Dietary sesamin is converted to enterolactone in humans

Sesamin, a major sesame seed lignan, has many biological actions. The specific mechanisms for most of these actions as well as the full metabolic pathway of sesamin in humans are unclear. Two experiments were carried out to determine whether postprandial plasma enterolactone is related to sesamin concentration in sesame seeds and whether enterolactone is the major product of the in vitro fermentation of sesamin. Four subjects (3 women, 1 man) were given a single dose of sesame seeds after they consumed a low-lignan diet for 1 wk. Blood was collected at baseline and at time intervals after intake and plasma was analyzed for plant and mammalian lignan concentrations. Additionally, pure sesamin standard was incubated in vitro with human fecal inoculum to mimic the fermentation process in human gut. We calculated individual pharmacokinetic variables and found high interindividual variation in the plasma plant lignan concentrations. The mammalian lignan appearance rate in plasma shows that sesamin is a major precursor of enterolactone in vivo. In the in vitro experiment, enterolactone was the major metabolite and 3 intermediates were identified, allowing the elucidation of sesamin metabolism in humans. Enterolactone was the major metabolite of sesamin both in vivo and in vitro. The abundance of sesamin in sesame seeds indicates that they are a major food source of enterolactone precursors.     

Marriage still protects pregnancy

OBJECTIVE: To assess the risk factors and outcome of pregnancy outside marriage in the 1990s, in conditions of a high percentage of extramarital pregnancies and high standard maternity care, used by the entire pregnant population. DESIGN: Hospital-based cohort study. SETTING: A university-teaching hospital in Finland. POPULATION: The 25,373 singleton pregnancies of known marital and cohabiting status. METHODS: Odds ratios (ORs) with 95% confidence intervals were calculated to estimate the effect of extramarital childbearing on pregnancy outcome. Multiple logistic regression analyses were conducted to control for confounding maternal risk factors. MAIN OUTCOME MEASURES: Small-for-gestational age (SGA) infants, preterm birth (less than 37 completed weeks), low birthweight (LBW; under 2500 g). RESULTS: Of the study population, 67.5% were married and 32.5% were unmarried; 24.2% of all mothers were cohabiting. Unmarried status was strongly associated with social disadvantage and particular risk factors, specifically unemployment, smoking and previous pregnancy terminations, which in turn had an impact on obstetric outcome. There were significantly more SGA infants among unmarried mothers (P < 0.001), with an absolute difference of 45%; more preterm deliveries (P= 0.001), with an absolute difference of 17.5%; and more LBW infants (P < 0.001), with an absolute difference of 26%. The differences in adverse pregnancy outcomes between study groups (i) all unmarried women, (ii) cohabiting women and (iii) single women, remained significant after multivariate analysis at adjusted ORs of 1.11, 1.11 and 1.07 for SGA, 1.17, 1.15 and 1.21 for LBW and 1.15, 1.15 and 1.29 for the preterm births, respectively. CONCLUSION: Even in the 1990s when cohabitation was already common, pregnancy outside marriage was associated with an overall 20% increase of adverse outcomes, and free maternity care did not overcome the difference.     

Diagnostic accuracy of alzheimer’s disease: A neuropathological study

This prospective study focused on the accuracy of diagnosis of Alzheimer's disease (AD). We recruited 100 dementia patients and 20 controls who underwent a systematic evaluation. The clinical diagnosis of probable AD or possible AD according to the NINCDS-ADRDA criteria was assigned in 69% of the patients, 21% had vascular dementia (VaD) (DSM-III-R) and 8% had mixed AD-VaD; only 2 patients (2%) had the Lewy body variant of AD (AD-LB). During a 3-year period 57 patients died, 53 of them (93%) being autopsied. Neuropathological examination according to the CERAD criteria showed definite AD in 27 out of 28 (96%) patients diagnosed as probable AD. In the possible AD group, the diagnostic accuracy was also high, 86% showed at least some degree of AD pathological alterations. The neocortical senile plaque scores correlated significantly with tangle scores in patients with AD pathology, and there was a significant negative correlation between age of onset and neocortical tangle scores. The concordance between the clinical diagnosis and pathological findings was clearly lower in VaD than in AD. In the clinical VaD group, 8 of 10 patients had at least some degree of AD changes together with vascular changes and only 2 of 10 patients had pure VaD. This study confirms the high accuracy of the NINCDS-ADRDA criteria for diagnosing AD. In contrast, uncertainty in the clinical diagnosis of VaD should be taken into account, for example, in drug trials with VaD patients. Received: 3 May 1995 / Revised: 26 June 1995 / Revised, accepted: 11 September 1995     

Millivolt-scale DC shifts in the human scalp EEG: evidence for a nonneuronal generator

Slow shifts in the human scalp-recorded EEG, including those related to changes in brain CO(2) levels, have been generally assumed to result from changes in the level of tonic excitation of apical dendrites of cortical pyramidal neurons. We readdressed this issue using DC-EEG shifts elicited in healthy adult subjects by hypo- or hypercapnia. A 3-min period of hyperventilation resulted in a prompt negative shift with a rate of up to 10 microV/s at the vertex (Cz) and an extremely steep dependence (up to 100 microV/mmHg) on the end-tidal Pco(2). This shift had a maximum of up to -2 mV at Cz versus the temporal derivations (T3/T4). Hyperventilation-like breathing of 5% CO(2)-95% O(2), which does not lead to a significant hypocapnia, resulted in a near-complete block of the negative DC shift at Cz. Hypoventilation, or breathing 5% CO(2) in air at normal respiratory rate, induced a positive shift. The high amplitude of the voltage gradients on the scalp induced by hyperventilation is not consistent with a neuronal origin. Instead, the present data suggest that they are generated by extracortical volume currents driven by a Pco(2)-dependent potential difference across epithelia separating the cerebrospinal fluid and blood. Since changes in respiratory patterns and, hence, in the level of brain Pco(2), are likely to occur under a number of experimental conditions in which slow EEG responses have been reported (e.g., attention shifts, preparatory states, epileptic seizures, and hypoxic episodes), the present results call for a thorough reexamination of the mechanisms underlying scalp-recorded DC-EEG responses.     

Two exonic single nucleotide polymorphisms in the microsomal epoxide hydrolase gene are associated with polycystic ovary syndrome

OBJECTIVE: To determine whether genetic variability in the gene encoding microsomal epoxide hydrolase (EPHX) contributes to individual differences in susceptibility to the development of polycystic ovary syndrome (PCOS). DESIGN: Retrospective case-control study. SETTING: University-based clinic. PATIENT(S): One hundred twelve white women with PCOS and 115 healthy controls. INTERVENTION(S): None. MAIN OUTCOME MEASURES: The presence of two single nucleotide polymorphisms (SNPs), T-->C (Tyr113His) in exon 3 and A-->G (His139Arg) in exon 4, in the EPHX gene. Single point analysis was expanded to pair of loci haplotype analysis to examine the estimated haplotype frequencies of the two SNPs, of unknown phase, in the PCOS and control groups. Estimated haplotype frequencies were assessed using the maximum-likelihood method, using an expectation-maximization algorithm. RESULT(S): Single point allele and genotype distributions in exon 3 and exon 4 of the EPHX gene were not statistically different between the groups. However, according to the haplotype estimation analysis, we observed a significantly elevated frequency of haplotype C-G (His113-Arg139) in the PCOS group versus the control group. The odds ratio for PCOS associated with the low activity haplotype C-G (His113-Arg139) was 2.28 (95% confidence interval 1.1-4.8). CONCLUSION(S): The use of two intragenic single nucleotide polymorphisms jointly in haplotype analysis of association demonstrated that the genetically determined low activity haplotype C-G (His113-Arg139) was significantly associated with PCOS.     

Obstetric outcome in women with endometriosis--a matched case-control study

BACKGROUND: Immunological deficiencies, altered angiogenic activity, infiltrative potential and growth factors are plausible factors behind endometriosis. The aim of this study was to determine whether endometriosis interferes with the course or outcome of pregnancy. STUDY DESIGN: In this matched case-control study, we analyzed obstetric outcome among 137 women with endometriosis and 137 controls matched as regards IVF procedures and parity who gave singleton births at Kuopio University Hospital between January 1994 and December 2000. In affected women, the diagnosis was histologically verified, whereas the controls were eligible for the study only if they had undergone laparoscopy/tomy in connection with tubal sterilization, or infertility unrelated to endometriosis. RESULTS: No statistically significant differences were detected in reproductive risk factors in women with endometriosis, with the exception of mean maternal age (31.2 years in the cases vs. 34 years in the controls). The mean birth weight (+/-SD) among those delivering at term (>37 completed weeks) was 3,600 (+/-542) g in the control group and 3,547 (+/-456) g in the study group. Placental weight was comparable in both groups. Overall pregnancy characteristics and pregnancy outcome measures were similar in women affected by endometriosis when compared with the control group. CONCLUSIONS: Any potential negative effect of endometriosis on obstetric outcome was undetectable.     

Presenting and long-term clinical implications and fecundity in females with obstructing vaginal malformations

OBJECTIVE: To evaluate presenting and long-term clinical consequences in females with obstructing vaginal anomalies. DESIGN: A retrospective study. SETTING: A university hospital in southern Finland. PARTICIPANTS: Twenty-six females with obstructing vaginal malformations. The conditions were classified into transverse vaginal obstruction (transverse septum or imperforate hymen) and longitudinal vaginal obstruction (longitudinal vaginal septum). INTERVENTIOS: 13 out of 16 women with transverse vaginal obstruction underwent incision of the imperforate hymen and three underwent excision of a complete transverse vaginal septum. Ten patients with obstructing hemivagina had incision of the longitudinal vaginal septum. MAIN OUTCOME MEASURES: Presenting symptoms and delay in diagnosis, outcome of primary surgical treatment, possible late complaints associated with obstruction, fecundity, perinatal outcome, and presence of other anomalies were studied. The mean followup period in the transverse and longitudinal obstruction group respectively was 13 years (range 1-29) and 16 years (range 1-44). RESULTS: Transverse vaginal obstructions were diagnosed within less than a month from the primary symptoms, while the diagnosis of longitudinal obstruction was delayed for an average of 27 months. Two out of three females with transverse vaginal septum underwent re-operation for vaginal constriction and three out of 10 with longitudinal vaginal septum had re-excision of the septum. All females with longitudinal obstruction had uterine and renal malformations as opposed to those with transverse vaginal obstruction. In the transverse vaginal obstruction group, two out of the six females who had their renal status assessed had double ureters. Dysfunctional uterine bleeding (19% in the transverse and 40% in the longitudinal obstruction group), dyspareunia (30% and 0%) and dysmenorrhea (19% and 20%) were the most common complaints during the followup. No endometriosis was found in the group that underwent a subsequent laparotomy or laparoscopy (18/26). Female infertility was not found in those 14 females who were attempting to conceive. Twenty-five (89%) out of 28 pregnancies ended in delivery, the live birth rate being 82% in the longitudinal and 94% in the transverse obstruction group. CONCLUSION: Accurate diagnosis together with adequate treatment may reduce the need for re-operations in cases with obstructing vaginal malformations. No specific gynecologic long-term clinical symptoms were identified in obstructing vaginal anomalies.     

The influence of smoking on the pregnancy-associated plasma protein A,free beta human chorionic gonadotrophin and nuchal translucency

Objective To analyse the effects of smoking on first trimester parameters used in prenatal screening for Down's Syndrome.
Design A chart study.
Setting Primary care centres and maternity clinics of the participating universities' and central hospitals.
Population Three thousand and one hundred fifteen women screened by nuchal translucency measurement and 4436 women screened by maternal serum samples. Only normal singleton pregnancies were included.
Methods The mean multiples of median of pregnancy associated plasma protein A (PAPP-A), free beta human chorionic gonadotrophin (β-hCG) and nuchal translucency were compared by independent samples t test after logarithmic transformation of the data between smokers and non-smokers.
Main outcome measures PAPP-A and free β-hCG concentrations and nuchal translucency measurements.
Results PAPP-A was significantly reduced and nuchal translucency increased if the mother smoked. The smokers were more frequently considered as being at high risk for Down's Syndrome.
Conclusions Correcting PAPP-A median for smokers down by 20% might improve the accuracy of the risk evaluations given to individual women. If the association between increased nuchal translucency and smoking can be confirmed, it poses interesting questions as to the reasons for increased nuchal translucency among normal pregnancies.     

Anatomic and functional assessment and risk factors of recurrent prolapse after vaginal sacrospinous fixation

BACKGROUND: To identify risk factors in recurrence and to evaluate anatomic and functional results of vaginal sacrospinous ligament fixation and pelvic floor reconstruction for genital prolapse. METHODS: One hundred and thirty-eight women underwent surgery for uterovaginal or vault prolapse. Follow-up data were available for 122 cases; 83% were examined and others were interviewed by telephone. The median (range) follow-up was 24 (1-141) months. Cox regression was used to identify risk factors associated with recurrence; uni- and multivariate regression was used to identify risk factors underlying postoperative infections because infections were found to be a risk factor of recurrence. Recurrence-free survival was estimated using the Kaplan-Meier method. RESULTS: Seven (5%) patients suffered severe cardiopulmonary complications including one postoperative death due to a pulmonary embolism. Twenty-six (21%) patients suffered a recurrence, 14 with cystocele. Ten patients with recurrence were symptomatic and six underwent a re-operation. The Cox regression model showed that vaginal cuff infection raised the odds ratio (OR) for recurrence to 6.13 [confidence interval (CI) 1.80-20.83] and urinary tract infection to 3.65 (CI 1.40-9.47). In both uni- and multivariate analysis, lack of intravenous antibiotic prophylaxis, age less than 73 years and vaginal ulcerations were statistically significant risk factors for postoperative infection. Eleven (33%) out of 33 sexually active women reported improvement and three (9%) complained of dyspareunia. CONCLUSIONS: Transvaginal sacrospinous ligament fixation with pelvic floor repair is an effective means of correcting both vault prolapse and uterine procidentia. Women who wish to preserve coital function will also benefit from this operation. Postoperative infection is an independent and most important individual risk factor underlying recurrence. Prophylactic antibiotics seem to be effective in reducing the rate of postoperative infections.