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Biomedical subjects

G Wells

Publications and source records attributed to G Wells.

214 records · Page 12Linked to original sources
PubMed1978

Protein energy malnutrition and nutritional anaemia in preschool children in rural KwaZulu.

The prevalence of protein energy malnutrition (PEM) and nutritional anaemia was investigated in 392 black children, aged 13--60 months, living in a poor rural area. Breast feeding was practised extensively in the population (median duration 14 months). The overall prevalence of PEM was 16,4%, but severe PEM occurred in only 2,7% of the children. Anaemia was present in 6,7% of children, and was almost invariably associated with iron deficiency. Biochemical evidence of iron, folate and vitamin B12 deficiency was detected in 36%, 14,8%, and 0,3% of children respectively. Anaemia was almost confined to the 1-year-old group, but biochemical evidence of iron deficiency, while highest in this age group, continued into the 2-4-year age group. No relationship was found between ecological factors such as income, educational status, etc. and any of the anthropometric, biochemical or haematological variables. The prevalence of PEM and anaemia in these poor rural children is lower than that of a comparable group of underprivileged urban children, thus emphasizing that city slum conditions are producing considerable nutritional problems in their wake. It is of importance to investigate further why some children who are severely deprived in many ways do not necessarily manifest a proportional degree of nutritional deprivation.

Black or African American↗
PubMed1978

Analytical subcellular fractionation of jejunal biopsy specimens: enzyme activities, organelle pathology and response to corticosteroids in patients with non-responsive coeliac disease.

1. Jejunal biopsies from five patients with non-responsive coeliac disease have been subjected to analytical subcellular fractionation and enzymic microassay in order to compare the organelle pathology of this group with untreated but glutensensitive patients. 2. Compared with the gluten-sensitive group these non-responsive patients showed marked reduction of the endoplasmic reticulum enzymes, normal activities of lysosomal enzymes and slightly less severely reduced brush border activities. 3. It is suggested that the present biochemical studies in combination with previous clinical reports and measurements of DNA and protein synthesis by cultured mucosal biopsies delineate non-responsive coeliac disease as a distinct entity. 4. The patients were treated with oral prednisolone (20 mg daily) for between 5 and 9 weeks and the properties of the jejunal biopsies restudied. 5. Although morphologically there was only a partial restoration of the villus architecture the enzymic alterations and organelle abnormalities returned essentially to normal values.

Adult↗
PubMed1978

The effects of prednisolone on the rat enterocyte at a subcellular level.

1. Enterocytes, isolated from the proximal jejunum and distal ileum of normal and prednisolone-treated rats, were homogenized and fractionated by isopycnic centrifugation on sucrose density gradients. The distributions of marker enzymes for the principal subcellular organelles, RNA and protein were determined and related to the activities per enterocyte. 2. In enterocytes fromthe jejunum and ileum of prednisolone-treated animals the activities of particulate brush-border enzymes and of both soluble and mitochondrial malate dehydrogenase were increased compared with those of the control system. The equilibrium density of the brush borders was enhanced in the prednisolone-treated jejunum. The modal densities of the other organelles were unaltered by prednisolone administration. 3. There was a large increase in the total RNA content of enterocytes from the jejunum and ileum of prednisolone-treated animals. This was predominantly associated with a distinct particulate component, indicative of a proliferation of the rough endoplasmic reticulum and consistent with an enhanced rate of protein synthesis. 4. Studies of latent brush-border enzyme activities, the mechanical fragility of isolated brush borders and electron microscopy suggest that steroid administration results in no marked alterations in the gross conformation of the brush-border membrane or in the orientation of the enzymes within the membrane.

Alkaline Phosphatase↗
PubMed1977

Analytical subcellular fractionation of guinea-pig myocardium.

1. Homogenates of guinea-pig left ventricle were fractionated by differential pelleting and by centrifugation on continuous sucrose density gradients. 2. The principal subcellular organelles of myocardium, characterized by their marker enzyme content, were resolved by density gradient centrifugation in a small-volume zonal rotor. The equilibrium densities (p) of the principal organelles are (with marker enzymes in parentheses): sarcolemma, 1-12 (5'-nucleotidase); lysosomes, 1-16 (N-acetyl-beta-glucosaminidase); mitochondria, 1-17 (cytochrome oxidase); peroxisomes, 1-18 (catalase); cytosol (lactate dehydrogenase). 3. The subcellular distribution of various adenosine triphosphatase activities and previously unassigned enzymes was determined. Leucyl-beta-naphthylamidase and gamma-glutamyl transpeptidase showed both cytosol and sarcolemma components. Ca2+-dependent adenosine triphosphatase showed dual localization to the mitochondria and to the sarcolemma.

Adenosine Triphosphatases↗
PubMed1977

Enzymic analysis of endomyocardial biopsy specimens from patients with cardiomyopathies.

Myocardial biopsies have been obtained from patients with hypertrophic or congestive cardiomyopathies. Marker enzymes for the principal subcellular organelles of the myocardium were estimated using highly sensitive assay procedures. The results were compared with those obtained in tissue from patients with valvular heart disease with good or poor left ventricular function. Left ventricular myocardial tissue from patients with hypertrophic cardiomyopathy showed essentially normal levels of enzymic activities. In congestive cardiomyopathy, right ventricular tissue showed reduced levels of mitochondrial enzymes with increased levels of lactate dehydrogenase. Left ventricular tissue from patients with congestive cardiomyopathy showed reduced levels of mitochondrial and myofibril enzymes but high levels of lactate dehydrogenase. The reduced levels of myofibril Ca++-activated ATP in congestive cardiomyopathy is similar to that found in patients with impaired left ventricular function secondary to valvular disease. It is suggested that defective mitochondrial function is a characteristic feature of congestive cardiomyopathy and that the increased levels of lactate dehydrogenase reflect a compensatory response.

Cardiomyopathies↗
PubMed1976

Enzymic analysis of cardiac biopsy material from patients with valvular heart-disease.

Cardiac tissue obtained by left-ventricular endomyocardial biopsy from patients with valvular heart-disease was assayed for marker enzyme activities of subcellular organelles and these were correlated with left ventricular function as assessed by haemodynamic studies. In patients with poor left ventricular function, calcium-dependent adenosine-triphosphatase (A.T.P.ase) activity, predominantly localised to the myofibrils, was strikingly reduced. Activity of lactate dehydrongenase, a cytosol enzyme, was significantly increased in tissue from patients with poor left ventricular function. The activity of enzymes associated with sarcolemma (5'-nucleotidase), mitochondria (glutamate dehydrogenase and monoamine oxidase), microsomes (neutral alpha-glucosidase), and lysosomes (acid phosphatase, N-acetyl-beta-glucosaminidase) was no different in patients with good or poor left ventricular function. It is suggested that reduced myofibrillary A.T.P.ase concentration is the biochemical basis for the impaired ventricular function.

Acid Phosphatase↗
PubMedDate not supplied

Are therapeutic decisions supported by evidence from health care research?

BACKGROUND: One of the most common decisions physicians face is deciding which therapeutic intervention is the most appropriate for their patients. In recent years much emphasis has been placed on making clinical decisions that are based on evidence from the medical literature. Despite the emphasis on incorporation of evidence-based medicine into the undergraduate curriculum and postgraduate medical training programs, there has been controversy regarding the proportion of interventions that are supported by health care research. OBJECTIVE: To investigate the proportion of major therapeutic interventions at our institution that are justified by published evidence. METHODS: One hundred fifty charts from the internal medicine department were reviewed retrospectively. The main diagnosis, therapy provided, and patient profile were identified and a literature search using MEDLINE was performed. A standardized search strategy was developed with high sensitivity and specificity for identifying publication quality. The level of evidence to support each clinical decision was ranked according to a predetermined classification. In this system there were 6 distinct levels, which are explained in the study. RESULTS: Of the decisions studied, 20.9% could be supported by placebo-controlled randomized trials and 43.9% by head-to-head trials. Half of these were shown to be significantly superior to the treatment against which it was being compared. For 10 of the 150 clinical decisions, evidence was found demonstrating alternative therapies as being more effective than that selected. CONCLUSIONS: Most primary therapeutic clinical decisions in 3 general medicine services are supported by evidence from randomized controlled trials. This should be reassuring to those who are concerned about the extent to which clinical medicine is based on empirical evidence. This finding has potential for quality assurance, as exemplified by the discovery that a literature search could have potentially improved these decisions in some cases.

Decision Support Techniques↗
PubMedDate not supplied

CXC chemokines generate age-related increases in neutrophil-mediated brain inflammation and blood-brain barrier breakdown.

Children are at greater risk than adults of permanent brain damage and mortality following head injury or infection [1-5]. Rodent models have demonstrated a 'window of susceptibility' in young animals during which the brain parenchyma is at greater risk of acute neutrophil-mediated breakdown of the blood-brain barrier [6-7]. The exact mechanism of this age-related susceptibility to brain inflammation has yet to be defined, but animal models have revealed that the potent pro-inflammatory cytokine interleukin-1beta (IL-1beta) initiates an intense acute neutrophil-mediated inflammatory response in the brains of young rats and mice that is not seen in adults [6]. Here, we demonstrate the rapid induction of CXC chemokines (which contain a Cys-X-Cys motif), in particular the cytokine-induced neutrophil chemoattractant CINC-1, following the intracerebral administration of IL-1beta. The CXC chemokines produced a more intense neutrophil response in young rats than in adults. The IL-1beta-induced blood-brain barrier breakdown in young rats could be attenuated by an anti-CINC-1 neutralising antibody. These results show that the immature central nervous system (CNS) is dramatically more susceptible to the chemotactic effects of CXC chemokines. Blocking the CXC chemokine activity associated with brain inflammation inhibits neutrophil-mediated blood-brain barrier damage and represents a significant therapeutic possibility.

Adult↗
PubMedDate not supplied

The impact of risk on preference values: implications for evaluations of postmenopausal osteoporosis therapy.

OBJECTIVE: The objective was to assess the impact of different levels of risk of disease on a woman's preferences for health states. Women were provided with health scenarios incorporating different levels of lifetime risks for breast cancer, hip fracture, and coronary heart disease (CHD). In this way, we were able to determine the incremental effect of changes in risks of each disease on preference values. METHODS AND DATA: Preference values and utility scores were obtained for six health scenarios by both the feeling thermometer (FT) and standard gamble (SG) methods. Scenarios presented the different lifetime risks of CHD, breast cancer, and hip fracture associated with and not associated with long-term use of hormone replacement therapy (HRT) and raloxifene. Risks of breast cancer were based on perceived risks and population risks. The sample population consisted of 40 healthy female volunteers aged between 45 and 65 years randomly selected from the Ottawa-Carleton district. RESULTS: Based on their perceived risk of breast cancer, the women had higher value scores for the raloxifene risk profile than for both HRT (p = .002) and no therapy (p = .003), with similar results for analyses based on population risks and from utility scores. Regression analysis showed that the risk of breast cancer (p < .001) was the only disease risk that was statistically significantly associated with women's preferences. CONCLUSIONS: Women had significant preferences over the different risk profiles, primarily due to the incremental effect on changes in values for the risk of breast cancer. Therefore, studies evaluating therapies for osteoporosis should consider patient preferences for living with different risk profiles.

Aged↗
PubMedDate not supplied

Low disease activity state in rheumatoid arthritis: concepts and derivation of minimal disease activity.

With recent advances in therapy, the proportion of patients achieving a satisfactory state of minimal disease activity (MDA) is becoming a more important measure with which to compare different treatment strategies. MDA is between high disease activity and remission and anyone in remission will also be in MDA. This paper summarizes the process of coming to a definition of minimal disease activity in rheumatoid arthritis. Two equivalent preliminary definitions of minimal disease activity for use as secondary outcome measures in clinical trials in RA are proposed: a core-set definition based on the WHO/ILAR core set and a DAS-based definition based on the DAS28.

Antirheumatic Agents↗
PubMedDate not supplied

The physiological disposition of aerosolized 4-[(3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl)sulfonyl]-gamma -oxobenzenebutanoate (L-648,051) in rats.

14C-labeled 4-[(3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl)-sulfonyl]-gamma- oxobenzenebutanoate (L-648,051) was suspended in Freon under pressure and injected into rat lungs via a tracheal cannula. The particle size of the drug was 1 to 5 microns and the mean dose was approximately 0.2 mg/kg. Levels of radioactivity in the lung/trachea declined in a monoexponential manner. Absorption, estimated from radioactivity remaining in the lung and trachea, was 73% in 1 hr and 95% in 4 hr. L-648,051 and its pharmacologically active metabolite L-657,098 (formed by ketoreduction of the butanoic acid moiety of L-648,051) accounted for 96% of the radioactivity in the lung at 10 min after the dose and 91% after 60 min. The lung:plasma concentration ratio of active drug (L-648,051 plus L-657,098) was at least 176:1 at 10 min and 17:1 at 60 min (compared with 1:1 after 2 mg/kg iv) suggesting that aerosol administration of L-648,051 in humans may result in an ideal therapeutic ratio, with high levels of pharmacologically active ingredient in the lung and low levels in the plasma.

Aerosols↗
PubMedDate not supplied

The antigenic relationship between Brettanomyces-Debaryomyces strains and the Salmonella cholerae-suis O antigen.

The immune sera for Brettanomyces lambicus, B. claussenii, Debaryomyces hansenii and D. marama agglutinated Salmonella cholerae-suis (0:6(2), 7). The immune serum for S. cholerae-suis agglutinated B. lambicus, B. clausenni, D. hansenii and D. marama. Absorption and agglutination cross-tested demonstrated common antigen factor(s) in the tested yeasts and Salmonella 0:7 antigen.

Antigens, Bacterial↗