Intrapartum fetal heart rate patterns and neonatal intraventricular hemorrhage

A goal for the obstetrician and neonatologist is to screen for risk factors associated with intraventricular hemorrhage (IVH) in the low-birthweight infant. Perinatal events that lead to neonatal metabolic and cardiovascular derangements seem to provoke IVH, and conflicting reports have implicated labor as being contributory. A fetal heart rate (FHR) abnormality during premature labor may be a predictor of subsequent neonatal IVH. For this reason, 5 years of FHR tracings at two university medical centers were reviewed for inborn infants who were delivered after premature labor and weighed less than or equal to 2000 gm. Sixty-four infants developed IVH, but pre-existing labor with a discernible FHR pattern was recorded in only 38 (59%) cases. Interpretations were reassuring in 17 (45%) cases, suspicious in 7 (18%) cases, and ominous in 14 (37%) cases. This proportion of FHR patterns was not significantly different from a matched group of premature infants without IVH during the same period. Interpretations of intrapartum FHR patterns of low-birthweight infants are limited, especially before 30 weeks gestation, and not useful in predicting neonatal IVH.     

Mechanisms responsible for the thermal sensitivity of adrenal microsomal monooxygenases.

Studies were done to determine the mechanism(s) responsible for the thermal lability of adrenal microsomal monooxygenases. Preincubation of guinea pig adrenal microsomal suspensions at 37 degrees C caused large time-dependent declines in benzo(a)pyrene (BP) hydroxylase and benzphetamine (BZ) demethylase activities. Similar preincubations with hepatic microsomes had little effect on enzyme activities. The decreases in adrenal enzyme activities were completely prevented by co-incubation of microsomes with cytosol, but were not diminished by reduced glutathione, ascorbic acid, or bovine serum albumin. Partial protection was afforded by EDTA, suggesting that lipid peroxidation might be involved, but malonaldehyde production was not demonstrable and MnCl2, a potent inhibitor of lipid peroxidation, did not affect the decline in enzyme activities. The decreases in the rates of BP and BZ metabolism were prevented by including NADPH or NADP+ in the preincubation medium. The preincubation conditions causing losses of adrenal enzyme activities did not affect cytochrome P-450 concentrations or substrate binding to cytochromes P-450, as indicated by type I difference spectra. NADH-cytochrome c reductase activity also was not affected, but there were decreases in NADPH-cytochrome c reductase activity that were proportionately similar to the declines in drug-metabolizing activities. Direct assessment of NADPH-cytochrome P-450 reductase revealed similarly large decreases in enzyme activity resulting from preincubation of adrenal microsomes. The results demonstrate a need for extra caution when doing preincubation experiments with adrenal microsomal preparations, and suggest that the thermal lability of adrenal monooxygenases is attributable to effects at the active site of NADPH-cytochrome P-450 reductase.     

Lung biopsy in chronic lymphocytic leukemia

Nine patients with chronic lymphocytic leukemia (CLL), with pulmonary involvement confirmed by biopsy, presented with progressive cough and/or shortness of breath and had interstitial infiltrates on chest radiographs. Biopsies showed a dense lymphocytic infiltrate that followed bronchovascular bundles. We considered CLL the predominant finding, and the cause of the patient's pulmonary disease, in eight cases; in one, a histologically nonspecific organizing pneumonia was the main lesion and CLL was an incidental finding. Culture results were available in six cases and were negative except in one case with presumed contaminants. A granulomatous reaction was present in five cases and was necrotizing in two, although culture results were negative. The only case with a recognizable organism had noninvasive fungal hyphae growing in many of the small airways. All of the patients' respiratory symptoms improved after chemotherapy and/or steroid therapy, and the chest radiographs also showed clearing.     

Usefulness of the minute ventilation test in predicting successful extubation in newborn infants: a randomized controlled trial.

OBJECTIVE: We performed a prospective, randomized clinical trial to compare the usefulness of the minute ventilation test (MVT) with clinical judgement in predicting readiness for extubation in preterm newborns with respiratory distress syndrome requiring surfactant therapy and mechanical ventilation. STUDY DESIGN: A total of 42 preterm infants with respiratory distress syndrome were randomized when they reached preselected ventilator settings. The primary outcome measure was the time from study entry to extubation, provided the infant remained extubated for at least 24 hours. RESULTS: Infants evaluated by the MVT were extubated in a significantly shorter period of time (mean of 8 hours) than those evaluated clinically (mean of 36 hours). The extubation failure rate was similar in the two groups. CONCLUSION: The MVT is an easily performed objective measure that can be used to predict readiness for extubation in preterm infants. In this study, it significantly shortened the time for extubation and was not associated with a higher rate of reintubation.     

Detection of foot-and-mouth disease virus-infected cattle by assessment of antibody response in oropharyngeal fluids.

The detection of foot-and-mouth disease virus (FMDV)-persistent carriers among convalescent ruminants is of paramount importance in the aftermath of a field outbreak. To this purpose, FMDV-specific antibody should be investigated first, since virus isolation procedures from such carriers are seriously constrained. The complexity of the overall picture may be compounded by possible emergency vaccinations in the affected areas at the beginning of the outbreak. In this case, it is suggested that mucosal rather than serum antibody be investigated. In fact, we showed that FMDV-infected cattle regularly mount an antibody response in oropharyngeal fluids, in contrast to vaccinated cattle. Antibody could be revealed by neutralization assays and/or an immunoglobulin A (IgA)-specific kinetic enzyme-linked immunosorbent assay (ELISA). Cattle vaccinated once seldom showed a mucosal antibody response, which could be only detected by a total immunoglobulin-specific kinetic ELISA. Very few, if any, cattle showed a mucosal IgA response after repeated vaccinations. Our kinetic, IgA-specific ELISA generally allowed an early detection of FMDV-infected cattle; in particular, it proved to be more sensitive than the usual indirect, antigen-trapping ELISA in experiments on saliva samples.     

Asphyxia neonatorum

Various biochemical and structural changes affecting the newborn's wellbeing develop as a result of perinatal asphyxia. Central nervous system abnormalities are frequent complications with high mortality and morbidity. Cardiac compromise may lead to dysrhythmias and cardiogenic shock. Coagulopathy in the form of disseminated intravascular coagulation or massive pulmonary hemorrhage are potentially lethal complications. Necrotizing enterocolitis, acute renal failure, and endocrine problems affecting fluid electrolyte balance are likely to occur. Even the adrenal glands and pancreas are vulnerable to perinatal oxygen deprivation. The best form of management appears to be anticipation, early identification, and prevention of potential obstetrical-neonatal problems. Every effort should be made to carry out effective resuscitation measures on the depressed infant at the time of delivery.     

Inhibition of voltage-gated K channels in synaptosomes by sn-1,2-dioctanoylglycerol, an activator of protein kinase C

Tracer efflux studies were used to determine the effect of activation of protein kinase C on K channel function in rat brain synaptosomes. Hippocampal synaptosomes were treated with sn-1,2-dioctanoylglycerol (diC8), a synthetic diacylglycerol (DG) analog that activates protein kinase C. DiC8 inhibited depolarization-induced 86Rb efflux through voltage-gated K channels but did not affect the component of efflux corresponding to Ca-activated K channels. In time-course experiments, diC8 inhibited two components of 86Rb efflux: efflux through a rapidly inactivating, voltage-gated K channel (responsible for the "A" current) and that through a slowly inactivating, voltage-gated K channel (believed to be the "delayed rectifier"). Experiments with specific blockers of these voltage-gated K channels supported this observation. Inhibition of K-stimulated 86Rb efflux by diC8 was time dependent: at least 15 sec of preincubation was required before the effect could be observed. The effect of diC8 was concentration dependent: 50 microM diC8 produced a half-maximal inhibition of K-stimulated 86Rb efflux. The idea that the inhibition of synaptosome K channels by diC8 resulted from activation of C kinase was supported by pharmacological evidence. The action of diC8 was mimicked by 1-oleoyl-2-acetylglycerol, another DG analog that activates protein kinase C, but not by deoxy-diC8, a DG analog that does not activate C kinase. Inhibition of C kinase by sphingosine or H-7 prevented the diC8 effect. These studies demonstrate that synaptosomes are a good model in which to study modulation of mammalian CNS K channels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ultrastructural and replicative features of foot-and-mouth disease virus in persistently infected BHK-21 cells

Summary Persistent foot-and-mouth disease (FMD) virus infection in vitro has been studied in a chronically infected cloned BHK-21 cell line. Virus growth during serial cell passages was followed by infectivity assay and immunocytochemical staining. Only a small percentage of cells (0.006–6%) was found to harbour virus during persistence. Light and electron microscopy showed the presence of cytoplasmic protuberances (blebs) at the surface of persistently infected cells. The curing of cell cultures was achieved by passaging them in the presence of polyvalent immune serum. The absence of virus in cured cells was confirmed by infectivity assay and immunocytochemistry. This finding, together with the low percentage of infected cells in cultures confirms that persistently infected BHK-21 cells satisfy the definitions of a carrier culture. The characteristics of the in vitro system and its relevance to the study of FMD carrier state in vivo are discussed.     

Nonmyeloablative bone marrow transplantation: Infectious complications in 65 recipients of HLA-identical and mismatched transplants.

Infections are a common complication of allogeneic bone marrow transplantation and the leading cause of transplantation-related mortality. It had been hypothesized that transplantation following nonmyeloablative preparative regimens would result in fewer infections by causing less mucosal injury, less graft-versus-host disease, and allowing earlier immune reconstitution. We have retrospectively reviewed the infectious complications of 65 consecutive patients with advanced hematologic malignancies who underwent bone marrow transplantation using a novel preparative regimen consisting of cyclophosphamide, thymic irradiation, and in vivo T-cell depletion. Cytomegalovirus (CMV) infection occurred in 52% of cases in which the donor or recipient had evidence of prior CMV exposure. Using a strategy of preemptive therapy and secondary prophylaxis with ganciclovir, no CMV disease occurred. Infections with gram-positive bacteria predominated over the first 100 days after bone marrow transplantation. Thereafter, the relative proportion of gram-negative infections increased without a significant increase in episodes of neutropenia. The rate of bacterial infections was not influenced by relapse of the underlying malignancy. Seven patients developed infections with Aspergillus species, which was the most common infectious cause of death in these patients. Infections with viruses other than CMV (n=10) and with protozoan organisms (n=2) also occurred. The use of HLA-mismatched donors, the occurrence of grade II-IV acute graft-versus-host disease, and treatment with corticosteroids did not influence the risk of CMV or bacterial or fungal infections in patients who underwent transplantation following this preparative regimen. Overall, the incidence and spectrum of infections in this series was similar to the reported incidence of infections following conventional myeloablative allogeneic stem cell transplantation. We conclude that a quantitative T-cell deficiency in these extensively T-cell depleted patients may be a risk factor for infection, even in the absence of graft-versus-host disease.