Biomedical subjects
Publications and source records attributed to M White.
Functional imaging may come to play an important role in the evaluation of CNS vasculitis by demonstrating pathology on the microcirculatory level. A positive finding of microvascular ischemia may assist in the diagnosis of CNS vasculitis. More importantly, the demonstration of normal microcirculation may reliably exclude CNS vasculitis.
BACKGROUND: The surgical approach to tetralogy of Fallot (TOF) continues to evolve and now many centers favor early repair for TOF. METHODS: Our experience includes 82 consecutive patients less than 1 year old with TOF (n = 74) and TOF with pulmonary atresia (n = 8) who were operated on between January 1992 and March 1998. Mean age at repair was 5.2 +/- 1.2 months and mean weight was 4.5 +/- 0.4 kg. Seven patients (anomalous left anterior descending artery [n = 1], pulmonary atresia with hypoplastic pulmonary arteries [n = 6]), underwent palliative procedures in the neonatal period followed by complete repair. Forty-nine patients (59%) were symptomatic (severe cyanosis or hypoxic spells), and 33 patients (41%) were asymptomatic. A combined transatrial-transpulmonary approach was employed in 28 patients (34%), and transannular patch or conduit for reconstruction of the right ventricular outflow tract (RVOT) was required in 54 patients (66%). The mean Nakata index was 160 +/- 25 mm2/m2. RESULTS: There were no hospital deaths. Mean post-repair peak right ventricular/systemic pressure ratio was 0.48 +/- 0.1. There were no late deaths or reoperations during a mean follow-up of 23 +/- 5 months. All patients are currently asymptomatic and in New York Heart Association class 1. Postoperative evaluation by two-dimensional and Doppler echocardiography or cardiac catheterization showed minimal pulmonary artery stenosis with a mean pressure gradient of 15 +/- 6 mm Hg across the RVOT. CONCLUSIONS: Our experience suggests that early repair of TOF can yield excellent results and initial palliation does not preclude early complete repair.
BACKGROUND: Reported cases of uterine rupture diagnosed by ultrasound have shown fetal membranes ballooning through uterine rupture sites, or adjacent areas of hemorrhage. CASE: A 27-year-old gravida 3, para 2 had open fetal surgery to repair a fetal myelomeningocele at 28 weeks' gestation. Her postoperative course was complicated by threatened preterm labor and anhydramnios. At 33 weeks' gestation, with maternal symptoms of bowel obstruction, ultrasound showed a fetal leg and section of umbilical cord protruding through the uterine wall. CONCLUSION: Even in the presence of anhydramnios, uterine wall rupture was identified, because ultrasound evaluation of the uterine wall showed prolapsed fetal parts and umbilical cord. Persistent anhydramnios after open fetal surgery should prompt a search for uterine rupture.
A complex interplay of inflammatory cells and chemical mediators is responsible for allergic inflammation. It is now understood that the allergic reaction consists of an early-phase response involving mast cell degranulation with the release of histamine and a late-phase response characterized by the migration of inflammatory cells. This review provides a summary of the early- and late-phase events associated with allergic inflammation and an overview of the principal chemical mediators involved in the inflammatory process.
An invitational meeting, entitled Complementary and Alternative Therapy: Decision Making by Cancer Patients and Their Physicians, brought together Canadian health care providers and researchers who had expertise in patient-physician communication with those who were knowledgeable about complementary therapy and cancer. The aim was to build on the existing knowledge base in both fields in order to determine the unanswered questions, the most important questions, and what methods can be applied for answering these questions. The interdisciplinary group employed a step-wise collaborative process to develop a suggested research agenda regarding decision making by physicians and their cancer patients regarding complementary therapy. The four themes identified are establishment of a registry for complementary therapy usage for cancer care; communication; outcomes measurement; and models of integration. It is hoped that these themes will be considered worthy of support by funding agencies and worthy of investigation by researchers.
Both aging and hypertension decrease the responsiveness of several receptor systems. The purpose of this study was to investigate the effect of aging versus hypertension on the blood pressure (BP), heart rate, and left ventricular (LV) responses to the alpha1-agonist phenylephrine in humans. Fourteen young (age, 21-40 years; range, 30+/-1 years; mean +/- SEM), and 18 older (age, 50-73 years; range, 60+/-1 years) healthy volunteers, as well as 10 young (age, 30-39 years; range, 36+/-1 years) and 15 older (age, 50- 64 years; range, 58+/-1 years) hypertensive subjects were studied. Phenylephrine was administered at four incremental rates for 8 min each. Cardiac responses were assessed by echocardiography. Phenylephrine caused twofold larger increases in systolic BP in young and older hypertensives and older normotensives, compared with young normotensives, but similar decreases in heart rate in all four groups. Younger normotensive subjects exhibited the largest decreases in stroke volume index, ejection fraction, and cardiac index in response to phenylephrine, despite similar increases in end-systolic stress for all groups. There is an age- and hypertension-related decrease in reflex vagal restraint in response to alpha1-adrenoceptor stimulation in humans, which leads to significant attenuation of the decrease in heart rate as well as in LV function in response to a pressor stimulus, and presumably therefore to enhanced systolic BP responses relative to young normotensive subjects.
BACKGROUND: Intravenous thymoglobuline (125 mg a day for 3 days, Institut Mérieux, France) has been used to induce immunosuppression following heart transplantation. Cyclosporine and prednisone, with and without azathioprine or mycophenolate mofetil were used as maintenance immunosuppression. OBJECTIVE: The objective of the study was to determine the clinical effect of antibody induction of immunosuppression following heart transplantation. METHODS: A retrospective analysis of the clinical experience at the Montreal Heart Institute. From 1988 to 1998, 163 patients were administered a 3-day course of intravenous thymoglobuline immediately following heart transplantation (Group 1). From 1983 to 1987 and during an isolated period in 1994, intravenous and oral cyclosporine was used immediately following heart transplantation in 48 patients (Group 2). Routine endomyocardial biopsies were performed in all patients and only moderate and severe rejection was treated. RESULTS: One, 5- and 10-year actuarial survival rate averaged 85%+/-3, 77%+/-4 and 67%+/-5 in Group 1 compared with 88%+/-5, 81%+/-6 and 76%+/-6 in Group 2 (p = 0.5). At 1 year, the freedom rate from an episode of acute rejection averaged 43%+/-4 in Group 1 and 30%+/-7 in Group 2 (p = 0.03) and the freedom rate from an episode of infection averaged 44%+/-4 in Group 1 and 31%+/-7 in Group 2 (p = 0.2). At 1, 5 and 10 years, the freedom rate from graft coronary artery disease averaged 93%+/-2, 68%+/-5 and 50%+/-7 in Group 1 compared with 93%+/-4, 58%+/-8 and 30%+/-8 in Group 2 (p = 0.1) and the freedom rate from cancer averaged 98%+/-1, 91%+/-3 and 67%+/-8 in Group 1 compared with 100%, 95%+/-3 and 77%+/-8 in Group 2 (p = 0.2). There was no side-effect related to the systemic injection of thymoglobuline. CONCLUSION: In a cyclosporine based protocol of immunosuppression, induction with an initial 3-day course of intravenous thymoglobuline is associated with a lower rate of acute rejection. Moreover, the risk of infection and of developing cancer is not increased whereas there was a trend towards a lower incidence of coronary atherosclerosis 5 and 10 years after transplantation.
PURPOSE: We previously demonstrated that aneuploidy-free oocytes may be preselected by testing the first and second polar bodies removed from oocytes following their maturation and fertilization. The present paper describes the results of the application of the method in 659 in vitro fertilization cycles from patients of advanced maternal age. METHODS: Using micromanipulation techniques, 3943 oocytes were tested by polar body sampling and fluorescent on situ hybridization analysis using specific probes for chromosomes 13, 18, and 21. RESULTS: Fluorescent in situ hybridization results were available for 3217 (81.6%) of 3943 oocytes studied, of which 1388 (43.1%) had aneuploidies; 35.7% of the aneuploidies were of first meiotic division origin, and 26.1% of second meiotic division origin. Most errors in the first meiotic division were represented by chromatid malsegregation. The transfer of embryos deriving from 1558 of 1829 aneuploidy-free oocytes in 614 treatment cycles resulted in 131 clinical pregnancies and 88 healthy children born after confirmation of the polar body diagnosis. CONCLUSIONS: Polar body testing of oocytes provides an accurate and reliable approach for prevention of age-related aneuploidies in in vitro fertilization patients of advanced maternal age.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
AIMS: To assess whether four proxy measures of abdominal obesity (waist circumference; waist-to-hip ratio (WHR); waist-to-height ratio and C index, a measure of body shape) were uniformly associated with features of the metabolic syndrome (triglycerides, high density lipoprotein (HDL) cholesterol, 2-h glucose) in three ethnic groups. METHODS: Anthropometric and biochemical data were collected in 629 Europeans (320 men, 309 women), 380 Chinese (183 men, 197 women) and 597 South Asians (275 men, 322 women) aged 25-64 years in Newcastle upon Tyne, UK. Linear regression models were used to determine whether relationships differed between ethnic groups. RESULTS: Linear regression analysis showed that most proxy measures of abdominal obesity were associated with features of the metabolic syndrome. There were significant interactions between WHR and ethnicity and C index and ethnicity in the relationship with log triglycerides when comparing European and Chinese women. Interactions existed between all proxy measures and ethnicity in the relationship with log triglycerides and HDL cholesterol when comparing European and South Asian women. In men, interactions between ethnicity and waist circumference, WHR and C index when comparing Europeans and South Asians, and between ethnicity and WHR and C index when comparing South Asian and Chinese for log 2-h glucose were significant (P < 0.001). All interactions remained significant when differences in smoking, alcohol and physical activity were taken into account. CONCLUSIONS: Not all the proxy measures of abdominal obesity were consistently related to features of the metabolic syndrome across the ethnic groups studied. However, waist circumference and waist to height ratio were the most consistent and WHR the least when comparing across the ethnic groups.
BACKGROUND: Rejection is the most significant problem in the field of transplantation. The current goal of transplant immunology is to develop better immunotherapeutic protocols that are aimed at specifically suppressing alloreactivity and preserving an otherwise intact immune system. We have previously shown that mice will accept renal allografts indefinitely with normal renal function after two injections of a monoclonal antibody to the CD45RB protein. Furthermore, this antibody will reverse acute rejection when therapy is delayed until day 4 and will still induce tolerance. The mechanisms of this therapeutic benefit are not known. METHODS: BALB/C mice were used as recipients of major multiple histocompatibility complex-mismatched kidneys using C57BL/6 as donors. Immunoperoxidase microscopy and Northern blots for cytokine gene expression were used to study the renal allografts. Fluorescence-activated cell sorter (FACS) analyses of peripheral blood lymphocytes were performed. Phosphotyrosine peptide phosphatase assays were performed on splenic lymphocyte membranes. RESULTS: A CD45RB monoclonal antibody (MB23G2) induced tolerance and partially depletes peripheral blood lymphocytes. A therapeutically ineffective CD45RB monoclonal antibody (MB4B4) merely coated the circulating lymphocytes. Furthermore, MB23G2 stimulated more tyrosine phosphatase activity than MB4B4 in mouse T-cell membranes. CONCLUSIONS: The clearance of peripheral blood lymphocyte populations and stimulation of protein tyrosine phosphatase activity may be important in the mechanism of tolerance induction by CD45RB therapy, which may be clinically relevant in the therapy of organ rejection in humans.
The records of 239 immunosuppressed patients receiving amphotericin B for suspected or proven aspergillosis were reviewed to determine rates of nephrotoxicity, dialysis, and fatality. The mean and median durations of treatment were 20.4 and 15.0 days, respectively. The creatinine level doubled in 53% of patients and exceeded 2.5 mg/dL in 29%; 14.5% underwent dialysis; and 60% died. A multivariate Cox proportional hazards analysis showed that patients whose creatinine level exceeded 2.5 mg/dL (hazard ratio [HR], 42.02; P<.001), allogeneic bone marrow transplantation (BMT) patients (HR, 6.34; P<. 001), and autologous BMT patients (HR, 5.06; P=.024) were at greatest risk for requiring hemodialysis. Use of hemodialysis (HR, 3. 089; P<.001), duration of amphotericin B use (HR, 1.03 per day; P=. 015), and use of nephrotoxic agents (HR, 1.96; P=.017) were associated with greater risk of death, whereas patients undergoing solid organ transplantation were at lowest risk (HR, 0.46; P=.002). These data indicate that elevated creatinine levels during amphotericin B treatment are associated with a substantial risk for hemodialysis and a higher mortality rate, but the risks vary in different patient groups.
Plasma endotoxin and lipopolysaccharide-binding protein (LBP) levels were measured in a group of 253 patients at the onset of severe sepsis and/or septic shock. Endotoxin levels were significantly greater than control levels (n=33; mean +/- SD, 5.1+/-7.3 pg/mL) in 78.3% of patients. Median endotoxin levels in patients with sepsis were 300 pg/mL (25%-75% interquartile range, 110-726 pg/mL). LBP levels were elevated in 97% of patients compared with normal control values of 4.1+/-1.65 microgram/mL. Median LBP levels in patients with sepsis were 31.2 microgram/mL (interquartile range, 22.5-47.7 microgram/mL). Median endotoxin levels at study entry were more highly elevated (515 vs. 230 pg/mL; P<.01), and LBP levels were less highly elevated (28.0 vs. 33.2 microgram/mL; P<.05) in nonsurvivors than survivors over the 28-day study period. No correlation was found between endotoxin and LBP levels. The quantitative level of both endotoxin and LBP may have prognostic significance in patients with severe sepsis.
Cell therapy-use of cells to deliver active factors-is an emerging technique in treatment of neurodegenerative disease. Successful devices maintain cell viability and functionality over extended implant periods. Use of dividing cell lines to deliver therapeutic factors has been studied extensively. One emerging issue is the tendency of cells to continue proliferation within the intracapsular environment-potentially outstripping nutrient supply. This work presents a method of controlling proliferation and delivering therapeutic molecules within a dose range. The method entails encapsulation into a hollow fiber device of discrete numbers of cell-containing microcarriers. Proliferation control is attained by embedding cell-containing microcarriers in nonmitogenic hydrogels. PC-12 cells secreting L-dopa and dopamine was the model cell line tested. Feasibility of the method in controlling growth of normally rapidly dividing cells in the intracapsular environment was demonstrated in vitro and in vivo. Control nonmicrocarrier PC-12 cell devices had approximately fourfold greater expansion in cell number compared to experimental microcarrier-containing devices over 4 weeks in vitro and in vivo after implant into rat striatum. Ability to control dose released over a several-fold range was demonstrated with encapsulated PC-12 cells delivering neurotransmitters and C2C12 mouse myoblast cells delivering neurotrophic factors (CNTF).
Auditory evoked potentials (AEP) were used to monitor central nervous system effects during induction and recovery from anaesthesia produced by infusion of propofol 30 mg kg-1 h-1 in 22 healthy male patients. Non-parametric and parametric modelling techniques were used successfully to calculate the parameter keo which linked pharmacokinetic with pharmacodynamic aspects of drug action in only 15 of the study patients. In the non-parametric analysis, keo was found to have a mean value of 0.2 (range 0.1-0.36) min-1. Estimation of keo allowed calculation of the effect-site concentration (Ce50) associated with 50% of AEP effect for the population (2.08 micrograms ml-1; 95% confidence limits 1.7-2.45). There were no significant differences between keo values calculated by non-parametric and individual parametric modelling techniques. During recovery, 50% of patients demonstrated evidence of waking at an effect-site concentration of 2.28 micrograms ml-1.
BACKGROUND: Despite frequent calls to improve undergraduate medical public health teaching, little is known about whether curricula have changed. We report a survey of undergraduate public health teaching in UK medical schools in 1996. The survey aimed to assess whether the General Medical Council's 1993 recommendations to strengthen undergraduate medical education in public health have been implemented. METHODS: We asked heads of academic departments of public health at all 26 UK medical schools to complete a questionnaire and provide supporting documentation for each undergraduate public health course or module. We compared results from the 1996 survey with those from a similar survey in 1992. RESULTS: Twenty-one out of 26 (81 per cent) medical schools responded. All responding medical schools included public health teaching within their curriculum. The median number of public health courses per medical school was unchanged since 1992. A wide variety of topics were taught. Core public health subjects were taught at most schools, though over a quarter of medical schools did not cover some core topics. Between 1992 and 1996 the proportion of time devoted to teaching by lectures decreased, whereas the following all increased: teaching by small group methods; the proportion of courses using methods of assessment encouraging active learning; and the contribution of public health courses to the final degree assessment. CONCLUSION: The findings suggest that many of the General Medical Council's recommendations for improving the delivery of undergraduate education are being addressed by public health teaching in UK medical schools. However, addressing the gaps in undergraduate public health teaching revealed in this survey is a continuing challenge for academic public health departments. Medical schools should review the content of their undergraduate public health teaching to ensure that tomorrow's doctors are adequately equipped with public health knowledge and skills.
Bullous congenital ichthyosiform erythroderma (BCIE) is a dominantly inherited keratinizing disorder characterized by erythroderma and blistering in neonates and generalized epidermolytic hyperkeratosis (EH) in adulthood. Previously, it has been shown that BCIE can be caused by mutations in either of the genes encoding K1 or K10, the keratins predominantly expressed in suprabasal layers of the epidermis. Using direct sequencing of genomic PCR fragments, we have analyzed 4 British families with BCIE, all of whom were found to carry mutations in K10. In 1 family, the affected person was found to have an unusual dinucleotide transversion mutation, 2138CC-->AA, causing two amino acid substitutions, D155E and R156S, also in the 1A domain of the K10 polypeptide. In 2 further kindreds, the previously reported "hotspot" mutations 2139C-->T and 2140G-->A were found. These mutations predict amino acid substitutions in the helix 1A domain of K10, designated R156C and R156H respectively. The proband in the fourth family was found to carry a novel mutation 4724T-->C, predicting the amino acid change L452P in the helix 2B domain of K10. All mutations were confirmed in the affected persons and were excluded from a population of 50 normal, unrelated individuals by restriction enzyme analysis. The location of these mutations in the highly conserved helix boundary motif sequences of K10 are consistent with previously reported dominant negative mutations in K10 and other keratins. Despite the unusual nature of two of these mutations, in particular the double missense mutation, the phenotypes of the affected individuals in these 4 families were entirely typical of BCIE.