Colonic microbiota can promote rapid local improvement of murine colitis by thioguanine independently of T lymphocytes and host metabolism.

OBJECTIVE: Mercaptopurine (MP) and pro-drug azathioprine are 'first-line' oral therapies for maintaining remission in IBD. It is believed that their pharmacodynamic action is due to a slow cumulative decrease in activated lymphocytes homing to inflamed gut. We examined the role of host metabolism, lymphocytes and microbiome for the amelioration of colitis by the related thioguanine (TG). DESIGN: C57Bl/6 mice with or without specific genes altered to elucidate mechanisms responsible for TG's actions were treated daily with oral or intrarectal TG, MP or water. Disease activity was scored daily. At sacrifice, colonic histology, cytokine message, caecal luminal and mucosal microbiomes were analysed. RESULTS: Oral and intrarectal TG but not MP rapidly ameliorated spontaneous chronic colitis in Winnie mice (point mutation in Muc2 secretory mucin). TG ameliorated dextran sodium sulfate-induced chronic colitis in wild-type (WT) mice and in mice lacking T and B lymphocytes. Remarkably, colitis improved without immunosuppressive effects in the absence of host hypoxanthine (guanine) phosphoribosyltransferase (Hprt)-mediated conversion of TG to active drug, the thioguanine nucleotides (TGN). Colonic bacteria converted TG and less so MP to TGN, consistent with intestinal bacterial conversion of TG to so reduce inflammation in the mice lacking host Hprt. TG rapidly induced autophagic flux in epithelial, macrophage and WT but not Hprt-/- fibroblast cell lines and augmented epithelial intracellular bacterial killing. CONCLUSIONS: Treatment by TG is not necessarily dependent on the adaptive immune system. TG is a more efficacious treatment than MP in Winnie spontaneous colitis. Rapid local bacterial conversion of TG correlated with decreased intestinal inflammation and immune activation.

Antenatal cardiotocogram quality and interpretation using computers.

OBJECTIVE: To test the application in practice of computerized fetal heart rate (FHR) analysis in pregnancy. DESIGN: Randomized distribution of subjects with computerized analysis automatically revealed or concealed. SETTING: A district general hospital and a teaching hospital outside London. SUBJECTS: 2869 pregnant women studied within a year. OUTCOME MEASURES: Quality and duration of the cardiotocogram; quantitative measurement of FHR variation; number of stillbirths. RESULTS: With interactive advice to the operator, records were of improved quality (up to 28% without signal loss) with potentially much reduced recording time. The short-term FHR variation measured in the last records before intervention is reported for the first time. CONCLUSION: The benefits of using the computers include improvement in record quality and saving of time. In addition, where interpretation depended on estimation of FHR variation there was prima facie evidence of observer misinterpretation; visual analysis was unreliable. A larger trial is now required with more rigorous constraints on intervention.

Hereditary thrombophilia in a family with three independent protein S and C mutations. A cause of adverse perinatal outcome.

A non-related couple with two independent protein S and a protein C mutation had two of their three children suffering from severe thrombosis resulting in neonatal death of the firstborn. With prenatal testing an accurate prediction of phenotype was possible for the second child but the third infant was more severely affected than had been predicted from the genotype.

Large fetal heart rate decelerations at term associated with changes in fetal heart rate variation.

OBJECTIVE: The objective was to determine whether large antepartum decelerations in fetal heart rate were associated with a switch from high to low fetal heart rate variation, suggestive of a change in sleep state, and whether the variation predicted outcome. STUDY DESIGN: Retrospective computerized analysis of 10,272 cardiotocographic records from 3998 patients at 37 to 42 weeks' gestation from four centers in England and Italy identified 140 good-quality records with large decelerations (more than 20 lost beats in area). RESULTS: In otherwise normal cardiotocograms a large deceleration had a 40% chance of association with a downward change in fetal heart rate variation (69% when the deceleration exceeded 100 lost beats). The change resembled that occurring naturally with behavioral states. Uterine contractions did not always precede large decelerations. When they did, the lag time (peak of contraction-trough of deceleration) increased from 28 seconds (at 20 to 29 lost beats) to > 100 seconds with increase in deceleration area. Of patients with large decelerations 76% had a normal vaginal delivery. CONCLUSION: Large decelerations near term, present in up to 5% of patients with otherwise normal fetal heart rate and variation, are often associated with a fall in fetal heart rate variation characteristic of a change in sleep state, without ominous significance.

Antenatal cardiotocogram quality and interpretation using computers.

OBJECTIVE: To test the application in practice of computerized fetal heart rate (FHR) analysis in pregnancy. DESIGN: Randomized distribution of subjects with computerized analysis automatically revealed or concealed. SETTING: A district general hospital and a teaching hospital outside London. SUBJECTS: 2869 pregnant women studied within a year. OUTCOME MEASURES: Quality and duration of the cardiotocogram; quantitative measurement of FHR variation; number of stillbirths. RESULTS: With interactive advice to the operator, records were of improved quality (up to 28% without signal loss) with potentially much reduced recording time. The short-term FHR variation measured in the last records before intervention is reported for the first time. CONCLUSION: The benefits of using the computers include improvement in record quality and saving of time. In addition, where interpretation depended on estimation of FHR variation there was prima facie evidence of observer misinterpretation; visual analysis was unreliable. A larger trial is now required with more rigorous constraints on intervention.

Effectiveness of routine ultrasonography in detecting fetal structural abnormalities in a low risk population.

OBJECTIVE: To review the efficacy of routine prenatal ultrasonography for detecting fetal structural abnormalities. DESIGN: Retrospective study of the ultrasonographic findings and outcome of all pregnancies in women scanned in 1988-9. SETTING: Maternity ultrasonography department of a district general hospital. SUBJECTS: 8785 fetuses. MAIN OUTCOME MEASURES: Correlation of prenatal ultrasonographic findings with outcome in the neonate. RESULTS: 8733 babies were born during 1988-9, and 52 pregnancies were terminated after a fetal malformation was identified. 8432 (95%) of the fetuses were examined by ultrasonography in the second trimester. 130 fetuses (1.5%) were found to have an abnormality at birth or after termination of pregnancy, 125 of which had been examined in the second trimester. In 93 cases the abnormality was detected before 24 weeks (sensitivity 74.4%, 95% confidence interval to 66.7% to 82.1%. Two false positive diagnoses occurred, in both cases the pregnancies were not terminated and apparently normal infants were born. This gives a specificity of 99.98% (99.9% to 99.99%). The positive predictive value of ultrasonography in the second trimester was 97.9% (92.6% to 99.7%). Of the 125 abnormalities, 87 were lethal or severely disabling; 72 of the 87 were detected by the routine screening programme (sensitivity 82.8%, 73.2% to 90.0%). CONCLUSION: Routine fetal examination by ultrasonography in a low risk population detects many fetal structural abnormalities but can present several dilemmas in counselling.

Pattern of eyelid motion predictive of decision errors during drowsiness: oculomotor indices of altered states.

Sequential patterns of eye and eyelid motion were identified in seven subjects performing a modified serial probe recognition task under drowsy conditions. Using simultaneous EOG and video recordings, eyelid motion was divided into components above, within, and below the pupil and the durations in sequence were recorded. A serial probe recognition task was modified to allow for distinguishing decision errors from attention errors. Decision errors were found to be more frequent following a downward shift in the gaze angle which the eyelid closing sequence was reduced from a five element to a three element sequence. The velocity of the eyelid moving over the pupil during decision errors was slow in the closing and fast in the reopening phase, while on decision correct trials it was fast in closing and slower in reopening. Due to the high variability of eyelid motion under drowsy conditions these findings were only marginally significant. When a five element blink occurred, the velocity of the lid over pupil motion component of these endogenous eye blinks was significantly faster on decision correct than on decision error trials. Furthermore, the highly variable, long duration closings associated with the decision response produced slow eye movements in the horizontal plane (SEM) which were more frequent and significantly longer in duration on decision error versus decision correct responses.

The influence of episiotomy on the neonatal survival and incidence of periventricular haemorrhage in very-low-birth-weight infants.

The neonatal survival and incidence of periventricular haemorrhage (PVH) in very-low-birthweight (VLBW) infants who present by the vertex are not influenced by the use of episiotomy. This study does not support the routine use of episiotomy for pre-term vertex deliveries.

A behavioral technique for recovery from the psychological trauma of hysterectomy.

Three groups of women (ns = 10) undergoing hysterectomy were subjects in an evaluation of biofeedback and relaxation techniques applied to recovery from psychological trauma of hysterectomy. Dependent measures included requests of pain medications, anxiety levels, finger-tip temperature, subjective units of discomfort, and number of days post-operative care. Although the results were mixed on most variables, the number of days post-operative care was significantly less in the relaxation/biofeedback group.

The role of alcohol in unplanned pregnancy.

About 25% of all pregnancies are unplanned. While age, marital status, social class and contraceptive practice have all been considered, little attention has been paid to alcohol as a possible aetiological factor. The present study based on a questionnaire was devised to ascertain the role of alcohol in conception. One hundred and sixteen pregnant women participated and these were attending the ante-natal clinic for the first time. In only 2 cases was alcohol thought to be a likely factor in conception although only a few had never consumed alcohol. A further study on 100 clients attending the regional day care abortion unit revealed that less than one tenth felt that alcohol was a factor in the conception. Unplanned pregnancies may result from alcohol consumption in less than 10% of cases, lack of motivation to use some form of contraception would appear to play a more prominent part.

Transfer before delivery on Merseyside: an analysis of the first 140 patients.

Pregnant women (140) were transferred to the Regional Unit between May 1979 and December 1981 for delivery of preterm infants considered to be at risk. The 144 live infants and seven stillbirths that were delivered had a mean birthweight of 1.37 kg and a mean gestation of 29 weeks; there were nine abortions. In 1980 the uncorrected neonatal survival for very low birthweight infants was significantly better for those transferred before delivery (81%) than for infants born in the Region and not transferred (52%). The survival of very low birthweight infants transferred after delivery was 53%.