Fetal serum alpha-fetoprotein in alloimmunised pregnancies

OBJECTIVES: Maternal serum alpha-fetoprotein (AFP) levels have been known to be increased in red blood cell alloimmunisation. Since AFP is now thought be a pro-erythropoietic factor, we wished to evaluate fetal serum levels of AFP in cases of alloimmunised pregnancies. METHODS: We studied AFP levels in 32 fetal serum samples from women with red blood cell alloimmunisation at the time of the first fetal blood sampling. We expressed the levels of AFP and haemoglobin as absolute numbers and as delta values (number of SDs by which the observed value differed from the normal mean for the same gestation). Main outcome measures were fetal serum AFP levels and fetal haemoglobin concentration. RESULTS: Overall, fetal AFP level was higher than normal in the cases (delta values 2.4 +/- 5.5 SD). However, mildly affected non-hydropic cases had higher levels than severely affected fetuses with hydrops. CONCLUSIONS: Fetuses affected by red blood cell alloimmunisation have increased levels of serum AFP but these levels fall back to low levels in severe anaemia especially with hydrops, which could represent the failing of a compensatory erythropoietic mechanism. Our results suggest that fetal haematopoiesis is activated early in red blood cell alloimmunisation but was subsequently impaired.     

Misoprostol for women's health: a review

OBJECTIVE: To review published literature on misoprostol for women's health indications to provide a synthesis of available information and highlight areas in need of additional research. DATA SOURCES: Studies were identified through searches of medical literature databases including MEDLINE, Cochrane Database, and Popline, in addition to a review of references from identified articles. STUDY SELECTION: We included all studies reported in English and published before March 31, 2001, which evaluated the efficacy of misoprostol alone for labor and delivery, evacuation of the uterus after pregnancy failure and induced abortion. Studies were not excluded based on quality or sample size. TABULATION, INTEGRATION, AND RESULTS: Misoprostol shows promise for all of the women's health indications addressed. Currently available data, though, are often hard to interpret because of variations in regimen, dose, and outcome measures. The low cost, ease of administration and storage, and widespread availability of misoprostol make it particularly appealing for developing countries. Because many of the women's health problems for which misoprostol could be prescribed currently cause significant mortality and morbidity, increased access to and information on use of misoprostol could help improve women's health especially where these problems are most severe. CONCLUSION: Further research is needed to identify optimal regimens for misoprostol for obstetric and gynecologic health indications. Registering misoprostol with national drug regulatory authorities for any of several women's health indications could help increase access to and safe use of this drug. Provider training would be a logical subsequent step.     

The effect of in utero exposure to indomethacin on the need for surgical closure of a patent ductus arteriosus in the neonate

OBJECTIVE: Our purpose was to determine the effect of in utero exposure to indomethacin on the need for surgical closure of a patent ductus arteriosus (PDA). STUDY DESIGN: Perinatal variables were compared between infants at <32 weeks who required surgical closure of PDA after failed medical management and those who did not. Statistical analysis was performed by Student t, Mann-Whitney, chi(2), and multiple logistic regression tests. RESULTS: Eight of 77 infants with PDA failed therapy and required surgery. Maternal demographics, gestational age, birth weight, and delivery route were similar in both groups. In utero exposure to indomethacin was more common in neonates requiring surgery versus those who did not, particularly when exposure was for >72 hours (50.0% vs 8.7%, odds ratio 10.5, 95% CI 1.6-72.1, P =.008). CONCLUSION: Need for surgical closure of PDA appears to be increased by in utero indomethacin exposure. These findings should be considered in the overall context of the risk versus benefits of tocolysis.     

Predicting death from HIV/AIDS: a case-control study from Florida public HIV/AIDS clinics

BACKGROUND: After markedly decreasing for 3 years, HIV/AIDS mortality declined only slightly in 1999. METHODS: The authors conducted a case-control study in four Florida urban public health HIV clinics to evaluate modifiable factors associated with HIV/AIDS mortality in a non-research setting. Structured chart review was conducted for 120 case-patients who died in 1999 and for 240 randomly selected control-patients. Risk factors associated with death in univariate analysis were entered into three conceptually related, matched logistic regression models. RESULTS: In the final multivariate model, homelessness (adjusted odds ratio [AOR], 9.98; 95% confidence interval [CI], 2.34-42.5), Medicaid insurance (AOR, 3.10; 95% CI, 1.43-6.74), having a documented adherence problem (AOR, 3.50; 95% CI, 1.64-7.47), injection drug use (AOR, 2.46; 95% CI, 1.11-5.43), non-specific liver failure (AOR, 76.9; 95% CI, 6.79-870.9), interrupted highly active antiretroviral therapy (HAART) secondary to side effects (AOR, 4.00; 95% CI, 1.46-10.9), and not receiving HAART (AOR, 2.62; 95% CI, 1.03-6.68) were independent predictors of mortality. CONCLUSIONS: In addition to medical and clinical indicators, several sociobehavioral-demographic factors remained important throughout the multivariate analysis. Improvement in care should include a focus on social circumstances of infected people. Special attention to the homeless, those with adherence problems, and those with liver disease is clearly indicated.     

Peripheral deletion of autoreactive CD8 T cells by cross presentation of self-antigen occurs by a Bcl-2-inhibitable pathway mediated by Bim

By transgenic expression of ovalbumin (OVA) as a model self antigen in the beta cells of the pancreas, we have shown that self tolerance can be maintained by the cross-presentation of this antigen on dendritic cells in the draining lymph nodes. Such cross-presentation causes initial activation of OVA-specific CD8 T cells, which proliferate but are ultimately deleted; a process referred to as cross-tolerance. Here, we investigated the molecular basis of cross-tolerance. Deletion of CD8 T cells was prevented by overexpression of Bcl-2, indicating that cross-tolerance was mediated by a Bcl-2 inhibitable pathway. Recently, Bim, a pro-apoptotic Bcl-2 family member whose function can be inhibited by Bcl-2, was found to play a critical role in the deletion of autoreactive thymocytes, leading us to examine its role in cross-tolerance. Bim-deficient T cells were not deleted in response to cross-presented self-antigen, strongly implicating Bim as the pro-apoptotic mediator of cross-tolerance.     

Supporting clinical leaders in achieving organisational change

Clinical leaders in nursing may feel stuck in the middle of conflicting demands from the various members of their organisation and patients' needs. The LEO programme aims to help these clinical leaders identify their problems, agree action plans and ask for the support they need in bringing about positive change in their workplace.     

CD38 expression on CD8(+) T cells as a prognostic marker in vertically HIV-infected pediatric patients

Increased expression of CD38 on CD8(+) T cells is associated with activation of the immune system, progression of HIV disease, and death in adults. The prognostic significance of these cells in HIV-infected children, where the picture is complicated by age-related differences in CD38 expression, remains controversial. Measuring the unimodal expression of CD38 on CD8(+) T cells in adults and children by flow cytometry is best accomplished by quantitating the antigen on the cell surface. To our knowledge, this technique has not previously been reported in a pediatric population. Vertically HIV-infected children were age matched for mild (n = 26) and severe (n = 23) clinical disease. Eleven age-matched HIV-negative controls were included for comparison. Quantitation of CD38 on CD8(+) T cells was performed at baseline and 1 y later. The ages of the children in the three clinical groups did not differ significantly (p = 0.6004). HIV-infected children had significantly increased CD38 measurements in comparison with the HIV-negative controls (p = 0.0131), and the severe disease group tended to have higher measurements than the mild disease group. Increased CD38(+)CD8(+) T cells were significant predictors of death within the first year (p = 0.043). These findings support the view that increased CD38 expression on CD8(+) T cells has the same prognostic significance in pediatric as in adult HIV disease.     

Folate cofactors regulate serine metabolism in fetal ovine hepatocytes

The fetal liver is the primary site of fetal serine production. The regulation of this unique fetal hepatic serine production is unknown. We hypothesized that serine production would be responsive to folate cofactor supply or hormonal regulation. To test this hypothesis, we determined the effect of key folate cofactors and insulin and glucagon on serine and glycine metabolism in primary culture of fetal ovine hepatocytes. Hepatocytes were cultured in serum-free, low-folate media [5 nM 5-methyl-tetrahydrofolate (THF)] with or without 50 nM 5,10-methylene-THF (MTHF) or 5-formyl-THF (FTHF). Serine and glycine production (P) and utilization (U) were determined by stable isotope dilution with [1-(13)C]serine and [1-(13)C]glycine for 24 h. The effect of insulin (1 microM) or glucagon (1 micro M) was determined in a similar manner. Under basal conditions, serine P (43.2 +/- 5.1 micromol/mg DNA per 24 h) is greater than serine U (24.1 +/- 3.1 micromol/mg DNA per 24 h), whereas glycine U (27.3 +/- 3.0 micromol/mg DNA per 24 h) exceeds glycine P (16.7 +/- 1.9 micromol/mg DNA per 24 h). MTHF results in a significant decrease in serine U (16.0 +/- 2.7 micromol/mg DNA per 24 h; p = 0.02 versus low folate), with no change in serine P. FTHF reduces serine P (36.2 +/- 4.9 micromol/mg DNA per 24 h; p = 0.01), but does not alter serine U. There were no effects on glycine metabolism with 50 nM MTHF or FTHF. Serine P and U were inversely correlated whereas glycine P and U were directly correlated with the media concentration of MTHF or FTHF. Glucagon treatment increased serine U by 260 +/- 65% versus low folate (p = 0.0004) but did not change serine P. Insulin treatment led to parallel increases in both serine P and U. Both folate cofactor availability and hormone concentrations regulate serine metabolism in the fetal liver. We speculate that serine metabolism may be a marker of fetal hepatic folate cofactor supply.