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Biomedical subjects

L Ward

Publications and source records attributed to L Ward.

At least 91 records · Page 5Linked to original sources

Effects of the NMDA antagonists CPP and MK-801 on radial arm maze performance in rats.

The dose- and time-dependent effects of N-methyl-D-aspartate receptor/channel antagonists on radial 8-arm maze performance were examined in rats. Both CPP (1.0-30 mg/kg), a competitive NMDA antagonist, and MK-801 (0.1-1.0 mg/kg), a noncompetitive NMDA antagonist, produced dose-dependent increases in the number of errors made to sample all 8 baited arms. The effective doses of both drugs produced maximal performance impairments 2 hr after IP injection, and no effects after 24 hr. In a second radial arm maze task where only 4 arms were baited, CPP (10 mg/kg) had a somewhat greater effect on the number of working memory errors than on reference memory errors. MK-801 (0.1, 0.33 mg/kg) had no effects on either this task or on a task involving a 1-hr delay between correct choices 4 and 5 on the 8 choice task. CPP (10 mg/kg), however, impaired performance on this latter task. These results indicate that doses of NMDA antagonists, sufficient to block hippocampal long-term potentiation, also disrupt radial arm maze performance.

Animals↗

Two outbreaks of Salmonella enteritidis phage type 4 infection associated with the consumption of fresh shell-egg products.

In 1988 there were two outbreaks of infection with Salmonella enteritidis phage type 4 in adjacent local authorities. The first affected 18 of 75 helpers and guests who attended a private function. Investigations revealed that home-made vanilla ice-cream containing uncooked eggs was the vehicle of infection and the causative organism was identified at the premises of the egg producer. The second affected 84 of 422 delegates attending a conference dinner, and 12 of 50 hotel staff at risk. A dessert made with lightly-cooked egg yolk and raw egg white was associated with infection, and the epidemic strain was cultured from the shell of an egg and an environmental sample from the producer's farm. It is of interest that one outbreak involved free-range and one battery-produced eggs, and that in one the vehicle was prepared at home and in the other in commercial premises. In neither incident was any deficiency in standards of egg production or catering practice discovered.

Animals↗

A national outbreak of Salmonella typhimurium DT 124 caused by contaminated salami sticks.

An outbreak of Salmonella typhimurium DT 124 infection which affected 101 people in England in December 1987 and January 1988 was detected through surveillance of laboratory reports from medical microbiology laboratories of the NHS and PHLS. Within 1 week of noting the increase in reports, epidemiological and microbiological investigations identified a small German salami stick as the vehicle of infection and the product was withdrawn from sale. The epidemiological investigation highlighted the occurrence of a long incubation period, bloody diarrhoea. Prompt recognition and investigation of the outbreak prevented further cases of severe infection.

Adolescent↗

An outbreak of paratyphoid fever in the UK associated with a fish-and-chip shop.

An outbreak of Salmonella paratyphi B infection in the UK associated with a fish-and-chip shop is reported. The source of infection for the first three cases was believed to be a food handler who was infected overseas 6 years earlier. His wife whose faeces and urine were originally culture negative continued to run the shop but subsequently her faeces became positive on one occasion. She was considered to have been the source of two further cases, and secondary household spread of infection from these two cases resulted in one symptomatic and two asymptomatic infections. A second household contact of the proprietor also became a faecal excretor 2 months later. We recommend that food handlers living in households or in intimate contact with cases or carriers of S. paratyphi B should be put off work until all household contacts cease excreting the organism.

Adolescent↗

Salmonella enteritidis phage type 4 infection: association with hen's eggs.

Epidemiological and microbiological investigation of the four outbreaks of Salmonella enteritidis phage type (PT) 4 that occurred in Wales in 1988 implicated foods containing shell eggs from hens as the vehicle of infection. In a case-control study of sporadic cases there was a significant association between infection and egg consumption in the 3 days before illness. These findings provide data to support the warnings from the Departments of Health in the United Kingdom about risks of infection from eating raw or undercooked hens' eggs.

Adult↗

Progression of chronic renal failure is related to glucocorticoid production.

Progression of chronic renal failure during 35 treatment periods in 27 patients was measured as the rate of change of bimonthly radioisotope GFR for an average of 15 months. Treatments were comprised of: (1) mild protein restriction; (2) more severe protein and phosphorus restriction plus essential amino acids; or (3) the same diet plus ketoacids. Progression was significantly (P less than 0.025) correlated with urinary 17-hydroxycorticosteroid excretion in all three treatment groups; overall r was 0.78 (P less than 0.0001). Multiple regression analysis showed that the following factors were not additional significant determinants of progression: urea N excretion, phosphate excretion, protein excretion, serum calcium times phosphorus product, serum alkaline phosphatase, serum uric acid, serum triglycerides, serum cholesterol, etiology, mean arterial pressure, or enalapril treatment. However, when urinary 17-hydroxycorticosteroid excretion was factored by GFR (with which it was correlated), additional significant regressors appeared: serum triglycerides and polycystic kidney disease, which tended to be associated with more rapid progression, and ketoacid treatment, which tended to be associated with slower progression. Mean 17-hydroxycorticosteroid excretion differed significantly between the three treatment groups, in the order (1) greater than (2) greater than (3) (though not when factored by GFR). Changing from essential amino acids to ketoacids (or vice versa) without change in diet was associated with lower 17-hydroxycorticosteroid excretion on ketoacids (but not when factored by GFR).(ABSTRACT TRUNCATED AT 250 WORDS)

17-Hydroxycorticosteroids↗

The reaction of acetaldehyde with brain microtubular proteins: formation of stable adducts and inhibition of polymerization.

Stable adducts were formed by treatment of bovine brain microtubular proteins (MTP) with acetaldehyde, followed by gel filtration to remove excess acetaldehyde. The extent of stable adduct formation was determined using [14C]acetaldehyde and was correlated with acetaldehyde concentration and reaction time. Significant inhibition of MTP polymerization was observed at adduct concentrations of 0.6 mol acetaldehyde/mol tubulin dimer. The data suggest that repeated exposure of MTP to low concentrations of acetaldehyde, as would occur in the brain and other tissues of alcoholics, may inhibit MTP polymerization with neurological consequences.

Acetaldehyde↗

Effects of acetaldehyde on polymerization of microtubule proteins.

The in vitro effects of ethanol and acetaldehyde on polymerization of calf brain microtubular proteins (MTP) were examined. While ethanol up to 100 mM had no effect on the polymerization of MTP, acetaldehyde above 0.5 mM had an inhibitory effect. This effect was not dependent on the presence of microtubule-associated proteins (MAPs), since acetaldehyde had a similar effect on the polymerization of highly purified tubulin. Electron microscopy revealed that the number and the length of microtubules at equilibrium was reduced by the presence of acetaldehyde. Acetaldehyde raised the critical concentration for tubulin assembly and caused greater inhibition at lower tubulin concentrations. Acetaldehyde augmented the depolymerizing effects of Ca2+ on preassembled microtubules. In addition, acetaldehyde itself caused depolymerization of microtubules but only in the absence of MAPs. Long-term (19.5 h) incubation of MTP with acetaldehyde led to significant loss of polymerization ability which could not be reversed by removal of acetaldehyde. This loss of activity was apparently independent of the observed formation of reducible adducts between acetaldehyde and MTP.

Acetaldehyde↗

Progression of chronic renal failure in patients given ketoacids following amino acids.

Twelve patients with chronic renal failure who exhibited a progressive decline in 24-hour creatinine clearance, despite being given for 2 to 10 months a diet containing 0.3 g per kg ideal weight of protein and 7 to 9 g mg per kg ideal weight of phosphorus, supplemented with vitamins, CaCO3, and 10 g per day of essential amino acids, were changed to a supplement containing predominantly ketoacids. In six patients whose serum creatinine was 7.5 mg/dl or greater at changeover, progression continued unabated. In six patients with serum creatinine levels at changeover of 6.6 to 7.4 mg/dl, one was non-compliant with the diet and progressed to dialysis. In the other five, progression, measured as the rate of change of a bimonthly radioisotope clearance, has been undetectable during the ensuing one to two years. There has been no change in urea appearance, blood pressure, phosphaturia or proteinuria. Nutrition has been maintained. Thus this ketoacid supplemented regimen apparently halted the progression of moderately-severe chronic renal failure for at least a year in a small group of patients in whom restriction of protein and phosphate intake without ketoacids failed to halt progression. In more severe renal failure, no effect on progression was seen.

Adult↗

A Rapid Procedure for Purifying Pectate Lyase from Erwinia carotovora Based on Substrate Affinity.

To purify pectate lyase produced by Erwinia carotovora subsp. carotovora, we used the supernatant from 48-h-old cultures grown in broth containing sodium polypectate and yeast extract. The supernatant was combined with the enzyme substrates sodium polypectate and polygalacturonic acid, which were then precipitated with CaCl(2). After the precipitate was washed, pectate lyase was eluted with 1.0 M NaCl.

Journal Article↗

Progression of chronic renal failure in patients given keto acids following amino acids.

Twelve patients with chronic renal failure who exhibited a progressive decline in 24-h creatinine clearance despite being given, for 2-10 months, a diet containing 0.3 g of protein/kg ideal weight and 7-9 mg of phosphorus/kg ideal weight supplemented with vitamins, CaCO3, and 10 g per day of essential amino acids, were changed to a supplement containing predominantly keto acids. In 6 patients whose serum creatinine levels were 7.5 mg/dl or greater at changeover, progression continued unabated. In 6 patients with serum creatinine levels at changeover of 6.5-7.4 mg/dl, one was non-compliant with the diet and progressed to dialysis. In the other 5, progression, measured as the rate of change of a bimonthly radioisotope clearance, has been undetectable during the ensuing 1-2 years.

Amino Acids, Essential↗

Comparison of mesna with forced diuresis to prevent cyclophosphamide induced haemorrhagic cystitis in marrow transplantation: a prospective randomised study.

A prospective randomised study was carried out to compare the effect of mesna (2-mercaptoethane sulphonate sodium) with that of forced diuresis in preventing cyclophosphamide induced haemorrhagic cystitis in marrow transplant recipients. Sixty-one consecutive BMT recipients were randomised for treatment with forced diuresis or mesna. The incidence of macroscopic haematuria was significantly lower in the mesna treated group (chi 2 = 4.03, P less than 0.05). No specific side effects of mesna were detected. The lymphopenia induced by cyclophosphamide in the aplastic recipients was similar in the mesna and forced diuresis groups suggesting that mesna has no effect on the lymphocytotoxic activity of cyclophosphamide, although 6 out of 7 episodes of graft failure documented in the study occurred in mesna treated patients. As a result of this study our present policy is to use mesna in all BMT recipients but to continue careful documentation of the incidence of graft failure.

Adolescent↗