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Biomedical subjects

C Brown

Publications and source records attributed to C Brown.

At least 379 records · Page 21Linked to original sources

Modulating influence of dietary lipid intake on the prostaglandin system in adult men.

We evaluated the effect of moderate dietary changes on the prostaglandin system by measuring the urinary excretion of 7 alpha-hydroxy-5,11-dioxo-tetranorprostane-1,16-dioic acid (PGE-M). In a crossover design, twenty-four free-living male subjects in good health (24 to 54 years of age) were fed two diets: (i) Regular (R) diet, 41% energy (en%) from fat, P/S 0.59, M/S 0.96; (ii) Experimental (E) diet, 19 en% from fat, P/S 1.31, M/S 1.48. Diet R contained 13.9 g/day of neutral detergent fiber (NDF) and about 600 mg/day of cholesterol per 3200 kcal; Diet E contained 35.5 g/day NDF and about 280 mg/day cholesterol. Each controlled-diet period lasted ten weeks. The menu cycle was 7 days, and all diets were calculated to provide adequate amounts of essential nutrients. The PGE-M excretion rates were determined in 24-hr urine by stable-isotope dilution gas chromatography-mass spectrometry in the selected ion-monitoring mode. Low-fat Diet E, with an intake of 6.6 en% from polyunsaturates, was associated with an average 14.2% reduction in PGE-M daily output, compared to high-fat Diet R with a 9.3 en% from polyunsaturates (P = 0.046). These results support the view that dietary lipid changes can significantly alter the in vivo production of E-series prostaglandins. We cannot conclude, however, if this apparent diet effect was brought about by the change in linoleate intake alone or was the result of complex biochemical interactions among individual fatty acids, both saturated and unsaturated.

Adult↗

Mechanistic investigation of species-specific thyroid lesions induced by treatment with the histamine H1 antagonist temelastine (SK&F 93944) in rats.

Temelastine (SK&F 93944), an H1 histamine receptor antagonist, induces thyroid histopathological lesions in the rat, indicative of thyroid follicular cell stimulation, at oral doses of 10-33 mg/kg body weight/day. These changes do not occur in the dog or mouse. Endocrinological short-term studies support an increased thyroid follicular activity (increased radioiodide accumulation) with decreased circulating thyroxine (T4) at oral doses at or above 300 mg/kg body weight/day and increased circulating thyroid stimulating hormone (TSH). This is thought to be responsible for the thyroid follicular stimulation following Temelastine treatment. No direct inhibition of thyroid function occurs. Temelastine produces these species-specific changes by enhancing thyroxine clearance from the circulation in the rat, but not in the dog or mouse. In vitro studies with cultured rat hepatocytes suggest that the mechanism behind these changes is a drug-induced increase of hepatocellular T4 binding and uptake which leads to an enhanced metabolic clearance of the hormone.

Animals↗

The prevalence of orthodontic extractions.

The controversy regarding extractions for orthodontic treatment continues and today is invoked by some as a feature of the "standard of care." For this and other reasons, it is necessary to have contemporary data on the general prevalence of orthodontic extractions and the interpractice range of extraction rates in current specialty practice and, if possible, also to establish possible reasons for, and consequences of, the extraction versus nonextraction decision. Although all treatment decisions are made on a case-by-case basis, practitioners appear to have personal preferences for or against extractions and hence adopt policies with different degrees of aversion to or bias toward extraction therapy. A number of factors enter into the extraction decision. These include features of the malocclusion, objectives of treatment, and the technique selected to accomplish desired results. The present study does not address such issues but merely serves to provide epidemiologic data to estimate extraction frequency in contemporary orthodontic practice. Accordingly, a telephone survey of all licensed orthodontists in Michigan was conducted to determine their subjective estimates of extraction rates for patients in their practices. There were 238 respondents, for a response rate of 90.2%. Reported rates range from 5% to 87%. We then selected five practices from the extremes of the reported extraction rates. Three practices from the high end and two from the low end were included for an examination of patient records. Records of a total of 438 patient whose treatment had been completed were reviewed. The actual extraction rates for these practices ranged from 25% to 85%, which differed considerably from the clinicians' subjective estimates.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation Studies as Topic↗

Hematopoietic activity of granulocyte/macrophage colony-stimulating factor is dependent upon two distinct regions of the molecule: functional analysis based upon the activities of interspecies hybrid growth factors.

Granulocyte/macrophage colony-stimulating factor (GM-CSF) is an acidic glycoprotein that stimulates hematopoiesis in vitro and in vivo. Despite a high degree of sequence homology, the GM-CSFs from human and murine sources fail to crossreact in their respective colony-forming assays. On the basis of this finding, a series of hybrid molecules containing various proportions of human- and murine-specific amino acid sequences were generated by recombinant DNA techniques and assayed for species-specific activity against human and murine marrow target cells. Two regions of GM-CSF, residues 38-48 and residues 95-111, were found to be critical for hematopoietic function. These regions are structurally characterized by an amphiphilic helix and by a disulfide-bonded loop, respectively, and are homologous in position in the human and murine growth factors. In addition, competition assays suggested that, together, these regions bind to the GM-CSF receptor.

Animals↗

Staff perceptions of shared governance.

Future research must consider a number of potential influencing variables, focus on before and after comparisons and comparisons among types of shared governance models, and include replications and longitudinal studies. In addition, qualitative, descriptive data regarding the life of the organization will be beneficial in interpreting the more quantitative findings. The ideal of controlling all variables is simply not possible when one is studying a complex organization. With ingenuity, creativity, and a blend of methodologies, however, researchers may come considerably closer to understanding more about how and why shared governance can work effectively.

Adult↗

Platelet specific alloantigens on the platelet glycoprotein Ia/IIa complex.

The majority of platelet alloantigens are located on platelet glycoproteins IIb/IIIa. This report describes a codominant allelic system carried on the glycoprotein Ia/IIa complex, which we originally designated as Zava/Zavb but which is identical to the Bra/Brb system. Furthermore Zava was found to be identical to Hca. The alloantigens could not be detected using a direct binding enzyme immunoassay (EIA) with intact platelets, but were readily detected using a glycoprotein capture EIA and by radioimmunoprecipitation techniques. The two index cases (designated as homozygous Zava and Zavb) had alloantibodies against the corresponding antigen and did not react with their own platelets. Using these alloantibodies and a monoclonal antibody that reacts with the platelet glycoprotein Ia/IIa complex (12F1), we demonstrated that all Ia/IIa molecules carry either Zava or Zavb and we found that Zava and Zavb are on discrete populations of Ia/IIa. Following immunodepletion using either anti-Zava or anti-Zavb, all detectable Ia/IIa complexes from the respective homozygous platelets were removed. Immunodepletion of heterozygous Zava/Zavb with either anti-Zava or anti-Zavb did not reduce the amount of Ia/IIa complexes precipitable using the alternate alloantiserum. Population studies (n = 50) indicated the phenotypic frequency of Zava/Zava is less than 1%; Zava/Zavb is 18% and Zavb/Zavb is 82%. Four different alloantisera that had either anti-Zava or anti-Zavb reactivity also carried reactivity against the Baka or Bakb antigens which may suggest an association in the immune response to these alleles.

Adult↗

Evaluating labour ward services: the art of the possible.

Midwives have contended that midwifery and obstetric workloads could not be measured and that only a 1:1 ratio of mother to midwife should occur, at least in the labour ward environment. This would appear to be true if traditional hospital statistics are used. However, this project set out to measure workload and staffing requirements. Using clinically based process and outcome criteria, dependency classification enabled daily, weekly and monthly workload and patterns of workload to be studied. Contrary to widely held beliefs it was demonstrated that mothers could be classified according to levels of need which form consistent patterns of distribution. A mean average of the total time spent on the labour wards by mothers was calculated for each level of need using 11 months' data. This produced a positive correlation with the dependency classification. Dependency classification and total time spent on the labour wards provides a mechanism for measuring workloads. To enable economic use of resources, a level of dependency for which a 1:1 ratio of staff:mother is considered essential has to be agreed. To assist with this decision two surveys designed to collect information concerning the percentage of the mothers' time spent in contact with the nursing/midwifery staff was conducted. The results were remarkably similar and again demonstrated a positive correlation with dependency classification. It was recognized that midwifery is a chronically understaffed service and that midwives working within the service felt unable to give the care they considered a woman in labour deserves.(ABSTRACT TRUNCATED AT 250 WORDS)

England↗

[Tolerance and safety of the use of perindopril].

Angiotensin-converting enzyme inhibitors (ACEI) constitute an effective and well tolerated class of drugs for the treatment of arterial hypertension. Yet they have been blamed for the occurrence of side-effects the most frequently reported of which are renal function impairment, hypotension and cough. For this reason, the renal function of hypertensive patients has been evaluated after short - and long - term treatment with perindopril. In patients with normal renal function on short-term treatment (1 and 5 days) perindopril produced an increase of renal plasma flow without change in glomerular filtration. In long-term treatment (up to 18 months), no significant change in plasma creatinine level was observed. In old age hypertensive patients or in patients with chronic renal failure glomerular filtration was also preserved, apart from rare cases of creatinine clearance reduction, notably after addition of hydrochlorothiazide. A very slight and clinically not significant rise of kaliemia was noted when perindopril was used as single-drug treatment. Cases of symptomatic hypotension were rare (0.2 p. 100), even in situations of water and salt depletion. Among the other side-effects of ACEI, cough, which has more recently been described, has carefully been looked for. Its incidence has been determined in a double-blind trial comparing perindopril (1.2 p. 100) with captopril (2.4 p. 100). It has also been evaluated in a long-term study involving 632 hypertensive patients, 391 of whom were treated for 1 year; its incidence then was 2.9 p. 100, and drug withdrawal was required in 8 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

Primary and community health services in Newcastle upon Tyne--a joint statement of intent.

In the absence of a single primary health care authority (except in Scotland) district health authorities and family practitioner committees must cooperate in planning health services for the community. Equally, in the field, the potential for teamwork between salaried district health authority nursing staff and the independent general practitioners remains largely unrealized. Yet the government has restated its commitment to the development of primary health care teams as the best means of delivering health care in the community. In Newcastle upon Tyne the local medical committee and the community health services management team have set out their shared aspirations for future development in a joint 'Statement of intent'. This statement, since endorsed by the district health authority and family practitioner committee, includes a number of key principles as a basis for future joint working. These principles emanate from an understanding of the complementary nature of general practice and district health authority community services, and firmly support the primary health care team approach. This statement of intent could serve as a useful model for collaboration and planning of services elsewhere in the country.

Community Health Services↗

Tolerance and safety of perindopril.

Angiotensin converting enzyme inhibitors (ACEIs) constitute a safe and effective therapeutic class for the treatment of hypertension. However, they have been incriminated in the development of certain adverse effects, the most frequently reported being alteration in renal function, development of hypotension and cough. This justified the evaluation of renal function after short-term and long-term treatment with perindopril in hypertensive subjects. In patients with normal renal function, during short-term treatment (1 and 5 days), perindopril induced an increase in renal plasma flow without any modification of the glomerular filtration rate. During long-term administration (up to 18 months of treatment), no significant variation in plasma creatinine was observed. In elderly hypertensive patients or patients with chronic renal failure, the glomerular filtration rate was also preserved, apart from a few rare cases of decreased creatinine clearance, particularly after the addition of hydrochlorothiazide. A slight increase in plasma potassium, with no clinical significance, was observed when perindopril was used as single-agent therapy. Symptomatic hypotension was rarely reported with perindopril (0.2% of cases), even under conditions of salt and water depletion. Amongst the other adverse effects of ACEIs, cough, more recently identified, was investigated in detail. Its frequency was determined in a double-blind study comparing perindopril (1.2%) and captopril (2.4%). It was also evaluated in a long-term study in 632 hypertensive patients (391 treated for 1 year); its incidence was 2.9% and it was responsible for discontinuation of treatment in 8 cases. In this study, 36 patients stopped treatment prematurely because of an adverse effect (5.7%). No harmful drug interactions were reported. The combination of a thiazide diuretic potentiates the antihypertensive effect of perindopril and is perfectly tolerated. The favorable safety profile of perindopril should be related to the correct determination of effective doses.

Angiotensin-Converting Enzyme Inhibitors↗

Use of the computer program EQUIL to estimate pH in model solutions and human urine.

The computer program EQUIL was designed to calculate relative supersaturations of solute components of common urinary stones. In an extended software version, quantitative consideration of charge balance for a priori or a posteriori pH estimation was added. The reliability of this computation was tested with hydrogen ion titration of buffer solutions containing HEPES [N-(2-hydroxyethyl)piperaizine-N'-ethanesulfonic acid] as well as samples of normal human urine. In the model solutions with HEPES, the difference between calculated pH values and the measured pH was smaller than 1.2% for any titration step within the buffer zone (pH 8.5-6.8). The pH values calculated for whole urine differed from the measured pH by 7% to 53%, and the calculated charge inbalance ranged from 2.6 to 9.6 mM. This net cation inbalance indicates that there is a need to account for other anionic components, including hippurate, amino acids, and isocitrate. In experimental solutions, charge balance calculations with EQUIL can be of great utility because they permit a priori estimation of pH or computation of the composition at a desired pH.

Buffers↗

Stimulation of LDL receptor activity in Hep-G2 cells by a serum factor(s).

The regulation of low-density lipoprotein (LDL) receptor activity in the human hepatoma cell line Hep-G2 by serum components was examined. Incubation of dense monolayers of Hep-G2 cells with fresh medium containing 10% fetal calf serum (FM) produced a time-dependent increase in LDL receptor activity. Uptake and degradation of 125I-LDL was stimulated two- to four-fold, as compared with that of Hep-G2 cells cultured in the same media in which they had been grown to confluence (CM); the maximal 125I-LDL uptake plus degradation increased from 0.2 microgram/mg cell protein/4 h to 0.8 microgram/mg cell protein/4 h. In addition, a two-fold increase in cell surface binding of 125I-LDL to Hep-G2 cells was observed when binding was measured at 4 degrees C. There was no change in the "apparent" Kd. The stimulation of LDL receptor activity was suppressed in a concentration-dependent manner by the addition of cholesterol, as LDL, to the cell medium. In contrast to the stimulation of LDL receptor activity, FM did not affect the uptake or degradation of 125I-asialoorosomucoid. Addition of FM increased the protein content per dish, and DNA synthesis was stimulated approximately five-fold, as measured by [3H]thymidine incorporation into DNA; however, the cell number did not change. Cellular cholesterol biosynthesis was also stimulated by FM; [14C]acetate incorporation into unesterified and esterified cholesterol was increased approximately five-fold. Incubation of Hep-G2 cells with high-density lipoproteins (200 micrograms protein/ml) or albumin (8.0 mg/ml) in the absence of the serum factor did not significantly increase the total processed 125I-LDL. Stimulation of LDL receptor activity was dependent on a heat-stable, nondialyzable serum component that eluted in the inclusion volume of a Sephadex G-75 column. Uptake of 125I-LDL by confluent monolayers of human skin fibroblasts was not changed by incubation with FM or by incubation with Hep-G2 conditioned medium. Taken together, these data demonstrate that LDL receptor activity in Hep-G2 cells is stimulated by a serum component. Furthermore, this serum factor shows some specificity for the LDL receptor pathway in liver-derived Hep-G2 cells.

Acetates↗

Effects of cholinergic and anticholinergic drugs on ketamine-induced linguopharyngeal motor activity.

Benztropine mesylate (Cogentin) and physostigmine salicylate (Antilirium), were tested for changes in tongue protrusions, retrusions, and swallowing acts in rats anesthetized with a 100 mg/kg IM injection of ketamine hydrochloride. These ketamine-induced linguopharyngeal events were monitored by means of a force displacement transducer fed onto a polygraph. Benztropine (0.05-1 mg/kg) caused mild to moderate reductions in the rate of these events for a short period of time, up to about 30 min. With physostigmine (5-25 micrograms/kg), linguopharyngeal activity was markedly increased, up to 50-fold by the highest dose within 5 min and returned almost to the baseline within 60 min. With lower doses, more moderate responses were obtained. If methscopolamine (1.4, 3, 6 mg/kg IM) preceded physostigmine, the physostigmine enhancement was preserved.

Animals↗

Application of DNA hybridization techniques in the assessment of diarrheal disease among refugees in Thailand.

The epidemiology and etiology of acute diarrheal disease were determined in a Hmong refugee camp on the Thai-Laotian border from April 11 to May 14, 1985. DNA hybridization techniques were used to detect Shigella species, enteroinvasive Escherichia coli, and enterotoxigenic E. coli. A monoclonal enzyme-linked immunosorbent assay was used to detect rotavirus, and standard microbiology was used to detect other enteropathogens. The age-specific diarrheal disease rates were 47 episodes per month per 1,000 children less than five years old and 113 episodes per month per 1,000 children less than one year old. Rotavirus, enterotoxigenic E. coli, Campylobacter, and Cryptosporidium were the predominant pathogens in children less than two years old. The DNA probe hybridized with 94% of 31 specimens identified as enterotoxigenic E. coli by the standard assays and with none of the specimens in which the standard assays were negative. The probe for Shigella and enteroinvasive E. coli hybridized in eight of 10 stools that contained Shigella and four of 314 stools from which Shigella and enteroinvasive E. coli were not isolated. The use of DNA probes allows specimens to be collected in remote areas with a minimum amount of equipment and technical expertise so that they can be easily transported to a central laboratory for further processing.

Acute Disease↗