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Biomedical subjects

J Robinson

Publications and source records attributed to J Robinson.

At least 415 records · Page 23Linked to original sources

Comparison of direct plating with the use of enrichment culture for isolation of Aeromonas spp. from faeces.

Direct plating of faecal specimens on blood agar was compared with the use of enrichment culture for isolation of Aeromonas spp. from faeces during a large epidemiological study. Of enterotoxigenic strains isolated by direct plating, 89% were associated with acute diarrhoea and 7% with an episode of diarrhoea during the month before collection, but 79% of enterotoxigenic strains isolated only after enrichment were not associated with acute diarrhoea. With Aeromonas spp., as with intestinal pathogens, it appears that enrichment allows isolation of the bacteria when in low faecal concentrations likely to be found in convalescent patients, carriers and those with subclinical infection. The routine use of enrichment for isolation of faecal aeromonads, by detecting Aeromonas spp. in low numbers in patients without diarrhoea, is likely to confuse interpretation of epidemiological studies seeking to clarify the relationship between Aeromonas spp. and acute diarrhoea.

Aeromonas↗

Prostaglandin F2 alpha-induced functional luteolysis: interactions of LH, prostaglandin F2 alpha and forskolin in cyclic AMP and progesterone synthesis in isolated rat luteal cells.

The acute antigonadotrophic action of prostaglandin F2 alpha (PGF2 alpha) was examined in dispersed luteal cell preparations from immature superluteinized rat ovaries. Cell suspensions prepared by collagenase digestion and purification over a Percoll density gradient were incubated for 1 h in Eagle's minimum essential medium in the presence and/or absence of LH, PGF2 alpha, N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate (dbcAMP) and forskolin. Medium was assayed for total progesterone and adenosine 3',5'-cyclic monophosphate (cAMP). Luteal cell preparations showed typical steroidogenic (progesterone) responses to LH, mimicked by both dbcAMP and forskolin. Whilst the threshold LH dose to increase cAMP synthesis was greater than that for progesterone (100 micrograms/l compared with 1 microgram/l), 24 mumol forskolin/l was the threshold dose for both cAMP and progesterone responses. Furthermore, combined doses of LH and forskolin synergistically raised cAMP yet produced less than additive increases in progesterone. Similarly, combinations of dbcAMP plus forskolin produced less than additive progesterone increases. These data suggest that forskolin may not act as a simple mimic of LH. Prostaglandin F2 alpha dose-dependently inhibited forskolin-induced cAMP and progesterone synthesis and also inhibited progesterone synthesis induced by dbcAMP. These data suggest that the antigonadotrophic effect of PGF2 alpha has more than one locus of action, i.e. it both inhibits an adenylate cyclase event associated with cAMP generation and blunts the cellular response to cAMP. The present uncertainty over the exact locus of forskolin's action within the adenylate cyclase complex limits further delineation of the inhibitory action of PGF2 alpha on LH-responsive adenylate cyclase.

Animals↗

Extravascular hemolysis following the administration of cefamandole.

Hemolytic anemia occurred in a 70-year-old female after a five-day course of intravenous cefamandole. The patient's serum contained an IgG antibody which was reactive with red blood cells which had been coated in vitro with cefamandole but not with uncoated cells. An in vitro assay of allogeneic mononuclear phagocytosis of cefamandole-coated red cells sensitized with the patient's anti-cefamandole indicated that the anti-cefamandole could induce significant phagocytosis. The anti-cefamandole was easily inhibited in vitro by cefamandole as well as by a variety of related cephalosporins indicating broad cross-reactivity, with the antigenic site primarily the 7-amino-cephalosporanic acid nucleus. Penicillins could inhibit the anti-cefamandole but only when using concentrations 3-10 X those of cephalosporins. Eleven examples of anti-penicillin tested failed to react with cefamandole-coated red cells. Screening of 344 random sera from hospitalized patients found only five (1.5%) reactive with cefamandole-coated red cells; three of these sera were also reactive with penicillin-coated red cells. The patient's hemolysis subsided following cessation of the drug. This is the first report of anti-cefamandole-induced hemolytic anemia.

Aged↗

Pemphigus vulgaris and malignancy.

A case of oral squamous cell carcinoma with pemphigus vulgaris is reported and the literature is reviewed. Association between the above entities has essentially been founded upon the specificity of cancer-associated antigen. To date, such an antigen has not been adequately defined, and, therefore, any causal relationship between the 2 processes on the grounds of antigenic-specificity of cancer cells remains unjustified. Hence, pemphigus and malignancy may occur as a coexisting phenomenon.

Antigens, Neoplasm↗

Use of non-carbonated soft drinks to provide safe drinking water.

Non-carbonated, low-calorie soft drink concentrates (cordials), when diluted according to manufacturers' instructions, had significant antibacterial effects in vitro. Bacteria affected include Vibrio cholerae, Aeromonas hydrophila, Shigella sonnei, Salmonella typhimurium and Escherichia coli. With vibrios, bacterial counts were reduced from 10(6)/ml to undetectable numbers in less than 10 min. Escherichia coli in an initial concentration of 10(6)/ml became undetectable after incubation for 1 h with one brand of cordial. Naturally contaminated water can be rendered potable by incubation with cordials at room temperature for 1 h. This may be a way to reduce the risk of water-borne diarrhoea, particularly where the cleanliness of drinking waters cannot be otherwise assured, for example when making up oral rehydration fluids and for travellers in high-risk areas.

Bacteria↗

Pharmacokinetics and pharmacodynamics following single and repeated nightly administrations of loprazolam, a new benzodiazepine hypnotic.

The pharmacokinetics of oral loprazolam and pharmacodynamic responses on the morning following nightly drug administration were examined after single and after seven consecutive 1 mg doses in six non-fasting healthy subjects. The serum concentration-time profiles for unchanged loprazolam measured by a specific high pressure liquid chromatography/gas chromatography (h.p.l.c./g.c.) method and for benzodiazepine material measured by radioimmunoassay (RIA) were qualitatively similar although RIA levels were consistently higher. Approximate elimination half-life of unchanged loprazolam after single doses was 8.0 h. For RIA measured material, approximate half-life was 11.7 h following acute administration and 12.8 h after seven consecutive doses. Compared to results after single doses, maximum serum concentration and AUC were greater following 1 week's treatment. Using RIA results, the increases were 27.2% (95% CL 6.9 to 47.4%) and 35.1% (95% CL 15.8 to 54.3%) respectively and using h.p.l.c./g.c. data, 11% (95% CL - 22.6% to 44.5%) and 41% (95% CL - 50.9 to 133.0%). After repeated doses of loprazolam, there were no significant changes with respect to results after single doses in psychomotor function assessed objectively by critical flicker fusion threshold or choice reaction time, or in sleep quality or behaviour on awakening assessed subjectively by 10 cm analogue scales. Mean time to maximum serum concentration was 4.95 h with considerable inter-individual variability (range 1-12 h) and there was a lag time of 1-1.5 h before drug was detectable in blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Single dose pharmacokinetics and pharmacodynamics of oral loprazolam in the elderly.

The pharmacokinetics of the benzodiazepine hypnotic, loprazolam (1.0 mg orally), and the pharmacodynamic response to single oral doses (0.5 mg and 1.0 mg) have been compared in young and elderly healthy volunteers. No difference between the groups in peak plasma concentration (Cmax) or in the time to peak (tmax) was found, but the elimination half-life t1/2,z and area under the plasma concentration-time curve (AUC) were significantly greater in the elderly group. The immediate effects of loprazolam on all three performance tests used (postural sway, critical flicker fusion threshold (CFFT) and choice reaction time (CRT] and on subjective sedation tended to be more pronounced in the elderly subjects, though intersubject variability in response was high in both groups. The corresponding plasma concentrations did not differ significantly between the two groups. The higher (1.0 mg) dosage was associated with significant residual (11 h) impairment of standing steadiness in the elderly subjects. No other hangover effects were observed. The results are compatible with previous evidence of increased 'sensitivity' to benzodiazepines in the elderly and suggest that a lower (0.5 mg) starting dose of loprazolam would be appropriate for older recipients. Further investigation would be necessary to establish whether clinically relevant accumulation of loprazolam occurs in the elderly following repeated dosage.

Administration, Oral↗

Effects of single and multiple doses of ketoconazole on adrenal function in normal subjects.

The plasma cortisol response to 0.25 mg tetracosactrin given by intramuscular injection was suppressed by nine oral doses of 200 mg ketoconazole given 12 hourly to nine normal female subjects. No effect was noted following a single 200 mg oral dose of ketoconazole. This suppressive effect was reversible within at least 5 days of discontinuation of ketoconazole.

Adrenal Cortex↗

Correlative studies of Verruca vulgaris by H & E, PAP immunostaining, and electronmicroscopy.

Twenty-one specimens of Verruca vulgaris were used for an investigation to define what portion of the papillomatous structures seen in H & E stain will correspond to the areas of positive staining for papilloma virus antigen utilizing the peroxidase-antiperoxidase immunostaining technique. Vacuolar spaces filled with thready material and large ovoid parakeratotic cells seen in H & E stain stained positively for papilloma virus antigen. In the granular layer, viral antigens stained heavily, the nuclei of cells showing koilocytosis. Both round and irregularly shaped kerathohyaline granules did not stain positively for viral antigen stain. Eight of the 21 specimens showed marked positivity for papilloma virus antigen. Three other cases were positive in only focal sites. Of the 8 immunostained-positive selected cases used for ultrastructural studies, only 2 showed the viral particles. The study suggests that the PAP immunostaining is a more sensitive and yet less cumbersome method than electronmicroscopy for demonstration of papilloma virus.

Antigens, Viral↗

Are we teaching students that patients don't matter?

Medical students may fear that their training leeches away the caring attitudes which attracted them to medicine. Some research suggests they are right. The medical school has a duty to support and encourage their values, but the reverse may happen. Students are taught about legal consent but not ethical consent. They may see or participate in concealment of medical mistakes and learn to practise deceit. The use of unconscious females for gynaecology teaching may encourage the wrong attitudes to patients. Trainee GPs may learn that the doctors' rights are more important than those of the patient. Measuring patients' views should be included in research protocols.

Bioethical Issues↗

Effect of p-nitrophenyl-beta-D-xyloside on proteoglycan synthesis and extracellular matrix formation by bovine corneal endothelial cell cultures.

The effect of p-nitrophenyl-beta-D-xyloside on proteoglycan synthesis and extracellular matrix (ECM) formation by cultured bovine corneal endothelial (BCE) cells was investigated. BCE cells actively proliferating on plastic dishes produced in the absence of xyloside an ECM containing various proteoglycans. Heparan sulfate was the main 35S-labeled glycosaminoglycan component (83%). Dermatan sulfate (14%) and chondroitin sulfate (3%) were also present. Exposure of actively proliferating BCE cells to xyloside totally inhibited synthesis of proteoglycans containing dermatan sulfate or chondroitin sulfate and caused an 86% inhibition of heparan sulfate proteoglycan synthesis. The heparan sulfate proteoglycans that were extracted from the ECM produced by BCE cells exposed to xyloside had a smaller size and a reduced charge density compared to their counterparts extracted from the ECM of cultures not exposed to xyloside. In contrast to the inhibitory effect of the xyloside on proteoglycan synthesis, exposure of actively proliferating BCE cells to xyloside stimulated synthesis of free chondroitin sulfate and heparan sulfate chains. All of the xyloside-initiated glycosaminoglycan chains were secreted into the culture medium. The proteoglycan-depleted matrices produced by BCE cells exposed to xyloside were used to study the effect of these matrices on proteoglycan synthesis by BCE cells. BCE cells growing on proteoglycan-depleted ECM showed a considerable increase in the rate of proteoglycan synthesis compared to BCE cells growing on normal ECM. Moreover, the pattern of glycosaminoglycan synthesis by BCE cells growing on proteoglycan-depleted ECM was changed to one which resembled that of BCE cells actively proliferating on plastic dishes. It is postulated that BCE cells are able to recognize when an ECM is depleted of proteoglycan and to respond to it by increasing their rate of proteoglycan synthesis and incorporation into the ECM.

Animals↗

Induction of plasminogen activator in a human diploid fibroblast cell line (MRC-5) by conditions which cause induction of interferon: the role of calcium ions.

The human diploid fibroblast cell line, MRC-5, derived from embryo lung tissue produced only small quantities of plasminogen activator (PA) when harvested using a standard nutrient medium (Eagle's Minimal Essential Medium, MEM). Use of a schedule designed to induce high concentrations of fibroblast interferon in these cells also resulted in production of considerably enhanced levels of PA. The kinetics of PA production differed from those of interferon production; specifically, PA was produced for at least 6 days following induction despite the toxicity of the inducers whereas interferon synthesis continued for only 1 day. Further investigation of the induction conditions for PA revealed that double-stranded RNA which was absolutely required for interferon production was not required for induction of PA. Indeed, the stimulus for enhancement of PA production appeared to be solely an elevated concentration of calcium ions in the extracellular medium. The possible physiological relevance of this induction of PA by elevated concentrations of calcium ions is discussed.

Calcium↗

Proteoglycans in basement membranes.

Previous studies have shown that sulphated proteoglycans are integral components of basement membranes. We have used mouse parietal yolk sac cells as a model system for our studies. These cells produce several basement membrane components, including a heparan sulphate proteoglycan and a chondroitin sulphate proteoglycan. The structure of the heparan sulphate proteoglycan has been described previously. The chondroitin sulphate proteoglycan has an Mr of 200 000-300 000 and contains 10-20 chondroitin sulphate chains (Mr = 14 000-16 000), attached to a core protein that on polyacrylamide gel electrophoresis appears as a doublet (with Mr = 34 000 and 27 000). Further structural analysis suggests that the majority of the polysaccharide chains are clustered around one segment of the core protein. The polysaccharide chains carry sulphate residues predominantly attached to C-4 of the galactosamine unit. More than 60% of the uronic acid residues are of the glucuronic configuration, the rest being iduronic acid. The parietal yolk sac cells secrete about equal amounts of the two proteoglycans into the culture medium, whereas heparan sulphate proteoglycan is the predominant proteoglycan found in the extracellular matrix of these cells. This proteoglycan appears to be anchored in the matrix by interactions involving the core protein rather than the polysaccharide chains.

Animals↗

Dissolution profile determination of a multicomponent product using a rapid liquid chromatographic analysis.

A system was developed which is capable of monitoring the dissolution profiles of each of the active components in a two-component combination product. The UV spectra of the two drugs (metoprolol and hydrochlorothiazide) overlap considerably, making conventional UV analysis of either component unrealistic. By resolving the two drugs on a high-performance liquid chromatographic (HPLC) system both can be quantitated after separation. The analysis is sufficiently short to allow for the use of a six-station dissolution tester in tandem with an HPLC for determination of dissolution profiles. The HPLC system and equipment, can monitor six samples of this product at 5-min intervals in real analysis time.

Chemistry, Pharmaceutical↗