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Biomedical subjects

N Edwards

Publications and source records attributed to N Edwards.

At least 37 records · Page 2Linked to original sources

Prevention of rejection in cardiac transplantation by blockade of the interleukin-2 receptor with a monoclonal antibody.

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.

Acute Disease↗

Increased CSF volumes are associated with diminished subjective responses to cocaine infusion.

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.

Adult↗

Nasal continuous positive airway pressure reduces sleep-induced blood pressure increments in preeclampsia.

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.

Adult↗

Behavioral and pharmacological treatment methods for pregnant smokers: issues for clinical practice.

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.

Adult↗

Intravenous immunoglobulin reduces anti-HLA alloreactivity and shortens waiting time to cardiac transplantation in highly sensitized left ventricular assist device recipients.

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.

Graft Rejection↗

Changing hospitals.

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Economics, Hospital↗

Emergency admissions. Over the threshold.

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.

Emergencies↗

Building community health nursing in the People's Republic of China: a partnership between schools of nursing in Ottawa, Canada, and Tianjin, China.

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.

China↗

Surgical management of the patient with an implanted cardiac device: implications of electromagnetic interference.

OBJECTIVE: To identify the sources of electromagnetic interference (EMI) that may alter the performance of implanted cardiac devices and develop strategies to minimize their effects on patient hemodynamic status. SUMMARY BACKGROUND DATA: Since the development of the sensing demand pacemaker, EMI in the clinical setting has concerned physicians treating patients with such devices. Implanted cardiovertor defibrillators (ICDs) and ventricular assist devices (VADs) can also be affected by EMI. METHODS: All known sources of interference to pacemakers, ICDs, and VADs were evaluated and preventative strategies were devised. RESULTS: All devices should be thoroughly evaluated before and after surgery to make sure that its function has not been permanently damaged or changed. If electrocautery is to be used, pacemakers should be placed in a triggered or asynchronous mode; ICDs should have arrhythmia detection suspended before surgery. If defibrillation is to be used, the current flow between the paddles should be kept as far away from and perpendicular to the lead system as possible. Both pacemakers and ICDs should be properly shielded if magnetic resonance imaging, positron emission tomography, or radiation therapy is to be used. The effect of EMI on VADs depends on the model. Magnetic resonance imaging adversely affects all VADs except the Abiomed VAD, and therefore its use should be avoided in this population of patients. CONCLUSIONS: The patient with an implanted cardiac device can safely undergo surgery as long as certain precautions are taken.

Clinical Protocols↗

Haemodynamic responses to obstructive sleep apnoeas in premenopausal women.

OBJECTIVES: Obstructive apnoeas during sleep are associated with marked cyclical blood pressure fluctuations in men with obstructive sleep apnoea (OSA). Haemodynamic responses to OSA in women are largely unknown. We aimed to investigate haemodynamics during apnoeic events in women with OSA and to assess the influence of the menstrual cycle on these responses. DESIGN AND METHODS: Full overnight polysomnography and continuous non-invasive blood pressure monitoring was performed in 13 women with OSA during follicular and luteal phases of the menstrual cycle. Change in blood pressure (deltaBP) from pre- to post-apnoea termination was measured for each apnoeic cycle. RESULTS: Only 10 of 13 subjects ovulated. In women who ovulated, pressor responses to apnoea termination occurred in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, but substantially increased during the luteal phase of ovulatory cycles [NREM change in mean arterial pressure (deltaMAP) 12 +/- 3 mmHg during the follicular phase and 20 +/- 3 mmHg during the luteal phase, P < 0.001; REM deltaMAP 11 +/- 3 mmHg during the follicular phase and 23 +/- 3 mmHg during the luteal phase, P < 0.001]. Sleep apnoea severity did not change during the cycle in NREM sleep, but was reduced in REM during the luteal phase. Changes in pressor responses were absent in non-ovulating subjects. CONCLUSIONS: Obstructive apnoeas in women were associated with marked blood pressure changes, similar to those previously reported in men. While respiratory events improved slightly in the luteal phase, blood pressure responses to these events increased by approximately 100%. Thus, the menstrual cycle has discordant effects on the respiratory and cardiovascular effects of OSA in women.

Adult↗

Changes in Canadian women's mammography rates since the implementation of mass screening programs.

OBJECTIVES: This study reports on Canadian mammography rates between 1990, when mass screening programs were launched, and 1994/95. METHODS: Mammography rates from 2 national surveys were compared according to the presence of a provincial screening program. RESULTS: Mammography rates among women aged 50 to 69 years (the targeted group) increased significantly, by 16%; increases were twice as high in provinces with screening programs. Among women in their 40s (nontargeted group), the changes were insignificant and independent of screening program status. CONCLUSIONS: Screening programs appear to have influenced the mammography rates of targeted women aged 50 to 69 years.

Adult↗

The incidence of T2-weighted MR imaging signal abnormalities in the brain of cocaine-dependent patients is age-related and region-specific.

BACKGROUND AND PURPOSE: Cocaine and its metabolites can produce vasospasm, and cocaine-dependent patients are at increased risk for stroke. Based on previous case reports, we hypothesized that the incidence of hyperintense brain lesions observed on T2-weighted MR images would also be increased in asymptomatic cocaine-dependent individuals. METHODS: Sixty-two male "crack" (smoked) cocaine-dependent participants ranging in age from 25 to 66 years were compared with 116 normal male control participants ranging in age from 25 to 80 years. Those with histories of neurologic symptoms or illnesses were excluded. The severity of hyperintense lesions was rated on a 0- to 3-point scale, and ratings of 3 were used in the data analysis as an indicator of a probable pathologic process. Three regions were separately rated: the cerebral white matter, insular subcortex white matter, and subcortical gray matter (basal ganglia and thalamus region). RESULTS: Significantly increased risk of severe lesions was observed in the two white matter regions of the cocaine-dependent group (odds ratio of 16.7 and 20.3) but not in the subcortial gray matter region (odds ratio of 1.4). In the insula subcortex white matter, the risk of lesions increased with age in the cocaine-dependant sample, but remained essentially absent among normal controls through the age of 80 years. In the cerebral white matter, the relationship of age and risk of lesion among normal participants was similar in shape to that in cocaine-dependent participants, but equivalent risk was seen 20 years earlier among cocaine-dependent participants. CONCLUSIONS: Cocaine-dependent participants had a significantly increased age-related risk of white matter damage. The possible clinical implications of this damage are discussed.

Adult↗