Genotypes of glutathione transferase M1 and P1 and their significance for lung DNA adduct levels and cancer risk

The A-G polymorphism at codon 104 in the glutathione S-transferase P1 (GSTP1) gene was examined in 138 male lung cancer patients and 297 healthy controls. The patients had significantly higher frequency of the GG genotype (15.9%) and a lower frequency of AA (38.4%) than the controls (9.1% and 51.5%, respectively). The level of hydrophobic DNA- adducts were determined in lung tissue from 70 current smokers. Patients with the GG genotype had a significantly higher adduct level than patients with AA (15.5 +/- 10.2 vs 7.9 +/- 5.1 per 10(8) nucleotides, P = 0.006). We also analyzed the deletion polymorphism in the GSTM1 gene in 135 male patients and 342 controls. The patients were stratified according to histology, smoking dose, age, adduct level and mutational types found in the tumors (Ki-ras and p53 genes). The results consistently indicated that the GSTM1 null genotype was associated with a slightly increased lung cancer risk. When the combined GST M1 and P1 genotypes were examined, patients with the combination null and AG or GG had significantly higher adduct levels than all other genotype combinations (P = 0.011). The distribution of combined genotypes was also significantly different in cases and controls, mainly due to increased frequency of the combination GSTM1 null and GSTP1 AG or GG among patients.      

Follistatin and activin A in extra-embryonic coelomic and amniotic fluids and maternal serum in early pregnancy

Follistatin is a specific binding protein which controls bioavailability of activins and inhibins which have an important role in fetal development. In the first trimester of pregnancy bioactive dimeric inhibins are found at high concentrations in the extra- embryonic coelomic fluid, but the distribution of follistatin and activins is not known. We have used recently developed immunoassays for follistatin, activin A and activin AB to determine their presence in the intrauterine compartments during early pregnancy. Follistatin was present in highest concentrations in the extra-embryonic coelomic fluid (11.72 +/- 1.70 ng/ml; median +/- SEM), with less in maternal serum (6.35 +/- 4.58) and lowest amounts in amniotic fluid (0.97 +/- 0.52). Follistatin concentrations in extra-embryonic coelomic fluid were highly correlated with both dimeric inhibin isoforms. Activin A was present in only barely detectable amounts in some samples of extra- embryonic coelomic fluid (41% of samples) and maternal serum (26%) and was undetectable in all amniotic fluid samples. Activin AB was undetectable in all compartments. The presence of follistatin in the amniotic and extra-embryonic coelomic fluids may regulate the availability of bioactive activins and inhibins which are released into the intrauterine compartments during the development of the fetus and placenta in early pregnancy.      

Sex hormone‐binding globulin and androgen levels in immigrant and British‐born premenopausal British Pakistani women: Evidence of early life influences?

In women, raised insulin levels are associated with low sex hormone-binding globulin (SHBG) and high androgen levels, which are in turn linked to infertility. Since insulin resistance and hyperinsulinemia are major health problems for South Asians living in Western countries, we predicted that British Pakistani women would have low SHBG and raised androgen levels compared to European women. Given low birth weights in Pakistan, and known links between low birth weight and insulin resistance in later life, we also predicted that immigrant women born in Pakistan would have lower levels of SHBG and higher levels of androgens than British-born British Pakistani women. We assessed SHBG, testosterone, and the free androgen index (FAI) from a single serum sample taken on days 9-11 of the menstrual cycle from 20-40-year-old women living in the UK: 30 immigrants from Pakistan, 30 British-born British Pakistani women, and 25 British-born women of European origin. Age-adjusted analyses showed no significant differences in SHBG, testosterone, or FAI between British-born Pakistani and European-origin women. However, immigrant British Pakistani women had a significantly higher FAI than British-born British Pakistani women. Adjustment for body mass index, waist-to-hip ratio, and smoking status did not affect these results, but further adjustment for height, a marker of early environment, reduced the P-value for the difference in FAI between immigrant and British-born British Pakistani women to below significance. It is possible that the poorer early environment of immigrant British Pakistani women was at least partially responsible for their relatively high levels of free androgens.     

Pediatric liver transplantation. Part II. Diagnostic imaging in postoperative management

The postoperative diagnostic imaging examinations of 44 children who underwent 59 orthotopic liver transplantations were reviewed. The imaging modalities used for the evaluation of suspected complications include plain roentgenography, ultrasonography (US), computed tomography (CT), nuclear scintigraphy, arteriography, percutaneous and operative cholangiography, and endoscopic retrograde cholangiopancreatography. The main postoperative complications included ischemia, thrombosis (hepatic artery and portal vein), infarction, obstruction or leakage of the biliary anastomosis, hepatic and perihepatic infection, and allograft rejection. US, the most frequently used abdominal imaging modality, was best suited for detection of biliary duct dilatation, fluid collections in or around the transplanted liver, and hepatic arterial, inferior vena caval, and portal vein thrombosis. CT was especially helpful in corroborating findings of infection and in locating abscesses. Technetium 99m sulfur colloid (early- and late-phase imaging) provided a sensitive, although nonspecific, means of assessing allograft vascularization and morphology. Angiography showed vascularity most clearly, and cholangiography was the most useful in the assessment of bile duct patency. A diagnostic imaging algorithm is proposed for evaluation of suspected complications.     

Antiphosphatidyl serine antibodies are more common in normotensive women with small for gestational age pregnancies

BACKGROUND: Small for gestational age (SGA) babies are more common in women with antiphospholipid antibodies but data are limited about the prevalence of antiphospholipid antibodies in women who have delivered SGA babies. AIM: To determine whether elevated levels of anticardiolipin, antiphosphatidyl serine and/or antibeta2 glycoprotein I antibodies are more common in normotensive women who delivered SGA babies compared with women who delivered appropriate for gestational age babies. METHODS: Case-control study. Cases were normotensive women who delivered an SGA baby (birthweight <10th%) without chromosomal or congenital abnormality. Controls were healthy women who delivered a baby at term with birthweight >10th percentage. RESULTS: A total of 137 women with SGA pregnancies and 290 controls had antiphospholipid antibodies measured. The prevalence of anticardiolipin and antibeta2 glycoprotein I antibodies did not differ between SGA cases and controls. Antiphosphatidyl serine IgG antibodies were more common in women with SGA pregnancies than controls seven (5%) versus five (1.7%), relative risk (RR) 1.84 (1.12-3.03). There was no difference in the prevalence of 'any antiphospholipid antibodies' between SGA 10 (7.2%) and controls 16 (5.6%). There was a trend to more abnormal umbilical Doppler studies in SGA pregnancies with positive antiphospholipid antibodies three (50%) versus 19 (24%), RR 2.9 (0.62-13). CONCLUSIONS: Antiphospholipid antibodies were uncommon in this cohort of SGA pregnancies. Further studies are needed in SGA pregnancies with abnormal umbilical Doppler studies to determine if screening for antiphospholipid antibodies is worthwhile in this severe subgroup.     

Does aspirin have a role in improving pregnancy outcome for women with the antiphospholipid syndrome? A randomized controlled trial

OBJECTIVE: This pilot investigation was undertaken to assess the efficacy of low-dose aspirin therapy for the treatment of women with antiphospholipid antibodies when recurrent miscarriage is the only sequela. STUDY DESIGN: A double-blind, randomized, placebo-controlled trial was conducted in the setting of the recurrent miscarriage clinic of a tertiary referral obstetric hospital. The participants were 50 women with a history of recurrent miscarriages (>/=3) and antiphospholipid antibodies. Women with systemic lupus erythematosus or a history of thrombosis were excluded. Women were recruited after full investigative screening at the recurrent miscarriage clinic. Women with >/=3 fetal losses and persistently positive results for antiphospholipid antibodies were randomly allocated to receive either aspirin (75 mg daily) or placebo. Investigators, clinicians, and patients were blinded to the treatment. Rates of live births, antenatal complications, and delivery and neonatal outcomes were recorded prospectively. Data were compared by chi(2) analysis with Yates' correction, the Fisher exact test, or the Student t test as appropriate. RESULTS: There were 10 exclusions after random assignment because of inappropriate inclusion. Eighty-five percent of the placebo (17/20) group and 80% of the aspirin-treated group (16/20) were delivered of live infants. This difference was not significant. There were no significant differences in antenatal complications or neonatal morbidity between the groups. CONCLUSIONS: This preliminary study suggests that low-dose aspirin has no additional benefit when added to supportive care for women for whom recurrent early fetal loss is the only sequela of the antiphospholipid syndrome. This live birth rate with supportive care alone exceeds the published live birth rates for women with antiphospholipid antibody-mediated recurrent fetal loss who were treated with heparin or corticosteroids. This trial, like all other trials in this field, is small, but its results bring into question the need for pharmacologic intervention for women with antiphospholipid syndrome for whom recurrent fetal loss is the only sequela. Our results highlight the need for a large randomized controlled trial to identify the optimal treatment for this group of women and justify the inclusion of a placebo arm in any such trial.