Public health must make best use of leadership resources.
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Biomedical subjects
Publications and source records attributed to N Edwards.
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STUDY OBJECTIVES: Pre-eclampsia is currently the predominant cause of maternal and fetal morbidity and mortality. Diurnal blood pressure variation is flattened or reversed in pre-eclampsia; however, sleep has not been extensively investigated in this disease. Our objective was therefore to study sleep architecture in this group of patients. STUDY DESIGN: Full polysomnography using the Compumedics Sleepwatch System or Compumedics p-series. SETTING: NA. PATIENTS: 25 pre-eclamptic patients and 17 primigravidas with normal pregnancies and no history of cardiovascular disease or sleep disorder. With the exception of one subject, all pre-eclamptics were taking clonidine (a known suppressant of rapid eye movement-REM-sleep) for control of their hypertension. INTERVENTIONS: NA. RESULTS: Pre-eclamptic subjects had markedly altered sleep architecture, with a markedly increased percentage of time spent in slow-wave sleep (SWS) (21 * 2% versus 43 * 3%, p<0.001). There was a longer latency to rapid eye movement (REM) sleep (92 * 11 mins vs. 205 * 23 mins in control and pre-eclamptic subjects, respectively, p<0.001) and reduced time spent in REM (18 * 1% and 10 * 2% in control and pre-eclamptic subjects, respectively, p<0.001). CONCLUSIONS: While the increased REM latency and decreased REM time are most likely due to clonidine, this is unlikely to also account for the increased SWS. Two possible explanations for this include cerebral edema and release of cytokines, which are known to alter sleep structure.
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The study evaluated the relationship between age and frontal and temporal lobe volumes in young cohorts of cocaine-dependent (CD), amphetamine-dependent (Am), and normal control subjects. Ten CD, nine Am, and 16 age- and gender-matched control subjects underwent magnetic resonance imaging (MRI). The volume of the frontal and temporal lobes was measured from an identically positioned slab of seven contiguous 3-mm-thick coronal images. Follow-up measures of the gray and white matter subcomponents of these volumes were also obtained. Both CD and Am groups had a significantly smaller temporal lobe volumes, but only the CD group demonstrated a significantly greater decline in temporal lobe volume with age (intracranial volume, education, and race were controlled for in all statistical analyses). Segmenting the brain regions into gray and white matter revealed that the negative correlation between age and temporal lobe volume of CD patients was mostly due to a significant age-related decline in the gray matter subcomponent. Negative trends between age and gray matter volumes were also observed in the Am and normal groups. In the frontal lobes, age was negatively correlated with gray matter volume in the control, CD, and Am groups. Unlike the consistent decreases in gray matter volumes, white matter showed non-significant increases in volume with age. The data suggest that CD patients may have an accelerated age-related decline in temporal lobe gray matter volume and a smaller temporal lobe volume compared to normal controls. In the frontal lobe, age-related gray matter volume reductions occur in all three groups. These age-related cortical gray matter volume reductions may be a biological marker for the risk of addictive behavior, which also decreases with age.
BACKGROUND: Alloantigen-activated T cells express the high-affinity interleukin-2 receptor. Specific blockade of this receptor with the human IgG1 monoclonal antibody daclizumab may prevent rejection of allografts after cardiac transplantation without inducing global immunosuppression. METHODS: We randomly assigned 55 nonsensitized patients undergoing a first cardiac transplantation to receive either induction therapy with daclizumab (1.0 mg per kilogram of body weight), given intravenously within 24 hours after cardiac-transplantation surgery and every two weeks thereafter, for a total of five doses, or generalized immunosuppressive therapy. Concomitant immunosuppression was achieved in both groups with cyclosporine, mycophenolate mofetil, and prednisone. The primary end points were the incidence and severity of acute rejection, and the length of time to a first episode of biopsy-confirmed rejection. RESULTS: Of the 55 patients in the study, 28 were randomly assigned to receive daclizumab and 27 served as the control group. During induction therapy, the mean frequency of acute rejection episodes (defined as a histologic grade of 2 or higher according to the classification of the International Society of Heart and Lung Transplants) was 0.64 per patient in the control group and 0.19 per patient in the daclizumab group (P=0.02). Acute rejection developed in 17 of 27 patients in the control group (63 percent), as compared with 5 of 28 patients in the daclizumab group (18 percent; relative risk, 2.8; 95 percent confidence interval, 1.1 to 7.4; P=0.04). Throughout follow-up, there were nine patients with episodes of acute rejection of histologic grade 3 in the control group, as compared with two in the daclizumab group (P= 0.03), and the time to a first episode of rejection was significantly longer in the daclizumab group (P=0.04). There were no adverse reactions to daclizumab and no significant differences between the groups in the incidence of infection or cancer during follow-up. CONCLUSIONS: Induction therapy with daclizumab safely reduces the frequency and severity of cardiac-allograft rejection during the induction period.
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We evaluated the hypothesis that ventricular and cortical CSF volume increases are associated with reductions in the magnitude of euphoric effects produced by intravenous IV cocaine infusion in cocaine dependent (CD) individuals. Eleven CD patients participating in a cocaine-infusion study and eleven control subjects underwent magnetic resonance imaging (MRI). Two CSF regions of interest (lateral ventricles and frontal cortex CSF) and two comparison regions (third ventricle and posterior cortex CSF) were measured. Self-reported ratings of the intensity of euphoric response ("high") were obtained from the CD subjects at 3, 10, and 30 minutes after IV administration of cocaine. A significant negative correlation was observed between the volume of the lateral ventricles and subjective ratings of the "high" experienced at 3 minutes, but not at 10 and 30 minutes after cocaine infusion. In contrast, a significant negative correlation between frontal cortex CSF volume and the intensity of euphoric response was observed at 30 minutes after IV cocaine. No significant associations were observed between the volumes of the two comparison regions and any subjective ratings of "high." No significant volume differences were observed between the CD and control groups in any region. The results suggest larger lateral ventricular volumes are associated with a decrease in immediate euphoria while larger frontal cortex CSF volumes are associated with a decrease in the duration of the euphoria induced by cocaine infusion. The age-related brain volume reductions underlying the volume increase in these two CSF spaces may be the neurobiological basis of the age-related reduction in the rates of addiction.
Preeclampsia is the predominant cause of admissions to neonatal intensive care. The diurnal blood pressure pattern is flattened or reversed in preeclampsia. We hypothesized that snoring and partial upper airway obstruction contribute to nocturnal rises in blood pressure. We tested this hypothesis by controlling sleep- induced upper airway flow limitation and snoring with nasal positive pressure. Eleven women with preeclampsia underwent two consecutive polygraphic sleep studies with simultaneous beat-to-beat blood pressure monitoring. Average blood pressure for the night overall and in each sleep stage was calculated. Sleep architecture was similar on the two study nights. Sleep-induced partial upper airway flow limitation occurred in all patients in the initial study. Autosetting nasal continuous positive airway pressure (CPAP) applied at a mean maximal pressure of 6 +/- 1 cm H(2)O eliminated flow limitation throughout sleep on the treatment night. Blood pressure was markedly reduced on the treatment night [(128 +/- 3)/(73 +/- 3)] when compared with the initial nontreatment study night [(146 +/- 6)/(92 +/- 4)], p = (0.007)/(0.002). We conclude that partial upper airway obstruction during sleep in women with preeclampsia is associated with increments in blood pressure, which can be eliminated with the use of nasal CPAP.
Active and passive exposure to tobacco smoke are the most serious and preventable causes of poor maternal, fetal, and infant outcomes in the United States. Unfortunately, the majority of pregnant smokers do not quit smoking before or during pregnancy or after childbirth. We describe a standardized behavioral counseling model and discuss issues to consider in recommending the use of pharmacotherapy during pregnancy. Although the Food and Drug Administration no longer classifies nicotine replacement therapy (NRT) as contraindicated during pregnancy, precautions should be carefully considered for use in this population. This paper provides a synopsis of the risks of exposure to tobacco smoke during pregnancy and the postpartum; estimates the population at risk and the potential for increased cessation if effective health education methods during pregnancy were routinely provided; presents a meta-analysis of "best practice" patient education methods for pregnant smokers; and estimates the number of pregnant heavy smokers who might be eligible for NRT. We suggest five issues for the physician to consider before recommending NRT medications to pregnant patients who are heavy smokers. The judicious use of NRT medications may significantly reduce harm to the infants of heavy smokers. More evidence derived from large population-based research, however, is needed to provide guidance to the physician about NRT eligibility, dose, scheduling, and effectiveness in clinical practice.
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BACKGROUND: Recipients of left ventricular assist devices (LVADs) develop prominent B-cell hyperreactivity. We investigated the influence of anti-HLA antibodies on waiting time to cardiac transplantation in LVAD recipients and compared the effects of 2 immunomodulatory regimens on anti-HLA serum reactivity. METHODS AND RESULTS: Fifty-five previously nonsensitized LVAD recipients of a TCI device implanted between 1990 and 1996 were studied. Patients with anti-HLA antibodies received monthly courses of either intravenous immunoglobulin (IVIg) or plasmapheresis, in conjunction with cyclophosphamide. The effects of these regimens on anti-HLA alloreactivity and waiting time to transplantation were then determined by Kaplan-Meier log-rank statistics, nonparametric Wilcoxon rank-sum test, and Student's t test. Prolongation in transplant waiting time was related to serum IgG anti-HLA class I alloreactivity. Infusion of IVIg (2 g/kg) caused a mean reduction of 33% in anti-HLA class I alloreactivity within 1 week. Waiting time to transplantation was significantly reduced by IVIg therapy and subsequently approximated that in nonsensitized patients. Side effects of IVIg (2 g/kg) were minimal and related primarily to immune complex disease. Although plasmapheresis caused a similar reduction in alloreactivity to IVIg, this effect was achieved after longer treatment. Moreover, plasmapheresis was associated with an unacceptably high frequency of infectious complications. In patients resistant to low-dose (2 g/kg) IVIg therapy, high-dose (3 g/kg) IVIg was effective in reducing alloreactivity but was associated with a high incidence of reversible renal insufficiency. CONCLUSIONS: These results indicate that IVIg is an effective and safe modality for sensitized recipients awaiting cardiac transplantation, reducing serum anti-HLA alloreactivity and shortening the duration to transplantation. The therapeutic and safety profile of IVIg would appear to be superior to plasmapheresis.
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Analysis of emergency admissions to six hospitals over three weeks in winter found marked differences in the severity of cases. Some admissions could have been avoided if more investigations had been available on an outpatient basis. Where community services are easily accessible and available seven days a week, those admitted to hospital are likely to be more severely ill. British guidelines are needed on medical admissions.
Community health nursing in China is an emerging specialty. A multi-component collaborative endeavor between the Schools of Nursing of Tianjin Medical University, China, and the University of Ottawa, Canada is described. This project, funded by the Canadian International Development Agency, commenced in 1989. It has laid the groundwork for an expanded role for community health nurses in Tianjin, a municipality of 11 million people located in Northeast China. The historical context for the evolution of community health nursing in China and the emergence of community health nursing as a priority area within the project are described. Major project activities are highlighted, illustrating several underlying principles for strengthening the educational preparation of baccalaureate nurses who can apply community health skills. These include creating a critical mass of faculty who can teach community health nursing, modelling classroom and clinical teaching of community health nursing, bridging the gap between nursing in the community and nursing, in the hospital, and developing a prototype for baccalaureate community health nursing experience. Lessons learned from this initiative are summarized.