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Biomedical subjects

R Bennett

Publications and source records attributed to R Bennett.

At least 19 recordsLinked to original sources
PubMed1992

Lack of care giver hand contamination with endemic bacterial pathogens in a nursing home.

Prevalences of Clostridium difficile and multiply resistant Staphylococcus aureus (MRSA) were determined in nursing staff and residents of a 233-bed long-term care facility. Twenty of 38 (52.6%) patients in the long-term care ward and three of 69 (4.3%) in the skilled-nursing ward were colonized with MRSA; 16 of 48 (33%) patients in the long-term care ward and seven of 52 (13%) in the nursing home ward were colonized with C. difficile. None of the 79 staff members whose hands were cultured had chronic C. difficile hand carriage and MRSA was present on only three of 79 (3.9%). Over a 6-month period, 128,000 pairs of gloves were worn. Since C. difficile and MRSA are rarely present on washed hands of care providers, appropriate handwashing and gloving should make a significant contribution to reducing the spread of these agents in long-term care facilities.

Adult↗
PubMed1992

Expression of Ulex europaeus agglutinin I lectin-binding sites in squamous cell carcinomas and their absence in basal cell carcinomas. Indicator of tumor type and differentiation.

Lectins bind tightly to carbohydrate moieties on cell surfaces. Alterations in lectin binding have been reported to accompany epidermal cell differentiation, marking alterations in membrane sugars during this process. The presence of UEA I (Ulex europaeus agglutinin I) L-fucose-specific lectin-binding sites has been used as a marker for terminally differentiated (committed) keratinocytes. In this article, we report the presence of UEA-I-binding sites on squamous keratinocytes of well-differentiated squamous cell carcinomas, with patchy loss of UEA I positivity on poorly differentiated cells of squamous cell carcinomas, suggesting a possible use for this technique in the rapid assessment of less differentiated areas within the squamous cell tumor. The absence of UEA-I-binding sites on basal cell carcinomas may be related to an inability of cells comprising this tumor to convert the L-D-pyranosyl moiety on basal cells to the L-fucose moiety, resulting in an inability of basal cell carcinoma cell to undergo terminal differentiation into a committed keratinocyte.

Basal Cell Carcinoma↗
PubMed1992

Several antecedent strategies in reduction of an environmentally destructive behavior.

The effects of response-specific prompts, prompts identifying long-term and short-term consequences, a combination of long-term and short-term consequences, and a combination of short-term consequences and response-specific prompts on the reduction of environmentally destructive lawn-walking were investigated. The response-specific prompt alone was effective, and its effectiveness was enhanced by the identification of short-term and long-term consequences; however, the mere identification of short-term and long-term consequences alone was not effective.

Behavior Therapy↗
PubMed1992

Leukocyte integrin activation.

Certain stages of the immune response require interaction of leukocytes with each other and with non-hematopoietic cells. One of the systems implicated in these interactions involves an integrin, LFA-1 (Lymphocyte Function Antigen-1), expressed by all leukocytes at their cell surface, and a molecule belonging to the immunoglobulin superfamily, ICAM-1 (Intercellular Adhesion Molecule-1). The avidity of LFA-1 for ICAM-1 is transient. It is modulated both by regulation of ICAM-1 expression and by activation of LFA-1 molecules constitutively expressed on leukocyte membranes. This activation, which induces a conformational change in the molecule, depends on the presence of divalent cations, notably Mg++. This has been demonstrated by using a specific monoclonal antibody, MAb 24. In addition to being a ligand for LFA-1, ICAM-1 is sometimes used as a cell receptor by pathogens such as Plasmodium falciparum, the causative organism of malaria. Very careful study of the binding site of this pathogen using specific antibodies, mutagenesis studies and the construction of a three-dimensional model of the molecule suggests some interesting therapeutic possibilities for the treatment of malaria.

CD3 Complex↗
PubMed1991

Identification of p8,14 as a highly abundant heterodimeric calcium binding protein complex of myeloid cells.

In this report we describe the biochemical characterization of neutrophil and monocyte p8 and p14. Together the two proteins comprise approximately 45% of cytosolic protein in neutrophils and approximately 40-fold less in monocytes. They fractionated together in several chromatographic procedures and were found to exist as a noncovalently associated complex with a stoichiometry of 1:1, named p8,14. Cross-linking experiments showed p8,14 to form heterodimers under conditions simulating the cytosol. An apparent molecular mass of 35,000 daltons was obtained for the p8,14 complex in molecular sizing experiments which suggests the presence of modifications or distinctive structural features. Two major forms of p14 can be identified by two-dimensional gel electrophoresis, both of which form heterodimers with p8. The lower molecular weight variant of p14 lacks Cys-3 (Met-Thr-Cys-Lys-Met...) suggesting that differing translational start sites account for these two forms of p14. A protocol has been devised for the rapid purification of milligram quantities of p8 and p14 from neutrophil cytosol using fast-protein liquid chromatography.

Blotting, Western↗
PubMed1991

The pharmacokinetics and distribution of pamidronate for a range of doses in the mouse.

The pharmacokinetics of the bisphosphonate drug pamidronate (APD, 3-amino-1-hydroxypropylidene-1,1-bisphosphonate) have been investigated in the mouse by using 14C-APD and following the tissue concentrations for up to 90 days postdose. The accumulation of APD in bone was the highest of all tissues and was linear with increasing dose up to the maximum dose employed (30 mg/kg), which is indicative of the uptake process being a simple chemical phenomenon. Despite the known effects of APD on bone turnover rates and osteoclast activity, the dose appeared to have no significant influence on the biological half-life of APD in bone which was found to be 90-140 days. A high dose of APD (5 mg/kg) appeared to prolong its uptake phase by bone, however, a net movement of APD from the soft tissues is the likely explanation for this finding. The concentrations of APD in the soft tissues investigated (liver, spleen, kidney, lung, and muscle) declined in a biphasic manner, initially in parallel with the fall in the plasma concentration and followed by a gradual fall in APD's concentration in the soft tissues due to renal elimination and a redistribution favoring the calcified tissues. The liver and spleen contained higher concentrations of APD relative to the other soft tissues. The 0-24 hour renal excretion of APD was found to fall with increasing dose above 2.5 mg/kg; this may be due to either nephrotoxicity or increased uptake by soft tissues. For doses over 20 mg/kg, there was some evidence of nephrotoxicity. The data from these studies have been used to formulate a simple physiological model for APD disposition.

Animals↗
PubMed1991

The potential role of the ovine pharyngeal tonsil in respiratory tract immunity: a scanning and transmission electron microscopy study of its epithelium.

The mucosal epithelium of the pharyngeal tonsil was studied in 10 conventionally raised sheep by scanning and transmission electron microscopy. The surface of the tonsil was covered by two types of topographically and ultrastructurally distinct epithelium. The epithelium overlying the lymphoid follicle region (follicle-associated epithelium) was compressed by adjacent ciliated epithelium and consisted of predominantly non-ciliated cells of varying height. The majority of these cells possessed microvilli or microfolds of varying number, height and density on their surface. Small numbers of squamous cells and, occasionally, intermediate cells were also present in these areas. Ultrastructurally, the microvillous cells showed features similar to M cells which occur in other mucosal sites. They contained cytoplasmic vesicles and vacuoles and formed intercellular digital junctions. Between these cells was a heavy infiltration of lymphoid cells. Focal disintegration of the mucosal epithelium was occasionally seen. The epithelium covering non-follicle areas consisted of mainly ciliated cells interspersed with some goblet cells and squamous cells, morphologically resembling those elsewhere in the respiratory tract. These findings have provided evidence which confirms that the ovine pharyngeal tonsil is part of the respiratory tract-associated lymphoid tissue.

Animals↗
PubMed1990

Human red blood cell insulin-degrading enzyme and rat skeletal muscle insulin protease share antigenic sites and generate identical products from insulin.

The mechanisms of cellular insulin degradation remain uncertain. Considerable evidence now exists that the primary cellular insulin-degrading activity is a metallothiol proteinase. Two similar degrading activities have been purified and characterized. Insulin protease has been purified from rat skeletal muscle and insulin-degrading enzyme from human red blood cells. Whereas the two degrading activities share a number of similar properties, significant differences have also been reported; and it is not at all established that they are the same enzyme. To examine this, we have compared antigenic and catalytic properties of the two enzymatic activities. Monoclonal antibodies against the red blood cell enzyme adsorb the skeletal muscle enzyme; and on Western blots, the antibodies react with an identical 110-kDa protein. Immunoaffinity-purified enzymes from both red blood cells and skeletal muscle degrade [125I]iodo(B26)insulin to the same products as seen with purified insulin protease and with intact liver and kidney. Chelator-treated muscle and red blood cell enzymes can be reactivated with either Mn2+ or Ca2+. Thus, insulin-degrading enzyme and insulin protease have similar properties. These results support the hypothesis that these activities reside in the same enzyme.

Animals↗
PubMed1990

Reduced risk of NSAID gastropathy (GI mucosal toxicity) with nonacetylated salicylate (salsalate): an endoscopic study.

This randomized, investigator-blinded, parallel group endoscopic study evaluated the effects of salsalate and naproxen on the gastroduodenal mucosa over a 3-month period in patients with RA. Using therapeutic doses of the drugs, 8 of 21 patients (38%) in the naproxen group had endoscopically shown active ulcers (seven patients) or diffuse erosions (one patient), whereas none of the 18 patients treated with salsalate (0%) had such lesions (P = .003). Five of the eight naproxen-treated patients with evidence of GI damage were asymptomatic at the time of endoscopic verification of their lesions. The most significant disadvantage of salsalate was its higher incidence of otologic problems accounting for six of the nine discontinuations with salsalate. However, the findings of this study suggest that patients receiving salsalate are at lower risk for developing significant gastropathy than those treated with naproxen. The relative benefit-to-risk ratio of salsalate indicates that this drug should be considered as a significant alternative NSAID therapy.

Adolescent↗
PubMed1988

PAYE and locums.

Explore the source record for details and available documents.

England↗
PubMed1988

Metabolism and excretion of etoposide in isolated, perfused rat liver models.

The clearance of etoposide and formation of etoposide glucuronide have been measured in an isolated, perfused rat liver model to evaluate the effect of impaired hepatic function on etoposide kinetics. Hepatocellular injury was produced by pretreatment of rats with allyl alcohol or carbon tetrachloride; ligation of the bile duct simulated obstructive biliary disease. Etoposide clearance (3.59 +/- 1.06 ml/min) was reduced by both carbon tetrachloride (2.07 +/- 0.64 ml/min; P = 0.05) and allyl alcohol treatment (2.14 +/- 0.62 ml/min; P = 0.05). Biliary obstruction also impaired etoposide clearance but to a lesser extent than hepatocellular injury (2.47 +/- 0.69 ml/min; P = 0.20 versus control). In both hepatocellular and obstructive models, direct biliary etoposide excretion decreased. The metabolic clearance of etoposide to its glucuronide declined by 36% in the hepatotoxin models but was not decreased by biliary obstruction. Following hepatic injury, there is a reduction in the metabolism and excretion of etoposide by the liver. This effect is most marked on biliary drug excretion. Obstructive biliary disease does not significantly alter etoposide glucuronidation. Since most cancer patients have increased bilirubin on the basis of obstructive disease, little or no etoposide dose alteration will be needed. However, in the patient with significant hepatocellular injury, impaired etoposide clearance will be more pronounced, and etoposide dose alterations may be needed.

1-Propanol↗
PubMed1988

Identification of etoposide glucuronide as a major metabolite of etoposide in the rat and rabbit.

Isolated livers from male Sprague-Dawley rats were perfused at 20 ml/min for 3 h at 37 degrees C with 100 ml of an oxygenated, recirculating solution of 20% rat blood in Krebs bicarbonate buffer containing 20 micrograms/ml [3H]etoposide. Ninety % of administered radioactivity was eliminated in bile over a 3-h collection period. The clearance of etoposide was 3.56 ml/min indicating that, in the rat, it is not highly extracted. Its clearance is, therefore, independent of hepatic blood flow. Etoposide was both excreted into the bile and metabolized by the liver. Perfusate and bile samples analyzed by reverse-phase high-performance liquid chromatography techniques were found to contain three peaks of radioactivity. Positive and negative ion fast atom bombardment mass spectrometry identified the first two peaks as etoposide glucuronides and the third peak as parent drug. Following the i.v. administration of etoposide to rabbits, etoposide glucuronide was also identified in rabbit urine. The recovery of etoposide both from rabbit urine and rat bile was increased by preincubation with glucuronidase. However, the glucuronides were relatively resistant to the action of glucuronidase and showed varying sensitivity to the type of glucuronidase and the reaction conditions used. These studies document the presence of etoposide glucuronide as an etoposide metabolite in two mammalian species and suggest that previous clinical studies using beta-glucuronidase to quantitate glucuronide formation may have underestimated this metabolite due to its relative resistance to some glucuronidase preparations.

Animals↗
PubMed1988

A comparison of the pharmacokinetics of 14C-labelled APD and 99mTc-labelled APD in the mouse.

The disposition of 14C-labelled and 99mTc-labelled APD has been investigated in the Balb/c mouse following a single ip injection containing APD (total dose 5 mg/kg) labelled partly with carbon-14 and partly with technetium-99m. The plasma clearance of carbon-14 was twice that for technetium-99m and the accumulation of carbon-14 in bone was twice as great as that of technetium-99m. All other tissues assayed (liver, lung, kidney and muscle) contained higher concentrations of technetium-99m than carbon-14. There was a particularly marked accumulation of technetium-99m in the liver. We conclude that pharmacokinetic studies of diphosphonates cannot be conducted reliably with 99mTc-labelled compounds.

Animals↗
PubMed1988

Pneumonia in lambs inoculated with Bordetella parapertussis: bronchoalveolar lavage and ultrastructural studies.

Eight colostrum-deprived lambs were inoculated intratracheally with ovine isolates of Bordetella parapertussis. Fluids obtained by bronchoalveolar lavage had a large increase in total cell counts 24 hours after inoculation; up to 93% of cells were neutrophils. From 3 days after inoculation, the number of alveolar macrophages in lavage samples was markedly increased. From 5 days onwards, many alveolar macrophages had moderate to severe cytoplasmic vacuolation. Topographically, tracheal and bronchial epithelium was covered by a large amount of inflammatory exudate 24 hours after inoculation. Later, the tracheobronchial epithelium showed focal extrusions from ciliated cells, which were occasionally associated with B. parapertussis organisms. Ultrastructurally, cytopathological changes associated with B. parapertussis infection were mild focal degeneration of airway epithelium with slight loss of cilia, moderate to severe degeneration of type I and type II alveolar epithelial cells, and focal inflammation in the lungs. These results suggest that the primary targets of B. parapertussis infection are alveolar macrophages and the epithelial cells of bronchioles and alveoli.

Animals↗
PubMed1988

Clinical and analytical evaluation of two immunoassays for direct measurement of creatine kinase MB with monoclonal anti-CK-MB antibodies.

We examined the clinical and analytical performance of two immunoassays (Becton Dickinson CK-MB; Ciba-Corning Magic Lite CK-MB) in which monoclonal anti-CK-MB antibodies are used for directly measuring creatine kinase (EC 2.7.3.2) isoenzyme MB (CK-MB) in serum, and also one electrophoretic method (Ciba-Corning). Within- and between-assay precision for both immunoassays was good at the upper reference limits (less than 10% CV). Analytical recoveries ranged from 102 to 114%. Both immunoassays were free from interference by CK-BB, mitochondrial-CK, macro-CK, adenylate kinase, and CK-MM. Retrospectively, we evaluated four categories of patients, using both immunoassays and electrophoresis: normal controls, acute myocardial infarction (AMI) patients, severe skeletal muscle trauma patients, and acutely ill patients known not to have AMI. In general, there were excellent correlations among all three methods. CK-MB activity (U/L) measured by the Becton Dickinson immunoassay was approximately 50% of the mass concentration (microgram/L) of the Magic Lite immunoassay and 50% of the activity concentration (U/L) determined by electrophoresis. Both immunoassays were easy to perform and sensitive to the low CK-MB concentrations often found with low total-CK activities.

Adult↗