40 cm above the floor. Small food wells (3cm in diameter) were placed at the end of each arm (Fig:3). Rats were exposed for 10 min to observe how rats were using the spatial cues and working memory for choice of arm. Rearing, grooming, urination and fecal bolus count were also observed to assess the level of stress due to sleep deprivation method.
RESULTS
The scores were tabulated, mean and standard deviation was calculated using student t-test (Table 1.1) Significant increase (P< 0.05) in the time spent in left arm of T maze was observed in sleep deprived rats when compared with control group rats. In T maze rearing, grooming and fecal bolus count were also increased and urination was decreased in sleep deprived rats than control group (Table 1.2). In Radial arm maze, impairment in the memory level was observed by significant increase (P< 0.05) in the error scores of sleep deprived rats than control rats (Table 2).
DISCUSSION
In our study, we have found that 5 hours of sleep deprivation for 5 days produces various behavioral alterations linked with memory impairments. Sleep is a common feature of many sleep disorders in humans. For this reason effect of behavioral and memory performances were seen in animal models of interest2 . Sleep deprivation can have negative consequences on both the body and the mind interfering with physical energy and cognition. Memory loss is often associated with old age, but even young people may experience the cognitive impairment if they have sleep reduction. This study also correlates well with the report given by Health News Team (2011) which shows that adenosine reduction after sleep deprivation that could be due to the increased levels of nucleosides which might lead to decrease in memory loss and attention deficits. In our study, we have identified that sleep deprivation is a potent stressor inducing behavioral changes which is also similar to the findings of Shyamala et. al., (2012) reported that REM sleep deprivation enhanced the plasma corticosterone level. Increased level of lipid peroxidation was also reported with free radical induced neuronal damage, in thalamus and hypothalamus. The sleep deprivation performed by using flower pot method showed a significant increase in error scores of radial arm maze when compared with control group rats which indicates impairment in memory level which is also similar to the findings Shenghui Li, 2009, who reported that 48 hours of REM sleep deprived rats showed impairment in retention of acquired spatial reference memory in Morris water maze than control group. The impairment continuously existed even after 24 and 48 hours of release from sleep deprivation could be due to decrease in the levels of acetylcholine and synaptic connections in hippocampus, which mainly impairs spatial reference memory. This shows REM sleep is mainly required for memory consolidation (Chumin Zhu et. al., 2008). The increase in error scores in Radial arm maze also correlates well with the findings of Saha et. al.,2010, who explained that the alteration of memory and behavior could be due to decrease in level of melatonin which leads to increase in free radicals, a probable effect of sleep deprivation. Simultaneously, there was an increase in the time spent in left arm of T maze of sleep deprived rats showing inability to recognize the spatial cues which might be due to inactivation of Zif268 gene during sleep deprivation which inhibits consolidation of memory. (Carmel et. al., 2003). He also reported that sleep deprivation impaired performance on hippocampus – dependent spatial learning task, reduced neuronal excitability in CA1 pyramidal neurons. He also explains that consolidation of memory was reduced due to inhibition of CA1 pyramidal neurons and dendate gyrus granule cell because of long term potentiation of synaptic strength inhibition.
CONCLUSION
Thus rats on exposed to sleep deprivation showed impairment in memory. Failure to acquire adequate sleep produces various changes in the development of memory due to several cellular and molecular level alterations inhibiting hippocampal functioning. But still the exact mechanism causing the alterations in memory remains unclear. Hence further studies involving molecular parameters might help in understanding the mechanism of memory impairment following sleep deprivation.
ACKNOWLEDGEMENT
We are very much thankful to all the authors whom we have referred for this study.
Englishhttp://ijcrr.com/abstract.php?article_id=801http://ijcrr.com/article_html.php?did=8011. Essentials of Medical Physiology, Anil Baran Singha Mahapathra, Third Edition, Higher Neural Functions, Sleep Page no 469, ISBN 81- 86793-60-0
2. Sergio Tufik, Monica L. Andersen, Lia R.A. Bittencourt and Marco T. De Mello.Paradoxical Sleep Deprivation: neurochemical, hormonal and behavioral alterations. Evidence from 30 years of research. Anais da Academia Brasileira de Ciências (2009) 81(3): 521-538
3. Fundamentals of Medical Physiology, Lingala Prakasam Reddy, third edition, Sleep, page 129,130; ISBN: 81-8191-016-8
4. Jerome M. Siegel, The Neurobiology of Sleep, Semin Neurol 2009; 29;277-296
5. Kathryn J. Reid, Phyllis C. Zee, Circadian Rhythm Disorders, Semin Neurol 2009; 29;393-405
6. Sleep Wikipedia, http://en.wikipedia.org/wiki/Sleep
7. Sleep deprivation Wikipedia, http://en.wikipedia.org/wiki/Sleep_deprivation
8. Deborah Suchecki, Leticia L, Lobo, DeBora C . Hipolide And Sergio Tufik, Increased ACTH and corticosterone secretion induced by different methods of paradoxical sleep deprivation. J. Sleep Res. (1998)
7, 276–281 Accepted in revised form 25 June 1998; received 26 November 1997
9. Chumin Zhu, Progressive paradoxical sleep deprivation impairs partial memory following learning tasks in rats
10. Robert M J Deacon and J Nicholas P Rawlins Tmaze alternation in the rodent, 27 June 2006; doi:10.1038/nprot.2006.2
11. Researchers Discover How Lack of Sleep May Cause Memory Loss By Health News Team• May 18th, 2011 • Category: Memory Problems, True Health News
12. Cordova CA, Said BO, McCarley RW, Sleep deprivation in rats produces attentional impairments on a 5-choice serial reaction time task. SLEEP 2006; 29(1): 69-76.
13. D.C. Mathangi, R. Shyamala and A.S. Subhashini, Effect of REM sleep deprivation on the antioxidant status in the brain of Wistar rats. Annals of Neurosciences, Volume 19, Number 4 October 2012
14. Stress, http://www.medicinenet.com/script/main/art.as p?articlekey=488
15. Text book of medical physiology, Indu khurana, 2006, learning and memory, ISBN: 978-81-8147-850-4
16. Makoto Mizuno,Kiyofumi Yamada,Ana Olariu,Hiroyuki Nawa, and Toshitaka Nabeshima, Involvement of Brain-Derived Neurotrophic Factor in Spatial Memory Formation and Maintenance in a Radial Arm Maze Test in Rats, The journal of Neuroscience, September 15, 2000, 20(18):7116–7121
17. Shenghui Li, Ying Tian, Yu Ding, Xinming Jin, Chonghuai Yan, Xiaoming Shen, The effects of rapid eye movement sleep deprivation and recovery on spatial reference memory of young rats, Learning and behavior, August 2009, Volume 37, Issue 3, pp 246-253.
18. Habibur Rahman, P. Muralidharan, D. Sivaraman, Dipankar Saha. Continuous sleep deprivation for 5 days produces loss of memory in mice and may be a cause of Alzheimer’s disease Scholars Research Library. Annals of Biological Research, 2010, 1 (4) : 185-193.
19. Bruno Bozon, Sabrina Davis, and Serge Laroche, A Requirement for the Immediate Early Report Gene zif268 in Reconsolidation of Recognition Memory after Retrieval. Neuron, Vol. 40, 695–701, November 13, 2003.
20. Maquet,P.,. The role of sleep in learning and memory. Science, 2001, 294, 1048-1051.
21. Reimund, E., The free radical flux theory of sleep. Medical Hypothesis, 1994, 43, 231-233.
22. Smith TD, Adams MM, Gallagher M, et. al. Circuit- Specific alteration in hippocampal synaptophysin immune reactivity predict spatial learning impairment in aged rats. J.Neuroscience; 20(17): 6587-93.
23. Smith. CT, Nixon MR, Nadar RS. Post training increases in REM Sleep intensity implicate REM sleep in memory processing and provide a biological marker of learning potential. Learn Mem 2004; 11 (6): 714-9.
24. Youngblood BD, Zhou J. Smagin GN, et. al. Sleep deprivation by the “flowerpot” technique and spatial reference memory. Physiol Behavior 1997; 61 (2): 249-56.
25. T.W. Boonstra, J.F.Stins, A. Daffertshofer, P.J.Beek, Effects of aleep deprivation on neural functioning: an integrative review. Cell.Mol.Lofe Sci. 64 (2007) 934-946.
26. Geraldine Rauchs, Beatrice Desgranges, Jean Foret, Francis Eustache, The relationships between memory systems and sleep stages. J.Sleep Res (2005) 14, 123-140
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241614EnglishN2014July22HealthcareVALIDATION OF BONE GRAFTS IN PERIODONTAL THERAPY-A REVIEW
English0716Kalpana GokulEnglish D. ArunachalamEnglish S. BalasundaramEnglish Aruna BalasundaramEnglishBackground: Bone grafts are widely used in the treatment of periodontal osseous defects. However, many are unfamiliar with their preparation, exact mechanism of action and processing as well as their use as safe and effective graft materials in periodontal therapy. Also, the clinical benefits of this therapeutic practice require further clarification through a proper review. Aim: The purpose of this review is to access the efficacy of bone replacement grafts in proving demonstrable clinical improvements in periodontal osseous defects. Methods: Data Sources: A literature search was conducted on several medical databases. For study inclusion, all studies that used bone graft in the treatment of periodontal osseous defects were included. Around 80 relevant articles were selected for this review. Results: A large body of evidence clearly indicates that grafts consistently lead to better bone fill than non grafted controls. As more is learned about the biologic process of periodontal regeneration, new graft materials are expected to make the task of periodontal regeneration even more predictable. Conclusion: Bone replacement grafts (BRG) are widely used in the treatment of periodontal osseous defects. Our review of literature strongly suggests better bone fill, gain in clinical attachment level and reduced probing depths with the use of various grafts as compared to non grafted sites. However, the clinical benefits of this therapeutic practice require further clarification through a systematic review of randomized controlled studies. Keywords: bone grafts, periodontal regeneration, prognosis
Englishbone grafts, periodontal regeneration, prognosisINTRODUCTION Bone grafting is a surgical procedure that replaces missing bone. Bone generally has the ability to regenerate completely but requires a very small fracture space or some sort of scaffold to do so. Most bone grafts are expected to be reabsorbed and replaced as the natural bone heals over a few months’ time. Bone grafts can effect bone replacement through three different mechanisms: osteogenesis, osteoinduction and osteoconduction. [1] Osteogenesis refers to organic material capable of forming bone directly from osteoblast.[1] An osteogenic graft is derived from or composed of tissues involved in the natural growth or repair of bone. It is for this reason that they can even encourage bone formation in soft tissues or activate more rapid bone growth in bone sites. [2], [3] Osteoinductive materials are capable of inducing the transformation of undifferentiated mesenchymal cells into osteoblasts or chondroblast and enhance bone growth or even grow bone where it is not expected. [1] This process, first described by Urist, does not necessitate the presence of living cells in the grafts. Some factors now known as Bone Morphogenetic Proteins (BMPs) located primarily in cortical bone are involved in this mechanism. [4] Osteoconduction is characteristic of a material (often organic) which permits bone apposition from existing bone and requires the presence of bone or differentiated mesenchymal cells.[5],[6] Osteoconduction provides a physical matrix or scaffolding suitable for the deposition of new bone. Osteoconductive grafts do not produce bone formation themselves when placed within soft tissue.[2], [3] It permits Osteogenesis when cells already committed to bone formation are present in a closed environment. A material is said to be osteoconductive when its structure and its chemical composition facilitate new bone formation from existing bone. This means that this material has to be inserted in a bony site, an orthotopic site. CLASSIFICATION OF BONE GRAFTS Human bone Auto grafts Extra oral Intraoral Allografts Fresh frozen bone Freeze-dried bone allografts Demineralized freeze-dried bone allografts Bone substitutes Xenografts Bovine-derived hydroxyapatite Coralline calcium carbonate Alloplastic grafts Polymers Bioceramics Tricalcium phosphate Hydroxyapatite Bioactive glasses Mechanism of action - autogenous bone grafts[2] To understand the mechanism of action of bone grafts, biology of bone healing has to be clearly understood. The bone repair process begins with an inflammatory response that prompts granulation tissue to proliferate in the wound site. This granulation tissue brings in capillaries, fibroblasts, and osteoprogenitor cells. Similarly, revascularization is initiated within the first few days following the grafting procedure. Blood vessels originating from the host bone invade the graft. If the graft material contains vital osteogenic precursor cells that survive the transplantation process, these cells may contribute to new bone formation. Osteoblasts, are produced by the osteoprogenitor cells in the granulation tissue, stimulate organic matrix of woven bone and to initiate mineralization. This healing mass of new tissue is called the callus, and it is an architecturally disorganized mass. Woven bone - replaced by lamellar bone as bone remodeling units invade the healing area. This entire process is called osteogenesis.
Autogenous bone grafts are composed of organic and inorganic structures. Resilience, toughness, and continuity are related to collagen, of the organic component. Stiffness, hardness and rigidity are characteristics of the inorganic aspect; a crystalline, ceramic-like material which is primarily hydroxyapatite (HA). This inorganic matrix contains organic components of osteocytes, osteoclasts, osteoblasts, osteogenic signaling proteins and various amount of mesenclymal tissue. Grafted autogenous bone heals in three phases. During the first phase, the surviving cells are responsible for the formation of osteoid by osteogenesis. They are most active within the first four weeks after bone grafting. [7] The blood vessels from the host bone and the connecting tissue invade the graft. Bone cells from the host tissue follow the blood vessels and remodel the graft by a coupled resorption and formation phenomenon.[8] The BMP derived from the mineral matrix of the grafted bone through the resorbing action of osteoclast, acts as a mediator for the second phase. [4], [9] The BMP and other proteins must be released prior to the osteoinduction cycle. Phase three occurs as the inorganic component of bone acts as a matrix and source of minerals during replacement of the matrix by the surrounding bone and resembles an osteoconductive mode of action. The three phases overlaps in the time sequence and are not separate phases of growing bone from the grafted autogenous material. Grafted autogenous bone can be trabecular (cancellous), cortico-cancellous or cortical. The cancellous portion of grafts provides the cells for osteogenesis and survives best when a blood supply from the host bone is readily available. Cortico-cancellous block grafts permit contouring and adaptation of the graft to the recipient bed anatomy. The trabecular portion is placed on the host bone and the cortical aspect is positioned on the surface of the graft. The cancellous portion is primarily responsible for the living bone cells and osteogenesis and therefore placed closest to the new blood vessels which arrive from the host bone and enter the graft at a rate of 0.5mm/day. [10] The cortical graft supports osteogenesis only from the surviving cells fewer than trabecular bone and also provides more of the BMP compared with trabecular bone for the second osteoinductive phase [11] The cortical aspect also provides a more resistant scaffold for the third osteoconductive phase. In addition, it may act as a barrier to soft tissue invasion thus excluding the need for a GTR membrane and provide an extended period for blood vessels to enter the graft from the host bone [1] Autogenous bone grafts: Harvested from the patient's own body and is the gold standard among graft materials because they are superior at retaining cell viability. These grafts contain live osteoblasts and osteoprogenitor stem cells and heal by osteogenesis. Avoid the potential problems of histocompatibility differences and the risk of disease transfer. Autogenous cancellous bone graft is the most effective bone graft material possessing all 3 characteristics. Limitations include the increased operative time, limited availability and significant morbidity related to blood loss, wound complications, local sensory loss and, most importantly, chronic pain. [4] Donor site pain persisting for more than 3 months has been reported in up to 15% of patients having an iliac graft harvested. The amount of pain seems to be proportional to the extent of dissection required to obtain the graft. [5] Mellonig JT, Bowers GM reported 3 to 3.5 mm of clinical bone fill is usually obtained in intraosseous defects when the site is grafted compared with less than 1 mm of fill in sites that are not grafted.[12] Histologic evaluations suggest that at least partial periodontal regeneration occurs after autogenous grafting. In the early stages of autograft healing, new bone originates from the surviving osteoprogenitor cells, and in later stages, it originates from the osteoinduction response of the host bone. The area of new bone interdigitation and the quantity of donor bone that is resorbed is higher for cancellous bone grafts compared with cortical grafts. Autogenous bone should be used whenever possible in graft cases. [12] Autogenous bone from intraoral sites : In 1923, Hegedus attempted to use bone grafts for the reconstruction of bone defects produced by periodontal disease. Sources of bone include- bone from healing extraction wounds, bone from edentulous ridges, tori, the maxillary tuberosity, bone trephined from within the jaw without damaging the roots, newly formed bone in wounds especially created for the purpose, and bone removed during osteoplasty and ostectomy Types of autogenous bone grafts osseous coagulum, Bone blend of cortical and cancellous intraoral bone, cortical bone chips, Bone swaging and Intraoral Cancellous Bone Marrow Transplants Autogenous bone from extraoral sites – In 1969 Cushing claimed that extra oral cancellous bone and marrow offer the greatest potential new bone growth. In 1968 Schallhorn obtained this material either from anterior or posterior iliac crest. Mechanism of action of allograft: [7] Bone allografts are procured usually within 12 hours of death of a suitable donor. Cortical bone is harvested in a sterile manner. Long bones are the source for periodontal bone allografts. The cortical bone is rough cut to a particle size ranging from 500 um to 5mm. The graft material is then immersed in 100% ethyl alcohol or a similar solvent for 1 hour to remove fat that may inhibit osteogenesis. The cortical bone is ground and sieved to a particle size range of approximately 250 to 750 um. 5. Decalcification with 0.6 or 0.5 N hydrochloric acid removes the calcium, leaves the bone matrix, and exposes the bone-inductive proteins. The bone is washed in a sodium phosphate buffer to remove residual acid. The cortical bone is frozen at -80°C for 1 to 2 weeks to interrupt the degradation process. During this time, the results from bacterial cultures, serologic tests, and antibody and antigen assays are analyzed. If contamination is found, the bone is discarded or sterilized by additional methods and so labeled. Freeze-drying removes more than 95% of the water content from the bone. Allografts are obtained from cadavers or from patients’ living relatives or non-relatives. Basically these bone grafts are of the same species but different genotypes. After processing, they are stored in bone banks. The advantages of allografts are availability, elimination of the donor site in the patient, decreased anesthetics and surgery time, decreased blood loss, and fewer complications. However, it is associated with some disadvantages which relate to bone tissues coming from another individual. Consequently the medical history must be thoroughly checked to eliminate donors with history of infection, malignant neoplasm’s, degenerative bone diseases, hepatitis B or C, sexually transmitted diseases, autoimmune disease and other problems which affects the quality of the bone and the health of the recipient. [13] There are 3 main types of bone allografts: 1. Frozen, freeze-dried (lyophilized), 2. Demineralized freezed dried bone (DFDB), 3. Mineralized deproteinized and irradiated allograft. Fresh allografts are the most antigenic. Freezing or freeze-drying the bone significantly reduces its antigenicity. Allografts are not osteogenic and so, bone formation takes longer and results in less volume than can be achieved with autogenous grafts [1] . Allograft is said to form bone by osteoinductive effect on surrounding undifferentiated mesenclymal cells in the soft tissue over the graft as the blood vessels grow into the graft. It may also form bone by the osteoconduction phenomenon when the host bone resorbs the material and grows into its scaffold. Mineralized Freeze-Dried Bone Allograft (FDBA):
It was introduced to periodontal therapy in 1976. This material is osteoconductive. Although FDBA contains inductive proteins, the polypeptides are sequestered by calcium. This material is resorbed and replaced by host bone very slowly. Freezedried bone allograft is the only graft material that has undergone extensive field testing for the treatment of adult periodontitis. FDBA is still used today, but a large-scale research review showed that FDBA mixed with autogenous bone is more effective at increasing bone fill than FDBA alone. [14] Sanders et al in 1983 found that more than 50% bone fill was achieved in 80% of test cases grafted with FDBA plus autogenous bone but in only 63% of controls grafted with FDBA alone. Mellonig and co-workers - reported bone fill exceeding 50% in 67% of the defects grafted with FDBA and in 78% of the defects grafted with FDBA plus autogenous bone. [15] FDBA, however, is considered an osteoconductive material, whereas decalcified FDBA (DFDBA) is considered an osteoinductive graft. Decalcified freeze-dried bone allograft (DFDBA): Also referred to as allogeneic, autolyzed, antigenextracted (AAA) bone. Experiments by Urist have established the osteogenic potential of DFDBA. [4] Demineralization in cold, diluted hydrochloric acid exposes the components of bone matrix, closely associated with collagen fibrils, which have been termed bone morphogenetic protein. Bowers et al in 1991 evaluated osteogenin combined with DFDBA, DFDBA alone, osteogenin combined with bovine collagen, and bovine collagen alone in human periodontal osseous defects. The ability of each material to regenerate a new attachment apparatus of bone, cementum, and periodontal ligament was evaluated in submerged and nonsubmerged environments using two patient populations. Mean results indicated that osteogenin combined with DFDBA significantly enhanced regeneration in a submerged environment. Mellonig and associates tested DFDBA against autogenous materials in the calvaria of guinea pigs and showed it to have similar osteogenic potential. [16] These studies provided strong evidence that DFDBA in periodontal defects results in significant probing depth reduction, attachment level gain, and osseous regeneration. The combination of DFDBA and guided tissue regeneration has also proven very successful. Human clinical studies have shown DFDBA grafts result in 2.5 to 3 mm of bone fill, which is somewhat less than autogenous bone.[16] Delipidization with ether, alcohol, acetone, hexachlorophene, common detergents may even enhance bone induction. [4] The osteogenic ability of different grafting materials, autogenous osseous coagulum, autogenous bone blend, FDBA and DFDBA, packed in nylon chambers, and implanted in guinea pig calvaria defects, were compared in an investigation.[14] The newly formed bone was determined by the incorporation of a radionuclide, 85 Strontium, and evaluated histologically at different time intervals ranging from 3 to 42 days. The authors concluded that DFDBA is a material of high osteogenic potential, while osseous coagulum and bone blend show less potential, and FDBA is the least effective.
Future Directions with DFDBA The enhanced osteogenic potential of DFDBA is the result of a variety of bone-inductive proteins located within the bone matrix. [4] These proteins have been termed bone morphogenetic proteins (BMPs). At the very least, nine BMPs (BMP-1 through BMP-9) have been cloned and characterized, and some are available in human recombinant form. Animal experiments have demonstrated that the BMPs have the ability to induce bone and repair bone defects at a variety of anatomic sites.[17] Therefore, more recent studies have attempted either to combine DFDBA with BMPs or to evaluate BMPs with a carrier. Gendler demonstrated by experiments that perforated demineralized bone matrix was a new form of osteoinductive material. [18] It was demonstrated that subcutaneous implantation of perforated decalcified bone matrix (PDBM) induced multiple centers of endochondral osteogenesis with subsequent resorption of bone matrix and replacement by new bone.
Mechanism of action of alloplast bioceramics Bioceramic alloplasts are primarily composed of calcium phosphate. Calcium phosphate biomaterials have excellent tissue compatibility and do not elicit any inflammation or foreign body response. These materials are osteoconductive. Two types of calcium phosphate ceramics are Hydroxyapatite (HA) and Tricalcium phosphate (TCP) Hydroxyapatite (HA)
Synthetic HA's have been marketed in a variety of forms, primarily as a porous or dense nonresorbable material or as resorbable, porous. HA ceramic's resorbability is determined by the temperature at which it forms. Dense HA grafts are osteoconductive, and act primarily as inert biocompatible fillers. They have produced clinical defect fill greater than flap debridement alone in the treatment of intrabony defects. [19] Histologically, new attachment was not achieved. They yield similar defect fill as other graft materials, and the clinical improvement achieved is more stable than with debridement alone. Yukna et al in 1989 demonstrated that over a 5-year period open flap debridement was not stable and regressed three to five times faster than sites treated with HA. Porous HA is obtained by the hydrothermal conversion of the calcium carbonate exoskeleton of the natural coral into HA. It has a pore size of 190 to 200μm, which allows fibrovascular in growth and subsequent bone formation into the pores and ultimately within the lesion itself. Clinical defect fill, reduction of probing depth, and attachment level gain have been reported. As with dense HA, any regeneration is limited to only the apical portion of the defect. Kenney et al provided histologic evidence suggesting that porous HA could stimulate osteogenesis, but because no evidence of new connective tissue attachment or cementum was noted. Another form of synthetic HA is a resorbable, low-temperature-processed, particulate material. The resorbable form is nonsintered with particles measuring 300 to 400μm. It has been proposed that nonsintered HA resorbs acting as a mineral reservoir inducing new bone formation via osteoconductive mechanisms. Its reported advantage is its slow resorption rate allowing it to act as a mineral reservoir at the same time acting as a scaffold for bone replacement. Tricalcium phosphate (TCP) It is mineralogically B-whitlockite. TCP is partially bioresorbable. Tricalcium phosphate is a porous form of calcium phosphate. The proportion of calcium and phosphate is similar to bone. It serves as biologic filler, which is partially resorbable and allows bone replacement of the implant material. Conversion of graft material is pivotal to periodontal regeneration. First, serving as a scaffold for bone formation, then permitting replacement with new bone. Tricalcium phosphate as a bone substitute has gained clinical acceptance, but results are not always predictable. Tricalcium phosphate does not seem to initiate osteogenesis.[20] The particles generally become encapsulated by fibrous connective tissue and do not stimulate bone growth. Some bone fill, however, has been achieved with tricalcium phosphate grafts. These ceramics form the new bone strictly by osteoconduction with the new bone formation taking place along their surface.[1] A chemical contact between the host bone and grafted material may be developed as well as possible stimulus for bone activity.[21]
HTR Polymer The acronym stands for hard tissue replacement. HTR (Bioplant) is a nonresorbable biocompatible microporous composite of polymethylmethacrylate (PMMA), polyhydroxyl ethylmethacrylate (PHEMA), and calcium hydroxide. Favorable clinical results have been achieved with HTR for the treatment of infrabony defects and furcation defects. Improved clinical results with this synthetic substitute have not always been achieved. Although Shahmiri et al in1992 demonstrated no clinical improvement in probing depth; most reports have supported the use of HTR as a bone substitute. Histologically, new bone growth has been found deposited on HTR particles.[22] It appears to serve as a scaffold for new bone formation when in close contact to alveolar bone.
Its hydrophilicity enhances clotting, and its negative particle surface charge allows it to adhere to bone. In moderately severe intrabony human periodontal defects, a mean defect resolution of 75% has been reported with HTR.[23] They also reported significant clinical defect fill and resolution can be achieved, supporting its use as a biocompatible alloplastic bone substitute. Furcation repair was better with HTR than that achieved with autogenous bone.[24] It is a clinically beneficial, biocompatible, osteophilic, and osteoconductive alloplastic bone substitute. Mechanism of action – Xenografts Two available sources of xenografts used as bone substitutes in clinical practice: bovine bone and natural coral. Both sources, through different processing techniques, provide end products that are biocompatible and structurally similar to human bone. Xenografts are osteoconductive. Commercially available bovine bone is processed to yield natural bone mineral minus the organic component. Advantage of the product as a bone substitute is that it is natural in that it can provide structural components similar to that of human bone, improving its osteoconductive capability over synthetically derived mineral. Boplant (Calf bone): treated by detergent extraction, sterilized, and freeze dried, has been used for the treatment of osseous defects. Kiel bone: is calf or ox bone denatured with 20% hydrogen peroxide, dried with acetone, and sterilized with ethylene oxide. Ospurum: Fosberg described the use of ospurum for treatment of periodontal defects.[25] This is Ox bone which is soaked in warm potassium hydroxide to remove connective tissue, in acetone to remove lipids, and in a soft solution to remove proteins. Anorganic bone: is ox bone from which the organic material has been extracted by means of ethylenediamine; it is then sterilized by autoclaving. Anorganic bovine bone is the HA skeleton, which retains a highly porous structure similar to cancellous bone that remains after chemical or low heat extraction of the organic component. Yukna has used a natural, anorganic, microporous, bovine-derived hydroxyapatite bone matrix, in combination with a cell-binding polypeptide that is a synthetic clone of the 15 amino acid sequence of type I collagen. The addition of the cell binding polypeptide was shown to enhance the bone regenerative results of the matrix alone in periodontal defects.
Historically, bovine xenografts have failed owing to rejection, probably because earlier materials used chemical detergent extraction that left residual protein and therefore produced adverse reactions and clinically unacceptable results. Currently available bovine-derived HA is deproteinated, retaining its natural microporous structure that supports cell-mediated resorption. This becomes important if the product is to be replaced with new bone. Two products are currently available: OsteoGraf and BioOss. Both have been reported to have good tissue acceptance with natural osteotrophic properties. Histologically, no fibrous tissue or space between the HA and newly formed bone is found. This is in contrast to histologic reports obtained with synthetic HA. Bovine-derived HA bone substitutes increase the available surface area that can act as an osteoconductive scaffold because of their porosity. This HA mineral content is comparable to that of bone, allowing it to integrate with bone. They have been used with success for the treatment of intrabony defects and ridge augmentation. Coralline calcium carbonate Biocoral is calcium carbonate obtained from a natural coral, genus Ponies, and is composed primarily of aragonite (>98% calcium carbonate). It is biocompatible and resorbable with a pore size of 100 to 200μm, similar to the porosity of spongy bone. Its porosity, at greater than 45%, provides large surface area for resorption and replacement by bone. In contrast to porous HA, derived from the same coral by heat conversion and nonresorbable, calcium carbonate is resorbable. It does not require a surface transformation into a carbonate phase as do other bone substitutes to initiate bone formation; hence, it should more rapidly initiate bone formation. Bicoral has a high osteoconductivity potential because no fibrous encapsulation has been reported. When compared with other bone substitutes, coralline calcium carbonate produces comparable results. Significant gain in clinical attachment, reduction of probing depth, and defect fill has consistently been reported. Mechanism of action of Bio active glass: There are two forms of bioactive glass currently available PerioGlass and bioGran. Bioactive glasses are composed of SIO2, CaO, Na2O, P3O5 and bond to bone through the development of a surface layer of carbonated HA. When exposed to tissue fluids in vivo, the bioactive glass is covered by a double layer composed of silica gel and a calcium phosphorus-rich (apatite) layer. The calcium phosphate-rich layer promotes adsorption and concentration of proteins used by osteoblasts to form a mineralized extracellular matrix. It is theorized that these bioactive properties guide and promote osteogenesis, allowing rapid and quick formation of new bone PerioGlas is osteoconductive. Has particle size ranging from 90 to 710 μm. 68% defect repair was achieved when used on surgically created defects in monkeys. [26] He also compared tricalcium phosphate, HA, and unimplanted controls, and showed PerioGlas to produce significantly greater osseous and cementum repair. It also appeared to retard epithelial downgrowth, which the authors contend may be responsible for its enhanced cementum and bone repair. [26] Biogran has particle size of 300 to 355 μm size range. Formation of hollow calcium phosphate growth chambers occurs with this particle size because phagocytosing cells can penetrate the outer silica gel layer by means of small cracks in the calcium phosphorus layer and partially resorb the gel. This resorption leads to the formation of protective pouches where osteoprogenitor cells can adhere, differentiate, and proliferate. According to the manufacturer, larger particles do not resorb in the same manner, which slows the healing process theoretically because bone healing must progress from the bony walls of the defect and smaller particles cause a transient inflammatory response, which retards the stimulation of osteoprogenitor cells. Biogran has a clinical advantage over the PerioGlas preparation, which has multiple particle sizes. Clinically, no comparison has been made between the products, and no human periodontal studies are available. A human study by Schepers et al in 1993 demonstrated that Biogran could be used successfully in the treatment of oral osseous defects.
CONCLUSION
Although complete periodontal regeneration is unpredictable with any regenerative therapy currently used, periodontal bone grafts show strong potential. Requirements for a successful graft includes Patient Selection, material Selection, Proper Flap Reflection and Wound Stability, Revascularization, Root Debridement, Postsurgical care .A large body of clinical evidence clearly indicates that grafts consistently lead to better bone fill than nongrafted controls. As more is learned about the biologic process of periodontal regeneration, new graft materials are expected to make the task of periodontal regeneration even more predictable.
Englishhttp://ijcrr.com/abstract.php?article_id=802http://ijcrr.com/article_html.php?did=8021. Misch CE, Dietsh F: Bone-grafting materials in implant dentistry. Implant Dent 1993;2:158- 167
2. Arun K. Garg . Bone Biology, Harvesting, Grafting for Dental Implants: Rationale and Clinical Applications, Chicago: Quintessence Publishing; 2004.
3. Wood RM, Moore DL. Grafting of the maxillary sinus with intraorally harvested autogenous bone prior to implant placement. Int J Oral Maxillofac Implants 1998; 3:209-14.
4. Urist MR: Bone formation by autoinduction. Science 1965;150:893-899. 5. Rejda BV, Peelen JGJ, deGroot K: Tricalcium phosphate as a bone substitute. J Bioeng 1977; 1:93-97.
6. Jarcho M: Calcium phosphate ceramics as hard tissue prosthetics. Clinical Orthop 1981;157:259-278.
7. Christopher Ogunsalu (2011). Bone Substitutes and Validation, Implant Dentistry - The Most Promising Discipline of Dentistry, Prof. Ilser Turkyilmaz (Ed.).
8. Roberts WE, Turley PK, Brezniak N, Fielder PJ: Implants. Bone physiology and metabolism. Calif Dent Assoc J 1987;15:54- 61.
9. Urist MR. Bone transplants and implants. Fundamental and clinical bone physiology. Philadelphia: JB Lippincott 1980; 331- 368.
10. Marx RE, Saunders TR: Reconstruction and rehabilitation of cancer patients. Reconstructive preprosthetic oral and maxillofacial surgery edited by Fonseca RJ and Davis WH,Philadelphia: WB Saunders: 1986, 347-28.
11. Longacre JJ, Converse JM, Knize DM. Transplantation of bone. In: Converse JM, editors. Reconstructive plastic surgery: principles and procedure in correction, reconstruction and transplantation. 2nd ed. Philadelphia: WB Saunders. 1977; 313-39
12. Mellonig JT, Bowers GM. Regenerating bone in clinical periodontics. A review. J Am Dent Assoc.1990; 121:497-502.
13. Fonseca RJ, Frost D, Zeitler D, Stoelinga PJW. 1986. “Osseous reconstruction of edentulous bone loss.” In Reconstructive preprosthetic oral and maxillofacial surgery, edited by Fonseca RJ, Davis WH. 117-65. Philadelphia: WB Saunders.
14. Mellonig JT. Freeze-dried bone allografts in periodontal reconstructive surgery. Dent Clin North Am 1991;35:505-520.
15. Mellonig J, Bowers G, Bright R, Lawrence J. Clinical evaluation of freeze-dried bone allograft in periodontal osseous defects. J Periodontol 1976; 47:125-129.
16. Mellonig J, Captain DC. Decalcified freezedried bone allografts as an implant material in human periodontal osseus defects. Int J Periodont Res Dent 1984; 6:41-55.
17. Wang E. A, Rosen V, D’Alessandro J. S, Bauduy M, Cordes P, Harada T et al Recombinant human bone morphogenetic protein induces bone formation. Proc. Natl. Acad. Sci. USA 1990; 87:2220-2224
18. Gendler E. Perforated demineralised bone matrix: a new form of osteoinductive biomaterial. J Biomed Master Res 1986; 20:687-697
19. Rabalais, M. L, Yukna, R. A., and Mayer. E. T.: Evaluation of durapatite ceramic as an ailoplastic implant in periodontal osseous defects. I. Initial six-month results. J Periodontol 1981;52:680-689
20. M H Amler. Osteogenic potential of non vital tissues and synthetic implant materials. J Periodontol 1987;58:758-761
21. Le Geros RZ. “Calcium phosphate materials in restorative dentistry: a review.” Adv Dent Res 1988;2:164-80.
22. Froum S J. Human histologic evaluation of HTR polymer and freeze-dried bone allograft. A case report. J Clin Periodontol. 1996;23:615-20.
23. M E Aichelmannreidy et al., "HTR polymer versus hydroxylapatite ceramic grafts in human periodontal defects". J Dent Res 1997;76:3432-3432
24. Yukna RA. Synthetic bone grafts in periodontics. Periodontol 2000. 1993;1:92-99.
25. Forsberg H. Transplantation of Ospurum and bone chips in the surgical treatment of periodontal diseases. Acta Odont Scand 1955:13;235-239
26. Fetner AE, Hartigan MS, Low SB. Periodontal repair using Perio Glass in non-human primates: Clinical and histologic observations. Compendium 1994;15:932–935.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241614EnglishN2014July22HealthcareCLINICAL PROFILE OF REFERRED OTALGIA IN A TERTIARY HEALTH CENTRE - A RETROSPECTIVE STUDY
English1724Geetha K. SiddapurEnglish Kishan R. SiddapurEnglishObjectives: Assessment of age and gender distribution amongst otalgia cases, identification and categorization of referred nerve pathways, etiological factors, and analysis of significance by statistically correlating occurrence of cervical spine degenerative disease (CSDD) with respect to age and gender factors. Methods: The study conducted is retrospective, which included otalgia cases examined between April 2010 and April 2014. A total of 693 cases of otalgia were identified by ENT (Ear Nose Throat) and head and neck examination, dental and orthopedic data from the respective in and out patient departments. Radiographic records were referred wherever relevant. Patients were separated into two cohorts. Group I included Cervical Spine Degenerative Disease cases (CSDD) and Group II, Non- cervical spine degenerative disease cases. The data collected was tabulated and statistically analyzed. Results: Of total 693 otalgia cases, referred otalgia (n=169 cases) accounted for 24.4%. Females outnumbered males, accounting for 66.9% of the cases. Age group 20-40 years was affected the most (48.5%), followed by 40-60years age group (29.6%). Dental pathology outnumbered the etiological factors (30.8%), followed by cervical spine degenerative disease (CSDD) [26.6%] and Temporo Mandibular joint dysfunction (TMJD) [19.5%]. Conclusion: Middle age group involvement in Group I (cervical spine degenerative disease cases) was in contrast to most other studies, where, elderly age group was most commonly affected. Therefore, high index of suspicion should be borne in mind to diagnose referred otalgia due to cervical spine degenerative disease in younger to middle age groups, without which, many such cases could be misdiagnosed or undiagnosed.
EnglishRetrospective, Primary, Referred otalgia, Auriculotemporal nerve, cervical spondylosisINTRODUCTION
Otalgia is a complaintofall ages, which is due to complex neuroanatomic innervation of the ear, head, and neck and can be classified as otogenic (primary) or nonotogenic (referred).1, 2 External and middle ear infections are associated with primary otogenic pain, which most otolaryngologists and primary care physicians are trained to diagnose.3 Common disease processes resulting in primary otalgia include otomastoiditis, cholesteatoma, and foreign bodies lodged within the ear canal. In close to 50% of cases, however, the source of the pain does not reside within the ear. Rather, originates from sources distant from the ear, so called “referred otalgia”4 .A negative otologic examination and persistent otalgia should suggest the possibility of referred otalgia. Otalgiaoriginating from a non-otologic source, poses difficult diagnostic challenge to even the most experienced otolaryngologist. Referred pain is an unpleasant sensation localized to an area separate from the site of the causative injury or other noxious stimulation. Often, referred pain is caused by nerve compression or irritation. In this circumstance, the sensation of pain will generally be felt in the territory that the nerve serves (i.e., somatic dermatone) even though the damage originates elsewhere (i.e., visceral tissue).5 Ear is unique in that no other structure in the body of comparable size has such unique sensory nerve supply. The sensory nerve supply of the ear is through a combination of four cranial nerves (Cranial nerves V, VII, IX, and X) and two superior cervical plexus nerves (C2 and C3). Presumably, this complex innervation is anexcellent survival tool, and any pain perceived in that area causes a heightened sense of alarm. The differential diagnosis is specifically related to the sensory innervations of the ear, and therefore it is required that otolaryngologists have therelevant knowledge of the complex neuroanatomic innervation of the external and middle ear. Among all causes of referred otalgia, dental pathology, which transmits referred pain via a branch of the trigeminal nerve, is the most common source of non-otogenic pain.6 Furthermore, the cause of referred otalgia can also be referred pain from the mouth, teeth, larynx, or thyroid gland; neural, vascular, or lymphatic structures of neck; or the esophagus.[7,8] However, with the aging population, physicians must also consider cervical spine degenerative disease (CSDD) as an increasingly common cause of referred otalgia involving the upper cervical plexus (greater auricular and lesser occipital nerve). Cervical spine degenerative disease (CSDD) includes osteoarthritis, cervical facet syndrome, spondylosis, disc herniation, and stenosis. In this retrospective study; age and gender distribution amongst otalgiacases, referred nerve pathway and etiological factors wereidentified and categorized. Strength of significance by statistically correlating occurrence of cervical spine degenerative disease with respect to age and gender factors has also been analyzed.
MATERIALS AND METHODS
The study conducted is retrospective, and included otalgia cases examined between April 2010 and April 2014 in Karpaga Vinayaga Institute of Medical Sciences & Research Centre, Tamil Nadu. A total of 693 cases of otalgia were identified by ENT (Ear Nose Throat) and head & neck examination, dental and orthopedic data from the respective in and out patient departments. Radiographic records were referred wherever relevant. Primary cases (524 otogenic cases), which also included those patients who had undergone previous ear surgery, were excluded. Patients with unspecified otalgia (169 referred otalgiacases) were selected. Patients were separated into two cohorts. Group I consisted referred otalgia caseswith clinical and/or radiographic evidence of Cervical Spine Degenerative Disease (CSDD), and Group II included referred otalgia cases with other etiological factors (Non- CSDD). There were 45 cases in Group I, and 124 in Group II. A positive imaging study showing cervical spine degenerative disease at or above C4 was assumed to be positive but did not exclude its diagnosis based on clinical evidence. Age and gender were also statistically analyzed between the two cohorts. Referred nerve pathway involvement was ascertained. The distributions of all diagnosed etiologic factors for referred otalgia (169cases) with their respective nerve pathways were categorized. The data thus collected was tabulated and statistically analyzed. Chi-square test was used wherever applicable. Significance level was assessed with P valueEnglishhttp://ijcrr.com/abstract.php?article_id=803http://ijcrr.com/article_html.php?did=8031. Shah RK, Blevins NH. Otalgia. OtolaryngolClin North Am 2003;36:1137–51.
2. Thaller SR. Otalgia with a normal ear. Am Fam Physician 1987;36:129–36.
3. SiddiqM, Samra M. Otalgia. BMJ 2008;336:276-77.
4. Jaber J, Leonetti P, Lawrason A and Feustel P. Cervical spine causes for referred otalgia.Otolaryngol Head Neck Surg 2008;138:479- 85.
5. Powers WH, Britton BH. Nonotogenicotalgia: diagnosis and treatment. Am J Otol 1980;2:97–104.
6. Kreisberg MK, Turner J. Dental causes of referred otalgia. Ear Nose Throat J 1987 Oct;66:398–408.
7. Scarbrough TJ, Day TA, Williams TE, et. al. Referred otalgia in head and neck cancer: a unifying schema. Am J ClinOncol 2003;26:e157– 62.
8. Yanagisawa K, Kveton JF. Referred otalgia. Am J Otolaryngol 1992;13:323–7.
9. Chen R,khorsandi S,Shatzkes D, Holliday R.The radiology of referred otalgia.American Society of Neuroradiology 2009.
10. Vedasalam S, Sipaul F, Porter G. Internal laryngocoele and referred otalgia. BMJ Case Reports2010;10.
11. Tuz H, Onder EM, Kisnisci RS. Prevalence of otologic complaints in patients with temporomandibular disorder. Am J OrthodDentof Orthopedic 2003;123:620-23.
12. van der Meulen M, Ohrbach R, Aartman I, Naeije M, Lobbezoo F. "Temporomandibular disorder patients' illness beliefs and selfefficacy related to bruxism". J Orofac Pain 2010;24:367–72.
13. Seedorf H, Jude H.Otalgia in patients with temporomandibular joint disorders. NCPI Laryngorhinootologie 2006;85:327-32.
14. James J, John P, Amy E, Paul J. Cervicalspinecauses for referredotalgia. Otolaryngology - Head and Neck Surgery 2008;138:479–85.
15. Kim D, Cheang P, Dover S, et. al. Dental otalgia. J LaryngolOtol 2007;121:1129– 34.
16. Danish SF, Zager EL. Cervical spine meningioma presenting as otalgia: case report. Neurosurgery 2005;56(3):E621
17. Kuttila SJ, Kuttila MH, Niemi PM, et. al. Arch.Otolaryngol Head Neck Surg 2001;127:401–5.
18. Saal JS, Saal JA, Yurth EF. Nonoperative management of herniated cervical intervertebral disc with radiculopathy. Spine 1996;21:1877–83.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241614EnglishN2014July22HealthcareTECHNICAL CHALLENGES AND SPECTRUM OF LESIONS IN FINE NEEDLE ASPIRATION CYTOLOGY OF BONE LESIONS
English2531C. NirmalaEnglish Priya PatilEnglish Shulba V. SejekanEnglish A. R. RaghupathiEnglishBone lesions can be approached on the basis of history, radiological examination, fine needle aspiration cytology (FNAC) and excision biopsy of the specimen. Objective: To analyze the technical challenges encountered with the procedure of fine needle aspiration cytology of bone lesions. Methods: A prospective study of fine needle aspiration cytology (FNAC) of bone lesions was done as an outpatient procedure in our institution except for small lesions which were done under radiological guidance. A core needle biopsy was done along with aspiration in all the cases. Aspirates were smeared, few were alcohol fixed and rest air dried and stained with H and E and MGG stains accordingly. The corresponding biopsies obtained were fixed in 10% formalin. Results: The current study is comprised of 25 index cases. The incidence of bone lesions was higher in the age group between 5 to 30 years with a male preponderance. Tibia emerged to be the most common bone to be involved. Sample adequacy was observed in 20 cases. Histopathological correlation was available for 23 cases. Of these, 11 cases were benign and 12 cases were malignant. Conclusions: FNAC is a very useful initial diagnostic modality in bone lesions. The main limitation noted in our study was obtaining an adequate material for cases with intact cortex and small lytic lesions. This study signifies the importance of advent of instruments which will aid in piercing the intact cortex and avoid open biopsy and its complication.
EnglishBone FNAC, lytic lesions, cortical erosionINTRODUCTION
Primary bone tumors are rare. Conditions mimicking primary bone tumors (e.g. Metastasis and non-neoplastic conditions) are far more common than the cases of true bone tumors1 . Bone lesions are diagnosed on the basis of history and radiological examination2. The other modalities include fine needle aspiration cytology (FNAC) and excision biopsy of the specimen. FNAC of bone lesions is a challenging procedure as bone is not as easily accessible as other tissue. FNAC of bone tumor was first attempted by Coley, Sharp and Ellis in 1931.3 The reluctance to perform FNAC at many centers is due to the difficulty in accessing hard tissue, inadequacy of material, lack of experienced cytopathologists in this field, lack of radiological guidance at all centers, calcified components, loss of architecture, etc. Many centers practice open biopsies, which is an invasive procedure, time consuming and requires hospitalization. Open biopsy is associated with complications like hematoma formation and pathological fractures. At centers with good radiological guidance, FNAC of bone lesions is emerging as a popular diagnostic modality. FNAC gives accurate results in a shorter duration and thus aids in rapid management. It is an out-patient procedure with minimal complications and also aids multiple site aspirations whereas open biopsy yields single site biopsy. FNAC serves as a very useful diagnostic aid in rural regions and other areas where facilities for surgical biopsies are insufficient.4 There have been varying results in the literature regarding the inadequacy rates ranging from 0– 5%5, 6 to 31–33%.7, 8 The other merits of using FNAC for diagnosing bone lesions include the advantage of utilizing the same material for special investigations like immunohistochemistry (IHC), cytogenetic, electron microscopy, culture etc.9 Together with an experienced cytopathologist, clinical and radiological findings, the accuracy of FNAC of bone approaches almost of that of the histopathology of the same lesion.10 The present study was conducted to assess the technical difficulties encountered with FNAC of bone lesions and also to evaluate the accuracy of FNAC as an initial diagnostic modality for bone lesions. MATERIALS AND METHODS A prospective study of FNAC of bone lesions was done as an outpatient procedure in our institution except for small lesions which were done under radiological guidance. The approach to patients with lytic bone lesions and intact cortex and biopsy was followed as depicted in flow chart 1, 2 and 3 respectively. For large lytic lesions with complete cortical erosion, a 10ml disposable syringe and 22guage needle were used. For deep seated lesions, disposable lumbar puncture needle was used. FNAC of small lytic lesions was done under Computed Tomography (CT) guidance. Few studies mention the use of co-axial drill11 to approach the shaft of long bones; we couldn’t use it due to non-availability of the instrument.A core needle biopsy was done along with aspiration in all the cases. 18 G (Trucut) biopsy needle was used for cortical lesions with erosions and Jamshedi needle was used for bone lesions with intact cortex. Aspirates were smeared, few were alcohol fixed and rest air dried and stained with H and E and MGG stains accordingly. The corresponding biopsies obtained were fixed in 10% formalin. Decalcification was done only in cases containing hard bony tissue followed by routine histopathological processing.
The slides were examined and criteria forassessing and grading the cellularity of the smear, pattern, cell type, cellular atypia and backgroundwere followed as mentioned by Ambreen Moatasim and Anwar UI Haque12in a study on bone lesions.The corresponding core biopsy slides were examined and a Cyto-histopathological correlation was done. Statistical methods: The diagnostic accuracy, sensitivity, specificity of FNAC diagnosis of benign and malignant lesions, positive and negative predictive value of the test was calculated. A positive Cyto-histopathologic correlation was taken as true positive (TP), Cyto-histopathologic disagreement was considered false positive (FP) i.e. cytology reported as malignant and histopathology diagnosed as benign, it was considered false negative (FN) when the cytology was reported as benign lesion and histopathology diagnosed as malignant lesion. Those cases which were diagnosed as benign by both FNAC and histopathology were considered as true negative (TN) 13 .
RESULTS
Our study comprised of 25 index cases. The incidence of bone lesions was higher in the age group between 5 to 30 years with a male preponderance. Tibia emerged to be the most common bone to be involved. The most common clinical symptom was pain followed by swelling, fracture and mixed symptoms. Sample adequacy was observed in 20 cases. Inadequate aspirates were obtained in 5 cases. 2 cases showed lesions located in the femur and its cortex could not be penetrated hence no material was obtained.The 3rd case was a pathological fracture in the shaft of the tibia, showed only hemorrhages on cytology smears, which on histopathology corresponded to metastatic deposits. 2 cases were lytic lesions of the spine and image guided FNAC could not be done. Histopathological correlation was available for 23 cases. 11 cases were confirmed as benign and 12 as malignant on histopathology. The benign lesions were tuberculous osteomyelitis (2), chronic osteomyelitis (2), simple bone cyst (1), aneurysmal bone cyst (2), benign spindle cell lesion (2) and ossifying fibroma (2). The malignant lesions were metastatic deposits (3), osteosarcoma (3), small round cell tumor (3), eosinophilic granuloma (1) and solitary myeloma (2). Among the 23 cases which had histopathological correlation, cytohistological concordance was noted in 19 cases (82.6%) and discordance in 4 cases (17.3%). The sensitivity was 91.6%, specificity 90.9%, diagnostic accuracy 91.3%, positive predictive value 91.65 and negative predictive value 90.9% DISCUSSION The present study highlights the cytological features in 25 cases of bone lesions. The location of the lesion, type of lesion, type of needle used, the experience of the aspirator and the presence of cortical erosion are factors affecting cellular yield. Lesions located in superficial palpable regions, deep seated lesions as in head and neck of femur, body of the spine are difficult to access and always require radiological guidance. Cellular yield also differs by type of lesion. Obtaining adequate material fromthe bone is a technical challenge to the performing pathologist due to the hard nature of the tissue. For large lytic lesions with cortical erosion, with or without soft tissue extension, FNAC can be performed with ease due to the soft nature of the tissue. Those lesions which are small, located in the medulla of the bone without cortical erosion pose difficulty in obtaining material for cytological study. Benign and fibroblastic lesions yield poor cellularity as compared to malignant ones.
Inflammatory lesions yield moderate cellularity. Shaft of long bones is impossible to be penetrated with the available needles and use of drilling machines has been used in a few studies. In our study drilling machine was not used due to nonavailability of the instrument. Presence of cortical erosion- a lesion already eroding the cortex, gives an easy access to obtain cells for study as compared to the dense non eroded cortex. Aspirateswere scanty and hemorrhagic in most of the benign cases. Cystic lesions, such as aneurysmal bone cysts and simple cysts, frequently yield insufficient material.14 In a case of lytic lesion of tibia, 20ml of altered blood (brownish fluid) was aspirated, which did not clot evenafter 15 minutes. The smears showed hemosiderin laden macrophages and a diagnosis of aneurysmal bone cyst was considered and confirmed on open biopsy. In another case of lytic lesion in the shaft of the fibula, 5ml of straw colored fluid was aspirated. Smears were cellular; biopsy confirmed a diagnosis of a solitary bone cyst. Aspirates from malignant primary and metastatic bone lesions were hemorrhagic in most of the cases.
Diagnostic yield was higher in lyticlesions than in sclerotic bone lesions similar to the observation done by Wu15 who in their study mention thatthe significantly lower diagnostic yield for sclerotic versus lytic bone lesions may be due to a “masking” of the underlying lesion by reactive sclerosis. Most often sclerotic lesions require a cutting needle or drill to breach the cortex and / or reactive bone and these samples can be degraded by crush artifacts, hindering histological evaluation and lowering diagnostic yield accuracy. Needles of shorter lengths yielded poor material, which composed of reactive zone only and were inadequate for opinion as notedsimilarly byNnodu et. al. 1 6 in their study. Patients who presented in the later course of the disease showed abreached cortex on x-ray. In these cases approach was easy. Intra cortical lesions posed a technical difficulty, in them bone aspiration and biopsy needles were used. Adequate material was obtained in 20/25 cases. 11 cases showed benign lesions and 12 malignant lesions. There were 3 metastatic cases. In a similar study by Nnodu et. al. 16, adequate material was obtained in90/96 cases, 40 were benign lesions and 47 malignant lesions. Metastasis was noted in 27 cases. One of the cases we reported was an eosinophilic granuloma in an 8 year old girl who presented with acute pain in lower limbs inthe right midthigh region. Clinically it was diagnosed as acute osteomyelitis. This case was a diagnostic challenge to us as initial aspirates were hemorrhagic and had scanty material and inconclusive. Repeat aspirates done under ultrasound guidance yielded cellular material which showed histiocytes along with eosinophils, neutrophils with few osteoclasts in the background. Few of the histiocytes showed characteristic nuclear grooving and finely granular chromatin pattern with inconspicuous nucleoli. With these features, a diagnosis of eosinophilic granuloma was made. Tarik Elsheikh et. al. 17 reported 3 cases of eosinophilic granuloma on FNAC, of which two were seen in male and one in female. All 3 cases were noted in below 15 years of age. One of the cases presented with mid-thigh pain, similar to the case we reported. They performed S-100 protein stain on the aspirated material to demonstrate intra cytoplasmic as well as intranuclear staining of the Langerhan’s cells in all three cases. The accurate diagnosis of metastatic lesions and myeloma on FNAC and cell block avoided unnecessary surgeries in these patients. They were managed with radiotherapy and chemotherapy. The risks of open biopsy include infection, bleeding (especially in metastases from renal carcinoma), weakening of the bone leading to pathological fracture, contamination of surrounding soft tissues, and discomfort associated with surgery18. These can be avoided if FNAC isused as the initial diagnostic modality for bone lesions. The sensitivity of our study was 91.6%, specificity 90.9%, diagnostic accuracy 91.3%, positive predictive value 91.65 and negative predictive value 90.9% as compared to the observations by Ravi et. al. 19 who reported FNAB findings in 91 cases of bone tumors. In their study, the overall sensitivity and specificity was 93.3%, and 94.5% respectively. The positive predictive value was 87.5%, while the negative predictive value was 97.2%. The diagnostic accuracy was 94.23%. Merits: FNAC provides a reliable and rapid diagnosis of bone lesions. Application of FNAC in bone lesions as a diagnostic tool proved to be useful as in most of the cases, treatmentdecisionswere made on the basis of FNAC diagnosis. FNAC as a diagnostic modality proved to be conclusive in metastatic bone lesions. Needle biopsies give accessibility to deep seated lesions and multiple specimens can be obtained without an increase in morbidity. Limitations: The major drawback of the current study is obtaining an adequate material for cases with intact cortex and small lytic lesions. Bone FNAC has not gained wide application because of difficulties in obtaining material for study due to the hard nature of the bone.The regular FNAC procedure can be followed in osteolytic lesions and in lesions with cortical erosions. Those lesions with intact hard cortex require specialized techniques to obtain material for cytological studies. Radiological guidance [x-ray, CT scan] is required in smaller and in deep seated non palpable lesions.
CONCLUSION
FNAC is a very useful initial diagnostic modality in bone lesions. The main limitation noted in our study was obtaining an adequate material for cases with intact cortex and small lytic lesions. This study signifies the importance of advent of instruments which will aid in piercing the intact cortex and avoid open biopsy and its complication.
ACKNOWLEDGEMENT
The authors are thankful to Bangalore Medical College and Research Institute for providing continuous academic support. Authors are thankful to the Head of the Department of Pathology, Bangalore Medical Collegeand Research Institute, Bangalore for the encouragement and support. The authors acknowledge the help received from the authors whose article are cited and included in the references of this manuscript. The authors are also grateful to authors / editors / publishers of all these articles, journals and books from where the literature to this article has been reviewed and discussed. We also acknowledge the generous help of Dr. Pooja Suresh, Assistant Professor, Pathology, Kasturba Medical College, Mangalore for reviewing the manuscript and recommending the required corrections.
Englishhttp://ijcrr.com/abstract.php?article_id=804http://ijcrr.com/article_html.php?did=8041. Davies A.M, Sundaram.M, James S.J. Bone Tumors: Epidemiology,Classification, Pathology. Imaging of Bone Tumors and Tumor-Like Lesions: Techniques and ApplicationsEds. Berlin, Germany: Springer, 2009, 1-15.
2. Sherwani R, Akhtar, K, Abrari A et. al. Fine needle aspiration cytology in the management of tumors and tumor like lesions of bone. JK Science 2006. 8(3), 151-6.
3. Coley BL, Sharp GS, Ellis EB: Diagnosis of bone tumors by aspiration. Am J Surg 1931; 13:214-24.
4. Chakrabarti S, Datta A S, Hira M. Critical Evaluation of Fine Needle Aspiration Cytology as a Diagnostic Technique in Bone Tumors and Tumor-like Lesions. Asian Pacific J Cancer Prev 2012; 13: 3031-5.
5. Khalbuss WE, Teot LA, Monaco SE. Diagnostic accuracy and limitations of fine needle aspiration cytology of bone and soft tissue lesions: a review of 1114 cases with cytological-histological correlation. Cancer Cytopathol 2009; 118 (1): 24–32.
6. Kilpatrick SE, Cappellari JO, Bos GD, Gold SH, Ward WG. Is fine-needle aspiration biopsy a practical alternative to open biopsy for the primary diagnosis of sarcoma? Am J Clin Pathol2001; 115:59–68.
7. Jorda M, Rey L, Hanly A, Ganjei-Azar P. Fine-needle aspiration cytology of bone: accuracy and pitfalls of cytodiagnosis. Cancer 2000; 90 (1): 47–54.
8. Dollahite HA, Tatum L, Moinuddin SM, Carnesale PG. Aspiration biopsy of primary neoplasms of bone. J Bone Joint Surg 1989; 71:1166–9.
9. Sahoo M, Sahai K, Nayak VM. Scapulohumeral tuberculosis diagnosed by fine needle aspiration cytology. Acta Cytol 1998; 42:435-6.
10. Kabukcuoglu F, Kabukcuoglu Y, Kuzgun U, Evren I. Fine needle aspiration of malignant bone lesions. Acta Cytol 1998; 42 (4): 875-82.
11. Whit LM, Schweitzer ME, Deely DM. Coaxial Percutaneous Needle Biopsy of Osteolytic Lesions with intact Cortical Bone. Am J Radiol 1996;166:143-4.
12. Moatasim A and Haque A UI.Spectrum of Bone Lesions Diagnosed on Fine Needle Aspiration Cytology. International J Pathol; 2005; 3 (2): 57-64.
13. Agrawal PK, Goyal MM, Chandra T, Agrawal S. Predictive Value of FNAB of bone lesions. Acta Cytol 1997; 41:659-65.
14. Ayala, A G and Zornosa J. Primary Bone Tumors: Percutaneous Needle Biopsy. Radiologic-Pathologic Study of 222 Biopsies. Radiology 1983; 149: 675–9.
15. Wu J S, Jeffrey D, Goldsmith, Perry J, Horwich, Shetty S K, Mary G, Hochman. Bone and Soft-Tissue Lesions: What Factors Affect Diagnostic Yield of Image-guided Core-Needle Biopsy? Radiology 2008; 248:962–70.
16. Nnodu OE, Giwa S, Eyesan SU, Abdulkareem FB. Fine needle aspiration cytology of bone tumors--the experience from the National Orthopaedic and Lagos University Teaching Hospitals, Lagos, Nigeria. Research CytoJournal 2006, 3:16.
17. Elsheikh T, Silverman JF, Wakely PE , Holbrook CT, Joshi V V. “Fine-needle aspiration cytology of Langerhans' cell histiocytosis (eosinophilic granuloma) of bone in children. Diagn Cytopathol 1991; 7 (3): 261–6.
18. Wedin R, Bauer HFC, Skoog L, Söderlund V, Tani E. Cytological diagnosis of skeletal lesions: fine-needle aspiration biopsy in 110 tumors. J Bone Joint Surg 2000;82:673–8.
19. Mehrotra R, Singh M, Singh P A, Mannan R, Ojha V K, Singh P. Should fine needle aspiration biopsy be the first pathological investigation in the diagnosis of a bone lesion? An algorithmic approach with review of literature. Cytojournal 2007; 4: 9–18.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241614EnglishN2014July22HealthcarePREVALENCE OF CRYPTOCOCCAL MENINGITIS AMONGST HIV SEROPOSITIVE CASES FROM A TERTIARY CARE HOSPITAL
English3237Rajani SharmaEnglish Nandini DuggalEnglish Shalini MalhotraEnglish Dinesh ShrivastavaEnglish Charoo HansEnglishBackground: Cryptococcal meningitis has emerged as an important opportunistic central nervous system (CNS) infection in Human immunodeficiency virus (HIV) positive patients. It is associated with a high mortality rate hence early diagnosis is necessary to improve the prognosis. Objectives: This study was undertaken to determine the prevalence of cryptococcal meningitis in HIV seropositive cases as well as to determine the correlation with CD4 counts. Methods: A total of 50 patients suspected to be suffering from chronic meningitis were subjected to cerebrospinal fluid (CSF) analysis (including India ink preparation, culture by conventional methods and antigen detection). Results: The prevalence of cryptococcal meningitis in this study was 30%. Outcome was fatal in 6/15 cases showing a mortality rate of 40 percent. The patients with CD4 count < 50 cells/ul had highest mortaliy rate i.e. 50%. Conclusion: High prevalence and mortality rate of cryptococcal meningitis in HIV-infected patients require a high index of suspicion and routine mycological surveillance to establish an early diagnosis and appropriate management.
EnglishCryptococcus neoformans, HIV, Immunocompromised, MeningitisINTRODUCTION
Cryptococcal meningitis is an opportunistic fungal infection which is relatively rare in immunocompetent individuals and occurs when host immune status becomes impaired. The predisposing conditions include HIV infection, diabetes, immune-suppressive therapy after solid organ transplantation, hematological malignancies, etc [1]. Cryptococcal meningitis is difficult to diagnose clinically as presenting symptoms are indistinguishable from other causes of subacute and chronic meningitis. It is associated with a high mortality rate, hence early diagnosis is necessary to avoid complications. Since the onset of acquired immunodeficiency syndrome (AIDS) epidemic, cryptococcal meningitis has emerged as an important opportunistic CNS infection in HIV positive patients [2, 3]. According to NACO and UNAIDS estimates [4], 2-3.1 million people were living with HIV infection in India and 33.4 million people worldwide at the end of 2008. It has been found that early diagnosis and appropriate treatment of cryptococcal meningitis can reduce the HIV related morbidity and mortality significantly. The present study was undertaken with a view to find the prevalence of cryptococcal meningitis in HIV seropositive cases. The correlation between CD4 count and the occurrence of cryptococcal meningitis in these cases was also analyzed.
MATERIAL AND METHODS
This study was conducted in the department of Microbiology of P.G.I.M.E.R and associated Dr. Ram Manohar Lohia Hospital, New Delhi between 2010 and 2011. Fifty HIV seropositive patients with clinical suspicion of chronic meningitis were enrolled in the study. CSF samples from these patients were received and processed for diagnosis of suspected cryptococcal meningitis. CSF sample was inoculated on two sets of SDA (Sabouraud’s Dextrose Agar) and they were incubated at 25°C and 37°C, separately, over a period of 4 weeks. All the cultures were examined daily during the first week and twice a week during the next 3 weeks. An India ink preparation of all the CSF samples was made to examine the presence of capsulated budding yeast cells. Latex agglutination on CSF samples was performed by using cryptococcal antigen detection kit (Meridian diagnostics). Further characterization of Cryptococcus isolates was done by various microbiological tests like sugar assimilation and fermentation, growth on Niger seed agar and on Canavanine glycine bromothymol blue agar. CD4 count estimation was done using FACS caliber (Beckton and Dickinson) system.
RESULTS
Out of fifty HIV positive patients with clinical suspicion of chronic meningitis, fifteen patients (30% isolation rate) were found to be positive for Cryptococcus. The positivity rate of India ink, culture on SDA and cryptococcal antigen test was found to be 100%. Cryptococcal meningitis was found to be more common in 30-39 yrs. age group with male: female ratio of 13:2. [Figure1] The most common symptom of cryptococcal meningitis was fever which was present in all the patients followed by headache for more than 2 weeks duration seen in 77% of males and in 100% female patients. Altered sensorium was seen in 77% of males and 50% of females while seizures were seen in 62% of males and 50% of females. [Figure 2] Amongst the fifteen patients of Cryptococcal meningitis, CD4 count Englishhttp://ijcrr.com/abstract.php?article_id=805http://ijcrr.com/article_html.php?did=8051. Clark TA, Hajjeh RA. Recent trends in the epidemiology of invasive mycosis. Curr Opin Infect Dis 2002; 15: 569-74.
2. Bicanic T, Harrison TS. Cryptococcal meningitis. British Medical Bulletin 2005; 72:99-118
3. Casadevall A, Perfect JR: Cryptococcus neoformans. 1st edition. Washington: American Society for Microbiology Press; 1998. 3
4. UNAIDS – AIDS Epidemic Update 2009:www.unaids.org 4
5. Jaiswal SP, Hemwani N, Sharma N, Athale S, Chitnis DS. Prevalence of fungal meningitis, among HIV positive and negative subjects. Indian J Med Sci 2002; 56:325-9. 5
6. Lakshmi V, Sudha T, Teja VD, Umabala P. Prevalence of central nervous system Cryptococcosis in Human Immunodeficiency Virus reactive hospitalized patients. Indian J Med Microbiol 2007; 25:146-9.
7. Patel A.K., Patel KK., Ranjan R., Shah S., Patel J.K. Management of cryptococcal meningitis in HIV infected patients: Experience from western India. Indian J Sex Transm Dis 2010; 31:22-26.
8. Kumar S, Wanchu A, Chakrabarti A, Sharma A, Bambery P, Singh S. Cryptococcal meningitis in HIV infected: Experience from a North Indian tertiary centre. Neurol India 2008; 56:444-49.
9. Manoharan G, Padmavathy BK, Vasanthi S, Gopalte R. Cryptococcal meningitis among HIV-infected patients. Indian J Med Microbiol 2001; 19:157-8.
10. Prasad KN, Agarwal J, Nag VL, Verma AK, Dixit AK, Ayyagiri A. Cryptococcal infection in patients with clinically diagnosed meningitis in a tertiary care centre. Neurol India 2003; 51:364-366.
11. Crowe SM, Carlin JB, Stewart KI, Lucas CR, Hoy JF. Predictive value of CD4 lymphocyte numbers for the development of opportunistic infections and malignancies in HIV-infected persons. J Acquir Immune Defic Syndr 1991; 4:770-6.
12. Powderly WG. Cryptococcal meningitis and AIDS. Clin. Infect. Dis.1993; 17:837–842.
13. Moosa MYS, Coovadia YM. Cryptococcal Meningitis in Durban, South Africa: A Comparison of Clinical Features, Laboratory Findings, and Outcome for Human Immunodeficiency Virus (HIV)-Positive and HIV-Negative Patients. Clinical Infectious Diseases 1997; 24:131-4.
14. Cameron ML, Barlett JA, Gallis HA, Waskin HA. Manifestations of pulmonary cryptococcosis in patients with acquired immunodeficiency syndrome. Rev Infect Dis 1991; 13:64-7.
15. Lipson BK, Freeman WR, Beniz J, et. al. Optic neuropathy associated with cryptococcal arachnoiditis in AIDS patients. Am J Ophthalmol 1989; 107(5):523-7.
16. Kumaraswamy N, Solomon P, Flaningan TP, Hemalatha R, Thyagarajan SP, Mayer KH. Natural history of human immunodeficiency virus disease in southern India. Clin Infect Dis 2003;36:79-85.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241614EnglishN2014July22HealthcareFEASIBILITY OF POST PARTUM INSERTION OFINTRAUTERINE CONTRACEPTIVE DEVICE- EXPANDING THE USE OF INTRAUTERINE CONTRACEPTIVE DEVICE IN POST PARTUM PERIOD - A CROSS SECTIONAL STUDY IN DEVELOPING COUNTRY, INDIA
English3848Sudha T. R. BanapurmathEnglish Girija B. S. DotradEnglish Nirmala DoreswamyEnglish ShyamalaEnglishAim: Post partum contraception is the best evidence based intervention in prevention of pregnancy and abortion related maternal morbidity and mortality in the developing countries. The unmet need for contraception among women in the postpartum period can be effectively fulfilled by post partum insertion of IUCD, in a single visit under the Government scheme of providing free maternity services during institutional delivery. PPIUCD is an effective, safe, reversible method of long term contraception with high reported expulsion and low perforation rate, compared to interval insertion. Objective: To evaluate the acceptability, safety, efficacy and feasibility of PPIUCD as a method of post partum contraception. Study design: This is a prospective cross sectional study conducted between October 2011 to December 2013 at Sri Chamarajendra Government Hospital, Hassan, Karnataka, India. 26,123 pregnant women were counseled (clients) for Post partum IUCD insertion as a method of contraception in pregnancy, early in labor and in the immediate post partum period (EnglishPost-partum intrauterine contraceptive Device (PPIUCD), Post placental, Client, Caesarian Delivery, Expulsion, Contraception, Counseling.INTRODUCTION
The maternal health is one of the health indicators of the country. The antenatal, labor and postpartum period is the crucial period of optimal maternal care that influences the outcome of pregnancy. Poor spacing between pregnancies, the unmet need for post partum contraception may lead to intervention in an unwanted subsequent pregnancy. Postpartum insertion of IUCD (PPIUCD) is a method of post partum contraception that may be utilized to overcome the unmet need of contraception, in a single hospital visit during institutional delivery. The postpartum period following three months after delivery, weaning from breast feeding and resuming sexual activity among married couple, is the risk period for unintended pregnancy. This necessitates the use of some postpartum reversible contraception which is met by PPIUCD insertion. Approximately 27% of women in India practice birth to birth interval of 18 hours, intractable post partum hemorrhage (atonic or traumatic) and abnormal uterine cavity.
However contraindications are few. This expands the client number for PPIUCD insertion. Limitations of PPIUCD as a method of post partum contraception are: High expulsion rate compared to interval insertion. The expulsion rate is 5-10%which means retention rate of 90-95%. Post placental and intra caesarian insertions have low expulsion rate. Expulsion rates may be reduced by appropriate fundal placement of IUCD which is acquired through skill training in PPIUCD insertion3, 5 .
RESULTS
The data of PPIUCD services provided, observations during follow up of clients were as shown in Observations (charts1a, b-chart 5).
Acceptibility
Acceptability for PPIUCD among women was 7.0%. The observation are as shown in charts 1and 2
Total number of monthly PPIUCD inserted as shown in chart-1
Observations:
1. Client characteristics
All the clients who accepted for PPIUCD insertion were in the reproductive age group (20-40yrs).
Follow up of clients: follow up of clients were conducted at 6, 10, and 14 weeks or earlier when necessary.During follow up, the observations were made regarding removal, expulsion and safety of PPIUCD. The Results were as followsEfficacy of PPIUCD as a contraceptive Efficacy of PPIUCD as contraceptive were assessed by pregnancy rate, Expulsion rate, removal and retention rate of IUCD. Pregnancy rate :- There were no pregnancies observed among clients in the study period. Hence the failure rate was 00% that shows that PPIUCD is efficient in prevention of pregnancy among the clients who continued to retain it. Expulsion of IUCD : 06/1832(0.32%) of clients reported spontaneous, expulsion within 10 weeks of insertion which was confirmed by clinical and Ultrasound examination. These clients were offered reinsertion but all of them refused. They were counseled for alternate methods of contraception. Missing strings Missing string was termed when the string was not seen at 6 weeks, at the external os of cervix, during per speculum vaginal examination of clients in the post partum clinic. Among the 289 clients followed for 14 wks post partum, missing strings during the follow up in the clinic was observed in 39 clients (13.5%). An ultrasound examination confirmed the presence of IUCD in the uterine cavity. Many clients who were examined clinically had the string curled in vagina or cervical canal. They were reassured and re-examined at 10 and 14 weeks. They continued with IUCD as a long term contraceptive. Safety of PPIUCD Safety of IUCD was assessed by the clients Reported Side effects and complications of IUCD such as infection, menstrual abnormality, perforation ,and expulsion. The complications were few and were managed symptomatically. They are shown in chart-5.
Rate of infection
None of the clients reported nor had infection (00%) in the present study. Menstrual abnormality There were no reports of menorrhagia nor any abnormal vaginal bleeding among the clients followed in the study period. Perforation of uterus No perforation of uterus by IUCD has been observed in the present study. Client reported symptoms Many clients reported to post partum clinic with lower abdominal pain and pricking sensation. They had urinary infection, constipation or non specific symptoms, and were reassured and treated accordingly. All these women continued to retain IUCD. Removal of PPIUCD 14/ 1832 clients requested for removal of IUCD due to personal and social reasons, but none got it removed for side effects such as infection, Menorrhagia and abdominal pain. Increase in awareness of advantages of PPIUCD, and reassurance by the attending health care worker later reduced the removal rate. Retention of IUCD 1812(98.90%) clients were willing to continue IUCD by 14 wks, 14 (0.76%) were not willing to get reinsertion of IUCD and preferred an alternate method of contraception. The Retention rate was 98.9%, which showed that PPIUCD was effective in meeting the unmet need of contraception in the post partum period.
DISCUSSION
Many studies have been published regarding the efficacy, safety of PPIUCD .This was a cross sectional study, at Sri Chamarajendra Government Hospital, Hassan District, Karnataka, India to evaluate the acceptability, feasibility, safety and efficacy of PPIUCD. Lara Ricalde R et. al. has reported an acceptance rate of 28.9% (1,024 /3,541) 6. In this study the acceptance rate was lower, probably due to low IUCD insertion rates in low resource settings in India. Mohammed et. al. observed that Acceptance rate was the same during antenatal and postpartum counseling, 26.4 and 31.8%, respectively10.. Indian experience 0f 2 years, PPIUCD services have been established in over 50 facilities across 19 states of India, with the Government of India undertaking more than 22,000 PPIUCD insertions in the target facilities, with 5% of women delivering in these institutions accepting PPIUCD as their choice of contraception17. In the present study the acceptance rate was higher (7%). The acceptability of intracaesarian placement of IUCD was highest followed by post placental IUCD insertion.
Among clients who accepted for PPIUCD, many refused for PPIUCD insertion due to demotivation by relatives and friends. This was observed as a major barrier for implementation of PPIUCD in this study. The rate of return for follow-up visit were 221 (94%), 210 (89%) and 183 (78%) at 6 weeks, 6 months and 12 months, respectively. Timing of IUCD insertion after vaginal and cesarean delivery were 74% and 26%. Continuation rates of IUCD were relatively high, 87.6% and 76.3%, at 6 and 12 months, respectively. The 1-year cumulative expulsion rate with CuT 380A device was 12.3%11. . In the present study the follow up was very low. Modifications of existing devices, such as adding absorbable sutures or additional appendages did not appear beneficial. Efficacy of interval insertion of IUCD was comparable with PPIUCD13. Most studies showed no differences between insertions done by hand or by instruments8, 16. The RHL review 2010, shows a total of nine trials with 7660 subjects, One trial (102 women) had compared immediate postpartum versus delayed insertion (6–8 weeks postpartum) of the levonorgestrelreleasing intrauterine system. A trial directly compared immediate versus delayed insertion reported that at 6 months the two groups were similar in terms of pregnancy prevention.21 FHI data show a significantly higher (p0.05) expulsion rate associated with insertions performed within the period of >10 minutes to 36 hours as compared to the immediate post placental period (within 10 minutes)8..we found no such relation regarding timing of insertion and expulsion rate. Complications observed were more in delayed post partum insertion than immediate post placental insertion6 . Other trials did not have uniform interventions; hence we were unable to aggregate them in this analysis. Advantages of immediate post-partum insertion include high motivation, assurance that the woman is not pregnant, and provider and client convenience6 , 1821,22,23. Lara Ricalde R et. al., observed no infection among clients. The expulsion rates were 10.4, removal rates for bleeding and pain were 4.9 and 4.8, for non medical reasons were 3.7 and 4.9 respectively for the Multiload Cu 375 and 7.7 for the CuT 380A by 10 weeks. There were no pregnancies, nor uterine perforation that is similar in this study. Xu J. et. al. observed a gross cumulative expulsion rate for the manual insertion group after 6, 12, 24, and 36 months were 8.61, 13.55, 15.78, and 16.90 %, respectively with gross expulsion rates for the ring forceps insertion group were 12.99, 17.23, 17.77, and 18.34 %, respectively. The differences between the two groups were not statistically significant12 . . In studies by Family Health International (FHI), expulsion rates varied widely between centers using similar devices. Expulsion rates ranged from 6-37/100 women at 6 months after insertion13.Sahajakittur and Kabade reported expulsion of 5.23%. No major complications and. perforation were observed in this series22. The expulsion rate in present study was very low (0.32%) in comparison with other studies, probably due to skilled training in fundal placement of IUCD. Thiersh et. al. reported that there were no pregnancies and use continuation was 77%.18 Indian experience showed that at 6 weeks postpartum, 90% of women have continued with the same IUCD. Infection rate was of 4.5% and 7% got the IUCD removed within the first 6 weeks of insertion due to bleeding and abdominal pain17.In the present study 0.76% were removed for non medical reasons, and 98.90% IUCD were retained at 14 weeks follow up.
CONCLUSION
PPIUCD is a feasible, safe and effective method of postpartum contraception among women in low resource settings, during a single visit for institutional delivery, to empower women to meet their unmet need of contraception that may be continued as a long term reversible contraception Limitation of the study In the present study 1) Sample size is small and further study with larger sample size is recommended. 2) Follow up rate is inadequate - hence there is a need to increase the follow up of clients for an analysis of data regarding safety and efficacy of PPIUCD. 3) Duration of follow up is short. Hence retention rate, safety and efficacy of IUCD as a long term reversible method of contraception could not be assessed.
IMPLICATIONS FOR RESEARCH
There is a need for long term follow up, retention rates and short- and long-term risk of pelvic infections associated with the high incidence of reproductive tract infections in low resource settings.
Recommendations
PPIUCD is a feasible method of contraception in post partum period that can be retained as a long term reversible contraception.Adequate training and supervision of delivery roomhealth providers/ staff in insertion of IUDs is Feasible. Midwives / staff nurses can be trained to insert the IUD after delivery through realistic demonstrations on Zo-E models (fig-1). Repeated PPIUCD sensitization and awareness programmes, client monitoring at Primary care centres, improvised accessibility of PPIUCD services by integrating post partum contraceptive services with Institutional maternity services, are recommended to upscale the PPIUCD services in low resource settings to prevent unintended pregnancy. This may be considered as an important evidence based intervention in averting maternal mortality in low resource settings.
ACKNOWLEDGEMENTS
We sincerely thank -The Ministry of Health and Family welfare, Government of India, and Karnataka state, and Our Mentors – JPIEGO, for training and providing technical assistance to start, implement, maintain the PPIUCD services.and in training other service providers. We thank all the women who accepted and participated in the study. Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles. Journals, manuals and books from where literature for this article has been reviewed and discussed. Funding The study was conducted in a government funded hospital under the provision of free maternity services. No special funding was obtained for this study.
Englishhttp://ijcrr.com/abstract.php?article_id=806http://ijcrr.com/article_html.php?did=8061. National Rural Health Mission Ministry of Health and Family Welfare Government of India. JSY. Available at http://www.mohfw.nic.in/layout_09- 06;.pdf.Accessed;19September;2012
2. India Reproductive health surveyNFHS, 2003,2010- Family planning Fact sheets of India
3. A global hand book for providers and PPIUCD training materials, JPIEGO.
4. The Population Council and the Program for Appropriate Technology in Health (PATH). The Copper T 380A IUCD: A Manual for Clinicians. 2nd ed. Seattle, Washington: PATH, 1989. Consensus 2011, provisional population totals; office of the Registrar General and census commissioner, India Ministry of home affairs, 31st March2011
5. Post Partum IUCD Reference Manual,November 2010:Family planning division,ministry of Health and Family welfare.
6. Grimes.D,SchulzK,VlietH,Stanwood.N;,Imme diatepost partum insertion of IUCD;TheCochranesystemicdatabase of systemic Reviews;2003;1,Art no.CD003036, DOI:1002/14651858.CD003036. PMID: 11406064 [PubMed - indexed for MEDLINE]
7. Performance standards for immediate PPIUCD counseling and services,April,20113;(NRHM,GOI);The USAID/WHO manual family planning.
8. Lara Ricalde R, Menocal Tobías G, Ramos Pérez C, Velázquez Ramírez N;-Random comparative study between intrauterine device Multiload Cu375 and TCu 380a inserted in the postpartum period,Departamento de planificación familiar del InstitutoNaciónal de Perinatología. Lomas Virreyes, México. lararoger@yahoo.com.mx pub med.
9. Morrison C, Waszak C, Katz K, Diabate F, Mate EM; Clinical out-comes of two early postpartum IUCD insertion programs in Africa. Contraception 1996;53:17-21.
10. Mohamed SA, Kamel MA, Shaaban OM, Salem HT;Acceptability for the use of postpartum intrauterine contraceptive devices: Assiutexperience.,Medprinc pract.2003,julsep;12(3):170-5
11. Celen S, Möröy P, Sucak A, Aktulay A, Dani?man N; Clinical outcomes of early postplacental insertion of intrauterine contraceptive devices.;Contraception,2004 Apr:69(4):279-82.
12. Xu J, Yang X, Gu X, Xu S, Zhou X, Chen Y, Xiao Z, Zhuang L Comparison between two techniques used in immediate postplacental insertion of TCu 380A intrauterine device: 36- month follow-up.; ReproductiveContraception.1999; 10(3):156- 62
13. Ero?lu K, Akkuzu G, Vural G, Dilbaz B, Akin A, Ta?kin L, HaberalAComparison of efficacy and complications of IUD insertion in immediate postplacental/early postpartum period with interval period: 1 year follow-up.; Cochrane Database Syst Rev. 2001;(2):CD003036. Update in: Cochrane Database Syst Rev. 2003;(1):CD003036.
14. Cole LP, Edelman DA, Potts DM, Wheeler RG, Laufe LE. Postpartum insertion of modified intrauterine devices;J Reprod Med. 1984 Sep;29(9):677-82
15. O'Hanley K, Huber DH;Postpartum IUDS: keys for success;.;Contraception. 1992 Apr;45(4):351-61.
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17. B.Sood et. al.,Jhpiego/India, New Delhi, IndiaR. Asif, E. Charurat, S. Das, S. Kumar, C.McKaig,,M.Rath,,S.Saha,R.Sethi,V. Srivastava,V.Yadav ;Revitalization of postpartum IUCD (PPIUCD) services: experience from India, http://dx.doi.org/10.1016/j. Contraception;Volume 86, Issue 2, August 2012, Pages 184–185,
18. Thiery M, Van Kets H, Van Der Pas H. Immediate postplacental IUD insertion: the expulsion problems. Contraception 1985;31;331-349
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21. Muthal-Rathore A. Immediate postpartum insertion for intrauterine devices: RHL commentary (last revised: 1 September 2010). The WHO Reproductive Health Library; Geneva: World Health Organization
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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241614EnglishN2014July22HealthcareA RARE CASE OF FIBROUS PSEUDO TUMOR
English4953Sudha V.English Ganthimathy SekharEnglish KarunakumarEnglish JayaganeshEnglish Vimal Chander R.EnglishFibrous pseudotumor or periorchitis is a reactive fibromatous proliferation that might involve the coverings of the testis, spermatic cord and epididymis. It is believed to be a reactive, non-neoplastic lesion that may clinically mimic testicular malignancy. Here, we present a case of fibrous pseudo tumor in a 72-year-old male.
EnglishPeriorchitis, pseudotumorINTRODUCTION
Benign intrascrotal fibrous proliferations (fibrous pseudotumor of scrotal contents) are uncommon with most arising from the paratesticular region. They have been variably designated as chronic proliferative periorchitis, inflammatory pseudotumor, pseudofibromatousperiorchitis or reactive periorchitis.1,2,3 These lesions are usually nodular and involve the testicular tunics. They may also be diffuse and involve the epididymis and spermatic cord. Clinically they mimic malignancy resulting in the treatment by radical orchidectomy.4,5,6
CASE HISTORY
A 72-year-old male came with the complaints of a right-sided inguinal swelling of three years duration. On examination, he was found to have an inguinal hernia with a nodular hard scrotal mass on the same side. There were no other significant physical findings. The scrotum and testis of the other side were normal. Right herniorraphy with high orchidectomy was performed .The orchidectomy specimen was sent for histopathological examination. We received a specimen of right testis with cord structures measuring 7x5x3 cm .The mass was hard in consistency with a nodular external surface. It was gritty and hard to cut. The cut surface revealed fibrosed and thickened wall with chalky white areas measuring about 3 cm in thickness with the testis at the lower pole measuring 2x2 cm .The testis and spermatic cord appeared normal grossly. [Figures 1 and 2] Light microscopic sections studied from the testis showed atrophic seminiferous tubules separated by clusters of hyperplastic Leydig cells. [Figures 3,4 and 5] The wall surrounding the testis showed dense fibrous tissue with keloid like bands of collagen and large areas of calcification. Sparse scattered mononuclear inflammatory cells were present. [Figures 6,7 and 8] DISCUSSION Fibromatous lesions of testicular tunics were recognized by Sir Astley cooper in 1830.4The term Fibrous pseudotumor was introduced by Mostofi and Price.5 It is an uncommon lesion with an incompletely understood etiology. It’s a reactive non neoplastic condition that most often affects patients in their second and third decade of life and is very rare before 18 years.5,7,8,9,10 Only 4 cases have been reported under 18 years.
Benign intrascrotal fibrous proliferations (fibrous pseudotumor of scrotal contents) are uncommon with most arising from the paratesticular region. They have been variably designated as chronic proliferative periorchitis, inflammatory pseudotumor, pseudofibromatousperiorchitis or reactive periorchitis.1,2,3 These lesions are usually nodular and involve the testicular tunics. They may also be diffuse and involve the epididymis and spermatic cord. Clinically they mimic malignancy resulting in the treatment by radical orchidectomy.4,5,6 CASE HISTORY A 72-year-old male came with the complaints of a right-sided inguinal swelling of three years duration. On examination, he was found to have an inguinal hernia with a nodular hard scrotal mass on the same side. There were no other significant physical findings. The scrotum and testis of the other side were normal. Right herniorraphy with high orchidectomy was performed .The orchidectomy specimen was sent for histopathological examination. We received a specimen of right testis with cord structures measuring 7x5x3 cm .The mass was hard in consistency with a nodular external surface. It was gritty and hard to cut. The cut surface revealed fibrosed and thickened wall with chalky white areas measuring about 3 cm in thickness with the testis at the lower pole measuring 2x2 cm .The testis and spermatic cord appeared normal grossly. [Figures 1 and 2] Light microscopic sections studied from the testis showed atrophic seminiferous tubules separated by clusters of hyperplastic Leydig cells. [Figures 3,4 and 5] The wall surrounding the testis showed dense fibrous tissue with keloid like bands of collagen and large areas of calcification. Sparse scattered mononuclear inflammatory cells were present. [Figures 6,7 and 8]
DISCUSSION
Fibromatous lesions of testicular tunics were recognized by Sir Astley cooper in 1830.4The term Fibrous pseudotumor was introduced by Mostofi and Price.5 It is an uncommon lesion with an incompletely understood etiology. It’s a reactive non neoplastic condition that most often affects patients in their second and third decade of life and is very rare before 18 years.5,7,8,9,10 Only 4 cases have been reported under 18 years.
Most patients present with a slowly growing mass in the subcutaneous or deep soft tissues and may be associated with systemic symptoms. Although uncommon, reactive fibrous proliferative lesions apparently represent the third most common benign tumor forming paratesticular condition after spermatic cord lipoma and epididymaladenomatoid tumor.4,11 Jones et al proposed a classification for benign fibrous proliferations of the testis and paratesticular region based on the neoplastic or non-neoplastic nature of the lesion and separated the lesions / tumors into various categories based on clinical and pathologic features, location, and immunohistochemical studies.1 They and others believe that certain intrascrotal fibrous proliferations are truly neoplastic;4, 12 however, it is generally agreed that fibrous pseudotumors, nodular and diffuse, are reactive, non neoplastic lesions.4,13 Although fibrous pseudotumors of the testicular tunics are accepted as reactive lesions, their pathogenesis is not well understood. They are often associated with hydrocele in 50 %, trauma, infection or inflammatory process in 30 %.5,14 Some suggest lymphatic obstruction have a role in the development of these lesions.5The cell of origin for fibrous pseudotumor appears to be the fibroblast or myofibroblast as suggested by Immunohistochemistry.9 The terms fibroma, non specificperitesticular fibrosis, nodular fibrous periorchitis, chronic proliferative periorchitis, proliferative funiculitis, nodular fibropseudotumour, inflammatory pseudotumor, reactive periorchitis, pseudofibrousperiorchitis, peritesticularfibromatosis, and fibrous mesothelioma have been used for this lesion partly reflecting the variable and overlapping spectrum of pathological findings and various etiological theories.1,2,3 Some have restricted the use of “Pseudotumor” to mass forming lesions and have used “Fibrous periorchitis” for more diffuse lesions. The morphology of the non-neoplastic lesions shows variable histology; some contain spindle cells with a whorled appearance and hyalinized collagen. The burnt out lesions are represented by focal (dystrophic) calcification and ossification. Histology may show cellular, granulation tissue type fibrous proliferation and markedly reactive stromal cells.15 There may be an inflammatory component including plasma cells, histiocytes, eosinophils and lymphocytes.
CONCLUSION
Fibrous periorchitis is distinctly uncommon reactive or non-neoplastic lesion, which should be considered in the differential diagnosis when one encounters a lesion with predominantly fibro collagenous stroma.
ACKNOWLEDGEMENT
Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.
Englishhttp://ijcrr.com/abstract.php?article_id=807http://ijcrr.com/article_html.php?did=8071. Jones MA, Young RH, Scully RE. Benign fibromatoustumours of the testis and the para testicular region: A report of 9 cases with proposed classification of fibromatoustumours and tumour like lesions. Am J Surgpathol 1997;21:296-305.
2. Benisch B, Peison B, Sobel HJ. Fibrous mesotheliomas (Pseudofibroma) of the scrotal sac: A light and ultra structural study. Cancer 1981;47:731-5.
3. Srigli JR, Hartwick RW. Tumors and cysts of paratesticular region.PatholAnnu1990;25:51- 108
4. Ulbright TM, Amin MB, Young RH. Tumors of the Testis, Adnexa, Spermatic Cord, and Scrotum.Atlas of Tumor Pathology.3rd series.Fascicle 25. Edited by Juan Rosai: Washington, DC: Armed Forces Institute of Pathology; 1999: 317-9.
5. Mostofi FK, Price EB. Tumors of the Male Genital System.In Atlas of Tumor Pathology.2nd series.Fascicle 8. Edited by Harlan I.Firminger: Washington, DC: Armed Forces Institute of Pathology, 1973:151-4
6. Parveen T, Fleischmann J, Petrelli M. Benign fibrous tumor of the tunica vaginalis testis. Report of a case with light, electron microscopic, and immunocytochemical study, and review of the literature. Arch Pathol Lab Med. 1992;116:277-80.
7. FetschJF,Montgomery EA, Meis JM. Calcifying fibrous pseudotumor. Am J SurgPathol1993;17:502
8. Jimenez-Heffernan JA,Urbano J, Tobio R, et al.Calcifying fibrous pseudotumor: a rare entity related to inflammatory pseudotumor.Actacytol 2000;44;932
9. Seethala RR, Tirkes AT, Weinstein S, Tomaszewski JE, Malkowicz SB, Genega EM. Diffuse fibrous pseudotumor of the testicular tunics associated with an inflamed hydrocele. Arch Pathol Lab Med 2003, 127:742-4
10. Bostwick DG. Spermatic cord and testicular adnexa. In: Bostwick DG, Eble JN (eds). Urologic Surgical Pathology. St Louis, MO: CV Mosby Co; 1997:647–674.
11. Tobias-Machado M, Correa Lopes Neto A, HeloisaSimardi L, Borrelli M, Wroclawski ER. Fibrous pseudotumor of tunica vaginalis and epididymis. Urology 2000; 56:670xx– 670xxii.
12. Parveen T, Fleischmann J, Petrelli M. Benign fibrous tumor of the tunica vaginalis testis. Arch Pathol Lab Med. 1992;116:277–280.
13. Oliva E, Young RH. Paratesticular tumor-like lesions.SeminDiagPathol. 2000;17:358.
14. Akbar SA, Sayyed TA, HasanJafri SZ, Hasteh F, Neill JSA. Multimodality imaging of paratesticular neoplasms and their rare mimics.Radiographics 2003; 23:1461–1476.
15. HollywoodK, Fletcher CDM. Pseudosarcomatousmyofibroblastic proliferations of the spermatic cord (“Proliferative funiculitis”)Histologic and immunohistochemical analysis of a distinctive entity. Am J surgpathol 1992;16:448-454
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241614EnglishN2014July22HealthcareCLINICO - MORPHOLOGICAL STUDY OF SKIN DISEASES
English5457R. ThamilselviEnglish K. SivakamiEnglish PammysinhaEnglish P.M. SubramaniamEnglishBackground: Skin diseases constitute a major public health problem. The pattern of skin diseases vary from one country to another country. Disease pattern also vary from tissue reactions to vesiculobullous lesions and malignant lesions. Aim: To analyze the clinico-morphological spectrum of skin lesions. Methods: A retrospective study was undertaken to determine the clinico-morphological spectrum of skin lesions from all the skin biopsies, received from Jan 2009 to Aug 2011 (2 and ½ years) in the Department of Pathology, Vinayaka Mission’s KirubanandaVariyar Medical College, Salem. Results: A total of 178 cases were reviewed and analysed. The highest number of patients were in the age group of 51-60 years.The incidence of dermatological diseases was more in male patients than female patients. Cystic lesions (26%) were the commonest lesions followed by infectious diseases of skin (13.4%), malignant tumors of skin (13%), alteration in the dermal collagen (8%). Most common site for various skin lesions was extremities followed by scalp region. Clinically the lesionswerevarying from papule, macule, vesicles, nodules to ulcers. The two major tissue reaction patterns, the psoriasiform and the lichenoid reactions were commonly seen in this study. Conclusion: In our study, cystic lesions, infectious diseases and malignant tumors of skin were the most common disorders. The contribution of histopathology to the final diagnosis and there by treatment were significant.
EnglishINTRODUCTION
Skin diseases constitute a major public health problem. The pattern of skin diseases vary from one country to another country. Disease pattern also varies from tissue reactions to vesiculobullous lesions and malignant diseases. The interpretation of skin biopsies requires the identification and integration of two different morphological features- the tissue reaction pattern, the lichenoid reactions and the psoriasiform reaction and other lesions with clinicomorphologicalpattern.
MATERIALS AND METHODS
A retrospective study was undertaken to determine the clinico-morphological spectrum of skin lesions from all the skin biopsies received from Jan2009 to Aug 2011 in the Department of Pathology, Vinayaka Mission’s KirubanandaVariyar Medical College, Salem. Specimens were received as punch biopsy or excision biopsy, in 10% formalin as fixative for histopathological examination. 2-3 μm sized sections were taken and stained with routine Hematoxylin and Eosin stain and special stains were used when necessary. All the cases were reviewed and analysed.
RESULTS
The age distribution pattern revealed that the maximum biopsies (20.2 %) were in the age range of 51-60 years. (Table-1) The incidence of dermatological diseases were more in males 115 cases (64.6%) than females. (Table-2) The anatomic distribution pattern showed that the upper & lower extremities were involved in the maximum number of cases (36.5%) followed by the scalp (13.4%) and neck (11.2%). Clinically the lesions varied from papule, macule, vesicles, nodules to ulcers & combination of all these. Cysts were the commonest skin lesions, among the cystic lesions, keratinous cyst (9.5%) (Fig-1&2) was the most common. In infectious diseases, Leprosy (10 cases 5.6%) was the commonest disease followed by Tuberculosis (6 cases 3.3%) and fungal infections (5 cases 3%). In neoplastic lesions, Basal cell Carcinoma (8 cases 4.4%) (Fig-3&4) was the commonest.In dermal collagenous diseases, calcinosis cutis (Fig 5&6) was the commonest (5 cases 3%) (Table-3) An analysis of the major tissue reaction patterns revealed that the most frequently encountered lesion was the lichenoid group (10 cases, 5.6%) (Fig 7&8) followed by psoriasiform lesion (7 cases 3.9%), (Fig-9&10) Bullous lesions 5%. (Fig11&12) Amongst the lichenoid group of lesions, lichen planus was the most frequentwhereas inpsoriasiform lesions, psoriasis vulgaris was the most common. DISCUSSION In the present study, maximum number of biopsies were seen in the 51-60 years of age, and the minimum number in the age range of 0-10 years. The sex distribution pattern of cases revealed that most of the patients were males ( 64.6%). Limbs were involved in the maximum number of cases (36.5%), followed by the Neck, face, eye (21.9%) and scalp (13.4%). Among the cystic lesions, keratinous cyst was the commonest as seen in literature. We found leprosy was the commonest disease as infectious lesion &majority of cases were presented as hypopigmented macules(1). Basal cell carcinoma (BCC) was themost common neoplasm and most frequently seen on the face (2) as in literature. In our study we had 5 cases of Idiopathic calcinosis cutis, which is cutaneous calcification of unknown cause with normal serum calcium.(3) Lichen planus was most frequently seen in the 20- 40 years of age, but the literature revealed the incidence is seenin 5 th - 6 th decades.(4 ) Lichen planus showed male preponderance in our series and is also described in the literature.Most of our cases of lichen planus occurred on the limbs as seen in the literature. (4,5)
The next most frequently seen lesion was psoriasis in the 40- 70 years of age range. Fry (6) mentioned that two-thirds occurred before the age of 30 years. Griffiths (7) and Bell et. al. (8). mentioned that classic psoriasis is seen in the older age. We found a male preponderance in psoriasis, however Bell et. al. (8) found a female preponderance and Fry found no sex predilection. Pemphigus vulgaris was the commonest lesion and seen in the 4th decade, as seen in literature Salmanpour et. al. (9) series and Aboobaker et. al. series.
CONCLUSION
In our study, cystic lesions were the commonest followed by infectious diseasesand malignant tumors of skin. Correlation of clinical diagnosis with the histopathological diagnosis was positive in 97.1% cases and negative in 2.8% cases. The contribution of histopathology to the final diagnosis and there by treatment were significant.
Englishhttp://ijcrr.com/abstract.php?article_id=808http://ijcrr.com/article_html.php?did=8081. Kar, P K. 1994. A clinic Pathological study of macular lesions in leprosy, Indian Journal of Leprosy, 66(4):435-442.
2. Erba P, Farhadi J, Wettstein R, Arnold A, Harr T, Pierer G. Morphoeic basal cell carcinoma of the face. Scand J PlastReconstrSurg Hand Surg. 2007;41(4):184-8
3. Cook BE Jr, Bartley GB. Epidemiologic characteristics and clinical course of patients with malignant eyelid tumors in an incidence cohort in Olmsted County, Minnesota. Ophthalmology. 1999; 106(4):746–50. 3.
4. James WD, Berger TG, Elston DM. Andrews' Diseases of the Skin: Clinical Dermatology. 11th ed. Philadelphia (PA): Elsevier/Saunders; 2011. p. 516-8
5. Boyd AS, Neldner KH. Lichen planus. J Am AcadDermatol 1991;25:593-613.
6. Fry L. Psoriasis. Br J Dermatol 1988;119:445- 61.
7. Griffiths CE, Christophers E, Barker JN, Chalmers RJ, Chimenti S, Krueger GG, et. al. A classification of psoriasis vulgaris according to phenotype. Br J Dermatol 2007;156:258- 62.
8. Bell LM, Sedlack R, Beard CM, Perry HO, Michet CJ, Kurland LT. Incidence of psoriasis in Rochester, Minn, 1980-1983. Br J Dermatol 1991;127:1184-7.
9. Salmanpour R. Shalkar H, Namaki MR, Rahman-Shenar MR. Epidemiology of Pemphigus in south Western Iran- a
10 years Retrospective study(1991-2000) International Journal of Dermatology 2006, 45(2):23-5
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241614EnglishN-0001November30HealthcareLATE PRESENTATION AMONG A COHORT OF FEBRILE PEOPLE NEWLY HIV INFECTED DIAGNOSED, DURING 2005-2012, IN ALBANIA
English5870Prendushi-Frasheri XhensilaEnglish Kraja DhimiterEnglish Shpata VjollcaEnglish Harxhi Arjan EnglishPilaca ArbenEnglish Pipero PellumbEnglish Shkurti-Leka KlodianaEnglish Dervishi MarjetaEnglish Shkjezi RenataEnglishComo NajadaEnglishAim: Antiretroviral therapy decreased mortality and morbidity in people living with HIV/AIDS especially when initiated early, before advanced immunodeficiency has developed. In daily practice, it‘s particularly challenging when dealing with HIV-positive, late presenters individuals. The aim of our study was to determine, frequency, demographic features and factors associated with late presentation among febrile persons, newly diagnosed as HIV infected, during 2005–2012 period of time, in Albania. Methods: All HIV-positive patients with no prior history of HIV infection, admitted to Infectious Diseases Service, University Hospital Centre ?Mother Teresa? of Tirana, from January 2005 to December 2012, were target of our study. ?Late presenter? was defined based on the definition of ?HIV in Europe Initiative?, 2009. Demographic, epidemiological, clinical characteristics, laboratory findings, and outcome data were collected. Results: In total 87 cases (92.6%) out of 94 patients newly diagnosed with HIV were late presenters. According to univariate analysis, the age, male gender, heterosexual contact, emigration and level of education were associated with late presentation for HIV diagnosis. In the multivariate analysis, age (30-39), male gender, heterosexual contact, migration status and level of education were the only independent risk factors for late presentation. Conclusion: A considerable proportion of people newly diagnosed HIV infected, enter late in health care, presenting advanced HIV disease and consequently are treated rather late. In order to be able to detect and treat them early as recommended by international guidelines, it‘s necessary to develop policies and interventions targeting social categories at high risk for late presentation.
EnglishFebrile, HIV infection, late presentation, CD4, risk factors.INTRODUCTION
Early commencement of antiretroviral treatment (ART) for persons living with human immune deficiency virus (HIV) or acquired immune deficiency syndrome (AIDS) can be beneficial and can save money in the long run (1,2). The benefits are better realized when people present early at each stage along the continuum of care, from early screening / testing for HIV infection, early linkage into care by those with confirmed HIV infection, to remaining in pre-ART care until timely treatment commencement decisions are made and, thereafter, maintaining high fidelity to essential long-term care and treatment contact (3,4) . Advanced HIV disease is evidenced by compromised immune status (often with CD4+ cell countEnglishhttp://ijcrr.com/abstract.php?article_id=809http://ijcrr.com/article_html.php?did=8091. Leombruni P, Fassino S, Lavagnino L, Orofino G, Morosini P, Picardi A. The role of anger in adherence to highly active antiretroviral treatment in patients infected with HIV. Psychother Psychosom. 2009;78:254–57.
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7. Sall L, Salamon E, Allgulander C, OweLarsson B. Psychiatric symptoms and disorders in HIV infected mine workers in South Africa. A retrospective descriptive study of acute first admissions. Afr J Psychiatry. 2009;12:206–12.
8. Kigozi IM, Dobkin LM, Martin JN, Geng EH, Muyindike W, Emenyonu NI, et al. Latedisease stage at presentation to an HIV clinic in the era of free antiretroviral therapy in subSaharan Africa. J Acquir Immune Defic Syndr. 2009;52:280–89.
9. Girardi E, Sabin CA, Monforte AD. Late diagnosis of HIV infection: epidemiological features, consequences and strategies to encourage earlier testing. J Acquir Immune Defic Syndr. 2007;46(1):3–8.
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27. Krentz HB, Gill MJ. The Direct Medical Costs of Late Presentation (Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241614EnglishN2014July22HealthcareHE OR SHE- FEMALE PSEUDO HERMAPRODITE- A CASE REPORT
English7180Parvathi S.EnglishAn Hermaphrodites\ Intersex individual may have biological characteristics of both the male and the female sexes and whose biological sex cannot be classified as clearly male or female and reproductive or sexual anatomy differs from the typical definitions of either sex. The presence of intermediate or atypical combinations of physical features that usually distinguish Female from Male due to congenital involving chromosomal, morphological, genital and/or gonadal anomalies, such as diversion from typical XX-female or XY-male presentations, e.g., sex reversal (XY female XX -male), genital ambiguity, or sex developmental differences. 1 in 2000 for every births(2,3). While doing supervision ?Suverna Arogya Chetana? –School children health checkup programme comes under NRHM, I found this boy aged about 12yrs studying in 7th standard in governament primary school. School teacher noticed since last 4ys.on examination he has breasts like girls, ambiguous genitalia and menstruating since last 4-6 months. This have been not only a focus of attention of anatomists but also at interest of Genetitians, Embryologists, paediatric endocrinologists, surgeons, physicians, psychiatrists, Forensic experts,socialist because it makes very sensitive issue on the boy?s family and society.
EnglishHermoproditism\Intersex ?Suverna Arogya Chetana? Genetitians, NRHM, Embryologists, paediatric endocrinologists, psychiatrists, Forensic experts.INTRODUCTION
An Hermaphrodites \Intersex individual may have biological characteristics of both the male and the female sexes and whose biological sex cannot be classified as clearly male or female.1 Disorders of sexual development (DSD), formerly termed Intersex conditions, the most fascinating conditions encountered by the practioner (5) 1 in 2000 for every births. But some born with subtler forms of sex anatomy variation(2,3) . 1 in 25000 for every births(6) In my case study 1 in 3500 population. Analysis of worldwide infant screening of 6.5 million newborns found the incidence of CAH to be 1/ 15,000 live births. Frequency was highest in neonates of European Jewish, Hispanic, Slavic, or Italian descent.(5)
CASE REPORT
While doing supervision ?Suvarna Arogya Chaitanaya? –School children health checkup programme under NRHM in the year 2012 . We found this boy aged about 12 yrs studying in 7th standard in government primary school. School teacher noticed since last 4ys. He has breasts like girls, Ambiguous genitalia. His new complaint is menstruating since last 4-6 months. His walking [style waddling gait] also changed like girls. Voice is also changed slow and low pitch voice but his thyroid profile normal.1 in 2000 for every births. But some born with subtler forms of sex anatomy variation.
HISTORY AND OBSERVATIONS
Narrator mother, father and teacher. This boy aged about 12yrs, while doing school health examination, noticed that he has following features.
Partially fused genital fold. Hyper pigmentation and mild rugosity seen. Opening of urethra about 3 cms away from root of the phallous. Hypospadiasis, labia majora fused. No palpable gonads. Scrotal sacs empty on both sides. Anal opening-normal, Menstruating last 4-6 months. PAST HISTORY Child sits and passes urine but he is not passed from the pallus but below it from the separate opening . NOT IMMUNISED.Studies in 7th standard, appropriate for age. FAMILY HISTORY : Consangui’neous Marriage SOCIO ECONOMIC STATUS - Grade IV-Poor General Physical Examination[GPE] poorlybuilt and nourished, very cooperative. Afebrile. ? P\R—82\mt ? BP----100\60 mm hg Anthropometry ? Weight- 24.35kgs. ? Height—111cms ? US-LS—56.7cms;54.3cms ? HC-47cms ? CC-53cms Growth chart ? PROPORTIONATE SHORT STATURE----Microcephaly ? CVS- S1 S2 heard. NO murmurs. ? P\A-soft and No organomegaly ? CNS and RS—NAD
FOLLOWING INVESTIGATIONS DONE
1. Random blood sugar : 84mgs %
2. Random urine sugar : nil %
3. Serum creatinine- : 0.78%
4. Heamoglobin : 10gm.
5. Clotting time : 4’42
6. Bleeding time : 3’24
7. Serology report : HbsAg - negative VDRL - non reactive
8. Blood and Rh type -- A positive
9. FBS ( FASTING BLOOD SUGAR) : 102mgs\dl
10. FBS (FASTING URINE SUGAR) : NIL
11. GTT-GTU-FASTNG BLOOD : G H Glucose;-Oral 75gms glucose to drinking water..RUS (RANDOM BLOOD SUGAR)—118mgs\d
12. RUS (RANDOM URINE SUGAR) : NIL THYROID TESTS
13. TOTALTRIODOTHYRONINE: T3- 68ngms\dl
14. TOTAL THYROXIN: 2mgms 15 TSH [THYROID STIMULATINGHARMONE] : > 150 16 OH REGISTERONE : [ 1.2]
Liver :Both lobes show normal size, shape, contour and echo pattern. No focal mass/ cyst. No dilated Intrahepatic biliary radicals. Gall bladder : Normal size , wall thickness and contents. NO calculus. CBD Normal. Pancreas: Shows normal size and echo pattern. Kidneys; size, shape, position, contour and echopatteren of both kidneys normal. No dialatation of calyses, pelvis and ureter . No calculus seen in kidneys PUJ or VUJ SPLEEN:Shows normal size and echo pattern. No obvious bowel mass . No ascites No mass seen in the right iliac fossa. Urinary Bladder- Normal. No calculus or growth.
UTERUS—Anteverted measures 32+20mm and normal. No fibroids seen. Endometrial thickness10mm OVARIES – RIGHT -- measures 32+20mm and normal. LEFT -- measures 32+20mm and normal. No adnexal mass. No free fluid in POD. IMPRESSION - NORMAL ABDOMINAL -PELVIC SONOGRAPHY
UTERUS—Anteverted measures 32+20mm and normal. No fibroids seen. Endometrial thickness10mm OVARIES – RIGHT -- measures 32+20mm and normal. LEFT -- measures 32+20mm and normal. No adnexal mass. No free fluid in POD. IMPRESSION - NORMAL ABDOMINAL -PELVIC SONOGRAPHY
Pelvis: Evidence of small uterus noted ,endometrial echoes not appreciable, uterus measures 27+9.4 + 8.4mm AP view. Impression: Small size uterus, no obvious evidence of ovaries. No testes noted, possibilty of pseudohermoprditism and other organs are normal. Both testis are not seen in the inguinal canal or abdomen
Serum cortisol (ACTH)level ; Morning -8am-CLIA—2.92micro g\dL Eevening -9pm- CLIA—8.59micro g\dL HIV 1 and II : NEGATIVE24. –Serum Sodium –137mEq/L Serum Sodium – 4.09mEq/L Serum Sodium – 103 mEq/L Serum Sodium –137mEq/L Karyotype: Done under the supervision of expert, - Blood sent to the National laboratory for analysis. 72hrs stimulated cultures with appropriate serum and antibiotics ( Medium RPMI-1640) 450- 550 banding resolution GTG banding technique. Metaphases-numbers---Counted---30 Analysed---30 Karyotyped--02 Photographed –02
Female chromosomal complement with no numerical or structural anomalies detected at the banding resolusion. Note—1. Microdeletions and cryptic chromosomes deletions may not be detected with cytogenetic analysis.
INTERPRETATION
Female pseudohermaproditism with 46xx karyotype NO
'Y'CHROMOSOME
DISCUSSION
Chromosomal sex determines gonadal sex, which determines phenotypic sex. The type of gonad present determines the differentiation/regression of the internal ducts (ie, müllerian and wolffian ducts) and ultimately determines the phenotypic sex. Gender identity is determined not only by the phenotypic appearance of the individual but also by the brain's prenatal and postnatal development as influenced by the environment (5) Gonadal differentiation During the 2nd month of fetal life, the indifferent gonad is guided to develop into a testis by genetic information present on the short arm of the Y chromosome. Testis determining factor (TDF) is a 35–kilobase pair (kbp) sequence on the 11.3 sub band of the Y chromosome, an area termed the sex-determining region of the Y chromosome (SRY). When this region is absent or altered, the in different gonad develops into an ovary. In my case study, genetic sex determined by the karyotype studies shows Karyotype—46xx Female chromosomal complement with no numerical or structural anomalies detected at the banding resolusion. USG and 2 D real time abdominal sonography study showsBoth testis are not seen in the inguinal canal or abdomen. Impression: Small size uterus, no obvious evidence of ovaries. no testes noted, possibilty of pseudohermoprditism and other organs are normal INTERPRETATION – Female pseudo hermoproditism with 46xx karyotype NO ?Y? CHROMOSOME?. absence of y chromosome along with postnatally complete absence of gonads, complete absence of both testis with development of feminine characters like breast development, since 4months regular menstruation. Etc… Correlates with my study clinically The existence of patients with 46,XX testicular DSD, who have testicular tissue in the absence of an obvious Y chromosome or SRY genetic material requires other genetic explanations for testicular development include DAX1 on the X chromosome, SF1 on band 9q33, WT1 on band 11p3, SOX9 on bands 17q24-q25, and AMH on band 19q13.3. Fetal ovaries develop when the TDF gene (or genes) is absent 5. Development of the internal ducts results from a paracrine effect from the ipsilateral gonad.Jost's classic research with rabbits greatly clarified the gonad's role in controlling subsequent development of internal sex ducts and external genital phenotype (3)
When testicular tissue is absent, the fetus morphologically begins and completes the internal sex duct development and external phenotypic development of a female. For development of male internal sex ducts and an external male phenotype, namely, testosterone and Mülleria inhibiting substance (MIS) is produced by the Sertoli cells of the testis beginning in the eighth fetal week. The prime role of MIS is to repress passive development of the müllerian ducts (eg, fallopian tubes, uterus, upper vagina). In a male fetus with normal testicular function, MIS represses müllerian duct development, while testosterone stimulates wolffian duct development or AMH(5) Wolffian structures located closest to the source of testosterone undergo the greatest degree of male differentiation. No wolffian development is expected in association with a streak gonad or a non–testosterone-producing dysgenetic testis. 5 Local testosterone production appears to enhance the inhibition of müllerian duct development produced by MIS, while estrogens may interfere with MIS action, resulting in a degree of müllerian duct development. This suggests that müllerian development may be more complex and the research helps explain the variable internal sex duct anatomy that occurs in some of the complex intersex states5. Differentiation of external genitalia The external genitalia of both sexes are identical during the first 7 weeks of gestation. Without the hormonal action of the androgens, testosterone and dihydrotestosterone (DHT), helps in translation and transcription of genetic material ie external genitalia appear phenotypically female. In the gonadal male, differentiation toward the male phenotype actively occurs over the next 8 weeks is moderated by testosterone, which is converted to 5-DHT by the action of an enzyme, 5-alpha reductase, present in the cytoplasm of cells of the external genitalia and the urogenital sinus lead to normal male external genital development from primordial parts, forming the scrotum from the genital swellings, forming the shaft of the penis from the folds, and forming the glans penis from the tubercle.5 Incomplete masculinization occurs when testosterone fails to convert to DHT or when DHT fails to act on cells of the external genitalia and urogenital sinus. Testosterone-related developmental change begins at approximately 6 weeks of gestation with a testosterone rise in response to a surge of luteinizing hormone (LH). Testosterone levels remain elevated until the 14th week. Most phenotypic differentiation occurs during this period. After the 14th week, fetal testosterone levels settle at a lower level and are maintained more by maternal stimulation through human chorionic gonadotropin (hCG) than by LH. Testosterone's continued action during the latter phases of gestation is responsible for continued growth of the phallus, which is directly responsive to testosterone and to DHT(5) CAH is the most common cause of ambiguous genitalia in the newborn. Mixed gonadal dysgenesis (MGD) is the second most common cause of DSD. Hypospadias occurs at a rate of 1 case per 300 live male births; in fewer than 1% of patients, hypospadias occurs in combination with undescended testes.
Ambiguous genitalia ; CAH is the most common cause of ambiguous genitalia in the newborn, it is inherited an autosomal recessive disorder .charcteristic by cortical enzymes so low hormonal input but increase in ACTH from the pituitary cause adrenal hyperplasia, leads to hyperplastic adrenals elaberate androgens and cause the masculisation of female fetus leading to female pseudo hermoproditism leading to hypertrophy of labia majora fused. , clitoris. His walking style and voice is changed slow and low pitch changed like girls but his thyroid profile normal. Female pseudo hermoproditism with 46xx karyotype posess ovaries and derivatives of mullarian ducts .but masculinised by clitoromegaly ,displacement of urethra and labial fusion.results in ambiguous genitalia.Its derivatives,either endogenenously through a hormonal abnormality or HRT.leads to increase in the testosterone in affected females are adrenogenital syndrome .due to multiple inherited enzymes defficiencies 21-hydroxylase and 11b hydroxylase -] abnormalitie can occurs along the path way of cortisol productions due to [AR] prodused during 8 and 9 week of gestational life.so increase in the testosterone level causes virulised female new born with intact Mullarian structures and ovaries. External source of norethisterone acetate and norethisterone OCP component produce this defect depending on the time of exposure and dose 7. In my study shows---- Ambigious genitalia Penis short Length of phallous-3.7mms Partially fused genital fold Hyper pigmentation and mild rugosity Opening of urethra about 3 cms away from root of the phallous. Hypospadiasis, labia majora fused. No palpable gonads. Scrotal sac empty. now. Menstruating since last 4-6 months.
In the embryo, the external genital structures are originally the same in males and females. Exposure to testosterone, the male hormone, causes differentiation into a penis and scrotum, promotes formation of the prostate, and other internal male reproductive structures. Lack of testosterone, as in females causes the external genitals to differentiate in a male pattern. Common ones include partial or complete insensitivity of the tissue to testosterone, inadequate production of testosterone, lack of the testes-determining region of the Y chromosome in a male, or its presence in a female, and malformations due to exposure of the fetus in utero to certain drugs. 8 Medical Treatment Current medical treatment for intersex individuals is in a state of flux. Infants born with obviously ambiguous genitals undergo many tests (chromosomal, hormonal, and anatomical) to determine the sex is based on the ability to create cosmetically unambiguous and functional genitals with the tissue present. In cases where future fertility is possible, this too is considered. Medical aspects: Infants born with ambiguous genitalia represent a true medical and social emergency. Salt-wasting nephropathy occurs in 75% of infants born with CAH, the most common cause of ambiguous genitalia. If unrecognized, the resulting hypotension can cause vascular collapse and death. Male infants with this syndrome may be phenotypically normal, and the diagnosis may be missed. Surgical correction Surgery is performed before the age of 18 months to make the genitals match, the assigned sex. ? Testes \ ovo testis are absent in my patient no question of orchidectomy and malignancy. External genitalia as to be corrected to make female type and supported by oestrogen therapy to help the feminization in puberty. 4 ? Scrotal cleft corrected by surgical interference with or without Hysterectomy, Tubectomy. Etc. it helps in masculization at puberty with parental testosterone. ? Vagina is too short and non capacious may requires plastic surgery- Clitarorraphy. After surgery, 21% incidence of diverticula formation, as well as strictures and fistulas in some patients. Short-term follow-up necessary . Average patient age in the hypospadia study was two months. Obviously, sexual function was not one of the "functional outcomes" considered.8
Medico legal aspects of intersex Depending upon the anatomical features of external genitalia rather on the gonads or chromosomal pattern , they rearedup as male or female. Female pseudo hermaphrodites; reared up as females, have normal internal sex organs. Capable of developing into normal fertile woman. He having large phallus or libido scrotal fusion may require surgical correction .
In my study reared up as male, Child sits and passes urine but he is not passed from the pallus but below it from the separate opening penis short-Length of phallous-3.7mms Partially fused genital fold Hyper pigmentation and mild rugosity Opening of urethra about 3 cms away from root of the phallous. Hypospadiasis, labia majora fused.No palpable gonads. Scrotal sacs empty. He needs surgical correction [to create cosmetically unambiguous].
CONCLUSIONS
This have been not only a focus of attention of anatomists but also at interest of Genetitians, Embryologists, oncologists, paediatric endocrinologists, surgeons, physicians, psychiatrists, Forensic experts because it makes very sensivitive issue on the boy, family and society.
ACKNOWLEDGEMENTS
Author acknowledges the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed. My sincere thanks go to teacher and my staff specially and I am grateful to my brother Anil for his moral support and encouragement in entire course of preparation.
Englishhttp://ijcrr.com/abstract.php?article_id=810http://ijcrr.com/article_html.php?did=8101. Intersex from Wikipedia, the free encyclopedia –Internet
2. Intersexuality and Body Image--Body Image: Understanding Body Dissatisfaction in Men, Women and ChildrenBy Sarah Grogan page 188-199
3. The Body Project • Bradley University • 1501 W. Bradley Avenue • Peoria, Illinois 61625 (309)6772402begin_of_the_skype_highlightin g(309)6772402FREEend_of_the_skype_highli ghting• thebodyproject@bradley.edu
4. Forensic medicine and toxicology – Narayanan, page-106-115
5. Ambiguous Genitalia and Intersexuality Author: Joel Hutcheson, MD; Chief Editor: Marc Cendron, MD emedicine.medscape.com/article/1015520- overview
6. Human Genetics –3 rd edition SD Gangane page 86
7. Human embryology-medical genetics 5 THedition–by Asim Kumar Datta, page- 85- 86
8. Human rights for intersexuals--The following essay was written by my daughter, AlthaeaYronwode, and appeared in the March 11, 1999, issue of Synapse, the campus newspaper of the University of Califonia at San Francisco Medical School.
9. Intersex-Sociologists for Women in Society Fact Sheet Prepared by Maura Kelly, Department of Sociology, University of Connecticut Spring 2007.
10. Assessment of Intersex by natfi.org
11. Paeatric Endocrinology -3 rd edition Mark A sperlng, MD page127—163
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13. Clinical Paeatric Endocrinology-william Hamilton pages180-188
14. Williams Text book of Endocrinology 10th edition pages 841-968