Background: Folate and methionine play a crucial role in DNA synthesis, repair and the epigenetic prole of cell. Hence, the alterations in the folate metabolism can lead to aberrant proliferation leading to neoplasia. Most of the studies have associated polymorphisms in methylene tetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genes with reduced risk of cervical and colorectal cancer. However, the association with breast cancer is still controversial. Further, the involvement of Glutamate carboxypeptidase II (GCPII) polymorphism in cancer is not known. In the present study, we analyzed if the individual and combined effects of polymorphisms in folate pathway genes viz., MTHFR 677C > T, MTHFR 1298A > C, MTRR 66A > G and GCP II 1561 C>T, have any role in altering the susceptibility to breast cancer. Methods: The DNA of 35 female breast cancer patients and 33 healthy individuals, in the Kashmiri population from India, were analyzed using a PCR-RFLP approach for the above mentioned polymorphisms. Results: Individuals carrying the MTHFR 677CT/TT and GCPII 1561 CT genotype showed a 3.5 (95% CI: 3.1-3.7, P<0.02) and 7.7 (95% CI: 6.7-9.1, P<0.001) fold decreased risk for breast cancer than the wild types (MTHFR 677CC and GCPII 1561 CC). Subjects with MTRR 66 G-allele showed a 4.5 fold decreased risk (OR: 0.22, 95% CI: 0.20, 0.24, P<0.0005) compared to the wild type (MTRR 66A). Further, subjects with combined polymorphisms in MTHFR, GCPII and MTRR loci revealed a signicant reduction of breast cancer risk. Conclusion: This study indicates (i) a protective role of polymorphisms in MTHFR, GCPII, MTRR against breast cancer in the study subjects, and (ii) combined effect of polymorphisms is more pronounced than single genetic polymorphism, thereby emphasizing the role of gene-gene interaction in the susceptibility to breast cancer.

Abstract: This study investigated antiepileptic effects of the main constituents of Nigella sativa (NS) seed (i.e. aqueous extract (AE), xed oil (FO), volatile oil (VO)) and the main components of its VO (i.e. thymoquinone, -pinene and p-cymene) using pentylenetetrazole (PTZ) and maximal electroshock (MES)-induced convulsions. The potential of these constituents to induce minimal neurological decit (MND) was also evaluated by using chimney test. Except for the FO, all of the NS seed constituents protected mice effectively against PTZ-induced convulsions. The activity of the VO in this model maybe attributed mainly to its content of thymoquinone and p-cymene and to a lesser extent, -pinene. VO and its component p-cymene effectively suppressed convulsions induced by MES. The contents of p-cymene present in the effective dose of the VO maybe partially responsible for its anti-seizure effects. All of the NS seed constituents induced varying degrees of MND in the chimney test. MND induced by VO may pertain to its contents of thymoquinone (63%), p-cymene (23%) and -pinene (<14%). Protective indices of p-cymene and thymoquinone were closer to one, but only in PTZ model. Exploration on the role of receptors suggests that picrotoxin and bicuculline-sensitive GABA receptors, most probably GABAA receptors, mediate an increase in GABAergic response. In the part dealing with the interaction of valproate with thymoquinone, it can be mentioned that thymoquinone increased the potency of valproate in both PTZ and MES models. Keywords: Anticonvulsant, Maximal electroshock seizure, Nigella sativa, Pentylenetetrazole, Potentiation, Valproate. Abbreviations: Nigella sativa = NS; aqueous extract = AE; xed oil = FO; volatile oil = VO; pentylenetetrazole = PTZ; maximal electroshock seizure = MES; protective indices = PIs; minimal neurological decit = MND.

Background: Chronic HBV and HCV infections are the major risk factors for the development of HCC through a multistep pathway that involves viral and non-viral dependent pathophysiological steps. Hepatic expression of the nuclear proliferative marker ki-67 and the p53 oncoprotein were found to be associated with poor outcome. So, the present study was done to evaluate the changes in expression of Ki-67 and p53 oncoprotein, and to determine p53 gene mutation in HBV/HCV-related HCC Egyptian patients. Methods: Eight HBV-and 22 HCV-positive HCC cases have been examined for the presence of p53 mutation by immunohistochemistry (IHC) and single-strand conformation polymorphism (SSCP), followed by direct DNA sequencing. HCV were genotyped by LiPA-II. Results: Our results have shown that the proliferative marker ki-67 LI and p53 were highly expressed and signicantly related to tumor grade in the Egyptian HCC cases (p<0.05). Also, p53 mutation was found in 16 HCC cases by IHC and in 14 HCC cases by SSCP, only 11 patients showed p53 mutation by sequencing. The highest mutation rate was scored for exon 7 (7 mutations) at codon 249; 4 out of 8 (50%) of HBV-related HCC cases and 3 out of 22 (13.6%) of HCV-related HCC cases, followed by exon 5 (3 mutations) at codons 133, 146, 176 in HCV-related HCC cases, then exon 8 at codon 275 in HCV-related HCC cases. The concordance between the IHC and sequencing analysis was 69%. Conclusion: The present study demonstrates the association between the proliferative marker ki-67 and p53 expression with the tumor grade of Egyptian HBV/HCV-related HCC cases. Our results also support the hypothesis that p53 mutations are rather a late event in the carcinogenesis. Also, they suggest that the nal steps of hepatocarcinogenesis are common and independent of the aetiology of the viral infection.

Background: The author examined the accuracy of the initial psychiatric diagnosis of primary medical providers requesting psychiatric consultation in a medical inpatient setting in a university hospital. Methods: A retrospective review of 217 consecutive psychiatric consultations was conducted in which the initial diagnostic impression of primary medical providers was compared with the nal psychiatric diagnosis. Results: The accuracy of psychiatric diagnosis was the highest for cognitive disorders 60%, followed by depression 50% and anxiety disorders 46%, whereas the accuracy of diagnosing psychosis was 0%. Conclusion: Thus, the accuracy of initial diagnoses made by primary medical providers is quite variable. Factors affecting these results are discussed.

Background: Pyrimidines are a well known group of compounds reported to have different biological activities. Prompted from the diversity of its wider use and being an integral part of genetic material, an effort was made to synthesize a novel series of amino-pyrimidine derivatives of pharmaceutical interest by condensing the guanidinyl derivative of nalidixic acid with different chalcones. Methods: The structures of all synthesized compounds were established on the basis of IR and 1HNMR spectral studies. All of the new compounds in this series were screened for antimicrobial activity. Gram +ve and Gram -ve strains were used to ascertain the spectrum of activity. ED50 values in the tail ick test were determined and recorded. Analgesic potential of compounds by using tail ick test in SWR male mice have also revealed promising results. Results: All of the derivatives were effective in Gram –ve test against E. coli. None of the compounds show any inhibition of Gram +ve strain S. aureus. m-Bromo substitution derivative of amino-pyrimidines showed appreciable activity against E. coli, while 2,4 dichloro and p-chloro substitution derivatives also demonstrated improved activity. Compound 4 was most potent. The order of potency for these derivatives was 4>5 6>1>2>7>3. Parallel to antimicrobial activity, m-bromo substitution derivative showed signicant (P<0.01) antinociceptive response in comparison to control, and this effect was comparable to aspirin group. Trimethoxy substitution of benzene ring demonstrated moderate activity, whereas p-bromo substitution essentially had no antinociceptive effects in mice. Conclusion: Comparing meta- and para- bromo substitutions, there had been signicant (P<0.01) difference in the antinociceptive response of both the bromo-substituted derivatives. It was observed that bromo-substitution at meta- position demonstrated comparatively higher potential for its antibacterial as well as antinociceptive properties. Keywords: Synthesis, Chalcones, Pyrimidine derivatives, Antinociception, Antimicrobial activity.

Background: Fetal sexual differentiation relies on the translation of chromosomal sex established at fertilization into gonadal sex and somatic sex as development proceeds. In cases where chromosomal, gonadal, and somatic sex are incongruent in human infants and children, rapid establishment of the diagnosis and implementation of medical and surgical management is of paramount importance, since the gender identity is so important to the psychological well-being throughout life. Objective: This work was done in order to test the value of PCR technique for rapid sex determination compared to classic cytogenetic technique. Methods: Subjects included 20, cases including 10 neonates with ambiguous genitalia, 2 adult females with delayed puberty and 8 adult males with infertility, in addition to 20 normal infants of both sexes as a control group. The diagnosis of sex was attempted through examination, cytogenetic study, ultrasonography, gonadal biopsy and hormonal analysis, in addition to PCR amplication for the detection of SRY and ATL1 gene loci on Y and X chromosomes respectively. Results: Four neonates were diagnosed as partial testicular feminization showed both positive bands for the Y and X chromosomes and a karyogram of 46/XY. Three neonates were diagnosed as true hermaphrodites showed positive amplication for both Y and X chromosomes with a mosaic karyogram 46,XX/XY. Three neonates were diagnosed as cases of adrenogenital syndrome showed positive amplication of only the Xchromosome and had a karyogram of 46/XX. One of the two adult females was diagnosed as turner syndrome showed positive amplication of the X chromosome and a karyogram of 45/XO; the other one was diagnosed as complete testicular feminization had a positive amplication of X and Y chromosomes and a karyogram of 46/XY. The 8 adult males with infertility showed a positive amplication of X and Y chromosome and a karyogram of 47/XXY (Klinefelter syndrome) in 7 cases and 46/XY gonadal dysgenesis in one case. Conclusion: We concluded that PCR as a simple, rapid and reliable technique can complement and also conrm cytogenetic studies in the diagnosis of sex in cases of sex chromosome disorders. Keywords: PCR, Sex, Intersex, Ambiguous genitalia.

Abstract: Interleukin (IL)-10 is a pluripotent cytokine with effects on numerous cell populations, in particular circulating and resident immune cells as well as epithelial cells. With its potent immunoregulatory capacities, its main biological function seems to be the limitation and termination of inammatory responses. Hence, its low level expression found in psoriasis may have pathophysiological relevance to this immune disease. Remarkably, the induction of IL-10 expression was found by conventional antipsoriatic therapies, supporting the hypothesis that it may be a key cytokine in psoriasis. Furthermore, the rst use in clinical trials in patients with established psoriasis showed that it had moderate antipsoriatic effects and was well tolerated. Moreover, long-term application in psoriatic patients in remission showed that it decreases the incidence of relapse and prolongs the disease free interval. The IL-10 antipsoriatic activity is suggested to be due to the effects on different cell populations, including antigen presenting cells and T-cells (type 1 / type 2 balance shift), but not through direct effects on keratinocytes. In conclusion, IL-10 seems to have major clinical and therapeutic implications in psoriasis. Further multicenter, placebo-controlled, double blind trials are required to be an established antipsoriatic therapy. We can come to the conclusion that IL-10 genetic polymorphism and expression is potentially a key immune marker in psoriasis.

Objectives: Rat collagen II–induced arthritis is a model of chronic inammation induced by mycobacterium butyricum and collagen II. It is characterized by similar pathophysiological and pathobiochemical changes as rheumatoid arthritis (RA) in humans. In the present study, the biochemical effects of vitamin E and allopurinol (Allo) on RA of rats were investigated. Methods: Forty male rats were divided into four groups (10 rats each): control group, collagen II-induced RA group (CII group), CII group treated with allopurinol (CII+ Allo ), and CII group treated with vitamin E (CII + Vit E). After 6 weeks of treatment, the plasma levels of lipid peroxides (LPO), nitric oxide (NO), ceruloplasmin (CP), superoxide dismutase (SOD), uric acid (UA) and glutathione (GSH) were detected using colorimetric methods. The plasma levels of PGE2 were measured using ELISA assay. The plasma levels of copper (Cu) and zinc (Zn) were determined using atomic absorption spectrometer. Results: In CII treated group, the levels of LPO, NO, PGE2, UA, CP and Cu were signicantly higher, but the levels of SOD, GSH and Zn were signicantly lower than controls. In CII + Allo treated group, the levels of SOD and GSH were signicantly increased, but the levels of PGE2, LPO, NO, UA, Cu and CP were signicantly decreased in comparison with CII–treated group. The levels of SOD, GSH and Zn were signicantly increased, but the levels of PGE2, NO and CP were signicantly decreased in the vitamin E treated group in comparison with CII–treated group. The levels of PGE2, LPO, Cu and Zn were signicantly lower in vitamin E treated group than Allo-treated group. In conclusion, the study suggests that proper antioxidant intake management may reduce free radical generation and improve antioxidant status in RA. Allopurinol and vitamins E may effectively normalize in different degrees the impaired the oxidant/antioxidant system and may be useful in delaying the complication of RA. Moreover, they display anti-inammatory action by decreasing PGE2 level in RA. Keywords: Rat, Rheumatoid arthritis model, Antioxidants, Allopurinol, Vitamin E. Running title: Effect of antioxidants on RA rats.

Background: Upper gastrointestinal bleeding (UGIB), a potentially fatal occurrence, can sometimes follow coronary artery bypass graft (CABG) surgery. However, little has been published about its prevalence, risk factors, and outcomes. Aim: This study aimed to determine the rate, etiologies, predisposing factors, and outcomes of UGIB following CABG. Method: The authors conducted a retrospective chart review of all UGIBs which followed CABGs performed at the University of Alberta Hospital from January 1, 1998 to December 31, 2002. Results: During the study period, 4,502 CABGs were performed at the UAH. Eighteen patients (0.4%) had a documented major UGIB (dened as evidence of melena, red or coffee-grounds emesis, blood per NG tube, or a decrease of Hgb by > 20 g/l and requiring a conrmation by endoscopy or radiological study). Two of these 18 patients (11%) had a past history of peptic ulcer disease, and one of these patients had had previous UGIB. Three patients (17%) had been taking proton pump inhibitors (PPI) before the UGIB occurred. At the time of UGIB, PPIs were prescribed for 16 patients (89%), and the PPIs achieved effective hemostasis as a single agent for 10 (62.5%). Of the 18 patients, 16 (89%) underwent upper GI endoscopy. Bleeding was found to be due to duodenal ulceration in 9 (56%), esophagitis in 4 (22%) and gastritis in 6 cases (33%); fty percent of these patients had multiple sites of bleeding. Endoscopic therapeutic intervention was needed by 6 patients (37.5%), and successful hemostasis was achieved for 5 of these patients (83%). One patient had a recurrence of bleeding and required surgery. One patient underwent surgery as the primary hemostatic therapy after a diagnostic endoscopy. The overall surgical rate was 11.1% for this patient cohort. In this cohort, three patients died, two from multi-organ failure, and the third, a surgically managed patient, had a cardiac arrest 72 hours post-surgery. The number of complication increased as both cardiopulmonary bypass and cross clamp time increased. There were no endoscopy-related complications. Conclusions: UGI bleeding following CABGs is relatively infrequent, occurring at a rate of 0.4% in this study. Upper gastrointestinal bleeding post-CABG is most frequently related to a duodenal ulcer, though 50% of the patients had multiple bleeding sites. prolonged bypass and cross clamp time associated with more complications. Keywords: Upper gastrointestinal bleeding, Coronary artery bypass surgery, Post-operative complications.

Background: Myopia is a common ocular disorder. Prevalence data with regard to myopia is scarce in India and almost nonexistent in Kashmir. Objective: To determine the prevalence of myopia in Srinagar City and to evaluate risk factors associated with the disease. Methods: 38 schools in the Srinagar were selected randomly and students were examined by our optometrist team. Children with refractive error of -0.25 D to -5.9 D were considered myopic, while those with -6 D and above were considered high myopic. Statistical analysis used: 2 Tests were used as appropriate to test whether potential risk factors were signicantly associated with myopia. Odds ratios (OR) and 95% condence intervals (95% CI) were calculated for risk factors that were independently associated with myopia in this population. Results: A total of 4,360 students of mean age 12.11 (95% condence interval [CI] = 11.99 – 12.22: range, 7-18) participated in the study. Myopia was found in 4.74% students. Increasing age was associated with the increased risk of having myopia. Girl students were more likely to have myopia than boys (OR = 1.52). The prevalence of myopia among girls was more than that of boys. Students from low socioeconomic conditions were having higher prevalence of myopia than their counterparts from higher socioeconomic counterparts. Conclusion: Reduced vision because of myopia is an important health problem in students in Srinagar City. Most of these students do not have the necessary correction spectacles. Effective strategies are needed to eliminate the cause of a signicant visual problem. Keywords: Myopia, Prevalence, Kashmiri population.

Abstract: Atrial brillation (AF) is the most common arrhythmia which is a focus of newer modalities of treatment, especially ablation techniques using innovative mapping techniques. Its incidence and prevalence increases with aging and presence of structural heart disease, the latter being less than 1% prior to age 40, rising to 8% at age 80. Concomittant morbidity and excessive mortality is related to the increased incidence of stroke and congestive heart failure. Once developed in a clinical setting, it tends to either persist or recur. Pharmacotherapy to control rate or rhythm tends to have a secondary failure, and therefore there is a growing interest in ablation techniques. The use of anticoagulation is also associated with bleeding risks and therefore the management of AF needs to be individualized in every patient. In this article, we shall be discussing clinical types of AF, etiology, the mechanism of genesis, symptoms, complications and approach to treatment in various clinical scenarios. Keywords: Atrial brillation, Radiofrequency ablation, Pharmacology.

Maternal mortality represents the largest and the most persistent gap between developed and developing countries. The maternal mortality ratio (MMR), which measures the risk of death at each pregnancy, is up to 40 times higher in some African countries than the countries of Northern Europe. MMR is believed to be the most sensitive indicator of women’s status in the society and of the quality and accessibility of maternal health services available to women. The primary purpose of the study was to determine the level of agreement in the cause and the category of death assigned by the hospital and the obstetrician who reviewed the completed VA questionnaire. The validation study was conducted during July-September 2006 by the National Institute of Population Studies (NIPS), which is also the executing agency for PDHS 2007. The primary objective of the study was to test the sensitivity and specicity of the VA questionnaire developed for PDHS 2007. An important lesson learned from this study is that the sensitivity of the VA technique can be further enhanced by rigorous training of the review panelists in the utilization of the information contained in the coded parts of the questionnaire.

Positron emission tomography has emerged as an important diagnostic tool in the management of lung cancers. PET is sensitive in the detection of lung cancer, but FDG (2-deoxy-2-18uro-D-glucose) is not tumor specic and may accumulate in a variety of non-malignant conditions occasionally giving false negative result. The addition of CT to PET improves specicity foremost, but also sensitivity in tumor imaging. Thus, PET/CT fusion images are a more accurate test than either of its individual components and are probably also better than side-by-side viewing of images from both modalities. PET/CT fusion images are useful in differentiating between malignant and benign disease, brosis and recurrence, staging and in changing patient management to a more appropriate therapy. With analysis and discussion, it appears that PET/ CT fusion images have the potential to dramatically improve our ability to manage the patients with lung cancer and is contributing to our understanding of cancer cell biology and in the development of new therapies. Keywords: Positron emission tomography (PET), CAT scan (CT), Lung carcinoma.

Abstract: Gujjar lung is a chronic lung disease caused due to the long-term exposure to pinewood smoke inhalation in Gujjar community and the people residing at the hilly regions of the Indian sub-continent. This is characterized clinically by progressive cough and dyspnea, distinct radiological patterns and pathological features of anthracotic nodules and brosis. A typical case with miliary mottling on chest radiograph is presented and the relevant literature reviewed. Keywords: Pine wood smoke, Milliary shadows, Anthracotic nodules, Interstitial lung disease.

Abstract: A 20-year-old male Saudi national presented initially with leucopenia and splenomegaly. The absence of other signs of disease, progressive pancytopenia and normal bone marrow examination posed a diagnostic dilemma as to the cause of hypersplenism. Subsequently, the patient had splenectomy the histopathological appearance of which was non-caseating granuloma. A high level of angiotension converting enzyme (ACE) was found in this patient. Sarcoidosis is a recognized cause of hypersplenism, and though the disease is not yet widely described in this part of the world. It is the most probable diagnosis in this patient. Keywords: Pancytopenia, Splennomegaly, Sarcoidosis.

Abstract: Migraine is a primary headache disorder which has received little attention from health care policies and physicians. This has led to ineffective management and more suffering to the patients and society. Migraine per se is a disabling disease which has its impact on the patient, family and work. It is associated with high incidence of psychiatric co-morbidities, especially depression and anxiety as well as other mental disorders. Depression affects around 80% of chronic migraineurs, an association that adds to the suffering. It has been conrmed as risk factors for developing radiographic and clinically evident ischemic cerebrovascular infarctions. Lately, it was associated with angina, myocardial infarction and intracerebral hemorrhage. Migraine plays a central role in the pathogenesis of these diseases, not just a simple association. These comorbidities and the disabilities migraine makes should change our views of migraine as a simple headache disorder, and directs our efforts to a better recognition and an effective management for the prevention of the disease associated morbidity.

Congenital neural malformations are complex anomalies, which stem from an abnormality in the embryological development of the nervous system. The development of the nervous system begins by the formation of the neural tube and its subsequent closure. The failure of closure results in neural tube defects (NTD). Defect in the formation of prosencehalon or rhombencephalon will result in holoprosencephaly or Dandy walker complex respectively. The formation of neuroblasts and their migration to cerebral cortex may be altered by many neuronal migration disorders. Lissencephaly, schizencephaly, and heterotopic gray matter are the most prominent. Conclusion: The objective of the study is relating congenital neural malformations to their corresponding embryological background, and so helping in better understanding the time and the way of the occurrence of such anomalies.