Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241108EnglishN2018April28HealthcareStudy on Environmental Factors Causing Head and Neck Cancer in Karachi, Pakistan
English0109Arifa AzizEnglish Yasmin Abdul RashidEnglish Zeenat ShaheenEnglish Safia AwanEnglishObjective: Head and neck cancer is one of the most prevalent cancers in South East Asia and its incidence is increasing with time. The objective of this study is to identify the environmental factors and their role in causing head and neck cancers for better future strategy in controlling and prevention.
Materials and Methods: Questionnaire form was developed, which includes questions about environmental factors causing head and neck cancer. Forms were filled by patients after taking their written consent. This study was conducted at Day Care Oncology and in Radiation department of Aga Khan University Hospital, after approval from institutional ethical review committee. It is a prospective study conducted from December 2016 to June 2017. Patients with head and neck cancer aged 18 years and above, of both genders were included. Statistical Package for the Social Sciences SPSS version 19 was used to perform statistical analysis.
Results: A total of 132 patients were included. Head and neck cancers were observed to be more common in males 101 (76.5%) as compared to females 29 (22%) and average age was found to be 50.4 ± 12.9 years in both genders. The commonest environmental factors causing head and neck cancer included various forms of smokeless tobacco including pan, mainpuri, supari and gutka. 132 patients 77 (58.3%) were using smokeless tobacco, 41(31.1%) were cigarette smokers and 6 (4.5%) were using alcohol. Among all the head and neck cancers, the most common was squamous cell cancer of buccal mucosa 63 patients (47.72%) and less common is the cancer of orbit 4 patients (3%).
Conclusion: Incidence of head and neck cancer, specifically squamous cell carcinoma of buccal mucosa is increasing with time. The commonest cause was found to be different forms of smokeless tobacco easily accessible to the public. Increasing public awareness through various means is the way forward in controlling this menace.
EnglishSmokeless tobacco, Buccal mucosa cancer, Public awareness ProgramsIntroduction:
Head and neck cancers are the most common cancers in developing countries (1)‚ especially in Southeast Asia. In the western population cigarette smoking and alcohol consumption are the main reasons for squamous cell carcinoma of head and neck whereas the use of smokeless tobacco and betel nut is the most common cause of head and neck squamous cell carcinoma in Southeast Asia. (2,3). Betel nut chewing is common in Pakistan and other Southeast Asian countries and is high risk factor in development of squamous cell carcinoma of buccal mucosa which is the most common type of oral cancers in Pakistan and India (4,5)‚ and oropharyngeal and tongue cancers are common in the Western world (6). These differences in site of disease may be related to the widespread habits in the respective regions. (7)
The different names in which smokeless tobacco is used in Pakistan and India include khaini, mava, paan (betel quid), zarda, snuff, mashiri, etc. (8) Smokeless tobacco both chewing tobacco and snuff is associated with an increased risk of cancer of the oral cavity and pharynx (9, 10) The incidence of laryngeal cancer and pharyngeal cancer, is approximately 50 percent higher in African American men (11). The outcome for head and neck squamous cell carcinoma of patients has not significantly improved in the past four decades even with great improvement in the skills, knowledge, surgical procedures and multi-disciplinary tumor boards establishments.(12) Regular awareness activities by health professionals and volunteers have not led to the improvements and it is observed that with many awareness programs which were conducted in various health centers for staff and public but analysis results showed that these programs are not very successful especially in control of factors causing this disease in Southeast Asia and the numbers of head and neck cancers are increasing every day both in rural and urban areas. There is a great need of government to help in control and stop the supply and use of various forms of smokeless tobacco which are the main causes of head and neck cancer and are easily available in the market.
There is a shortage of data on behavior and outcomes of these tumors from this region. The primary objective of this study is to share the demographics and identify various types of smokeless tobacco causing head and neck cancer and their control by increasing awareness programs.
Material and method:
This study was conducted at day care oncology and radiation department at Aga Khan University Hospital. The study protocol was approved by the ethical review committee of Aga Khan University Hospital, Karachi, Pakistan, with ERC # 4392-Onc-ERC-16. Questionnaire form was developed by a multidisciplinary team of Medical Oncologist, staff medical officer and head nurse of day care oncology and radiation department, demographic data and questions about environmental factors causing head and neck cancer were included in the form as shown in table 3. These forms were filled by patients after explaining the study to them and taking their written consent.
Study Design:
It is a prospective, cross sectional study conducted from December 2016- June 2017.
Patients with head and neck cancer receiving treatment at our institute aged 18 years and above, of both genders were included in this study. Statistical Package for the Social Sciences (SPSS) version 19 was used to analyze the collected data.
Results:
A total of 132 patients were included. There were 101 (76.5%) males as compared to females which were 29 (22%). Average age was 50.4 ± 12.9 years in both genders. Out of 132 patients 77(58.3%) were using various forms of smokeless tobacco, 41 patients (31.1%) were cigarette smokers and 6 patients (4.5%) were using alcohol. The most common site involved was squamous cell cancer of buccal mucosa observed in 63 patients (47.72%) and there were 4 patients (3%) of squamous cell cancer of orbit.
Discussion:
The incidences of head and neck cancers are increasing and are placed in the top ten malignancies globally (13). Squamous cell cancer of head and neck are placed sixth most frequently diagnosed cancer (14) and its proportion is much higher in males as compared to females with ratio of 2:1(15). This accounts for approximately one-fifth of all cancers in males and about one-tenth in females (16). Study on incidence and epidemiological characteristics of squamous cell cancer of head and neck was conducted in 1995-2002 in Karachi, results showed that approximately one-fifth (21%) of the head and neck cancers were seen in males and about one-tenth (11%) in females, buccal mucosa and larynx were the commonly affected sites, followed by pharynx. The mean age of the patients was 53.0 years (a rising incidence was observed in both genders, more apparent in males). About 30% of oral cancer cases, 28.6% of the nasopharyngeal, 6.3% of the oropharyngeal, and 2.6% of laryngeal cancers occurred in patients age 40 years and younger. The peak incidence was at 64-69 years for all three cancer sites, in both genders (17-19). If we compare results of study done in 1995-2002 with our study conducted in 2017, the results are almost the same with no improvement. There is no significant difference in results indicating that a lot of efforts which were done to decrease incidence of head and neck cancer were failed. Pakistan falls into a high risk zone for head and neck squamous cell carcinoma. (20). Poor nutrition, oral hygiene and dental problems may increase the risk of getting head and neck cancer. (21) In our study 44 patients (33.3%) had dental problems as shown in table-2. The exact reason of relationship between poor nutrition and head and neck cancer is not known. Heavy alcohol drinkers often have vitamin deficiencies, which may help explain the role of alcohol in increasing risk of these cancers. A good balanced diet can be associated with decreased risk of this disease. Diet has strong evidence with cancer development and data confirmed an apparent underlying relationship for a decreased head and neck squamous cell carcinoma risk with non-starchy vegetables, fruits, and food containing carotenoids. A recent study established that higher dietary pattern scores, with high intake of fruit and vegetable and low intake of red meat, were associated with decrease risk of squamous cell carcinoma. (22)
Finally, the importance of primary prevention needs to be highlighted. Check on the supply and the use of various forms of smokeless tobacco, areca nut, betel leaf, etc. as far as tobacco use few studies showed that it is difficult to change people's attitude and convince them to stop smoking. (23). In our study a total of 132 patients were included, patient's information was collected from patients in chemotherapy unit and radiation department at Aga Khan University Hospital Karachi, Pakistan. Analysis report showed that Head and neck cancers are observed to be more common in male 101 (76.5%) as compare to females 29 (22%) and average age is 50.4 ± 12.9 years in both genders as shown in figure-2. The commonest environmental factor causing head and neck cancer includes smokeless tobacco and tobacco chewing and out of 132 patients 77 (58.3%) were using them as shown in figure -3.Among all the head and neck cancers the most common is squamous cell cancer of buccal mucosa 63 patients (47.72%) and less common is the squamous cell cancer of orbit 4 patients (3%) as shown in figure-1. If both, results of 2002 and 2017 study, when compared are almost the same with very less difference in outcome showing that there is no improvement in control of head and neck cancer and there is a great need to think and apply some powerful strategy that can work in control of head and neck cancer. Squamous cell cancer of head and neck in Pakistan's is the next great health challenge. There is an urgent need to improve awareness about the disease and to introduce population based cancer registration and early detection programs. In addition, health services organization and human resources need to work together in developing plans to help prevent and fight with this disease. Finally, the importance of primary prevention needs to be highlighted. Limiting the use and removal of various forms of smokeless tobacco, areca nut, betel leaf, cigarette smoking and alcohol is perhaps the most suitable way to begin with. However it is very difficult to change current social attitudes, practices and perceptions in control of tobacco (23). Ninety percent of the oral cancer patients in rural areas belong to the lower or lower-middle socio-economic class, and 3.6% are below the poverty line based on Pareek's classification (24). Around 75% to 80% of patients with cancers present with late stage incurable disease and hence increased mortality (25), reason of delay could be both by patient in visiting doctor and in few cases physician related delay both of which contributes towards the late diagnosis. (26) another reason for delay in diagnosis in rural areas is the lack of easy access to healthcare, with one study demonstrating a delay of 67.5 days and 53.7 days in obtaining a first appointment for rural and urban patients, respectively. Other reasons of delay included poor socio-economic status of the patient, cost of care, and high rate of illiteracy (27). Great work was done during last many years and improvement in surgical procedures and establishment of multi-disciplinary tumor boards were done, but the results are the same with no improvement in the outcome for head and neck squamous cell carcinoma and it was seen that there is no significant improvement in the past four decades (28). As serious consequences of this rapidly developing epidemic are now becoming clear and it is very important to develop effective mechanisms that can be used to control this disease. This will require a deeper analysis of the risk factors, of the population at risk and of the treatment resources that are available, unfortunately this is the common problem with most of the developing world. The study of Kumar et al.11 showed that smoking cessation reduces but does not eliminate the risk of this cancer development, However, Marron et al.12 confirmed that cessation of tobacco smoking protect against the head and neck Squamous cell carcinoma development. The major risk factor for oral cancers among non-drinkers is tobacco use and among non-smokers is alcohol use (29, 30).
Conclusion:
In this field, there is urgent need of more research to find new ways in prevention and understanding in development of head and neck carcinomas and to improve therapeutic approaches and interventions. Now adays, the most effective measures to improve the prognosis of the head and neck cancers are prevention and early diagnosis.
Way forward
Awareness programs should be conducted for public and for general practitioner in rural and urban areas, this will help in both ways prevention plus early diagnosis.
Strict actions should be taken by government to stop manufacturing and supply, in market, of factors like various forms of smokeless tobacco which is the main cause of head and neck cancer in Karachi, Pakistan.
Acknowledgement
We are grateful to Afsheen Feroz head nurse day care and radiation oncology for her suggestions in preparing questionnaire form and all authors of references we have cited in our manuscript.We would also like to thank patients for their participation.
Englishhttp://ijcrr.com/abstract.php?article_id=2470http://ijcrr.com/article_html.php?did=2470
WHO 2008. The global burden of disease: 2004 update. Available at: www.who.int/evidence/bod (accessed January 27, 2014)
Graham S. Dentition, diet, tobacco and alcohol in the epidemiology of oral cancer. J Natl Cancer Inst. 1977; 59:1611–18. [PubMed]
Dayal PK, Mani NJ, Bhargava K. Prevalence of oral cancer and precancerous lesions in ‘pan’/'supari' chewers. Indian J Public Health. 1978; 22:234-45. [PubMed]
Guha N, Warnakulasuriya S, Vlaanderen J, Straif K. Betel quid chewing and the risk of oral and oropharyngeal cancers: a meta-analysis with implications for cancer control. Int J Cancer 2014; 135:1433.
Znaor A, Brennan P, Gajalakshmi V, et al. Independent and combined effects of tobacco smoking, chewing and alcohol drinking on the risk of oral, pharyngeal and esophageal cancers in Indian men. Int J Cancer 2003; 105:681.
Bhurgri Y, Bhurgri A, Usman A, et al. Epidemiological review of head and neck cancers in Karachi. Asian Pac J Cancer Prev. 2006; 7:195–200. [PubMed]
Sankaranarayanan R, Masuyer E, Swaminathan R, Ferlay J, Whelan S. Head and neck cancer: a global perspective on epidemiology and prognosis. Anticancer Res. 1998; 18:4779–86. [PubMed]
Mehta FS, Hamner JE. Tobacco Habits in India In: Tobacco-Related Oral Mucosal Lesions and Conditions in India. New Delhi, India:Jaypee Brothers; 1993. pp. 89–99.
Proia NK, Paszkiewicz GM, Nasca MA, et al. Smoking and smokeless tobacco-associated human buccal cell mutations and their association with oral cancer--a review. Cancer Epidemiol Biomarkers Prev 2006;15:1061.
Sapkota A, Gajalakshmi V, Jetly DH, et al. Smokeless tobacco and increased risk of hypopharyngeal and laryngeal cancers: a multicentric case-control study from India. Int J Cancer 2007; 121:1793.
Rosenquist K, Wennerberg J, Schildt EB, et al. Use of Swedish moist snuff, smoking and alcohol consumption in the etiology of oral and oropharyngeal squamous cell carcinoma. A population-based case-control study in southern Sweden. Acta Otolaryngol 2005; 125:991.
DeSantis C, Naishadham D, Jemal A. Cancer statistics for African Americans, 2013. CA Cancer J Clin 2013; 63:151.
Carvalho AL, Singh B, Spiro RH, Kowalski LP, Shah JP. Cancer of the oral cavity: a comparison between institutions in a developing and a developed nation. Head Neck 2004; 26: 31-8.
Asian pac j cancer prev. 2006 apr-jun;7(2):195-200
Akram, s., et al., emerging patterns in clinicopathological journal of medical sciences, 2013. 29 (3): p. 783
Deepti Garg, Charu Kapoor, Swati Gautam. MODERATELY DIFFERENTIATED SQUAMOUS CELL CARCINOMA: A CASE SERIES. Dental Journal of Advance Studies. 2014: 46-50
Bhurgri Y. Cancer Oral Cavity Trends in Karachi South, Asian Pac J Cancer Prev. 22005; 6:22-6.
Bhurgri Y, Bhurgri A, Usman A, Pervez S, Kayani N, Bashir I, et al. Epidemiological review of head and neck cancers in Karachi. Asian Pac J Cancer Prev 2006; 7:195-200.
Bhurgri Y, Bhurgri A, Parvez S, Bhurgri M, Kayani N, Ahmed R, et al. Cancer profile of Hyderabad, Pakistan1998–2002. Asian Pac J Cancer Prev 2005;6:474–80
Zheng TZ, Boyle P, Hu HF, Duan J, Jian PJ, Ma DQ, Shui LP, Niu SR, Scully C, MacMahon B: Dentition, oral hygiene, and risk of oral cancer:A case-control study in Beijing. Cancer Causes Control 1: 235–241, 1990
Carvalho AL, Singh B, Spiro RH, Kowalski LP, Shah JP. Cancer of the oral cavity: a comparison between institutions in a developing and a developed nation. Head Neck 2004; 26: 31-8.
Carvalho AL1, Singh B, Spiro RH, Kowalski LP, Shah JP. Cancer of the oral cavity: a comparison between institutions in a developing and a developed nation. Head Neck. 2004 Jan; 26 (1) :31-8.
Carvalho AL1, Pintos J, Schlecht NF, Oliveira BV, Fava AS, Curado MP, Kowalski LP, Franco EL. Predictive factors for diagnosis of advanced-stage squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg. 2002 Mar; 128 (3) :313-8.
Maher R, Devji S. Prevalence of Smoking among Karachi Population J Pak Med Assoc 2002; 52: 250-2
Pareek U, Trivedi G. Manual of Socio-Economic Status Scale (Rural) New Delhi: Manasayan Publishers; 1995.
Pai SA. Gutkha banned in Indian states. Lancet Oncol. 2002; 3:521. http://dx.doi.org/10.1016/S1470-2045(02)00862-8 [PubMed]
Carvalho AL1, Singh B, Spiro RH, Kowalski LP, Shah JP. Cancer of the oral cavity: a comparison between institutions in a developing and a developed nation. Head Neck. 2004 Jan;26 (1): 31-8
Chintamani Tuteja A, Khandelwal R, et al. Patient and provider delays in breast cancer patients attending a tertiary care centre: a prospective study. JRSM Short Rep. 2011; 2:76. http://dx.doi.org/10.1258/shorts.2011.011006. [PMC free article] [PubMed]
Carvalho AL, Singh B, Spiro RH, Kowalski LP, Shah JP. Cancer of the oral cavity: a comparison between institutions in a developing and a developed nation. Head Neck 2004; 26: 31-8.
Chuang SC, Jenab M, Heck JE, Bosetti C, Talamini R, Matsuo K, et al. Diet and the risk of head and neck cancer: a pooled analysis in the INHANCE consortium. Cancer Causes Control. 2012; 23(1):69-88. [ Links
Kumar B, Cordell KG, Lee JS, Worden FP, Prince ME, Tran HH, et al. EGFR, p16, HPV Titer, Bcl-xL and p53, sex, and smoking as indicators of response to therapy and survival in oropharyngeal cancer. J Clin Oncol. 2008; 26 (19):3128-37. [ Links ]
Marron M, Boffetta P, Zhang ZF, Zaridze D, Wünsch-Filho V, Winn DM, et al. Cessation of alcohol drinking, tobacco smoking and the reversal of head and neck cancer risk. Int J Epidemiol. 2010; 39(1):182-96. [ Links ]
Znaor A, Brennan P, Gajalakshmi V, Mathew A, Shanta V, Varghese C, et al. Independent and combined effects of tobacco smoking, chewing and alcohol drinking on the risk of oral, pharyngeal and esophageal cancers in Indian men. Int J Cancer. 2003; 105(5): 681-6. [ Links ]
Gillison ML. Current topics in the epidemiology of oral cavity and oropharyngeal cancers. Head Neck. 2007; 29(8):779-92. [ Links ]
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241108EnglishN2018April28HealthcareAssessment of Changes in Tongue Position in Class II Division 1 Patients Treated with Functional Appliances - An in-vivo Study
English1014Akanksha KumarEnglish Narendra SharmaEnglish Sunita ShrivastavEnglish Ranjit KambleEnglish Neha BhandariEnglishObjective: The objective of this study was to evaluate the effects of functional treatment on positional changes in tongue and to determine if any relationship exists between the functional appliance therapy in Class II division 1 and position of tongue.
Material and Method: Pre-treatment and post-treatment lateral cephalographs of 30 Class II division 1 patients within the age group of 8-12 years were taken and traced. After identification of determining landmarks, reference lines were marked and 4 linear measurements were evaluated – 2 each in horizontal and vertical plane. These linear measurements were compared for reliability using statistical analysis.
Results: Statistically significant (p < 0.05) differences were found in linear measurements indicative of alteration in tongue position in horizontal and vertical direction. There was a significant interrelationship between reduction of ANB angle and movement of tongue in forward direction.
Conclusion: The results suggest that Functional appliances are very effective in altering the position of tongue during treatment of Class II division 1 malocclusion.
EnglishTongue, Functional appliance, Class II malocclusionIntroduction
The form-function debate has always been a perpetual one for the orthodontic community. The effect of facial form on the function and vice-versa has been a subject of great interest and controversy for a research oriented orthodontic clinician.1
Bones grow, as many believed, in a predetermined manner by the genetic code of individual. This predetermined growth may be changed and altered by exposure to altered epigenetic environment or functional environment. Craniofacial form and the factors that alter them have, since many years, intrigued the minds of researchers. Pioneering works by Van der Klaauw and Moss have substantiated the effects of function in changing facial form.2,3
Class II malocclusion is one of the most frequently encountered problems in the orthodontic practice. It causes aesthetic, functional, and psychological problems of varying intensities.4 Class II division 1 malocclusion may present with skeletal features of mandibular retrognathism, midface protrusion and dental features of distal step molar, an unusually large overjet and/or variable combination of these features5,6. However, the majority of Class II malocclusions can be attributed to mandibular retrognathia rather than maxillary prognathism.7
Tongue is one of the muscular structures of the craniofacial region whose position is affected by different types of malocclusion. Takahashi et al8 recorded the EMG activities of craniofacial temporalis muscle in 10 patients and found that the position of the tongue varies greatly in patients with different malocclusions. Class II malocclusion with mandibular deficiency results in decreased tongue space leading to curvature of the posterior aspect of the tongue.9
Severe mandibular deficiency has been linked to reduced space between the cervical column and the mandibular corpus that leads to a posteriorly postured tongue and soft palate10. This increases the chances of impaired respiratory function during the day and possibly causing nocturnal problems as well, such as snoring, upper airway resistance syndrome (UARS), and Obstructive sleep apnea syndrome (OSAS)10. Thus tongue position can contribute significantly towards increasing the future risk of Obstructive sleep apnoea (OSA) in Class II malocclusion patients with reduced tongue space.
There are various treatment modalities available to correct Class II malocclusions including use of headgear, elastics, removable myofunctional appliances, fixed appliances, dental extractions or distalization of maxillary teeth and orthognathic surgery. Awareness of mandibular deficiency as the main contributing part of the Class II structural etiology had led to the increased popularity of mandibular advancement appliances or the functional appliances.
In 1902‚ Pierre Robin11 was the first to use an intraoral appliance to bring the lower jaw forward in newborns with mandibular deficiency, thereby preventing posterior relocation of the tongue during sleep and the occurrence of oropharyngeal collapse. Today, this concept is widely used in dentofacial orthopaedics to stimulate mandibular growth and functional appliances form the main stay of treatment of skeletal Class II involving mandibular deficiency in growing children.11,12
The term functional appliance refers to a variety of orthodontic appliances designed to induce a change in activity of the various muscle groups that influence the function and the position of the mandible in order to transmit forces to the dentition and the basal bone13. Altering the sagittal and vertical mandibular position causes changes in muscular forces and result in orthopedic and orthodontic changes.14-16
Several types of functional appliances currently used for Class II treatment are aimed at improving skeletal imbalances, arch form, and orofacial function.13 During treatment with functional appliance in patients with Class II division 1 malocclusion, mandible is positioned in inferior and anterior position.14-16 Consequently, alterations in tongue position can be one of the effects of functional appliance therapy. 13
Lateral Cephalogram is one of the most commonly used 2-dimensional imaging method for evaluation of tongue position with proven reproducibility17. Also it is economical and non-invasive with low dose of radiation.
Though there are numerous studies in literature evaluating the skeletal and dental changes brought about by functional appliances, there are very few studies, to our knowledge, which assesses the changes in tongue position in response to functional appliances. Thus this study was carried out with the aim to evaluate the effects of functional treatment on the positional changes in tongue and to determine if any relationship exists between the functional appliance therapy in Class II division 1 and position of tongue.
MATERIALS AND METHOD
The study was conducted in the Department of Orthodontics and Dentofacial Orthopaedics, Sharad Pawar Dental College and Hospital, Sawangi, Wardha in co-ordination with Department of Oral Medicine and Radiology, AVBRH, Sawangi, Wardha. Total 30 cases, within the age group of 8-12 years, were selected from the OPD of Department of Orthodontics, SPDC. After getting informed consent, they were subjected to cephalometric evaluation and treated with functional appliance for an average of 8 months.
The following criteria were established for the sample:
Patients with skeletal Class II malocclusion with a normal maxilla and functionally retruded mandible.
Class II molar and Class II canine relation.
Overjet equal to or greater than 4mm.
ANB angle - Greater than 4.5 degrees
Patient in active growth period, CVMI status – Stage 3 (transition) by Hassel and Farman vertebral index.
Positive VTO on clinical evaluation.
Patients with class I and class III malocclusion and patients with Class II division 1 malocclusion due to involvement of maxillary component were excluded from the study.
Patients with moderate crowding and severe lower proclination in the dental arches, craniofacial syndromes or systemic disease or having any history of any orthodontic treatment were not included in the sample.
After the selection of cases, informed consent was obtained from each patient and pre-treatment lateral cephalogram of all the selected cases were taken. All the cephalograms were recorded with the same exposure parameters (kVp – 72, scan time of 1.2 sec) with the same magnification and the same machine (Planmeca, Finland) in the Department of Oral Medicine and Radiology, SPDC.
All the selected samples were treated with functional appliance. Patients were routinely monitored for regular wear of the appliance and after 8 months of appliance delivery, posttreatment lateral cephalogram of all the treated cases were taken and the changes in tongue position compared thoroughly.
Various landmarks, reference planes and linear parameters used for the evaluation of the tongue position were based on methods described by Yassaei at al.9 Following points were traced in pre-treatment and post-treatment lateral cephalograms to determine positional changes of tongue. [Figures 1 and 2]
Cephalometric landmarks:
Od: The most posterior point of the odontoid process of the second cervical vertebrae
C4p: The most postero-inferior point on the 4th cervical vertebrae.
Pt: The most posterior point on the contour of the tongue.
Va (Valeculla): The deepest point of the valeculla.
Tb: Intersection point between the lower border of the mandible and contour
of the tongue.
Reference lines:
CL (cervical line): line connecting Od and C4p
CHL (cervical horizontal line): perpendicular line from Od to cervical line.
Tongue position:
Pt-CL: perpendicular distance from Pt to the cervical line. This variable indicates tongue position in horizontal plane.
Pt-CHL: perpendicular distance from Pt to the cervical horizontal line. This variable indicates tongue position in vertical plane.
Va-CL: perpendicular distance from valeculla to the cervical line. This variable indicates tongue position in horizontal plane.
Va-CHL: perpendicular distance from valeculla to the cervical horizontal line. This variable indicates tongue position in vertical plane.
Reliability:
All the lateral cephalograms were traced twice by hand onto acetate tracing paper. If the difference exceeded 1mm or 1 degree, third measurement was taken and the middle value of the two nearest measurements was used.
STATISTICAL ANALYSIS
A master file was created, and the data was statistically analyzed on a computer with Statistical Package for Social Sciences (version 11.5) (Chicago: SPSS Inc). The data was subjected to descriptive analysis for mean and standard deviation. Paired-t test was used to analyze the significance of differences in mean value before (T1) and after (T2) treatment. A value of pEnglishhttp://ijcrr.com/abstract.php?article_id=2471http://ijcrr.com/article_html.php?did=24711. S Shishir. Timing of Myofunctional Appliance Therapy. J Clin Pediatr Dent 35(2): 233–240, 2010
2. Moss ML, and Salentijn. The primary role of functional matrices in facial growth. Am J Orthod, 55: 566–77, 1969.
3. Moss ML. The functional matrix hypothesis revisited 3: The genomic thesis. Am J Orthod Dentofacial Orthop 1997;112: 338–342.
4. Kharbanda OP. Orthodontics: Diagnosis and Management of Malocclusion and Dentofacial Deformities. 2 nd ed. New Delhi: Elsevier India; 2013. P. 4, 57, 459-519.
5. Hägg U, Pancherz H. Dentofacial orthopaedics in relation to chronological age, growth period and skeletal development. An analysis of 72 male patients with Class II division 1 malocclusion treated with the Herbst appliance. European Journal of Orthodontics. Aug 1988;10(3):169-76.
6. Moyers RE, Riolo ML, Guire KE, Wainright RL, Bookstein FL. Differential diagnosis of Class II malocclusions: Part 1. Facial types associated with Class II malocclusions. American Journal of Orthodontics. Nov 1980;78(5):477-94.
7. McNamara Jr JA. Components of Class II malocclusion in children 8–10 years of age. The Angle orthodontist. Jul 1981;51(3):177-202.
8.Takahashi S, Kuribayashi G, Ono T, Ishiwata Y, Kuroda T. Modulation of masticatory muscle activity by tongue position. Angle Orthod 2005;75:35-9.
9. Moss JP. The soft tissue environment of teeth and jaws. British J Orthod 7(3):127-137,1980.
10. Ozbek MM, Memikoglu UT, Gogen H, Lowe AA, Baspinar E. Oropharyngeal airway dimensions and functional-orthopedic treatment in skeletal Class II cases. Angle Orthod. 1998;68: 327–336.
11. Robin P. Glossoptosis due to atresia and hypotrophy of the mandible. Am J Dis Child 1934;48:541-7.
12. Anita G, Suma S. Growth modulation in Class II malocclusion - facts or delusion. Indian Journal of Dental Advancements 2010;1 (1): 20-23.
13. S Yassaei, Z Bahrololoomi, M Sorush. Changes of Tongue Position and Oropharynx Following Treatment with Functional Appliances. J Clin Pediatr Dent 31(4):287-290, 2007.
14. Bishara SE, Ziaja RR. Functional appliances: a review. 95:250-258,1998.
15. Patel HP, Moseley HC, Noar JH. Cephalometric determination of successful functional appliance therapy. Angle orthod. 72(5): 410-417 2002.
16. Kulbersh VP, Berger JL, et al. Treatment effects of the mandiular anterior repositioning appliance on patients with class II malocclusion Am J Orthod Dentofac Orthod. 123(3): 286-95, 2003.
17. Malkoc et al. Reproducibility of airway dimensions and tongue and hyoid positions on lateral cephalograms. Am J Orthod Dentofacial Orthop;128:513-6, 2005.
18. Preston CB, Lampasso JD, Tobias PV. Cephalometric evaluation and measurement of the upper airway. Seminar in Orthodontics 2004;10:3-15.
19. Martin SE, Mathur R, Marshall I, Douglas NJ. The effect of age, sex, obesity and posture on upper airway size. Eur Resp J. 1997;10:2087–2090
20. Zhou L, Zhao Z, Luo D:The analysis of the changes of tongue shape and position, hyoid position in class II, division I malocclusion treated with functional appliances (FR-I). Hua Xi Kou Qaaing,; 18(2):123-5. 2000
21. Ordoubazari M, Farokhnia F, Tuki Z, Ezzati F: Comparison of oropharyngeal space in 9-14 years and 18-30 year old Iranian groups. Dental journal of Shahid Beheshti Medical University, 19 (2):95-100, 1998
22. Yamaoka M, Furusawa K, Uematsu T, Okafuji N, Kayamoto D, Kurihara S. Relationship of the hyoid and posterior surface of the tongue in prognathism and micrognathia. J Oral Rehab; 30:914-920,2003.
23. Takahashi S, Ono T, Ishiwata Y, Kuroda T. Effect of changes in the breathing mode and body position on tongue pressure with respiratory-related oscillations. Am J Orthod Dentofac Orthop;115:239-44,1999.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241108EnglishN2018April28HealthcareLab Diagnosis of Extra Pulmonary Tuberculosis: Comparison of Histopathology, Cytology, ZeihlNeelsen stain and Light Emission Diode Microscopy with Culture and Nucleic Acid Amplification Tests
English1519Meenal BagdiaEnglish Sanjay BijweEnglish Nilma HiraniEnglish Ameeta JoshiEnglish Abhay ChowdharyEnglish Manish AgrawalEnglish Amitkumar BagdiaEnglishAim: To compare various diagnostic methods for diagnosing Extra Pulmonary Tuberculosis.
Methodology: A total of 173 extra pulmonary specimens depending on the site of infection were collected aseptically in sterile containers for tuberculosis (TB) culture and Polymerase Chain Reaction (PCR)‚ and in formalin for the purpose of cytology and pathology. TB culture was performed using the MGIT 960 liquid system‚ after initial screening using Light Emission Diode (LED) microscopy and ZN staining‚ while all the samples were also processed by Gene Xpert .
Results: Gene Xpert showed a high sensitivity of 85.71% and negative predictive value (NPV) of 98.67% while LED-FM had a high specificity of 98%‚ which was the same as of ZN stain and a high positive predictive value (PPV) of 86.36%.
Discussion: Clinical presentation of Extrapulmonary tuberculosis (EPTB) is atypical; especially when the disease involves obscure occult sites and EPTB may not even be considered in the initial list of differential diagnosis. Diagnosis of extrapulmonary tuberculosis is challenging due to the paucibacillary nature as well as atypical clinical presentations. Definitive diagnosis of tuberculosis involves demonstration of M. tuberculi by microbiological‚ cytopathological or histopathological methods.
Conclusion: Extrapulmonary tuberculosis diagnosis should hence be made using more than one diagnostic methods. In our present study, Light Emission Diode- Fluorescent Microscopy (LED-FM) proves to be a sensitive‚ specific and cost effective method for diagnosis of extrapulmonary tuberculosis..
EnglishExtrapulmonary, Paucibacillary, Gene XpertIntroduction
Tuberculosis (TB) is the major cause of death worldwide. This disease usually affects the lungs, although other organs are involved in up to one-third of cases. If properly treated, TB is curable in virtually all cases. Early diagnosis of Mycobacterium tuberculosis (MTB) in clinical samples becomes important in the control of tuberculosis both for the treatment of patients and for preventing disease transmission in the community.
FNA cytology is a simple and affordable procedure for diagnosis of tuberculosis compared with core-needle biopsy or excision biopsy. FNA offers a wider scope for diagnosis of organ and tissue involvement. Histopathological examination is easy, quick and affordable and provides characteristic findings of M. tuberculosis. But, as the infecting organisms are less in number in extrapulmonary tuberculosis, the sampled site may not represent the infected area and thus, the chances of missing the infected site are increased.
Direct microscopy is used for rapid diagnosis of TB and other mycobacterial diseases, as a relatively longer period of time is required for mycobacteria to be detected by bacteriological culture. For Tuberculosis case detection, microscopy is essential part because of its low cost, rapidity, simplicity of procedure and high specificity.1
Culture is a very sensitive diagnostic technique for tubercle bacilli, detecting as few as 10 to 100 bacilli per ml of sputum.2However, on solid media, the bacilli grow slowly and colonies appear in about two weeks and may sometimes take up to eight weeks.
The rapid detection of M. tuberculosis and drug resistance in infected patients is essential for disease management, because of the higher risk of transmission in community and emergence of MDR-TB (Multidrug resistant tuberculosis) and EDR-TB (Extensively drug resistant tuberculosis).
Molecular methods like Gene Xpert and Loop Mediated Isothermal Amplification (LAMP) has been developed in last few years for rapid TB diagnosis.
Polymerase chain reaction (PCR) technique is highly emerging as of its high sensitivity and specificity but require more technical expertise and expensive lab. Also, several PCR-based molecular methods have been setup to detect resistance to rifampicin and isoniazid. Amongst the recent molecular diagnostic methods, two commercial DNA strip assays have been developed, the INNO-LIPA Rif TB (Innogenetics, Ghent, Belgium) and the Genotype MTBDR plus (Hain Life-Science, Nehren, Germany). Both the tests are based on reverse hybridization of amplicons (rpoB in the INNO-LIPA Rif TB and rpoB plus katG and inhAin the Genotype MTBDR plus) to immobilized membrane-bound probes, allowing the detection of mutations at the level of the most frequently mutated codons. The presence of a mutation is revealed by the absence of hybridization at the level of the wild-type probes (rpoB WT1 to WT8 for RIF and katG WT and inhA WT1 and WT2 for isoniazid), with a possible positive hybridization signal at the level of the mutant probes.3
Methods
The present study was carried out in the Department of Pathology in collaboration with Microbiology department, in a tertiary care hospital in Mumbai.
Study population and sample collection
A total of 173 patients were enrolled in this study over a period of 18 months. Patients suspected of extrapulmonary tuberculosis were included in the study while those with clinical impression of pulmonary tuberculosis were excluded.
In patients coming with mass, specimen was collected by aspiration. Aspiration was done using 23 gauze needle with attached 10 ml disposable syringe. Body fluids, coming to the department were also collected. The specimen collected was divided into three parts. One part was smeared onto slides, fixed immediately with 95% alcohol and stained by haematoxylin and eosin (H and E) for cytological examination. Second part was used to make another air dried slide for ZN stain, which was then followed by auramine stain. Last portion of the material was collected in Falcon tube and submitted to microbiology department, for PCR and culture.
Tissue samples were collected for histopathologic correlation, when ever biopsy was carried out. Tissue received was examined grossly for presence of exudates, appearance of caseous necrosis, miliary tubercles and matted appearance. Sections were taken and divided into two parts. One part was submitted in Falcon tube to microbiology section, for further procedures of Ziehl Neelsen (Z-N) stain, Fluorescent stain, Culture and Polymerase Chain Reaction(PCR). The other part of the tissue received was processed in an automatic tissue processor. After processing, the paraffin blocks were made. Five microns thick sections were cut on a rotary microtome and then stained with Haematoxylin & Eosin and Ziehl Neelsen (Z-N) stain. Tissue histology was said to be suggestive of TB, if evidenced by presence of granulomatous inflammation, consisting of epithelioid cells, Langhans giant cell and caseation necrosis, surrounded by a rim of lymphocytes. The bacilli appear as yellow to orange, slender, rod-shaped under fluorescent microscopy. In the smears stained by the Z-N method, bacilli appear bright red against the background material counterstained in blue.
All the above samples were collected and processed for LED microscopy and Gene Xpert. Following decontamination and concentration, samples were processed for liquid culture, using MGIT960 system (BD, India). Cultures positive by this system were then processed for Line Probe Assay (LPA).
The kit used at our center for LPA was Geno Type MTBDR Plus version 2.0 manufactured by Hain Life science, Germany which detects resistance to RIF and/or INH using culture isolates. The steps involved were
DNA extraction from cultured isolates
A multiplex Polymerase Chain Reaction (PCR)
Reverse hybridization, where probes (reaction zones or bands) on the strips are used to interrogate the M. tuberculosis target DNA associated with RIF and INH resistance by detecting sequences complementary to the probes on the strip.
The molecular identification of rifampicin (RIF) resistance was accomplished by detecting the most significant mutations in the 81-bp (base pair) region of the rpoB gene (which encodes the β-subunit of RNA polymerase, the essential enzyme that is inactivated by RIF). High-level resistance to isoniazid(INH) is detected by screening for the most common mutations in the katG gene (which encodes catalase, the enzyme that activates INH). Low-level resistance to INH is detected by screening for mutations in the promoter region of the inhA gene (which encodes the NADH enoyl ACP reductase, involved in cell wall biosynthesis).
Procedure for Gene Xpert involved using an automated instrument which worked on the principle of
Detection of the target sequences in simple or complex samples using real-time PCR and reverse transcriptase PCR.
Nucleic acid amplification.
Statistical analysis:
The analysis of the results obtained by comparing various diagnostic tests, was done using open EPI software. Sensitivity, specificity, positive and negative predictive value were calculated using culture as gold standard.
Results
Sample detected positive by any of the diagnostic tests was considered to be positive for extrapulmonary tuberculosis in the present study. Out of the total 173 cases, 108 cases were found to be positive for extrapulmonary tuberculosis (EPTB) by one or the other method.
Distribution of 108 extrapulmonary tuberculosis specimens were as follows:
? Lymph node aspirates (49 cases) – Most common
? Fluids (43 cases)
? Histological tissue specimens (11 cases)
? Pus (5 cases)
Most of the site of lymph node aspiration among extrapulmonary tuberculosis cases was from cervical lymph nodes (39 cases out of total 49lymph nodes); other sites included axillary, inguinal, submandibular and supraclavicular lymph nodes. Fluids included pleural fluid, ascitic fluid, bronchoalveolar lavage, cerebrospinal fluid, pericardial fluid and peritoneal fluid,out of which pleural fluid accounted for the majority (25 cases out of 43). Out of the total 108 EPTB cases, 97 were subjected for cytology, which included lymph node aspirates, fluids and pus samples. 11 were subjected for histopathological examination. All 108 samples were subjected to Culture and LED-FM, while LPA was done on the 23 culture positive samples and Gene Xpert on 83 samples, of which 58 cases were positive for extrapulmonary tuberculosis (EPTB). However as the Gene Xpert instrument was not available initially in our department, Gene Xpert could be performed in only 83 cases, out of which 58 cases were positive for extrapulmonary tuberculosis.
Given below are the findings showing comparison of various diagnostic modalities.
Discussion
The smear positivity for AFB on the conventional ZN method in our study was 9.28% while the positivity increased to 17.52% on the modified fluorescent method. In the study done by Vamseedhar Annam et al4, the positivity rates were 44.11% for the ZN method and 81.37% for the modified fluorescent method. The results showed that FM staining technique is more sensitive in the detection of AFB in EPTB samples compared to ZN stain.
In our study ZN smear positivity for AFB was 9.28%, while positivity by routine cytological examination was 89.7%. There are other various reports regarding the sensitivity of ZN smear for extra-pulmonary specimen ranging from as low as 0% to as high as 75%. This limitation has been reported to be due to inadequacy and paucibacillary nature of extrapulmonary specimen.5
In the present study, culture positivity was 20.61% and ZN smear positivity was 9.28%. This is in concordance with the study done by M. Kashif Munir et al5, where culture positivity of extra-pulmonary specimens was 18.46% and was considerably high as compared to the ZN smear positivity of 3.85%, thus proving that culture is a sensitive tool in the diagnosis of extra-pulmonary TB.
When cytology was compared with Gene Xpert out of 56 cases, cytology could detect 53 cases and Gene Xpert could detect 6. Gene Xpert detected 3 cases, which were negative by cytology. Out of these 3 cases, 2 were also negative by culture, ZN stain and LED microscopy.
According to our study out of total 11 EPTB samples, Histopathology could detect 10 of them, while LED- FM, culture and ZN stain detected 5, 3 and 5 respectively. Thus positivity rate of Histopathology was 90.90% while of LED- FM and ZN was 45.45% and of culture was 27.27%. In study done by B.R. Maldhure et al6, 67.07% of cases were diagnosed as tubercular pleural effusion by biopsy as compared to our study where positivity rate of Histopathology was 90.90%. Thus histopathology remains one of the most important methods for diagnosing tuberculosis.
In our study, all of the 2 specimens positive for histopathology were also positive for Gene Xpert. In study carried out by SA Patwardhan et al7, PCR positivity was 69.2% and Histopath positivity was 80%. Thus PCR is a rapid and useful method for diagnosis of TB lymphadenitis and definitely increases the positive predictive value of a positive histopathology report.
In our study, positivity of ZN stain was 5.17% (3/58), FM microscopy was 10.34% (6/58), culture was 12.06% (7/58) and Gene Xpert was 15.38% (8/58). In the study done by Mohammed Abdul Mohi Siddiqui et al8, positivity by ZN stain was 5%, culture was 15% and PCR was 70%. Thus PCR as a diagnostic tool has more sensitivity to diagnose extrapulmonary tuberculosis.
As per Table 5, sensitivity and specificity of FNAC was 60% and 45.25% respectively. In study done by Yohannes Derese et al9, the sensitivity and specificity of FNAC was 81% and 50% respectively. In general, cytopathological morphology in FNAC lacks specificity but has higher sensitivity because non-tuberculous granulomatous patients could also be diagnosed as TBLN. Therefore, relying on cytology alone could lead to false case reporting.
Sensitivity and specificity of Histopathology was 66.67% and 33.33% respectively in our study. In study conducted by SA Patwardhan et al7, the sensitivity and specificity of histopathology was 96% and 78.5% respectively. Histopathological examination is easy, quick and cheap and provides characteristic features of M. -tuberculosis. The presence of caseation necrosis and epithelioid cell granulomas is taken as diagnostic of tuberculosis on Histopathological examination. However, granulomatous lymphadenopathy has a wide differential diagnosis and many other clinical conditions can present the same histopathology as TB lymphadenitis, thus thus decreasing the specificity of histopathology.
ZN stain, in our study had sensitivity and specificity of 47.83% and 98% respectively. In study done by Yohannes Derese et al9, ZN stain for AFB had sensitivity and specificity of 22.9% and 92.4% respectively. The quality of the smear as well as the scanty bacilli found in the FNA could be the main factor for decreased sensitivity.
Sensitivity and specificity of LED-FM in our study was 82.6% and 98% respectively. Specificity of LED and ZN were highest in our study. In the study done by Gerardo Alvarez-Uria et al10, LED fluorescent microscopy has shown sensitivity of 84% and specificity of 98% against culture as the reference standard. The advantage of using the fluorescent staining method is that fluorescent-stained slides can be examined under low magnification allowing for much larger areas of the smear to be examined in a short period of time. The use of the fluorescent method greatly improves the diagnostic value especially in patients with a low density of bacilli that are likely to be missed on ZN-stained smears.
Sensitivity and specificity of Gene Xpert in our study was 85.7% and 97.36% respectively. Its sensitivity was the highest compared to other diagnostic tests in our study. In study done by Doris Hillemann et al11, Gene Xpert sensitivity and specificity was 77.3% and 98.2% respectively.
According to table 5, maximum sensitivity was of Gene Xpert, followed by LED microscopy and maximum specificity was of LED microscopy and ZN stain, followed by Gene Xpert. However, the cost of the Gene Xpert equipment is much higher (approximately 2000 INR in a subsidized laboratory) than LED microscopy, which is a major obstacle for its use in small scale laboratories. Although the Xpert assay does not require operator expertise or external quality controls and is able to provide information about rifampicin resistance, only four samples can be processed every two hours. The biggest limitation of DNA based molecular tests is that these tests can not differentiate between dead and live target organisms. So its relevance has to be judged in light of the overall clinical picture in cases where the patient has received anti-tubercular treatment recently.
Conclusion
Diagnosis of extrapulmonary tuberculosis is challenging due to the paucibacillary nature as well as atypical clinical presentations. Its diagnosis should hence be made by considering more than one diagnostic methods. In our present study, Light Emission Diode- Fluorescent Microscopy proves to be a sensitive, specific and cost effective method for diagnosis of extrapulmonary tuberculosis.
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.
Ethical clearance
Ethical clearance was taken from ethics committee.
Consent
Blanket consent was taken.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Englishhttp://ijcrr.com/abstract.php?article_id=2472http://ijcrr.com/article_html.php?did=24721]. Singhal R, Myneedu VP. Microscopy as a diagnostic tool in pulmonary tuberculosis. International Journal of Mycobacteriology 2015; 4:1–6.
2]. Ananthnarayan and Panikar's. Mycobacterium I: Tuberculosis. In: Textbook of Microbiology, 9th edition, 2013. Pgs 345-358.
3]. Nu-LAMP TB kit insert.
4]. Annam V, Kulkarni MH, Puranik RB. Comparison of the modified fluorescent method and conventional Ziehl-Neelsen method in the detection of acid fast bacilli in lymph node aspirates. Cyto Journal 2009;6:13
5]. Munir MK, Shabbir I, Iqbal R, Khan SU. Comparison of AFB Smear Microscopy and Culture from Specimens Received for the Diagnosis of Extra Pulmonary Tuberculosis. P J M H S 2009;1(1):59-61.
6]. Maldhure BR, Bedarkar SP, Kulkarnl HR, Paplnwar SP. Pleural Biopsy and Adenosine Deaminase in pleural fluid for the diagnosis of tubercular pleural effusion. Ind. J. Tub 1994;41:161.
7]. Patwardhan SA, Bhargava P, Bhide VM, Kelkar DS. A study of tubercular lymphadenitis: A comparison of various laboratory diagnostic modalities with a special reference to tubercular polymerase chain reaction. Indian Association of Medical Microbiologists 2011;29(4):389-94.
8]. Siddiqui MAM, Anuradha PR, Nagamani K, Vishnu PH. Comparison of conventional diagnostic modalities, BACTEC culture with polymerase chain reaction for diagnosis of extra-pulmonary tuberculosis. J Med Allied Sci2013;3(2):53-58.
9]. Derese Y, Hailu E, Assefa T, Bekele Y, Mihret A, Aseffa A, et al. Comparison of PCR with standard culture of fine needle aspiration samples in the diagnosis of tuberculosis lymphadenitis. J Infect Dev Ctries2012;6(1):53-57.
10]. Alvarez-Uria G, Azcona JM, Midde M, Naik PK, Reddy S, Reddy R. Rapid Diagnosis of Pulmonary and Extrapulmonary Tuberculosis in HIV-Infected Patients. Comparison of LED Fluorescent Microscopy and the Gene Xpert MTB/RIF Assay in a District Hospital in India. Tuberculosis Research and Treatment 2012.
11]. Hillemann D, Gerdes SR, Boehme C, Richter E. Rapid Molecular Detection of Extrapulmonary Tuberculosis by the Automated Gene Xpert MTB/RIF System. Journal of Clinical Microbiology 2011;49:1202–5
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241108EnglishN2018April28HealthcareInterplay between the Levels of Asymmetric Dimethylarginine and Nitric Oxide in Preeclampsia
English2024Mohit UpadhyeEnglish Aditya TolatEnglish Tanvi KarambelkarEnglish Ankita TikalkarEnglish Shruti MulgundEnglish Rupali PawarEnglish Rahul ChaudhariEnglish Subodhini AbhangEnglishBackground: Preeclampsia is a leading cause of maternal and fetal morbidity and mortality all over the world. Endothelial dysfunction is the chief mediator of clinical manifestations of preeclampsia, which are hypertension and proteinuria. Asymmetric dimethylarginineis an endogenous inhibitor of nitric oxide synthase that induces endothelial dysfunction by reversibly inhibiting nitric oxide production from l-arginine.
Materials and Methods: We conducted a prospective case-control study to estimate the levels of asymmetric dimethylarginine and nitric oxide in the maternal serum of pregnant women with and without preeclampsia. Pregnant women with non-severe preeclampsia (n=40) and healthy, normotensive women (n=40) admitted for normal vaginal delivery were enrolled in the study.
The serum levels of asymmetric dimethylarginine were estimated using ELISA and those of nitric oxide by Griess reaction.
Results: After analyzing the data we found that the levels of asymmetric dimethylarginine were significantly higher and those of nitric oxide significantly lower in cases. There was no significant correlation between the levels of asymmetric dimethylarginine and nitric oxide, suggesting a role of factors other than asymmetric dimethylarginine in the regulation of nitric oxide metabolism. Nitric oxide showed significant negative correlation with the systolic BP and mean arterial pressure of the cases whereas asymmetric dimethylarginine did not, which implies that nitric oxide is an important determinant of BP in preeclampsia.
Conclusion: The present study highlights the interplay between asymmetric dimethylarginine & nitric oxide and its role in the etiopathogenesis of preeclampsia. It is a complex, multifactorial interaction with no one-to-one relationship and can serve as the biochemical focus of the treatment of preeclampsia.
EnglishAsymmetric dimethylarginine, Nitric oxide, PreeclampsiaINTRODUCTION:
Preeclampsia, a hypertensive disease of pregnancy, is a major cause of maternal and fetal morbidity and mortality. Preeclampsia alone complicates about 3% of pregnancies whereas all hypertensive disorders together affect about 5 to 10% of pregnancies worldwide.(1) In India, the incidence of preeclampsia is reported to be 8 to 10% amongst registered pregnant women. Preeclampsia is defined as hypertension in pregnancy after ≥20 weeks of gestation with systolic blood pressure of ≥140 mmHg or a diastolic pressure of ≥90mmHg as measured twice, 4-6 hours apart and proteinuria ≥30mg per day (≥1+ on dip-stick) in a minimum of two random urine samples collected at least 4-6 hours, but not more than 7 days apart.(2)
During normal pregnancy, certain structural modifications take place in the myometrium and spiral arteries of the uterus. The villous cytotrophoblast invades into the myometrium and leads to the loss of endothelium and muscle fibres of the spiral arteries. This converts the spiral arteries into low resistance vessels.(3) Pre-eclampsia is caused by the defective invasion of the spiral arteries by cytotrophoblastic cells. This increases the resistance of spiral arteries leading to chronic placental ischemia. The ischemic placenta produces free radicals, oxidized lipids, cytokines, and serum soluble vascular endothelial growth factor leading to oxidative stress.(4)
All these factors cause severe endothelial dysfunction leading to the classical manifestations of preeclampsia that are hypertension and end-organ damage.(5) This adversely affects the fetal circulation causing intrauterine growth retardation or even intrauterine death of the fetus.(6)
Endothelial dysfunction leads to derangement in a number of biochemical parameters out of which asymmetric dimethyl arginine and nitric oxide are well-known factors.
Asymmetric dimethylarginine is one of the degradation products of methylated proteins. Its formation is catalyzed by the enzyme protein arginine methyltransferase type 1 and the methyl group is donated by S-adenosyl methionine.(7) Asymmetric dimethylarginine and other asymmetrically methylated residues are competitive inhibitors of nitric oxide synthase.(8) Asymmetric dimethylarginine is cleared by renal and non-renal routes such as pancreas, liver, brain and aorta in which it is degraded by the enzyme dimethyl arginine dimethylaminohydrolase (DDAH) into citrulline and dimethylamine.(9)
Asymmetric dimethylarginine is a mediator molecule of endothelial dysfunction implicated in the pathogenesis of many cardiovascular diseases. This action is mediated by the inhibition of nitric oxide synthase enzyme as well as direct endothelial toxicity. Asymmetric dimethylarginine has been suggested as a strong and independent risk factor for total mortality and cardiovascular outcome.(10)
The endothelial cells are chiefly responsible for the vascular homeostasis. They respond to a variety of stimuli by elaborating a host of vaso-active agents, primarily nitric oxide, also known as the endothelium-derived relaxing factor.(11) A principal intracellular target for nitric oxide is guanylate cyclase, which, when activated, increases the intracellular concentration of cyclic guanosine monophosphate, which in turn activates protein kinase G.(12) Acting through this pathway, nitric oxide induces relaxation of vascular smooth muscle and inhibits platelet activation and aggregation.(13)
High concentrations of asymmetric dimethylarginine are associated with inflammation, insulin resistance, dyslipidemia, and obesity.(14)Asymmetric dimethylarginine and nitric oxide have been studied more extensively in cardiovascular diseases. There are conflicting remarks about their role in preeclampsia in the literature. Hence it was of interest to understand the interplay of these two molecules in preeclampsia.
MATERIALS & METHODS
We conducted a case-control study in the Department of Biochemistry of B.J. Govt Medical College and Sasoon General Hospital Pune, a tertiary care teaching hospital, during the period of February-March 2017. Ethical clearance was obtained from the institutional ethics committee.
The study comprised of 40 cases of preeclampsia and 40 normotensive, healthy pregnant women as controls, admitted for normal vaginal delivery in Sasoon General Hospital in the above mentioned time period. The samples were collected immediately after admission to the labour room.
The diagnostic criteria for preeclampsia were, having an onset at ≥20 weeks of gestation, systolic blood pressure of ≥140 mmHg or a diastolic pressure of ≥90mmHg as measured twice 4-6 hours apart and ≥30mg per day of proteinuria (≥1+ on dip-stick) in a minimum of two random urine samples collected at least 4-6 hours but not more than 7 days apart. Normal pregnant women in their third trimester of pregnancy were taken as controls.
The inclusion criteria for cases were: age 18-30 years, patients in the third trimester of pregnancy, bp ≥140/90 mmHg at the time of sample collection, ≥1+ proteinuria on dip-stick test at the time of sample collection. Bothprimi and multigravida patients were included.
The exclusion criteria for both cases and controls were the presence of any comorbidities other than preeclampsia, any history of infections including HIV, HBV or HCV, gestational age less than 28 weeks and peeclampsia with complications i.e. severe preeclampsia.
After explaining all the details, a written informed consent was taken from each patient. A detailed history of the patients was recorded on a preformed questionnaire. After taking proper aseptic precautions 5ml of blood sample was collected in a plain vacutainer from each patient. The serum was separated and was stored at -20?C.
Asymmetric dimethylarginine was measured by Human asymmetric dimethylarginine ELISA kit and nitric oxide by cadmium reduction method (Griess reaction).(15)
STATISTICAL ANALYSIS
Unpaired t-test was performed to compare all the parameters between cases and controls. Pearson’s correlation coefficient was calculated to assess the correlation between asymmetric dimethylarginine, nitric oxide and blood pressure of the patients. Regression analysis was done for the parameters with a significant correlation.
RESULTS
The mean age in preeclampsia cases was 23.925±4.33 years and that in controls is 23.3±3.083 years. The mean systolic blood pressure of cases, being 153.75±11.55 mmHg, was significantly higher than that of controls i.e. 114.6±8.53 mmHg (PEnglishhttp://ijcrr.com/abstract.php?article_id=2473http://ijcrr.com/article_html.php?did=24731. Hutcheon JA‚ Lisonkova S‚ Joseph KS. Epidemiology of pre-eclampsia and the other hypertensive disorders of pregnancy. Best Pract Res Clin Obstet Gynaecol. 2011 Aug 1;25(4):391–403.
2. Uzan J‚ Carbonnel M‚ Piconne O‚ Asmar R‚ Ayoubi JM. Pre-eclampsia: pathophysiology‚ diagnosis‚ and management. Vasc Health Risk Manag. 2011;7:467.
3. LYALL F. Mechanisms regulating cytotrophoblast invasion in normal pregnancy and pre?eclampsia. Aust New Zeal J Obstet Gynaecol. 2006;46(4):266–73.
4. El-Sayed AAF. Preeclampsia: A review of the pathogenesis and possible management strategies based on its pathophysiological derangements. Taiwan J Obstet Gynecol. 2017 Oct 1;56(5):593–8.
5. Poston L. Endothelial dysfunction in pre-eclampsia. Pharmacol Rep. 2006;58 Suppl:69–74.
6. Meng W‚ Li R. Association between asymmetric dimethylarginine level and preeclampsia: a meta-analysis. Int J Clin Exp Med. 2017;10(6):8720–7.
7. Spoto B, Parlongo RM, Parlongo G‚ Sgro’ E‚ Zoccali C. The enzymatic machinery for ADMA synthesis and degradation is fully expressed in human adipocytes. J Nephrol. 20(5):554–9.
8. Böger RH. Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase‚ explains the “L-arginine paradox” and acts as a novel cardiovascular risk factor. J Nutr. 2004;134(10 Suppl):2842S–2847S; discussion 2853S.
9. Sibal L, Agarwal SC, Home PD, Boger RH. The Role of Asymmetric Dimethylarginine (ADMA) in Endothelial Dysfunction and Cardiovascular Disease. Curr Cardiol Rev. 2010;6(2):82.
10. Landim MBP‚ Filho AC‚ Chagas ACP. Asymmetric Dimethylarginine (ADMA) and Endothelial Dysfunction: Implications for Atherogenesis. Clinics (Sao Paulo). 2009;64(5):471.
11. Tousoulis D‚ Kampoli A-M‚ Tentolouris C‚ Papageorgiou N‚ Stefanadis C. The role of nitric oxide on endothelial function. Curr Vasc Pharmacol. 2012;10(1):4–18.
12. Cary SPL‚ Winger JA‚ Derbyshire ER‚ Marletta MA. Nitric oxide signaling: no longer simply on or off. Trends Biochem Sci. 2006 Apr 1;31(4):231–9.
13. Radomski MW‚ Palmer RMJ‚ Moncada S. Characterization of the l-arginine: nitric oxide pathway in human platelets. Br J Pharmacol. 1990 Oct 1;101(2):325–8.
14. Jeyabalan A. Epidemiology of preeclampsia: Impact of obesity. Nutr Rev. 2013;71(0 1):S18-25.
15. Cortas NK‚ Wakid NW. Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method. Clin Chem. 1990 Aug;36(8 Pt 1):1440–3.
16. Nair N‚ Gongora E. Oxidative Stress and Cardiovascular Aging: Interaction Between NRF-2 and ADMA. Curr Cardiol Rev. 2017 Jul 11;13(3).
17. Pettersson A‚ Hedner T‚ Milsom I. Increased circulating concentrations of asymmetric dimethyl arginine (ADMA)‚ an endogenous inhibitor of nitric oxide synthesis, in preeclampsia. Acta Obstet Gynecol Scand. 1998 Jan;77(8):808–13.
18. Caglar K‚ Yilmaz MI‚ Sonmez A‚ Cakir E‚ Kaya A‚ Acikel C‚ et al. ADMA, proteinuria‚ and insulin resistance in non-diabetic stage I chronic kidney disease. Kidney Int. 2006;70(4):781–7.
19. Lowe DT. Nitric Oxide Dysfunction in the Pathophysiology of Preeclampsia. Nitric Oxide. 2000;4(4):441–58.
20. Mao D‚ Che J‚ Li K‚ Han S‚ Yue Q‚ Zhu L‚ et al. Association of homocysteine, asymmetric dimethylarginine, and nitric oxide with preeclampsia. Arch Gynecol Obstet. 2010;282(4):371–5.
21. Vicente Lahera Navarro-Cid Josefa Victoria Cachofeiro Joaquin García-Estañ Luis. Nitric Oxide‚ the Kidney‚ and Hypertension. Am J Hypertens. 1997;10(1):129–40.
22. Sim J-Y. Nitric oxide and pulmonary hypertension. Korean J Anesthesiol. 2010 Jan;58(1):4–14.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241108EnglishN2018April28HealthcareComparison of Somatostatin and Famotidine for the Treatment of Nonvariceal Acute Upper Gastrointestinal Bleeding
English2527Caglayan GeredeliEnglishIntroduction: It is aimed to be researched if somatostatin is as effective as H2 blockers to stop the bleeding in centres where the endoscopic treatment is not available for the non-variceal upper GI bleeding cases
Methods: The patients who were admitted to the Department of Internal Medicine of Dicle University with the diagnosis of upper GI bleeding, and were not suitable for endoscopic treatment are subjected in our paper. One group was given 250 mcg bolus dose of somatostatin followed by 120 hours of infusion at a speed of 250 mcg/hour whereas the other group was given 20 mg intravenous famotidine every 12 hours. The amount of time required to stop bleeding, the amount of blood transfusion made during that 120 hours time period, the ratio of recurrent bleeding, and the ratio of the necessity of surgical intervention were noted.
Results: 42 patients were included in the study. 21 patients were in somatostatin group, and the other 21 patients were in H2 receptor blocker group. In both somatostatin and H2 receptor blockers groups, the cause of gastrointestinal bleeding was found to be duodenal ulcers in 71% of the patients and gastric ulcer in 14% of the patients. While bleeding had stopped in the first 48 hours in 95.2% of the patients in somatostatin group, the same thing happened in 90.4% of the patients in H2 receptor group. There were no statistical difference between the two groups (p=0.90). The average time passed to stop the bleeding was 15 hours (6-24 hours) for the somatostatin group, whereas it was 34 hours (6-72 hours) for the H2 receptor blocker group. Somatostatin stopped the bleeding in a shorter time which was statistically significant (P=0.01).while the required blood transfusion amount was an average of 3.5 (0-13) units for the somatostatin group, it was 4.4 (0-14) units for the group of H2 receptor blocker. There were no statistically significant difference (p=0.182). The surgical intervention was needed in 9.6% of the patients in somatostatin group, whereas it was needed in 14.2% of the patients in H2 receptor group (p=0.212).
Conclusion: While somatostatin statistically significantly stops the bleeding in a shorter time period as compared with H2 receptor blockers, no significant difference in blood transfusion requirement and surgical necessity were detected. Cost-effectiveness of somatostatin should be considered when it is used in GI bleeding cases.
EnglishAcute upper GI bleeding, Somatostatin, FamotidinIntroduction
Acute upper GI bleeding is a commonly seen health problem in the world(1). More than 100 of every 100000 patients who were admitted were found to have upper GI bleeding(1). 80% of upper GI bleeding stops spontaneously while 20% does not(1). Surgical intervention is required in 15% to 30% of the patients with an ongoing bleeding(1).
H2 receptor blockers, proton pump inhibitors and somatostatin are used in the medical treatment of upper GI bleeding(2,3). H2 receptor and proton pump inhibitors inhibit the acid secretion from stomach(3). Somatostatin, which is an endogenouspeptide that reduces the splenic blood flow, inhibits the motility and acid secretion of GI, and has a possible cytoprotective effect, is known to be effective in oesophageal variceal bleeding cases(4). However its effectiveness on non-variceal bleeding is uncertain. In our study, the comparison of the effectiveness of somatostatin in non-variceal bleeding with the routine H2 receptor blocker treatment was aimed.
Materials and Method
The study was conducted retrospectively at the Department of Internal Medicine of Dicle University. The patients who applied to the emergency service with the complaints of hematemesis and melena, and were undergone a gastroscopy in 24 hours following their admission to the internal medicine wards to find the cause of GI bleeding were selected. The patients who were older than 18 years old and had their arterial systolic blood pressures lower than 100mmHg, pulses higher than 100 and hematocrit levels below 30 were included. The patients who with serious coagulation defects and oesophageal variceal bleeding were excluded. The ones who were given famotidine (20 mg every 12 hours given intravenously) as treatment were selected for H2 receptor blocker group and the rest were given somatostatin (250 mcg bolus dose followed by 250mcg/h infusion for 72-120 hours). Both groups were given intravenous isotonic NaCl solution to stabilize them hemodynamically. The gastroscopy was repeated for the patients who stopped bleeding to confirm that the bleeding had stopped. The patients who stopped bleeding were then discharged 120 hours later with a prescription of famotidine 40mg. Patients' blood pressure and pulse rate were controlled hourly. Hematogram was performed every 6-12 hours to determine the need for blood transfusion. The patients whose blood pressure and pulse couldnot be stabilised in 24 hours and needed more than 8 units of blood transfusion were treated surgically. The comparison of the amount of time required for bleeding tobe stopped, the ratio of re-bleeding, the required amount of blood transfusion and the ratio of surgical intervention required was made.
Statistical Methods
The Statistical Package for the Social Sciences (SPSS) version 15.0 for Windows (SPSS Inc., Chicago, IL, USA) was used for the statistical analysis. The comparisons of the ratios in the groups were made using a chi-squared analysis and Mann-Wutnay U tests were used for the statistical analysis. P values smaller than 0.05 were decided to be evaluated as significant.
Results
42 patients were included in the study. 21 patients were given somatostatin, and 21 patients were given famotidine intravenously. Of the patients who received somatostatin treatment, 17 were male and 4 were female. 19 of the patients who were given famotidine were male whereas 2 of them were female. The mean age of the patients receiving somatostatin was 50 (24-73) while the mean age of the patients receiving famotidine was 48 (18-90). The causes of hemorrhage in both groups were similar (Table 1). Bleeding stopped in 95.2% of patients who were given somatostatin and 90.4% of patients who were given famotidine (Table 1). There was no statistical difference between the two groups by means of stoppage of the bleeding (p =0.850) The average time spent to stop the bleeding was 15 hours (6-24 hours) for the patients treated with somatostatin, whereas it was 34 hours (6-72 hours) for the ones treated with famotidine. There was a statistically significant difference between the two groups regarding the time required for the stoppage of bleeding (P=0.01). While the required blood transfusion amount was an average of 3.5 (0-13) units for the somatostatin receiving patients, it was 4.4 (0-14) units for the patients treated with famotidine. There was no statistically significant difference between the two groups in terms of blood transfusion (p=0.182). Re-bleeding developed in the 25% of the patients treated with somatostatin, whereas it re-occurred in 26.2% of the patients who were given famotidine. There was no statistically significant difference between the two groups in terms of rebleeding. (p=0.611) 9.6% of the patients treated with somatostatin needed surgical intervention, while 14.2% of the ones who were given famotidine did so. No statistical difference between the two groups with regards to surgical operation requirement was found (p=0.212). No mortality had been seen in neither of the groups during the 120 hours of admission.
Discussion
Somatostatin is effective in stopping the oesophageal variceal bleeding, but its effectiveness on non-variceal acute upper GI bleeding is controversial (5,6,7). Terres A et al, Antonioli A et al and Kayasseh et al has found somatostatin to be effective in stoppage of bleeding in upper GI bleeding cases. However in some other studies somatostatin is not found to stop the acute upper GI bleeding effectively (8-12). Our study showed that somatostatin effectively stops bleeding in cases with acute upper GI bleeding. In all the studies where the time required to stop the bleeding was evaluated (5,6,8,9) somatostatin was detected to decrease the bleeding time significantly. Our study also showed that the time required to stop the bleeding was 15 hours in cases where somatostatin was given, whereas it was 34 hours in the group that was given H2 receptor blockers. No significant difference between somatostatin and H2 blockers in terms of re-bleeding has been found in the studies made so far (8,10,11). In accordance with that, a significant difference couldnot be detected by means of re-bleeding in our study. Though some studies show that somatostatin decreases the need for blood transfusion in acute upper GI bleeding (6-8), a significant difference couldnot be detected in a few other studies. Our study also shows no significant difference between the two groups regarding blood transfusion (8-12). In some studies it has been detected that somatostatin decreases the requirement for surgical intervention (9,10). However, such effects of it couldnot be found in many other studies (5,7,9-12) An effect to reduce the necessity for surgical requirement couldnot be observed in our study as well.
Conclusion
To conclude, somatostatin had stopped the bleeding significantly and shortened the bleeding period significantly as compared with famotidine. However, no significant difference was found between the patients who were given somatostatin and H2 receptor blocker in terms of the ratio of re-bleeding, blood transfusion need and the necessity of surgical intervention.
Acknowledgements
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.
Source of funding: No funding source
Conflict of interest: No conflict of interest
Englishhttp://ijcrr.com/abstract.php?article_id=2474http://ijcrr.com/article_html.php?did=24741.Longstreth GF. Epidemiology of hospitalization for acute upper gastrointestinal hemorrhage: a population-basedstudy. Am J Gastroenterol. 1995 Feb;90(2):206-10.
2.Walan A1, Bader JP, Classen M, Lamers CB, Piper DW, Rutgersson K, Eriksson S
Effect of omeprazole and ranitidine on ulcer healing and relapserates in patients with benign gastric ulcer. N Engl J Med. 1989 Jan 12;320(2):69-75.
3.Collins R, Langman M. Treatment with histamine H2 antagonists in acute upper gastrointestinal hemorrhage. Implications of randomized trials. N Engl J Med. 1985 Sep 12;313(11);660-6.
4.Imperiale TF, Birgisson S Somatostatin or octreotide compared with H2 antagonists and placebo in the management of acute nonvariceal upper gastrointestinal hemorrhage: a meta-analysis. Ann Intern Med. 1997 Dec 15;127(12);1062-71. Erratum in: Ann Intern Med 1998 Feb 1;128(3);245
5.Torres AJ, Landa I, Hernández F, Jover JM, Suárez A, Arias J, Cuberes R, Santoyo J, Fernández R, Calleja J, et al Somatostatin in the treatment of severe upper gastrointestinal bleeding: A multicentre controlled trial. Br J Surg. 1986 Oct;73(10):786-9.
6.Antonioli A, Gandolfo M, Rigo GP, Bianchi Porro G, Cheli R, Brancato F, Lazzaroni M, Parodi MC, Maringhini A, Raimondo S, et al Somatostatin and cimetidine in the control of acute upper gastrointestinal bleeding. A controlled multicenter study. Hepatogastroenterology. 1986 Apr;33(2):71-4.
7.Kayasseh L, Gyr K, Keller U, Stalder GA, Wall M Somatostatin and cimetidine in peptic-ulcer haemorrhage. A randomised controlled trial. Lancet. 1980 Apr 19;1(8173):844-6.
8.Galmiche JP, Cassigneul J, Faivre J, Tranvouez JL, Ouvry D, Colin R, Pascal JP, Klepping C. Somatostatin in peptic ulcer bleeding--results of a double-blind controlled trial.Int J Clin Pharmacol Res. 1983;3(5);379-87.
9.Basile M, Celi S, Parisi A, Castiglione N, Parisi S Somatostatin in the treatment of severe gastrointestinal bleeding from peptic origin. A multicentric controlled trial. Ital J Surg Sci. 1984;14(1):31-5
10.Coraggio F, Scarpato P, Spina M, Lombardi S Somatostatin and ranitidine in the control of iatrogenic haemorrhage of the upper gastrointestinal tract. Br Med J (ClinResEd). 1984 Jul 28; 289(6439):224.
11.Magnusson I, Ihre T, Johansson C, Seligson U, Törngren S, Uvnäs-Moberg K. Randomised double blind trial of somatostatin in the treatment of massive upper gastrointestinal haemorrhage. Gut. 1985 Mar;26(3):221-6.
12.Basso N, Bagarani M, Bracci F, Cucchiara G, Gizzonio D, Grassini G, Percoco M, Procacciante F, Toti F. Ranitidine and somatostatin. Their effects on bleeding from the upper gastrointestinal tract. Arch Surg. 1986 Jul;121(7):833-5.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241108EnglishN2018April28HealthcarePredictive Importance of Platelet to Lymphocyte Ratio and Neutrophil to Lymphocyte Ratio for Pathologic Complete Response in Locally Advanced Breast Cancer Patients Receiving Neoadjuvant Chemotherapy
English2832Caglayan GeredeliEnglish Serdar AriciEnglishBackground: The peripheral blood platelet–lymphocyte ratio (PLR) and neutrophil- lymphocyte ratio (NLR) has been proposed as an indicator for evaluating systemic inflammatory responses in cancer patients.
Materials and Method: PLR and NLR was evaluated retrospectively in 167 breast cancer patients treated with the NACT and subsequent curative surgery.
Results: A total of 167 patients were analyzed.The median age of patients was 50 (min 22 – max 84). 113 patients (67,6%) were stage II and 54 (32,4%) were stage III. Patients with pathologically complete response (pCR) according to Miller-Payne grading system, constituted 55 (32.9%) of all patients 76.3% of patients with pCR had stage IIdisease and of 23.7% had stage III disease. Complete pathologic response rate was statistically significant higher in stage II group than stage III group (p=0.001). In subgroup analysis, pCR rates were 44.2%, 26.9%, 29.7% and 17.6% in HER 2 positive, Luminal B, triple negative and Luminal A groups, respectivly. No statistically significant relationship was found between peripheral blood NLR, PLR before neoadjuvant therapy and pCR in all groups (p = 0.244). However, there was a significant difference between peripheral blood PLR before neoadjuvant therapy in Stage II patients and pCR (p = 0.002)
Conclusion: In peripheral blood NLR and PLR was not effective predictive marker for pCR in patients who will receive NACT for stageII and stage III breast cancer but in peripheral blood low PLR was an effective predictive marker for pCR in patients who will receive NACT for stage III breast cancer.
EnglishPlatelet to Lymphocyte Ratio, Neutrophil to Lymphocyte Ratio, Pathologic Complete Response, Locally Advanced Breast Cancer, Neoadjuvant ChemotherapyIntroduction
Globally, breast cancer is the most frequently diagnosed malignancy, It is also the leading cause of cancer death in women worldwide(1).
Most patients with non-metastatic breast cancer should receive neoadjuvant chemotherapy therapy (NACT). The goal of treatment is to induce a tumor response before surgery and enable breast conservation. In a meta-analysis, by Mieog JS et al. demonstrated outcomes of NACT; compared with adjuvant chemotherapy reduced risk of radical mastectomy, increased risk of locoregional recurrence and equivalent overall survival and disesase free survival (DFS)(2). Mostly anthracycline based regimens used in neoadjuvant setting but non-anthracycline based regimens may be used. All of patients treated with NACT should undergo surgery.
Pathologic complete response (pCR) is associated with improvement in DFS (3,4). Miller-Payne histopatologic scoring system is used to asses the patholocig response by comparing cancer cellularity in core biopsy (before treatment) with the resected tumor (after treatment). pCR shows reduction in tumor cellularity higher than 90% and no residual invasive cancer(5).
Inflammation and cancer are closely related to each other. As a parameter that can reflect inflammation and host immune reaction, elevated blood neutrophil to lymphocyte ratio (NLR) has been reported to be correlated with poor prognosis in a variety of cancers, one of them breast cancer(6-10). Some studies reported controversial results (11,12).
Recently, platelet-to-lymphocyte ratio (PLR) has become an attractive, convenient, and cost-effective blood-derived prognostic marker as well as an inflammation-related and immune-related prognostic score to evaluate the prognosis of several solid tumors likely NLR. Association between PLR and colorectal, gastric and lung cancer is evaluated in some trials and reported PLR was a predictive marker for poor prognosis(13-17). However, breast cancer and PLR association is controversial.
In this study, we aimed to determine predictive impact of PLR and NLR by comparing with pCR, in patients treated by NACT.
Material and methods
This study was planned as a retrospective single center study. Medical informations wereobtained from the archive files of patients who were treated anthracyclin and taksan-based neoadjuvant chemotherapy between 2010-2017 years, for breast cancer in the medical oncology clinic of Istanbul Okmeydan education and research hospital. Patients without pathology report and laboratory test results were excluded. Disease staging was performed according to TNM 7. The age, menopausal status, pathologic results such as tumor size, histological type, lymph node status, grade, hormonal status, human epidermal growth factor receptor 2 (HER2) receptor status and laboratory data were obtained from the archive files of patients. Neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) were calculated from complete blood count obtained before first chemotherapy. The histologicalresponse for breast and axilla was assesedaccording to Miller-Payne grading system (MPG) .
Statistical Methods
SPSS 15.0 for Windows program was used for statistical analysis. Descriptive statistics was given as number and percentage for categorical variables, average, standard deviation, minimum, maximum for numeric variables. Two independent group comparisons of the numerical variable were performed with the Mann Whitney U test when normal distribution condition was not achieved. Comparisons of categorical variables ratios in groups were made with Chi Square Analysis. Monte Carlo simulation was applied when conditions were not met. Statistical significance level of alpha was accepted as p Englishhttp://ijcrr.com/abstract.php?article_id=2475http://ijcrr.com/article_html.php?did=2475
Cancer statistics, 2018. Siegel RL, Miller KD, Jemal A. CA Cancer J Clin. 2018 Jan;68 (1):7-30. doi: 10.3322/caac.21442. Epub 2018 Jan 4.
Mieog JS, van der hage ja, van de Velde CJ. Preoperative chemotherapy for women with operable breast cancer. Cochrane Database Syst Rev. 2007 Apr 18; (2):CD005002
Liedtke C, Mazouni C, Hess KR, André F, Tordai A, Mejia JA et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008 Mar 10;26 (8):1275-81. doi: 10.1200/JCO.2007.14.4147. Epub 2008 Feb 4
Von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012 May;30 (15):1796-80 Epub 2012 Apr 16.
Ogston KN, Miller ID, Payne S, Hutcheon AW, Sarkar TK, Smith I et al. A new histological grading system to assess response of breast cancers to primary chemotherapy: Prognostic significance and survival. Breast. 2003 Oct;12 (5):320-7.
Jiang Y, Xu H, Jiang H, Ding S, Zheng T et al. Pretreatment neutrophil-lymphocyte count ratio may associate with gastric cancer presence. Cancer Biomark 2016;16:523–8.
Minardi D, Scartozzi M, Montesi L,Santoni M, Burattini L, Bianconi M et al. Neutrophil-to-lymphocyte ratio may be associated with the outcome in patients with prostate cancer. SpringerPlus 2015;4:255.
Koh CH, Bhoo-Pathy N, Ng KL, Jabir RS, Tan GH, See MH et al. Utility of pre-treatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors in breast cancer. Br J Cancer 2015;113:150–8.
Hong X, Cui B, Wang M, Yang Z, Wang L, Xu Q et al. Systemic immune-inflammation index, based on platelet counts and neutrophil-lymphocyte ratio, is useful for predicting prognosis in small cell lung cancer. Tohoku J Exp Med 2015;236:297–304.
Chen J, Hong D, Zhai Y,Shen P. Meta-analysis of associations between neutrophil-to-lymphocyte ratio and prognosis of gastric cancer. World J Surg Oncol 2015;13:122.
Cihan YB, Arslan A, Cetindag MF, Mutlu H. Lack of prognostic value of blood parameters in patients receiving adjuvant radiotherapy for breast cancer. Asian Pac J Cancer Prev 2014;15:4225–31.
Ulas A, Avci N, Kos T, Cubukcu E, Olmez OF, Bulut N et al. Are neutrophil/lymphocyte ratio and platelet/lymphocyte ratio associated with prognosis in patients with HER2-positive early breast cancer receiving adjuvant trastuzumab? J BUON 2015;20`:714–22.
Chen N., Li W., Huang K.,Yang W, Huang L,Cong T et al. Increased platelet-lymphocyte ratio closely relates to inferior clinical features and worse long-term survival in both resected and metastatic colorectal cancer: an updated systematic review and meta-analysis of 24 studies. Oncotarget. 2017;8(19):32356–32369. doi: 10.18632/oncotarget.16020.
You J., Zhu G.-Q., Xie L, Liu WY, Shi L, Wang OC et al. Preoperative platelet to lymphocyte ratio is a valuable prognostic biomarker in patients with colorectal cancer. Oncotarget. 2016;7(18):25516–25527. doi: 10.18632/oncotarget.8334.
Gu X, Gao X.-S, Cui M, Xie M, Peng C, Bai Y et al. Clinicopathological and prognostic significance of platelet to lymphocyte ratio in patients with gastric cancer. Oncotarget. 2016;7(31):49878–49887. doi:10.18632/oncotarget.10490.
Lian L., Xia Y.-Y., Zhou C.,Shen XM, Li XL, Han SG et al. Application of platelet/lymphocyte and neutrophil/lymphocyte ratios in early diagnosis and prognostic prediction in patients with resectable gastric cancer. Cancer Biomarkers. 2015;15(6):899–907. doi: 10.3233/CBM-150534.
Gu X., Sun S., Gao X.-S., Xiong W, Qin S, Qi X et al. Prognostic value of platelet to lymphocyte ratio in non-small cell lung cancer: Evidence from 3,430 patients. Scientific Reports. 2016;6 doi:10.1038/srep23893.23893
Noh H, Eomm M, Han A.J. Breast Cancer. 2013 Mar;16(1):55-9. doi: 10.4048/jbc.2013.16.1.55. Epub 2013 Mar 31
Melek Karakurt Eryilmaz, Hasan Mutlu, Derya Kivrak Salim, Fatma Yalcin Musri, Deniz Tural, Hasan Senol Coskun. The Neutrophil to Lymphocyte Ratio has a High Negative Predictive Value for Pathologic Complete Response in Locally Advanced Breast Cancer Patients Receiving Neoadjuvant Chemotherapy. DOI:http://dx.doi.org/10.7314/APJCP.2014.15.18.7737
Yuka Asano, Shinichiro Kashiwagi, Naoyoshi Onoda, Satoru Noda, Hidemi Kawajiri, Tsutomu Takashima, Masahiko Ohsawa, Seiichi Kitagawa, and Kosei Hirakawa Platelet–Lymphocyte Ratio as a Useful Predictor of the Therapeutic Effect of Neoadjuvant Chemotherapy in Breast Cancer PLoS One. 2016; 11(7): e0153459. Published online 2016 Jul 29. doi: 10.1371/journal.pone.0153459
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241108EnglishN2018April28HealthcareAn Epidemiological Study of Overweight and Obesity in High School Children of Udaipur City, (Rajasthan)
English3337Shiv Lal SolankiEnglish Bhagraj CoudharyEnglish Bharat MehardaEnglish Abhilasha MaliEnglishBackground: Obesity is a condition of accumulation of abnormal or excessive fat in adipose tissue, to the extent that health may be impaired. Obesity is commonly caused by excessive food energy intake, lack of physical activity and genetic susceptibility. Few cases of obesity may be caused by endocrine disorders, medications and psychiatric illnesses.
Objectives: To study the socio demographic profile and the prevalence of overweight/obesity in school children of Udaipur city.
Materials and Methods: This cross-sectional study was conducted from July 2014 to June 2015, on 1000 students of class 8th, 9th, 10th of government and private schools of Udaipur city (Rajasthan). Pre-tested questionnaire was used to collect socioeconomic and demographic information with prior consent.
Results: Girls (12.6%) were more, overweight/obese, than boys (8.6%). Overall prevalence of overweight/obesity was 10.60%, and the prevalence was nearly double in private schools (14.0%) than government schools (7.2%). Prevalence of overweight/ obesity was (38.68%) in the study subjects aged ≥16years, followed by (28.30%) in 15 years, (27.36%) in 14 years and less values in age 13 and 12 years. (87.74%) of the subjects with overweight/obesity belonged to nuclear families, (89.63%) were from SES I, II, and III while (10.37%) to class IV and V.
Conclusion: Obesity is a key risk factor for emergence of chronic and non-communicable diseases, several years later in life; hence the school curriculum should include the regular educative sessions on nutritive values of different food stuff, hazards of obesity, protective food habits and healthy life style.
EnglishPrevalence, Nuclear family, Socio economic status, Gender
INTRODUCTION:
Adolescent population is frequently exposed to rapidly changing values, modernized means of communication, and hostile culture with adverse life style and unhealthy nutrition practices, which affects their health. The consumption of fast food is associated with increased risk of excess weight, body fat, poor dietary quality and diabetes.
At present children are changing the nature of their leisure activities, from actively participating in sports and physical activities to electronically played games,spend more time with computers, mobile phones resulting to sedentary life style practices. Diet and lifestyle are ostensibly major contributors to weight problems and varies with different socio-economic conditions. Obesity can be seen as the first wave of a defined cluster of non-communicable diseases called “New World Syndrome” creating an enormous socio-economic and public health burden in poorer countries1. Obesity is a serious health problem and its prevalence has increased dramatically over the past 20 years. Today it is estimated that over 250 million people in low and middle-income countries suffer from obesity and in India the obesity epidemic is a growing concern for public health planning. The International obesity task force (IOTF) has calculated the 10% global prevalence of obesity in children of 5-17 years. India is one of the capitals of diabetes and cardiovascular diseases. The WHO has already declared obesity, a global epidemic that constitutes one of the biggest current health problems.
Objectives
To study the socio demographic profile and the prevalence of overweight/obesity in school children of Udaipur city.
Materials and Methods
This cross-sectional study was conducted on 1000 students, of class 8th, 9th, 10th of government and private schools of Udaipur city. Pre-tested questionnaire was used to collect socio-economic and demographic information. Data were analysed using SPSS 20 software, for descriptive and inferential statistical significance tests
Results
Table 1. The prevalence of overweight in 1000 study subjects was (8.20%)‚ followed by obesity I (2.20%), obesity II (0.20%). The values in girls were high for prevalence of overweight (9.40%), obesity I (2.80%), obesity II (0.40%), compared to values among boys, overweight (7.00%), obesity I (1.60), and obesity II (0%) respectively.
Table 2. Out of 1000 study subjects, (10.60%) were overweight/obese. (12.60%) of girls were overweight/obese against (8.60%) of boys. Statistically significant association was found between overweight/obesity and gender of study subjects with p 6000, compared to low obesity in Rs 6000 (15.7%). The study16 reported (11.7%) of overweight/obesity in higher income group against (6.1%) in lower income group.
CONCLUSION
On the background of findings of prevalence pattern of overweight/obesity in present study, orientation sessions to be campaigned in the schools for primary prevention of obesity, for educating adolescents about the hazards of obesity, danger of emergence of hypertension, diabetes, coronary heart disease and chronic illnesses in future life. Obese school children to be counselled to restrain for taking high energy foods and to adopt the healthy life style practices with sports and physical activities. We have to strengthen the social mobilization activities to educate the public, for building healthy future generation, by creating awareness to combat childhood obesity.
ACKNOWLEDGEMENTS 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.
Funding: No funding sources.
Conflict of interest: None declared
Ethical approval: Approved by the Institutional Ethics Committee.
Englishhttp://ijcrr.com/abstract.php?article_id=2476http://ijcrr.com/article_html.php?did=2476
World Health Organization. The Asia-Pacific perspective: Redefining obesity and its treatment. 2000.
Ramesh K Goyal, Vitthaldas N Shah, Banshi D Saboo, Sanjiv R Phatak, Navneet N Shah, Mukesh C Gohel, Prashad B Raval, Snehal S Patel. Prevalence of overweight and obesity in Indian adolescent school going children: its relationship with socioeconomic status and associated lifestylefactors. Maharashtra Chapter of Association of Physician of India, JAPI, March 2010;58: 151-58.
Soniya V, Ashtekar, Sarita B, Mantri, Atul V, Wadagale. Prevalence and epidemiology of overweight and obesity among upper primary school children in Latur city. Med Pulse – International Medical Journal. 1 January 2014;1(1): 15-19.
Asha B., Mahendra B.J., Harish B.R. A study of correlates of overweight/ obesity among high school children of Mandya city, Karnataka. International Journal of Current Research. January 2015; 7(1): 11594-11598.
S. Brinda Devi, K. Anusuya Devi. Socioeconomic status, physical activity, and sedentary lifestyle of obese school children 6-15 years of age. International Journal of Food and Nutritional Sciences. Apr-Jun 2015; 4(3): 77-82.
Keerthan Kumar M., Prashanth K., Kavya Elizabeth Baby, Kavya Rashmi Rao, Kumarkrishna B., Krishnamurthy Hegde, Mrinal Kumar, Manish Shetty, Navya N., Kavya C.P., Sandeep Kumar G. and Rahul R. Prevalence of obesity among high school children in Dakshina Kannada and Udupi districts, NITTE University Journal of Health Science. December, 2011;1(4): 16-20.
HM Thippeswamy, N Kumar, S Acharya, K C Pentapati. Relationship between body mass index and dental caries among adolescent children in south India. West Indian Medical Journal. 2011;60(5): 581-586.
Dr. Naheed Vaida. Prevalence of obesity among children studying in government and private schools in district Anantnag age group (6-12 years), IOSR Journal of Pharmacy, February 2013; 3(1):04-11.
Anjali Mahajan, Prakash Vhand Nagi. Prevalence of overweight and obesity in urban school going adolescents in shimla city. International Journal of Nutrition, Pharmacology, Neurological Diseases. December 2014; 4(1):23-28.
Jasvinder Kaur Sangha, Amandeep Kaur Pandher and A. Kochhar. Anthropometric profile and adiposity in the obese Punjabi children & this parents. J. Hum. Ecol. 2006; 19(3): 159-162.
Christine M., Burt Solorzano, Christopher R, McCartney. Obesity and the pubertal transition in girls and boys. Reproduction. Sept 2010;140(3): 399-410.
Ramachandran A, Snehalatha C, Vinitha R, Thayyil M, Kumar CKS, Sheeba L, et al., Prevalence of overweight in urban Indian adolescent school children. Diabetes Res Clin Pract. 2002; 57(3):185-190.
Mohanty B, the prevalence of overweight / obesity in school going children of Pondicherry. Study sponsored by- Department of Science and Technology and Environment. Government of Pondicherry. 2007-08.
Avula Laxmaiah, Balakrishna N, Kamasamudram V Mohanan N. Factors Affecting Prevalence of Overweight Among 12 to 17 years-old Urban Adolescents in Hyderabad, India. Obesity. 2007; 15:1384-1390.
Jugesh Chhatwal, Manorama Verma, Sandeep Kaur Riar. Obesity among pre-adolescent and adolescents of a developing country (India). Asia Pac J Clin Nutr. 2004; 13(3):231-235.
Ravi Rohilla, Meena Rajput, Jyoti Rohilla, Manisha Malik, Dinesh Garg, Madhur Verma. Prevalence and correlates of overweight/obesity among adolescents in an urban city of north India. Journal of Family Medicine and Primary Care. October 2014; 3(4): 405-408. H.S. Kavita, N.C. Ashok. Prevalence of Obesity among Primary school children and its Association with Parental obesity and Socio-economic status. Medica Innovatica June 2013; 2(1):26-3
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-5241108EnglishN2018April28Life SciencesSome Endemic Medicinal Plants Confined to Limestone Habitats of Imereti, West Georgia (the Caucasus) and Their Conservation Statuses
English3841Tamar CheishviliEnglish Izolda MatchutadzeEnglishAim of study: The study was aimed at collecting data on traditional use and assessing conservation statuses of some of the Caucasus endemic medicinal plants confined to limestone habitats.
Materials and Methods: The data used in the study are a part of floristic investigations conducted from 1996 to 2008 in different parts Imereti, West Georgia (the Caucasus Biodiversity Hotspot). Data on distribution, ecology, population state (rare, scarce,
common), threats collected by the author were used for IUCN Red List assessment of the four target species.
Results: Conservation statuses of the four target species used in traditional medicine were assessed as follows: Corylus imeretica Kem.-Nath., Potentilla imerethica Gagnidze and M. Sochadze (endemic to Imereti) – VU; Cyclamen colchicum (Albov) Albov (endemic to Georgia) – VU; Quercus imeretina Stev. ex Woronow (endemic to the Caucasus) – VU.
Conclusions: The presented species need to be more thoroughly studied for their active compounds to justify the traditional usage of the species and search for possibilities of their use in modern medicine. Since natural resources of these species are limited and their populations experience negative effects of various factors acting as threats, relevant conservation measures are to be elaborated to protect their populations that may occur an important source for obtaining compounds with a potential to be used in medicine.
EnglishEndemic plants, Limestone habitats, Colchis, Caucasus Biodiversity HotspotIntroduction
Floristic region of Imereti (42°5'0'' N, 42°30'0'' E), situated in the eastern part of Colchis botanical-geographic province is characterized by great physico-geographic and floristic diversity [16, 15, 4, 5, 6, 7, 9, 11]. In the vertical cross-section between the lowest (the village Sanavardo, at the river Tskhenistskali, 15-20 m a.s.l.) and the highest sites of Imereti (Mt. Lebeuri on the Racha range, which is a branch of the Greater Caucasus; 2862 m a.s.l.) several vegetation zones are present from humid subtropical forests to alpine meadows. This is the reason for great floristic diversity and certain level of endemism in the region [20]. Special type of endemism features calcareous orographic units of Imereti formed in the Late Jurassic [1, 12, 17]. Some of the endemic plant species of the Caucasus Biodiversity Hotspot confined to limestone habitats and particularly occurring on limestone massifs of Imereti are traditionally used as medicinal plants [1, 12, 17].
Tradition of medicinal plant cultivation in special gardens has a long history in Colchis. Existence of Medea’s garden of medicinal plants a few millennia ago (XIII-XII centuries B.C.) is a rare historical phenomenon. The garden was grown in the botanical-geographic province of Colchis encompassing entire Colchis and Lazistan in Asia Minor. Although it was thought that Colchic plants suitable for the climate of Colchis were grown in the garden, results of botanical-geographic data analysis have suggested that plants of the garden were heterogeneous by their attitude to climate as well as florogenetic history with plants of arid and humid regions of the Mediterranean area, Near East, East Asia and Asia Minor being predominant [10]. But rich local plant genetic pool of West Georgia and in particular, Imereti region has also been used for medicinal purposes since ancient times [3]. Gelati monastery (XII century), a great monument of Imereti region with its neighboring churches and the Academy was an important center of spiritual and intellectual development of Georgia. Together with other fundamental disciplines medicine was taught in the Academy. Since the XII century the Xenon, a hospital, functioned at the Monastery. Some of the endemic medicinal species are still concentrated on the area of the former hospital at Gelati Monastery (XI c.) suggesting that the plants were cultivated and used in medicine for centuries since establishment of the monastic hospital [19].
Materials and Methods
The data presented in the paper are a part of a floristic study conducted from 1996 to 2008 in different parts Imereti, West Georgia, particularly, Kutaisi vicinity, Adjameti and Sataplia protected areas in the river Rioni basin, gorge of the river Tskaltsitela, forests adjacent to Gelati Monastery, Nakerala range, a branch of the Racha range, calcareous foothills of Imereti called Okriba, gorge of the river Kvirila of the river Rioni basin, Adjara-Imereti range belonging to the Lesser Caucasus system.
The plant material was collected in all the vegetation types present on the study area from 300 m to 2997 m a.s.l. The material collected during the reported survey is stored at the Herbarium of Kutaisi State University (KUT). Materials stored at the Herbaria of Ivane Javakhishvili State University of Tbilisi (TB) and Tbilisi Botanical Garden and Institute of Botany (TBI) were also used during the study.
Data on distribution, ecology, population state (rare, scarce, common), threats collected by the author were used for IUCN Red List assessment of trees and shrubs of the Caucasus at Tree Red Listing Workshop, 22-25 Sept, 2005, Tbilisi, GTSG; the Caucasus endemic plant species for the IUCN project supported by CEPF: Coordination and Development of Plant Red List Assessments for the Caucasus Biodiversity Hotspot (2006-2009).
Nomenclature follows Czerepanov [2], Gagnidze [8].
Results
Twenty-two of the Caucasus Biodiversity Hotspot endemic plant species occurring in Imereti, eight of which are endemic to this floristic region of Georgia, are confined to calcareous habitats that have encouraged formation of the endemic flora owing to ecological isolation.
Some of the species of the limestone habitats have been used by local population as medicinal plants; among them are: Corylus imeretica Kem.-Nath., Potentilla imerethica Gagnidze and M. Sochadze (endemic to Imereti); Cyclamen colchicum (Albov) Albov (endemic to Georgia); Quercus imeretina Stev. ex Woronow (endemic to the Caucasus).
Cyclamen colchicum (Albov) Albov
Distribution. Georgia: Abkhazeti, Racha-Lechkhumi, Samegrelo, Imereti.
Habitat. On rocks from lower montane to alpine zone.
Traditional usage. Tincture is used for treatment of liver diseases, neuralgia, frontitis, arthritis.
Conservation status. Global assessment – EN / B1ab(i,ii,iv,v)+2ab(i,ii,iv,v). Extent of occurrence (EOO) estimated to be less than 5,000 km2; Area of occupancy (AOO) estimated to be less than 500 km2; existence at 4--5 locations (calcareous habitats) and inferred and projected continuing decline in EOO, AOO, the number of locations/subpopulations and mature individuals caused by trampling by cattle. Population monitoring is necessary for elaboration of relevant conservation actions.
Distribution. Georgia: Svaneti, Racha-Lechkhumi, Imereti, Guria, Kartli.
Habitat. Limestone habitats in forests and forest edges in middle montane zone.
Traditional usage. Nut shell brew is used against cough and tincture against eczema and other skin diseases; leaf decoction and pericarp infusion against vein diseases.
Conservation status. Global assessment – VU / B2ab (iii). Restricted to forest. Threatened by exploitation of its habitat. The population is in continuing decline due to selective logging. Extent of occurrence is Englishhttp://ijcrr.com/abstract.php?article_id=2477http://ijcrr.com/article_html.php?did=2477
Chkheidze, O., 2004. Gomorphology of Imereti. Tbilisi. (in Georg.)
Cherepanov, S., 1995. Vascular Plants of Russia and Adjacent States (the former USSR). Cambridge University Press.
Eristavi, M., Sikharulidze, Sh., Mikatadze-Pantsulaia, Ts., Khutsishvili, M., Miller, J. S., McCue, K., Consiglio, T., Stone, J., 2004. Endemic Medicinal Plants of Georgia (Caucasus). CRDF grant # GBI-2312-TB-02.
Gagnidze, R.197, Botanical and geographic analysis of tall herbaceous vegetation of the Caucasus. Metsniereba, Tbilisi. (in Russ.)
Gagnidze, R.,1998. Situacion phytogeographique de la Georgia. Les limites de la ,,region Meditterranenne”. La Geographie en Georgia (eds.: Richar, J. F., Berouchashvili, N.). Orstom, Paris, pp. 95-102.
Gagnidze, R.,1999. Arealogical review of Colchic evergreen broodleaved mesophyllous dendroflora species. Recent shifts in vegetation boundaries of deciduous forests especially due to general global warning (eds.: Klötzeli, Fl., Walther, G. R.). Birkhaüser Verlag, Basel-Boston-Berlin, pp. 199-21
Gagnidze, R., 2004. Current problems and tasks of botanical geography of the Caucasus. Notulae Systematicae ac Geographicae Instituti Botanici Thbilissiensis 44-45, 8-46. (in Russ.)
Gagnidze, R., 2005. Vascular plants of Georgia. A nomenclatural checklist. Universaly, Tbilisi.
Gagnidze, R., Gviniashvili, Ts., Shetekauri, Sh., Margalitadze, N. 2002. Endemic genera in the Caucasian flora. Feddes Repertorium 113 (708), 616-630.
Gagnidze, R., Khelaia, N., Margalitadze, N., Batsatsashvili, K., Churadze, M., 2009. Botanical geographical aspects of plants cultivated in Medea’s garden of medical plants in Colchis. Georgian Medical News 4, 169, 94-97.
Gagnidze, R., Margalitadze, N., 2004. Holocene history of the high-mountain regions of botanical-geographical provinces of Georgia (according to pollen analysis). Caucasian Geographical Review 4, 63-67.
Gagnidze, R., Sochadze, M., 1982. Specis nova generis Potentilla ex calcaries Georgiae occidentalis. Notulae Systematicae ac Geographicae Instituti Botanici Thbilissiensis 38, 3-7.
IUCN Categories and Criteria, Version 3.1. 2001. http://www.iucnredlist.org/info/categories_criteria2001 (15 December 2009)
Ketskoveli, N., Kharadze, A., Gagnidze, R. (Eds.)., 1971-2005. Flora of Georgia.1-15. Metsniereba, Tbilisi. (in Georg.)
Kharadze, A., 1966. For botanical geographic division of high-mountainous regions of the Greather Caucasus. Problemy botaniki 8, 75-89. (in Russ.)
Kolakovsky, A.,1961. Flora and vegetation of Colchis. Publishing House of Moscow University, Moscow. (in Russ.)
Kutateladze, A.,1961. Plante endemicae in montibus calcaries Imerethiae. Notulae Systematicae ac Geographicae Instituti Botanici Thbilissiensis 22, 36-42. (in Georg.)
Shengelia, M., 1962. Georgia’s endemics in the flora of calcareous massifs of Imereti. Bull. of the Georgian Botanical Society 1, 21-39. (in Georg.).
Shengelia, M.,1975. Ancient Colchian-Iberian medicine. Tbilisi. (in Georg.)
Zazanashvili, N., Gagnidze, R., Nakhutsrishvili, G., 1996. High mountain vegetation on the new vegetation map of Georgia. Journal of Vegetation Science 6, 157-158.