Differences in post-mortem findings after stillbirth in women with and without diabetes.

AIMS: The reason for the fivefold increased risk of stillbirth in women with diabetes is not known. Further understanding of the underlying mechanisms may facilitate identification of pregnancies at increased risk. We have compared post-mortem reports in matched pairs of stillbirths in women with and without diabetes. METHODS: Post-mortem reports were provided by the Centre for Maternal and Child Enquiries. Stillbirths as a result of lethal congenital and genetic abnormalities were excluded. Whole body, placenta and organ weights and histo-pathological findings in cases and controls were compared and also related to published reference values. RESULTS: We analysed post-mortem reports on 23 matched pairs of stillbirths from 2009 to 2010. Mean placental weight in women with diabetes was 75 g less than in control subjects (95% CI -143 to -7 g; P = 0.032). In maternal diabetes, the thymus was often small and showed a 'starry sky' pattern on histology in 11 of 20 cases compared with four of 22 controls (P = 0.03). This histological finding was associated with a particularly low mean placental weight z-score -2.1 (1.1) standard deviations below a reference population corrected for gestational age. CONCLUSIONS: In over half of the stillbirths occurring in women with diabetes, there was a 'starry sky' appearance in the fetal thymus on histology, this being associated with a small placenta. These findings are consistent with a critical subacute metabolic disturbance being a prominent cause of the increased risk of stillbirth in pregnancies complicated by maternal diabetes.

No correlation between ultrasound placental grading at 31-34 weeks of gestation and a surrogate estimate of organ function at term obtained by stereological analysis.

We test the experimental hypothesis that early changes in the ultrasound appearance of the placenta reflect poor or reduced placental function. The sonographic (Grannum) grade of placental maturity was compared to placental function as expressed by the morphometric oxygen diffusive conductance of the villous membrane. Ultrasonography was used to assess the Grannum grade of 32 placentas at 31-34 weeks of gestation. Indications for the scans included a history of previous fetal abnormalities, previous fetal growth problems or suspicion of IUGR. Placentas were classified from grade 0 (most immature) to grade III (most mature). We did not exclude smokers or complicated pregnancies as we aimed to correlate the early appearance of mature placentas with placental function. After delivery, microscopical fields on formalin-fixed, trichrome-stained histological sections of each placenta were obtained by multistage systematic uniform random sampling. Using design-based stereological methods, the exchange surface areas of peripheral (terminal and intermediate) villi and their fetal capillaries and the arithmetic and harmonic mean thicknesses of the villous membrane (maternal surface of villous trophoblast to adluminal surface of vascular endothelium) were estimated. An index of the variability in thickness of this membrane, and an estimate of its oxygen diffusive conductance, were derived secondarily as were estimates of the mean diameters and total lengths of villi and fetal capillaries. Group comparisons were drawn using analysis of variance. We found no significant differences in placental volume or composition or in the dimensions or diffusive conductances of the villous membrane. Subsequent exclusion of smokers did not alter these main findings. Grannum grades at 31-34 weeks of gestation appear not to provide reliable predictors of the functional capacity of the term placenta as expressed by the surrogate measure, morphometric diffusive conductance.

Oxygen consumption of cycle ergometry is nonlinearly related to work rate and pedal rate.

The purpose of the study was to develop an equation to predict the oxygen cost of cycle ergometry. Forty subjects performed an incremental cycle ergometer test on three occasions at 50, 70, or 90 rpm in a counterbalanced order. Work rate was incremented every 5 or 6 min when steady rate values were achieved. To ensure accurate work rates, ergometer resistance was calibrated and flywheel revolutions were electronically measured. Oxygen consumption was measured with a computer interfaced system which provided results every minute. Oxygen consumption (mL.min-1) was the dependent variable, and independent variables were work rate (WR in kgm.min-1), pedal rate (rpm), weight (Kg), and gender (males, 0; females, 1). The following nonlinear equation was selected; VO2 = 0.42.WR1.2 + 0.00061.rpm3 + 6.35.Wt + 0.1136.RPM50.WR-0.10144.RPM90-WR-52-Gender, R2 = 0.9961, Sy.x = 106 mL.min-1, where RPM50: 50 rpm = 1, and RPM90: 90 rpm = 1, else = 0. It was concluded that the oxygen cost of cycle ergometry is nonlinearly related to work rate and pedal rate, linearly related to weight, and that females use less oxygen for a particular work rate.

Overexpression of p53 in Hodgkin's disease: lack of correlation with Epstein-Barr virus infection.

Recent work has shown that p53 gene mutations are frequently found in Epstein-Barr virus (EBV)-positive and EBV-negative cases of Burkitt's lymphoma but not in EBV-associated undifferentiated nasopharyngeal carcinomas (NPCs). Similar viral gene expression patterns are observed in undifferentiated NPCs and in EBV-positive cases of Hodgkin's disease (HD), suggesting that the contribution of the virus to the pathogenesis of these malignancies may also be similar. We have analysed 116 cases of HD for EBV association and for immunohistologically detectable overexpression of p53. p53 overexpression was detected in the tumour cell population of 37 (32 per cent) of the cases. Fifteen cases showed p53-specific labelling of more than 40 per cent of tumour cells; in six of these, virtually all tumour cells were stained. In eight cases, between 5 and 40 per cent of tumour cells were labelled, and in another 14 cases, less than 5 per cent of tumour cells expressed detectable amounts of p53. EBV-positive HD cases were found in all groups with different levels of p53 overexpression as well as amongst p53-negative cases. While a more detailed analysis of the p53 gene in HD is required, these data show that overexpression of p53 in HD is heterogeneous and that there is no simple correlation between EBV infection and p53 overexpression.

A comparison of the regional deposition in a model nose of a drug discharged from metered aerosol and metered-pump nasal delivery systems.

The morphology and airflow behavior in the nose are considered briefly in relationship to the various ways that are often used to evaluate the spray or aerosol discharged from inhalation delivery systems. A glass-model nose of a design based on published anatomic measurements is described. Its use is described for examining the major sites of drug deposition from nasal delivery systems. That no significant differences are detected between the regional deposition from a metered aerosol and a metered-pump product confirm what might be expected from the nasal anatomy. Most of the drug in each case is deposited in the anterior region of the nose by inertial impaction, and there is little nasal penetration of the drug. Inhaled airflow at 10 L/min through one side of the nose has little effect on regional deposition. The anteriorly deposited drug can be spread backward by mucociliary flow and general surface flow, factors that are essentially independent of the presentation used.

The diffusion of penicillin G and ampicillin through phospholipid sols.

The self-diffusion coefficients of penicillin G and ampicillin have been determined at 25 degrees in water and in the presence of a swamping concentration of electrolyte. The antibiotics diffused through phospholipid dispersions at a reduced rate due to interaction with the lipid aggregates. Ampicillin diffused through the phosphatidylcholine and phosphatidylethanolamine dispersions more rapidly than penicillin G, whereas the latter diffused more rapidly through the lysophosphatidylcholine dispersions. Estimates of binding have been made from these data and compared with those obtained from equilibrium dialysis studies. Surface tension measurements indicated that the antibiotics exhibited minimal surface activity. These results have been correlated with data obtained in other studies and a possible explanation has been advanced for the reported differences in vivo activity of penicillin G and ampicillin.