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Biomedical subjects

M Powell

Publications and source records attributed to M Powell.

At least 127 records · Page 7Linked to original sources

Reaction products of chloramphenicol acetyltransferases from enterobacteria and Haemophilus influenzae.

The reaction products of Types I, II and III chloramphenicol acetyltransferases (CATs) from reference strains of Escherichia coli and Type II CATs from clinical isolates of Haemophilus influenzae were examined by HPLC. Types I and III CATs produced 1, 3 diacetylchloramphenicol at pH 6.8 and 7.8 whereas Type II enzymes failed to produce this diester at either pH. All the CATs produced monoacetylchloramphenicol at both pH values. Neither mono- nor di-acetylchloramphenicol was stable. Breakdown of enzymically-produced mono- and di-esters proceeded more rapidly at pH 7.8 than at pH 6.8. Similar breakdown behaviour was observed with synthetically manufactured 1, 3 diacetylchloramphenicol.

Acetylation↗

In-vitro susceptibility of Haemophilus influenzae to meropenem compared with imipenem, five other beta-lactams, chloramphenicol and ciprofloxacin.

The in-vitro activity of the new carbapenem, meropenem, was compared with that of imipenem, five other beta-lactams, chloramphenicol and ciprofloxacin against 223 isolates of Haemophilus influenzae. This number included 115 ampicillin-susceptible, and 56 beta-lactamase positive isolates and 52 beta-lactamase negative isolates with reduced susceptibility to ampicillin. The activities of chloramphenicol and ciprofloxacin did not vary between groups of isolates delineated by their susceptibility to ampicillin. In contrast with ampicillin and piperacillin, the two carbapenems and three cephalosporins tested showed no reduction in activity against beta-lactamase producing isolates. beta-Lactam concentrations required for inhibition of 50% and 90% of beta-lactamase negative isolates with reduced susceptibility to ampicillin (MIC greater than or equal to 1 mg/l) were increased in comparison with similar concentrations required for the ampicillin-susceptible group. The differences in meropenem and imipenem activities between these two groups were much smaller than those observed for each of the other beta-lactams. MICs of meropenem were consistently the lower of the two carbapenems for all isolates. In addition, there were no notable increases in the concentrations of meropenem required for inhibition of the isolates least susceptible to imipenem (MIC greater than or equal to 4 mg/l), suggesting that differences in penetration and/or target-binding properties exist not only between the carbapenems and other beta-lactams, but also between meropenem and imipenem.

Ampicillin↗

The health policy implications of international trade in alcohol and tobacco products.

The aim of national alcohol and tobacco preventive health policy is to reduce consumption in order to reduce harm. However, the level of domestic consumption depends upon the interaction of international demand and supply and the development of international trade policy. Trade policy may conflict with or act as a constraint on the implementation of preventive health policy. Trends in alcohol and tobacco trade and developments in international trade policy affecting these products are examined in this paper in relation to health policy goals. Economic models of the links between trade flows, quantities consumed and health effects are then outlined as a preliminary step towards identifying the complex interaction between alcohol and tobacco trade and production, consumption, health and welfare. It is shown that consideration of the economic trade links are an important factor in the development of international and domestic health policy.

Alcoholic Beverages↗

Low-molecular-weight proteinuria in insulin-dependent diabetes mellitus: a study of the urinary excretion of beta 2-microglobulin and retinol-binding protein in alkalinized patients with and without microalbuminuria.

The urinary excretion of two low-molecular-weight proteins (beta 2-microglobulin and retinol-binding protein) was measured in 12 insulin-dependent diabetic patients with persistent microalbuminuria and an equal number with normal albumin excretion; reference ranges for the excretion of beta 2-microglobulin (beta 2M) and retinol-binding protein (RBP) were also obtained in 40 non-diabetic subjects. To ensure the stability of beta 2M in urine a urinary pH greater than or equal to 7 was achieved by giving oral sodium bicarbonate. beta 2M and RBP excretion was significantly higher in the diabetics than in the controls (p less than 0.01), but no higher in microalbuminuric than non-albuminuric diabetics. In the diabetics as a group a significant correlation was found between the excretion of beta 2M and RBP (r = 0.53, p less than 0.01), but more patients had an abnormal excretion of beta 2M than RBP (p less than 0.001). No significant correlation was found between the urinary excretion of either low-molecular-weight protein and duration of diabetes, insulin dose, HbA1, urinary glucose excretion or systemic blood pressure. Measured under appropriate alkaline conditions beta 2M appears to be more sensitive than RBP in detecting an abnormality of the renal proximal tubule which may be an early feature of diabetic renal involvement not characterized by microalbuminuria; microalbuminuria may have glomerular and tubular components.

Adolescent↗

Syringomyelia: how MRI aids diagnosis and management.

MRI is an invaluable tool in the diagnosis and assessment of treatment of syringomyelia. It also confirms the theory of the pathogenesis of the disease and suggests why some operations on the condition fail. A series of patients with Chiari I, with and without syringomyelia, have been studied with MRI both prior to surgery and following treatment. In four cases, with Chiari I alone and minor symptoms only, management has been conservative. No progression of symptoms or signs have been seen, MRI allowing syringomyelia to be excluded, both at diagnosis or development during follow-up. Patients with Chiari I, six with and one without syringomyelia, were split into two groups; those with symptoms and signs of cervico medullary compression (CMC) and those with pure cord amyotrophy with upper limb weakness and numbness of typical "cape type". In three CMC patients, foramen magnum decompression (FMD) with fascia lata grafting and high syringotomy, and in two FMD without syringotomy, were carried out. The procedure improved pain, CMC symptomatology and clinical signs, but had only minor effects on amyotrophic symptoms. Some improvement was seen after surgery in distention of the syrinx on MRI studies, but there was no progression in the syrinx cavities. In two patients with pure amyotrophic the syrinx cavities. In two patients with pure amyotrophic symptoms, primary syringoperitoneal shunting (SPS) was carried out, and a further two patients with primary FMD subsequently went on to SPS for amyotrophic symptoms and signs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Distribution and resistance patterns of Haemophilus influenzae: a European cooperative study.

The first European survey of the prevalence of antibiotic resistance in Haemophilus influenzae was conducted between February and October 1986. Eighty laboratories in nine countries participated (Austria, Belgium, France, FRG, The Netherlands, Spain, Sweden, Switzerland and the UK). A total of 1,961 clinical isolates was examined for type b encapsulation, beta-lactamase production and susceptibility to ampicillin, chloramphenicol, cefaclor, erythromycin and tetracycline, using a unique microdilution method. The proportion of isolates resistant to these antibiotics varied considerably between individual countries. The highest prevalence of ampicillin resistance was found in Spain (30.6%), and the lowest in the FRG (1.6%), with a mean value of 10% for all countries. Chloramphenicol resistance was highest in Spain (24.9%) and Belgium (10.9%) and lowest in The Netherlands (0.6%) and Austria (0.5%), with a mean value of 4.7%. Resistance to erythromycin ranged from 27% of the isolates in The Netherlands to 1.1% in Austria. For tetracycline, values ranged from 1.5% in the UK to 17.8% in Belgium and 25.4% in Spain. The lowest mean prevalence of resistance was observed for cefaclor (breakpoint 8 mg/l): 5% or less in all countries. These inter-country differences could only partially be explained by variations in the proportion of type b strains, the source of the isolates and the mode of collection.

Ampicillin Resistance↗

In-vitro activity of cefaclor, cephalexin and ampicillin against 2458 clinical isolates of Haemophilus influenzae.

The zone sizes and MICs of ampicillin, cefaclor and cephalexin were determined for 2458 clinical isolates of Haemophilus influenzae collected in 1986 during a national survey of the prevalence of resistance in this species. Cefaclor showed greater in-vitro activity than cephalexin against all isolates, with a modal MIC of 4 mg/l compared with 8 mg/l. MIC50 values for the 2201 ampicillin-sensitive and 157 beta-lactamase-positive resistant strains were similar for both cephalosporins (4 mg/l for cefaclor, and 8 mg/l for cephalexin). A further 100 strains with a reduced zone (less than 20 mm) to a 2 micrograms ampicillin disc showed a definite (MIC greater than or equal to 4 mg/l) or intermediate (MIC 1 or 2 mg/l) degree of intrinsic resistance to ampicillin. Both cephalosporins showed a marked and significant rise in MIC values for this group. Cefaclor is the more active agent against ampicillin-sensitive and beta-lactamase-positive H. influenzae but strains with an intrinsic mechanism of resistance to ampicillin are markedly less sensitive to both cefaclor and cephalexin.

Ampicillin↗

Mechanisms of chloramphenicol resistance in Haemophilus influenzae in the United Kingdom.

Of 2458 isolates of Haemophilus influenzae examined in a recent British survey, 42 were resistant to chloramphenicol. Two resistant isolates were of type b and 40 were non-capsulate. Spectrophotometric assay showed that all the resistant isolates produced chloramphenicol acetyltransferase (CAT). CAT activity did not increase following growth on heated blood agar containing chloramphenicol 2 mg/L but was reduced by 84-98% when extracts were treated for 30 min with 5', 5'-dithiobis-2-nitrobenzoate. These data suggest that H. influenzae CATs resemble the Type-II CATs produced by enterobacteria. Extrachromosomal DNA was detected in five only of the 42 resistant isolates and cured derivatives of two plasmid-containing strains retained their chloramphenicol resistance. These results suggest that the CAT gene is located on the chromosome.

Chloramphenicol O-Acetyltransferase↗

Association of arytenoid chondritis with equine lymphocyte antigens but no association with laryngeal hemiplegia, umbilical hernias and cryptorchidism.

Associations were sought between ELA A1-A10 and W11 antigens and the presence of laryngeal hemiplegia, arytenoid chondritis, umbilical hernias and cryptorchidism in Thoroughbreds and/or Quarter Horses. No significant associations were detected between laryngeal hemiplegia and any ELA antigen in Thoroughbreds. The association between arytenoid chondritis and A9 was significant with a relative risk (RR) of 15.6 and aetiologic fraction (EF) of 0.80 in Thoroughbreds. There were apparent associations based on RR between A4 and A5 in Quarter Horses with umbilical hernias (RR = 7.5 and 6.1 respectively); however, these were not statistically significant. No significant associations were detected with cryptorchidism in Quarter Horses when the control population included both sexes. When only unaffected males were used as the control group, there was an apparent increase in relative risk with A6 (from RR = 1.7 to 4.3); however this was not statistically significant. Cryptorchidism in Thoroughbreds showed an increased relative risk with A5 regardless of whether the control population included males and females (RR = 4.1) or only males (RR = 4.7) but the increases were not statistically significant.

Animals↗

Detection of ampicillin resistant Haemophilus influenzae in United Kingdom laboratories.

Susceptibility of Haemophilus influenzae clinical isolates to ampicillin reported by 23 laboratories, using a variety of methods, was compared with results obtained following retesting at The London Hospital Medical College. Beta lactamase production was not detected on initial isolation in 25 of 157 isolates (16%) found to be positive on retest. One hundred beta lactamase negative isolates, which gave reduced zone diameters (less than 20 mm) around 2 micrograms discs and required 1-64 mg/l ampicillin for inhibition, were detected at The London Hospital. Eighty five of these had been reported as sensitive to ampicillin by the laboratories of origin. Many of these 100 isolates showed reduced susceptibility to other beta lactam antibiotics. Accurate detection of non-enzymic reduced susceptibility to ampicillin may emerge as an important guide to the likely sensitivity of H influenzae isolates to the enzyme stable beta lactams.

Ampicillin Resistance↗

Unit or service standards.

As competition in the health-care market increases, issues such as accountability, patient satisfaction, and evaluation after quality of patient care have become progressively more important. This article describes the evaluation of a quality assurance program from a centralized, retrospective system to a unit-based, concurrent review process. Issues related to problem management, research, and education are identified.

Florida↗

Resistance of clinical isolates of Haemophilus influenzae in United Kingdom 1986.

Between 1 January and 31 March 1986, 2434 strains of Haemophilus influenzae collected from 23 laboratories in the United Kingdom were examined. With the same criteria as previous studies in 1977 and 1981 the prevalence of resistance was: ampicillin 7.8% (6.2% beta-lactamase producers and 1.6% non-producers), tetracycline 2.7%, chloramphenicol 1.7%, trimethoprim 4.2%, and sulphamethoxazole 3.5%. of the 87 capsulated strains, 15 produced beta-lactamase, nine were resistant to ampicillin but did not produce beta-lactamase, and two strains, one of which produced beta-lactamase, were resistant to chloramphenicol and tetracycline. Since 1977 the prevalence of resistance to ampicillin, chloramphenicol, and trimethoprim has increased significantly. During 1981-6 strains resistant to ampicillin but not producing beta-lactamase and strains resistant to trimethoprim have significantly increased.

Ampicillin↗

Inhibition of phospholipase A2 by "lipocortins" and calpactins. An effect of binding to substrate phospholipids.

The "lipocortins" are a group of proteins that have been reported to inhibit phospholipase A2 by direct interaction with enzyme. Two proteins which have been identified as lipocortin on the basis of inhibition of phospholipase A2 activity have recently been cloned and sequenced. These have been shown to be identical to the calpactins, which are membrane cytoskeletal proteins serving as major substrates of the tyrosine protein kinases. We have now found that two forms of calpactin (I and II) inhibit porcine pancreatic phospholipase A2 in an assay using Escherichia coli cells or extracted phospholipid vesicles as substrate, but only when the substrate concentration is very low. Both calpactins, as well as another, 73-kDa inhibitory protein, were found to bind purified phospholipids and E. coli cell membranes directly. Kinetic studies show that the inhibition of phospholipase A2 by calpactin can be overcome by high phospholipid substrate concentrations, whether E. coli cells or isolated phospholipid vesicles are used. For example, in the presence of 5 X 10(-10) M phospholipase A2 and 1 X 10(-7) M calpactin, the inhibition decreases from 100 to 0% as phospholipid in vesicles is raised from 2 to 8 microM. The evidence reported here strongly suggests that in vitro inhibition of phospholipase A2 by lipocortin is due to sequestering of the phospholipid substrate by the inhibitor protein, rather than a direct interaction with the phospholipase. These results raise questions about the physiological significance of the inhibition of phospholipases by calpactins.

Animals↗