Search PubMed⌕ Search

Biomedical subjects

M White

Publications and source records attributed to M White.

At least 235 records · Page 13Linked to original sources
PubMed1995

Plasma bactericidal/permeability-increasing protein concentrations in critically ill children with the sepsis syndrome.

Bactericidal/permeability-increasing protein (BPI) is a neutrophil azurophilic granule component that is bactericidal towards Gram-negative bacteria and inhibits lipopolysaccharide-mediated inflammatory responses. We conducted a prospective study to measure plasma BPI concentrations in 36 critically ill children with and without the sepsis syndrome. Plasma BPI concentrations ranged from 0.5 to 452 ng/ml. Patients with the sepsis syndrome had higher median plasma BPI concentrations than critically ill controls (5.1 vs. 1.8 ng/ml, P = 0.006). Patients with organ system failure had higher median plasma BPI concentrations than those with no organ system failure (4.5 vs. 1.3 ng/ml, P = 0.001). Plasma BPI concentrations were positively associated with pediatric risk of mortality score (P = 0.03, rs = 0.4). These data provide the first clinical insights regarding the role of endogenous BPI production in critically ill children and suggest that BPI may play an important role in host defenses.

Anti-Bacterial Agents↗
PubMed1995

Immunoreactivity and bioactivity of lipopolysaccharide-binding protein in normal and heat-inactivated sera.

The lipopolysaccharide (LPS)-potentiating effect of serum is due to LPS-binding protein (LBP), which facilitates the binding of LPS to CD14 receptors. We observed a remarkable heat sensitivity of recombinant LBP and various sera with respect to both immunoreactivity (measured by enzyme-linked immunosorbent assay) and bioactivity (potentiation of LPS induction of tumor necrosis factor in monocytes). Human sera were more active and more heat sensitive than fetal bovine sera. The commonly practiced heat inactivation of human serum (56 degrees C, 30 min) resulted in a 70% loss of bioactivity, which caused an apparent decrease in the potency of LPS.

Acute-Phase Proteins↗
PubMed1995

Compensatory alterations for insulin signal transduction and glucose transport in insulin-resistant diabetes.

Insulin binding activates the receptor tyrosine kinase toward the insulin receptor substrate-1 (IRS-1). Phosphorylated IRS-1 then interacts with the p85 alpha subunit of phosphatidylinositol 3-kinase (PI3K), Nck, growth factor receptor-bound protein 2 (GRB2), and Syp, thus branching insulin's signal for both mitogenic and metabolic responses. To determine whether the expression of these proteins is altered in insulin resistance, the levels of these proteins were compared in adipose and liver tissues of nondiabetic mice and obese insulin-resistant diabetic KKAy mice. IR and PI3K p85 alpha protein levels were significantly lower in KKAy mice than in control nondiabetic mice, whereas IRS-1 protein levels were not altered. In contrast, the protein levels of GRB2, Nck, Syp, and GLUT-1 were dramatically elevated in KKAy fat, with less striking changes in liver. Treatment of diabetic animals with pioglitazone, an insulin-sensitizing antihyperglycemic agent, partially corrected the expression of some of these proteins. Taken together, these findings suggest that the insulin-resistant diabetic condition is characterized by changes in expression of insulin signal transduction components that may be associated with altered glucose metabolism.

Adaptation, Physiological↗
PubMed1995

Development of public health training in Hungary--an exercise in international co-operation.

Following the fall of Communism, the countries of Central and Eastern Europe have been restructuring their health systems. Restructured medical education is vital to, and has been supported by, the European Union TEMPUS (Trans-European Mobility Scheme for University Studies) scheme. An example is a three-year project in Hungary to develop undergraduate and postgraduate medical education in public health. The project team (CNPHH) included representatives from all Hungarian medical schools and universities in Western Europe and Canada. The project involved assessing the needs of the Hungarian departments and developing a strategy involving transfer of skills in modern public health and educational methods, study visits and courses in Hungary and at Western universities, and capital funding. The project provides a model for others wishing to develop or restructure their education at national or local levels. This paper describes the methods used, outcomes achieved, and lessons learned.

Curriculum↗
PubMed1994

Health promotion priorities for general practice: constructing and using "indicative prevalences".

OBJECTIVE: To construct indicative prevalences for a range of diseases and risk markers and use them in planning health promotion interventions in primary health care. DESIGN: Indicative prevalences comprised point prevalence, incidence, and mortality measures. Use of data from Office of Population Censuses and Surveys, Northern Regional Health Authority, and Newcastle health and lifestyle survey 1991, and research papers to determine prevalence adjusted for age and sex in a hypothetical practice with a list of 10,000 patients. SETTING: Newcastle upon Tyne, England. RESULTS: Indicative prevalences were highest for common risk markers such as failure to achieve exercise targets (6871), moderate to extreme obesity (2785), and smoking (2689); moderate for overt disease such as angina (175) and stroke (20/year); and low for events such as suicide (1/year) and deaths from malignant melanoma (2/10 years). CONCLUSIONS: Given limited time and resources, brief interventions to reduce smoking and the systematic case finding and management of patients with hypertension, angina, and previous myocardial infarction are likely to be the highest priorities for health promotion in primary care.

Chronic Disease↗
PubMed1994

An IL-4 receptor region containing an insulin receptor motif is important for IL-4-mediated IRS-1 phosphorylation and cell growth.

Interleukin-4 (IL-4) treatment of 32D cells overexpressing insulin receptor substrate 1 (IRS-1) causes prompt tyrosine phosphorylation of IRS-1. Transfection of truncation mutants of the human IL-4 (huIL-4) receptor into 32D-IRS-1 cells demonstrated that the region from amino acid 437-557 is important for IL-4 signaling. This region of the IL-4 receptor (IL-4R) contains the motif 488PL-X4-NPXYXSXSD502 (insulin/IL-4R [I4R]) found in the insulin and insulin-like growth factor 1 receptors. Mutation of Y497 to F yielded receptors that caused little or no IRS-1 phosphorylation in response to huIL-4 when expressed in 32D-IRS-1 cells. Most cell lines expressing Y497F also failed to proliferate in response to huIL-4. Furthermore, a glutathione-S-transferase fusion protein containing the I4R motif-bound IRS-1, tyrosine kinase(s), and other unidentified phosphoproteins with molecular sizes of 140, 80, and 55 kd. Thus, the central tyrosine of the I4R motif has a major role in IL-4-mediated signal transduction in 32D cells.

Amino Acid Sequence↗
PubMed1994

Mycobacterium haemophilum: an emerging pathogen.

Mycobacterium haemophilum is emerging as a pathogen of immunocompromised patients particularly those with AIDS and organ transplants. Infection has also occurred in healthy children. Adults usually present with cutaneous manifestations, septic arthritis or occasionally pneumonia. Children have perihilar, cervical or submandibular adenitis. The organism grows on mycobacterial media supplemented with ferric ammonium citrate or hemin, incubated at 30 degrees C to 32 degrees C, two to three weeks after inoculation. The most active antimicrobial agents in vitro are amikacin, ciprofloxacin, clarithromycin, rifabutin and rifampin. Development of resistance to the rifamycins has been demonstrated after patients were treated for several months with several antimycobacterial agents, including the rifamycins. Treatment for several months with at least two agents demonstrated to have low MICs for the organism has been shown to be effective.

Animals↗
PubMed1994

Comparative hemodynamic effects of OPC-18790 and dobutamine in patients with advanced heart failure.

OPC-18790 (Otsuka America Pharmaceutical, Rockville, MD), a novel positive inotropic agent, produces titratable hemodynamic benefits in patients with advanced heart failure. In such patients, OPC-18790 has been shown to acutely increase the cardiac index, while reducing systemic vascular resistance and left ventricular filling pressure, without an associated increase in heart rate. This study was performed to compare the acute hemodynamic effects of OPC-18790 and the beta-adrenergic receptor agonist, dobutamine, in patients with advanced heart failure. OPC-18790 and dobutamine were compared on successive days in 13 patients with worsening New York Heart Association class III or IV heart failure. The mean (+/- SEM) left ventricular ejection fraction was 15 +/- 2% (range, 6-29%). Pretreatment hemodynamics were: heart rate, 96 +/- 2 beats/min; mean arterial pressure, 77 +/- 3 mmHg; cardiac index, 1.80 +/- 0.10 L/min/m2; pulmonary capillary wedge pressure, 27 +/- 1 mmHg; mean pulmonary arterial pressure, 41 +/- 2 mmHg; and systemic vascular resistance, 1,732 +/- 152 dynes.s/cm5. At infusion rates yielding comparable increases in the cardiac index (5 micrograms/kg/min for 2 hours for each drug), OPC-18790 produced significantly more favorable effects on heart rate (-2 +/- 3% vs 11 +/- 4%; P = .01), pulmonary capillary wedge pressure (-32 +/- 4% vs -17 +/- 8%; P = .04), mean pulmonary arterial pressure (-14 +/- 3% vs 6 +/- 11%; P = .06), stroke volume index (48 +/- 8% vs 29 +/- 7%; P = .02), stroke work index (70 +/- 11 vs 42% +/- 12%; P = .03), and rate pressure product (2 +/- 4% vs 14 +/- 4%; P = .05). The hemodynamic profile for OPC-18790 differs from dobutamine, with OPC-18790 exhibiting no increase in heart rate, greater preload reduction, and an increase in cardiac performance at a lower estimated metabolic cost.

Adrenergic beta-Antagonists↗
PubMed1994

Aging and cardiovascular responsiveness to beta-agonist in humans: role of changes in beta-receptor responses versus baroreflex activity.

OBJECTIVES: To assess age-related changes in the cardiac chronotropic and inotropic responses and arterial responses to beta-receptor stimulation and the potential role of the arterial baroreflex on these responses. METHODS AND RESULTS: Isoproterenol alone was infused in 14 young subjects (age, 30 +/- 2 years) and 15 older healthy volunteers (age, 60 +/- 2 years) and together with ganglionic blockade (trimethaphan) in eight young and eight older subjects. Isoproterenol was infused at 3 to 4 incremental rates. Cardiac function was assessed by echocardiography and peripheral arterial responses were measured by venous occlusion plethysmography. Before ganglionic blockade, isoproterenol at infusion rates from 0.005 to 0.03 micrograms/kg/min caused similar changes in heart rate, ejection fraction, and mean normalized systolic ejection rate in the young and older subjects. With concomitant use of trimethaphan, isoproterenol at infusion rates from 0.0025 to 0.01 micrograms/kg/min caused in young subjects a larger increase in heart rate (29 +/- 2 beats/min [young] versus 20 +/- 3 [older] at peak infusion; p = 0.03), ejection fraction (11% +/- 2% [young] versus 6% +/- 1% [older]; p < 0.01), and mean normalized systolic ejection rate (1.13 +/- 0.2 ml/sec [young] versus 0.48 +/- 0.09 [older]; p < 0.01). Whereas percentage changes in total peripheral resistance were larger in the young subjects, there were no significant age-related differences in the responses of forearm blood flow and resistance before or after ganglionic blockade. CONCLUSIONS: These results indicate an age-related decrease in beta-receptor responsiveness of both sinoatrial node and ventricular myocardium that is masked by a concomitant decrease in the baroreflex control of the heart.

Adult↗