Celiac Disease in Women With Infertility: A Meta-Analysis.

BACKGROUND: Celiac disease (CeD) is a systemic disease with manifestations not limited to small intestine. The data on association between CeD and infertility is contradictory. There are no recommendations for the screening of female patients with infertility for CeD. AIM: We conducted a meta-analysis to find out whether women with infertility are at higher risk of CeD. METHODS: Literature search was performed using the MeSH keywords "CeD," "gluten," and "infertility." Diagnosis of CeD was based on positive serology and biopsies showing villous atrophy. Data were extracted about CeD patients in 3 groups-women with infertility (including unexplained infertility), unexplained infertility, and controls. Pooled odds ratio (OR) and prevalence, with 95% confidence intervals (CI), were calculated. RESULTS: Of 105 relevant studies, 5 studies were included for calculation of pooled OR. Four additional studies, where data on controls were not available, were also considered for calculation of pooled prevalence of CeD. Women with infertility had 3.5 times higher odds of having CeD in comparison with control population (OR=3.5; 95% CI, 1.3-9; P<0.01). Similarly, women with "unexplained infertility" had 6 times higher odds of having CeD than controls (OR=6; 95% CI, 2.4-14.6). Of 884 women with infertility, 20 had CeD indicating a pooled prevalence of 2.3% (95% CI, 1.4-3.5). Of 623 women with "unexplained infertility," 20 had CeD. The pooled prevalence of CeD in women with unexplained infertility was 3.2 (95% CI, 2-4.9). CONCLUSIONS: CeD is more prevalent in women with "all-cause" infertility and "unexplained" infertility than that in general population.

Risk of Celiac Disease in the First- and Second-Degree Relatives of Patients With Celiac Disease: A Systematic Review and Meta-Analysis.

OBJECTIVES: First-degree relatives (FDRs) of patients with celiac disease (CD) are at high risk for CD and prevalence among them varies from 1.6 to 38%. The risk of having CD among FDRs if the FDR is sister, brother, mother, father, son, or daughter of index patient with CD is not known. We conducted a meta-analysis and calculated pooled prevalence of CD among FDRs, second-degree relatives (SDRs), and specific relations with index patient. METHODS: On search of literature, 2,259 articles appeared of which 54 articles were included in this meta-analysis. Diagnosis of CD was based on standard criteria. RESULTS: Pooled prevalence of CD was 7.5% (95% confidence interval (CI) 6.3%, 8.8%) in 10,252 FDRs and 2.3% (95% CI 1.3%, 3.8%) in 642 SDRs. Pooled prevalence of CD was highest in siblings (8.9%), followed by offsprings (7.9%) and parents (3.0%). Female FDRs had higher prevalence than male FDRs (8.4% vs. 5.2%, P=0.047). While sisters and daughters of index patient had the highest risk of having CD (1 in 7 and 1 in 8, respectively), the risk was 1 in 13 in sons, 1 in 16 in brothers, 1 in 32 in mothers, and 1 in 33 in fathers. There were also differences in the pooled prevalence of CD in FDRs according to their geographic location. CONCLUSIONS: Pooled prevalence of CD among FDRs is 7.5% and varies considerably with their relationship with the index patient. The risk of CD in FDRs also varies according to gender and geographical location.

Invasive carcinoma of cervix during pregnancy--a case report and review of literature.

Carcinoma of cervix is the commonest malignancy seen in Indian women in all age groups and therefore commonly seen in pregnancy. However, most of the cases remain in early stage and the occurrence of invasive cervical carcinoma is relatively uncommon in pregnant women. There is always a therapeutic dilemma faced by the gynaecologic oncologist and the maternal foetal specialist regarding management of pregnancy with cervical malignancy. A 30 years old, multiparous woman diagnosed to have squamous cell carcinoma of the cervix FIGO stage IB1 in the early second trimester was treated by radical hysterectomy followed by radiotherapy is being reported. The various therapeutic options and prognosis are discussed.

Pharmacogenetics of target genes across doxorubicin disposition pathway: a review.

Increased understanding of the molecular mechanisms of tumor heterogeneity combined with rapid advances in the field of pharmacogenetics and pharmacogenomics have fuelled studies on individualizing anticancer therapy. Doxorubicin (Adriamycin), is an anthracycline glycoside antibiotic originally produced by Streptomyces peucetius var. caesius, and is widely used either as a single agent or in combination with other chemotherapeutic regimens for curative, adjuvant, and palliative treatment in cancer patients. The pharmacogenetics of doxorubicin has not been well characterized. The polygenic influence of functional candidate gene variants across doxorubicin biochemical pathway is hypothesized to contribute to its heterogeneity in disposition, influencing the efficacy of treatment and occurrence of adverse effects like cardiomyopathy in patients undergoing doxorubicin based adjuvant and neo-adjuvant chemotherapy. The pharmacogenetics of Asian population differs from that of other ethnic groups, particularly from Caucasian and African populations, and indicates an important role of ethnicity in determining predictive end points during chemotherapy and in individualizing treatment. This review comprehensively examines the pharmacogenetics of the regulatory nuclear receptor Pregnane-X Receptor (PXR), influx (SLC22A16) and efflux drug transporters (ABCB1, ABCG2, ABCC5, ABCB5 and RLIP76) and drug metabolizing enzymes (CBR1, CBR3) across the biochemical pathway of doxorubicin in Asian breast cancer patients receiving doxorubicin based adjuvant chemotherapy. The influence of functional genetic variants on the inter-individual variability in pharmacokinetics of doxorubicin and its major metabolite are also discussed. The incorporation of non-genetic factors and subsequent validation of these findings in different patient and population groups will be valuable in tailoring doxorubicin dosage regimens to an individual to maximize therapeutic efficacy and minimize adverse reactions, leading to improved clinical outcomes.

Efficacy of mifepristone in reducing intermenstrual vaginal bleeding in users of the levonorgestrel intrauterine system.

OBJECTIVE: To evaluate the efficacy of mifepristone to reduce intermenstrual bleeding in levonorgestrel intrauterine system (LNG-IUS) users. METHOD: In this prospective, open-label, comparative study, 36 women using the LNG-IUS for menorrhagia received 100mg of mifepristone every 30 days for 3 months (group 1). Fifty age-matched LNG-IUS users who did not receive any drugs were used as the comparison group (group 2). Menstrual bleeding days, pictorial blood loss assessment chart (PBAC) score, and intermenstrual bleeding/spotting days were compared between the 2 groups at 3 months (during treatment) and at 6 months (3 months post treatment). RESULTS: Baseline characteristics were comparable between the groups. At 3 months, median duration and episodes of intermenstrual bleeding/spotting were significantly lower in group 1 compared with group 2 (6 vs 12.5 days, P=0.01; 2.5 vs 3, P=0.05, respectively). More women were satisfied with the LNG-IUS in the mifepristone group compared with the control group (75% vs 44%; P=0.004). At 6 months, the median duration of intermenstrual bleeding/spotting was significantly lower in group 1 compared with group 2 (6 vs 15 days; P=0.008). CONCLUSION: Mifepristone was effective in reducing the number of episodes and duration of intermenstrual bleeding/spotting in LNG-IUS users.

VKORC1 diplotype-derived dosing model to explain variability in warfarin dose requirements in Asian patients.

SUMMARY: Warfarin-induced bleeding complications and high inter-patient variability are major hindrances to oral anticoagulant therapy. The present study identifies the influence of VKORC1 diplotypes, CYP2C9 and CYP2C19 variants on warfarin disposition and dose requirements in Chinese patients (n=107). The study subjects were genotyped for VKORC1, CYP2C9 and CYP2C19 polymorphic variants. Weekly warfarin dose requirements and S-warfarin clearance were stratified by VKORC1, CYP2C9 and CYP2C19 pharmacogenetics. The major VKORC1 diplotypes were H1-H1 (62%), H1-H7 (18%) and H1-H(*)(b) (10%). Warfarin dose requirements were significantly lower in patients with VKORC1 H1-H1 and H1-H(*)(a) diplotypes compared to patients harboring the H1-H7 and H1-H(*)(b) diplotypes (P<0.05). Hepatic tissues with H1-H1 diplotype had significantly lower expression of VKORC1 mRNA compared with liver tissues carrying the H1-H7 and H1-H(*)(b) diplotypes (P=0.006). The percent variability explained by VKORC1 diplotype status was 59.1% while the CYP2C9 genotype status accounted for 6.9% variability in warfarin dose requirements. Patient age and weight were significant covariates accounting for 29% and 8.6% of warfarin dose variability, respectively. The present study shows that VKORC1 diplotype status, CYP2C9 genotype, age and weight are significant covariates, accounting for 73.4% of interindividual variability in warfarin dose requirements among Chinese patients. Translation of these findings into clinical guidelines for warfarin dosing may be required to assess its impact on the safety and efficacy of warfarin.

Psoas abscess in obstetrics.

Psoas abscess is rarely encountered in obstetric practice. This condition may be primary or secondary resulting from extension of an infectious process near the psoas muscle. We report a series of three patients with psoas abscess that were encountered in our obstetric practice. Two of these patients had a primary and one a secondary abscess. Two patients underwent laparotomy and drainage of abscess while one received medical treatment. All patients recovered uneventfully.

CBR1 and CBR3 pharmacogenetics and their influence on doxorubicin disposition in Asian breast cancer patients.

The present study aimed to identify polymorphic genes encoding carbonyl reductases (CBR1, CBR3) and investigate their influence on doxorubicin disposition in Asian breast cancer patients (n = 62). Doxorubicin (60 mg/m(2)) was administered every 3 weeks for four to six cycles and the pharmacokinetic parameters were estimated using non-compartmental analysis (WinNonlin). The Mann-Whitney U-test was used to assess genotypic-phenotypic correlations. Five CBR1 (-48G>A, c.219G>C, c.627C>T, c.693G>A, +967G>A) and CBR3 (c.11G>A, c.255C>T, c.279C>T, c.606G>A, c.730G>A) polymorphisms were identified. The CBR1 D2 diplotypes were characterized by the presence of at least one variant allele at the c.627C>T and +967G>A loci. Patients in the CBR1 D1 diplotype group had significantly higher clearance (CL) normalized to body surface area (BSA) (CL/BSA[L/h/m(2)]: median 25.09; range 16.44-55.66) and significantly lower exposure levels; area under curve (AUC(0-infinity)/dose/BSA [h/m(5)]; median 15.08; range 6.18-38.03) of doxorubicin compared with patients belonging to the CBR1 D2 diplotype group (CL/BSA[L/h/m(2)]; median 20.88; range 8.68-31.79, P = 0.014; and AUC(0-infinity)/dose/BSA[h/m(5)]; median 21.35; range 9.82-67.17, P = 0.007 respectively). No significant influence of CBR3 polymorphisms on the pharmacokinetics of doxorubicin were observed in Asian cancer patients. The present exploratory study shows that CBR1 D2 diplotypes correlate with significantly higher exposure levels of doxorubicin, suggesting the possibility of lowered intracellular conversion to doxorubicinol in these patients. Further evaluation of carbonyl reductase polymorphisms in influencing the treatment efficacy of doxorubicin-based chemotherapy in Asian cancer patients are warranted.

PXR pharmacogenetics: association of haplotypes with hepatic CYP3A4 and ABCB1 messenger RNA expression and doxorubicin clearance in Asian breast cancer patients.

PURPOSE: To characterize pregnane X receptor (PXR) polymorphic variants in healthy Asian populations [Chinese, Malay and Indian (n=100 each)], and to investigate the association between PXR haplotypes and hepatic mRNA expression of PXR and its downstream target genes, CYP3A4 and ABCB1, as well as their influence on the clearance of doxorubicin in Asian breast cancer patients. EXPERIMENTAL DESIGN: PXR genotyping was done by direct DNA sequencing, and PXR haplotypes and haplotype clusters were derived by expectation-maximization algorithm. Genotype-phenotype correlations were done using Mann-Whitney U test and Kruskal-Wallis test. RESULTS: Significant interethnic variations were observed in PXR pharmacogenetics among the three Asian ethnic groups. The expression of PXR mRNA in liver tissues harboring the PXR*1B haplotype clusters was 4-fold lower compared with the non-PXR*1B (*1A + *1C) haplotype clusters [PXR*1B versus PXR*1A; P=0.015; PXR*1B versus PXR*1C; P=0.023]. PXR*1B-bearing liver tissues were associated with significantly lower expression of CYP3A4 (PXR*1B versus non-PXR*1B, P=0.030) and ABCB1 (PXR*1B versus non-PXR*1B, P=0.060) compared with non-PXR*1B-bearing liver tissues. Doxorubicin clearance in breast cancer patients harboring the PXR*1B haplotypes was significantly lower compared with patients carrying the non-PXR*1B haplotypes [PXR*1B versus non-PXR*1B, CL/BSA (L h(-1) m(-2)): 20.84 (range, 8.68-29.24) versus 24.85 (range, 13.80-55.66), P=0.022]. CONCLUSIONS: This study showed that PXR*1B was associated with reduced hepatic mRNA expression of PXR and its downstream targets, CYP3A4 and ABCB1. Genotype-phenotype correlates in breast cancer patients showed PXR*1B to be significantly associated with lower doxorubicin clearance, suggesting that PXR haplotype constitution could be important in influencing interindividual and interethnic variations in disposition of its putative drug substrates.

A review of total laparoscopic hysterectomy using LigaSure uterine artery-sealing device: AIIMS experience.

STUDY OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of total laparoscopic hysterectomy (TLH) by using the Ligasure system for the sealing of uterine arteries. DESIGN: We conducted a retrospective review of cases who underwent TLH over 1.5 years. SETTINGS: This study was conducted in a tertiary care hospital setting, at the Department of Obstetrics and Gynecology, All India Institute of Medical Sciences (New Delhi, India). PATIENTS: A total of 110 patients of TLH done for uterine pathology [leiomyoma in 67 (60.9%), dysfunctional uterine bleeding in 34 (30.9%), and others in 9 (8.1%)]. INTERVENTIONS: Total laparoscopic hysterectomy, using the LigaSure system (Valleylab Inc., Boulder, CO), was done by the sealing of uterine arteries and Prashant Mangeshikar uterine manipulator for elevation of the uterus. RESULTS: The mean age of the patients was 43.1 +/- 0.602 years and mean body mass index was 25.19 +/- 0.39 kg/m(2). The mean operating time was 116.91 +/- 3.4 minutes, mean intraoperative blood loss was 173.09 +/- 11.64 mL, and the mean weight of the removed uterus was 224.14 +/- 17.62 g. Six patients were converted from a laparoscopic to an open procedure (large myoma in 4 and dense adhesion in 2) and 1 was converted to laparoscopically assisted vaginal hysterectomy (tear in vaginal cuff). One patient (0.9%) developed lung emphysema during the intraoperative period. Postoperative complications included paralytic ileus in 3 (2.7%), retention of urine in 2 (1.8%), and febrile morbidity in 12 (10.9%) patients. There were no bladder or bowel injuries. CONCLUSION: Laparoscopic hysterectomy by uterine artery sealing with LigaSure is a safe, efficient procedure with a low complication rate.

Influence of ABCB1 and ABCG2 polymorphisms on doxorubicin disposition in Asian breast cancer patients.

The influence of three high frequency ABCB1 polymorphisms (c.1236C>T, c.2677G>A/T, and c.3435C>T) and the ABCG2 c.421C>A polymorphism on the disposition of doxorubicin in Asian breast cancer patients receiving adjuvant chemotherapy was investigated in the present study. The allelic frequency of the ABCB1 c.1236T, c.2677T, c.2677A, and c.3435T variants were 60%, 38%, 7%, and 22%, respectively, and the frequency of the ABCG2 c.421A allele was 23%. Pairwise analysis showed increased exposure levels to doxorubicin in patients harboring at least one ABCB1 c.1236T allele (P = 0.03). Patients homozygous for the CC-GG-CC genotype had significantly lower doxorubicin exposure levels compared to the patients who had CT-GT-CT (P = 0.02) and TT-TT-TT genotypes (P = 0.03). Significantly increased clearance of doxorubicin was also observed in patients harboring CC-GG-CC genotypes when compared to patients harboring the CT-GT-CT genotype (P = 0.01). Patients harboring the CC-GG-CC genotypes had significantly lower peak plasma concentrations of doxorubicinol compared to patients who had TT-TT-TT genotypes (P = 0.03). No significant influences on doxorubicin pharmacokinetic parameters were observed in relation to the ABCG2 c.421C>A polymorphism. In conclusion, the present exploratory study suggests that the three high frequency linked polymorphisms in the ABCB1 gene might be functionally important with regards to the altered pharmacokinetics of doxorubicin in Asian breast cancer patients, resulting in significantly increased exposure levels and reduced clearance.

Influence of APOE genotypes and VKORC1 haplotypes on warfarin dose requirements in Asian patients.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Recent studies on pharmacogenetics of warfarin have implicated apolipoprotein E (APOE) polymorphisms to influence the vitamin K dependent coagulation cascade and hence the efficacy of warfarin. Studies among Caucasian and African Americans showed a significant but conflicting role of apolipoprotein E (APOE) isoforms in warfarin pharmacogenetics. The contribution of APOE isoforms in influencing variations in warfarin requirements in Asian subjects remains to be investigated. WHAT THIS STUDY ADDS: This is the first report of a population study in Asians exploring the role of isoforms encoded by three APOE alleles (epsilon 2, epsilon 3, epsilon 4) in influencing warfarin dose requirements. The present study showed that the APOE epsilon 3/epsilon 3 isoform is the predominant genotype in the Asian population. The study also showed that APOE isoforms may not be important in affecting warfarin pharmacodynamics in Asian patients. It also suggested that the impact of different APOE isoforms depended on the frequency of APOE genotypes in the population, in particular the epsilon 4 allele containing genotypes. AIMS: To investigate the influence of APOE genotypes and VKORC1 haplotypes on warfarin dose requirements in Asian patients. METHODS: A total of 174 Asian patients (Chinese, n = 96; Malays, n = 50; Indians, n = 28) who had stable daily warfarin doses for at least 1 month were recruited. Following genomic DNA extraction from venous blood, pharmacogenetic analysis of APOE and VKORC1 genes was done by DNA sequencing. RESULTS: The majority of the Asian patients (78%) harboured the APOE epsilon 3/epsilon 3 genotype. Different APOE genotypes were found not to have any significant influence on mean daily warfarin dose requirements. Warfarin dose requirements in the pooled Asian patients homozygous for the VKORC1 H1 haplotype were significantly lower compared with patients homozygous for the H7 haplotype (H1-H1 vs. H7-H7: 2.79 +/- 1.06 mg day(-1)vs. 5.45 +/- 2.3 mg day(-1), P < 0.001). CONCLUSIONS: The present study suggests that APOE variants have minimal impact on warfarin dose requirements in Asian patients, probably due to the low frequency of epsilon 4 allele containing genotypes.

Celiac disease: variations of presentations in adults.

BACKGROUND: Patients with celiac disease, who remain undiagnosed or asymptomatic in childhood, may present in adulthood with either typical or atypical features. METHODS: In a retrospective analysis, we reviewed the case records of 45 consecutive patients with celiac disease diagnosed in adulthood. The diagnosis of celiac disease was made on the basis of the modified European Society of Pediatric Gastroenterology, Hepatology and Nutrition criteria. The modes of presentation, clinical manifestations, endoscopic features and histological features were analyzed. RESULTS: The mean age of these patients at diagnosis was 28.7 (11.2) years. The median duration of symptoms before diagnosis was 2.5 years (range: 6 months to 40 years). Chronic diarrhea was the presenting manifestation in 20 (44%) patients only. Twenty-two (49%) patients were referred to us by hematologists, endocrinologists or gynecologists for evaluation of refractory anemia in 10 (2.2%), short stature in 6 (13.3%), metabolic bone disease in 2 (4.4%) and secondary infertility or delayed menarche in 4 (8.8%). Intestinal mucosal folds were scalloped in 31 (69%), attenuated in 34 (76%) and normal looking in 11 (24%) of them. Mild, moderate and severe villous abnormalities on intestinal mucosal biopsies were present in 10 (22.2%), 15 (33.3%) and 19 (42.2%) patients, respectively. CONCLUSIONS: More than half of adult patients with celiac disease present with atypical manifestations. A high index of suspicion is required for diagnosing variant forms of celiac disease in adults.

Novel SLC22A16 polymorphisms and influence on doxorubicin pharmacokinetics in Asian breast cancer patients.

OBJECTIVE: To identify novel polymorphisms in the solute carrier SLC22A16 gene and determine their influence on the pharmacokinetics of doxorubicin and doxorubicinol in Asian breast cancer patients. METHODS: SLC22A16 coding regions were screened in a total of 400 healthy subjects belonging to three distinct Asian ethnic groups (Chinese [n = 100], Malays [n = 100] and Indians [n = 100]) and in the Caucasian population (n = 100). Pharmacokinetic parameters of doxorubicin and doxorubicinol were estimated in Asian breast cancer patients undergoing adjuvant chemotherapy to investigate genotype-phenotype correlations. RESULTS: Four novel polymorphisms (c.146A>G [exon 2], c.312T>C, c.755T>C [exon 4] and c.1226T>C [exon 5]) were identified. The genotypic frequency of the homozygous c.146GG polymorphism was approximately twofold higher in the healthy Chinese (13%) & Malay (18%) populations compared with the Indian (7%) and Caucasian (9%) populations. The genotypic frequency of the c.1226T>C polymorphism was observed to be significantly higher among the Caucasian (11%) and Indian (8%) study subjects compared with the Chinese (1%) and Malay (1%) ethnic groups (p < 0.005 in each case). Breast cancer patients harboring the 146GG genotype showed a trend towards higher exposure levels to doxorubicin (AUC(0 negative infinity)/dose/body surface area [BSA] [hm(-5)]: 21.6; range: 18.8-27.7) compared with patients with either the reference genotype (AUC(0 negative infinity)/dose/BSA[hm(-5)]: 17.4; range: 8.2-26.3, p = 0.066) or heterozygotes (AUC(0 negative infinity)/dose/BSA[hm(-5)]: 15.4; range: 6.2-38.0, p = 0.055). The exposure levels of doxorubicinol were also higher in patients harboring the variant 146GG genotype (AUC(0 negative infinity)/dose/BSA[hm(-5)]: 13.3; range: 8.8-21.7) when compared with patients harboring the reference genotype (AUC(0 negative infinity)/dose/BSA[hm(-5)]): 9.8; range: 6.1-24.3, p = 0.137) or heterozygotes (AUC(0 negative infinity)/dose/BSA[hm(-5)]: 8.98; range: 3.7-20.6, p = 0.047). CONCLUSION: Among the four novel SLC22A16 polymorphisms identified, the c.146A>G and c.1226T>C polymorphisms exhibited interethnic variations in allele and genotype frequencies. This exploratory study suggests that the c.146A>G variation could contribute to the variations in the pharmacokinetics of doxorubicin and doxorubicinol in Asian cancer patients. Further in vitro studies are required to determine the functional impact of these novel polymorphisms on doxorubicin pharmacokinetics in cancer patients.

Pharmacogenetics of SLCO1B1: haplotypes, htSNPs and hepatic expression in three distinct Asian populations.

OBJECTIVE: The aim of this study was to characterize the population frequency of SLCO1B1 polymorphic variants in three distinct healthy Asian populations, namely Chinese (n = 100), Malay (n = 100) and Indian (n = 100), and to explore the association between haplotype-tagged single nucleotide polymorphisms (htSNPs) on hepatic SLCO1B1 mRNA expression. METHODS: The distribution of polymorphic variants in the SLCO1B1 gene at eight loci that spanned approximately 48 kb was investigated in the three different Asian ethnic groups and in 32 non-cancerous liver tissues from Chinese patients. RESULTS: Of the 26 polymorphisms screened, we found eight polymorphic variants that differed in genotypic and allelic frequencies between the Chinese, Malay and Indian populations. Significant interethnic differences were observed in the genotype frequency distributions across the promoter SNP [g.-11187G>A (P = 0.030)] as well as three coding region SNPs [c.388G>A (P < 0.001); c.571T>C (P < 0.001); c.597C>T (P < 0.001)] in the healthy subjects. Haplotype analysis revealed 12 different haplotypes in both the Chinese and Malay populations and 18 haplotypes in the Indian population. In both the Malay and Indian populations, the htSNPs were c.388A>G, c.571T>C and c.597C>T, whereas in the Chinese population they were g.-11187G>A, c.388A>G and c.597C>T. The c.388A>G and c.597C>T htSNPs accounted for more than 70% of the variations between the three major haplotypes in each Asian ethnic group. In terms of the c.388A>G htSNPs, genotypic-phenotypic association analyses revealed that there was no effect on SLCO1B1 expression in hepatic tissues; in addition, no genotypic-phenotypic associations were evident with regards to the c.597C>T htSNP. CONCLUSION: Future studies should investigate the phenotypic effects of the c.388A>G htSNP on the disposition of OATP1B1 substrates in Asian populations.

Hemoperitoneum from ruptured cyst in a hyperstimulated ovary: a sonographic mimic of ovarian hyperstimulation syndrome.

We report a case of a ruptured cyst in a hyperstimulated ovary that was initially misinterpreted as ovarian hyperstimulation syndrome (OHSS). A 22-year-old woman who was on oral clomiphene citrate for primary infertility presented with pain in the lower abdomen, hypotension, and tachycardia. Sonographic examination revealed multiple cysts in both ovaries and free fluid in the abdomen, and the initial diagnosis was OHSS. However, sonographically guided aspiration of free fluid revealed a hemoperitoneum, and the patient underwent emergent surgery. At laparotomy, an actively bleeding ruptured cyst in a hyperstimulated ovary was found to be the cause of the hemoperitoneum. Radiologists must be familiar with the imaging features of this condition to avoid misdiagnosing it as OHSS, because this could potentially delay urgently required surgery.

Anti-Saccharomyces cerevisiae antibody does not differentiate between Crohn's disease and intestinal tuberculosis.

The clinical, morphological, and histological features of intestinal tuberculosis (IT) and Crohn's disease (CD) mimic so much, that it becomes difficult to differentiate between them. The sensitivity of anti-Saccharomyces cerevisiae antibody (ASCA) IgG and ASCA IgA in CD is 60%-80%, whereas the specificity is almost 90%. There are no reports of study of ASCA in patients with IT, nor has it ever been used to differentiate CD from IT. Patients with ulcerative colitis (UC; n=25), CD (n=59), and IT (n=30) and 21 healthy controls were included in this study. The location and behavior of CD were classified according to the Modified Montreal classification. Five milliliters of blood was taken from them and serum was stored at -70 degrees C. ASCA antibodies (both IgG and IgA) were estimated using commercially available ELISA kits (AESKU Diagnostics, Germany). Anti-neutrophilic cytoplasmic antibody was measured by indirect immunofluorescence test. ASCA IgA was positive in 4.7%, 28%, 33.9%, and 43.3% and ASCA IgG was positive in 4.7%, 24%, 50.8%, and 46.6% of healthy controls and patients with UC, CD, and IT, respectively. Either ASCA IgG or ASCA IgA was positive in 9.5%, 40%, 61% and 66.6% of healthy controls, UC, CD, and IT, respectively. ANCA was positive in 0%, 32%, 10.1%, and 6.6% of healthy controls, UC, CD, and IT, respectively. ASCA IgG was positive in a significantly higher number of patients with CD (P<0.0001) and IT (P<0.0001) in comparison to healthy controls. ASCA IgA was positive in a significantly higher number of patients with UC (P<0.04), CD (P<0.013), and IT (P<0.006) in comparison to healthy controls. In comparisons between diseases, ASCA IgG was positive in significantly more patients with CD (P<0.001) and IT (P<0.001) in comparison to UC. There was no significant difference in ASCA IgA (33.9% vs. 43.3%), ASCA IgG (50.86% vs. 46.6%), or ANCA (10.7%, 7.4%) in patients with CD and IT, respectively. There was no correlation between ASCA and duration, location and behavior of CD, and IT. We conclude that ASCA IgG and ASCA IgA do not help to differentiate between IT and CD.

Pharmacogenetics of target genes across the warfarin pharmacological pathway.

Warfarin is a widely prescribed anticoagulant for thromboembolic disorders and exhibits wide inter-individual differences in its pharmacodynamic effects. Warfarin exerts its anticoagulant effect by inhibiting the enzymatic activity of vitamin K 2,3-epoxide reductase complex, subunit 1 (VKORC1) which regenerates reduced vitamin K as an essential cofactor for the post-translational gamma-carboxylation of glutamic acid residues on coagulation factors II, VII, IX and X, and the anticoagulant proteins C, S and Z. Recent studies have shown polymorphisms in genes involved in the uptake of vitamin K (apolipoprotein E [ApoE]), reduction of vitamin K 2,3-epoxide (VKORC1), metabolism of warfarin (cytochrome P450 2C9 [CYP2C9]), and gamma carboxylation (gamma-glutamyl carboxylase [GGCX]) to influence the pharmacokinetics and pharmacodynamics of warfarin in patients from different ethnic backgrounds, resulting in variable warfarin dose requirements. Understanding the causal relationship of these polygenic influences on warfarin dose requirements in patients of different ethnicity may be vital in reducing inter-patient variability and optimising anticoagulant therapy.

Acute pulmonary oedema following oxytocin administration: a life threatening complication.

Water Intoxication is not a common complication of oxytocin infusion. A 26 years primigravida developed acute onset severe pulmonary oedema in postpartum period to whom oxytocin was infused for the induction of labour and to prevent postpartum haemorrhage. The relative role of oxytocin and of electrolyte-free fluids in the pathogenesis of this problem is discussed.