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Biomedical subjects

H M Williams

Publications and source records attributed to H M Williams.

At least 19 recordsLinked to original sources

A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

Aged↗

Outbreak of Escherichia coli O157 in a nursery: lessons for prevention.

OBJECTIVES: To identify risk factors for transmission of verocytotoxin producing Escherichia coli O157 (VTECO157) and means of prevention. STUDY DESIGN: Outbreak investigation: retrospective cohort study. SETTING: A nursery (child care centre) in North Wales. SUBJECTS: Children attending (n = 104). METHODS: Faeces were examined using sorbitol MacConkey agar (SMAC), with cefixime, tellurite, and rhamnose; enrichment in modified tryptone soya broth; and immunomagnetic separation. Symptoms and exposure data were obtained from questionnaires to parents/guardians and children's toiletting and feeding records kept at the nursery. MAIN OUTCOME MEASURE: A "case" was defined as a child with verocytotoxin producing E coli O157 isolated from faeces, or a history of haemolytic uraemic syndrome (HUS) and antibodies to E coli O157 lipopolysaccharide, during the period 10 August to 30 September 1995. RESULTS: The attack rate was 31 in 104. Two children developed HUS. There were higher attack rates among girls and friends who played together. Cases were more likely to attend the nursery more frequently. The mean number of recorded bowel motions/child/half day was 0.51 in cases and 0.21 in well children. Child to staff ratios were high preceding and during the outbreak. CONCLUSIONS: A sick child is the most plausible source of infection with subsequent person to person transmission. The record of children's toiletting discriminated between cases and well children and might have allowed earlier detection of the outbreak. This simple record could be considered by other child care facilities as a means of giving early warning of problems with infectious intestinal diseases.

Child↗

Adolescents' reported usage of selected foods in relation to their perceptions and social norms for those foods.

This paper reports a study of factors associated with the consumption of 22 diverse foods among 2082 students aged 12-15 years in Tasmania, Australia. Students provided data by completing a printed questionnaire. Multiple linear regression was used to assess how well self-reported usual (past) frequency of consumption of a food could be estimated from their perceptions of the qualities of the food (their liking for it, its healthfulness) and their descriptive social norms for the food (its usage by parents and its usage by friends). For all foods, multiple R was significant (p < 0.0001), with values ranging from 0.28-0.64 (median for the 22 foods being 0.49). Standardized regression coefficients for liking and parental usage were highly significant (p < 0.0001) for all foods. However, consistently lower coefficients were found for friends' usage (11 with p < 0.01, but only three with p < 0.0001) and healthfulness (five with p < 0.01, but only one with p < 0.0001). The absolute and relative magnitudes of the regression coefficients varied substantially between the foods. Liking was a stronger predictor than parental usage for 11 of the foods, and parental usage out-ranked liking for the remaining 11. Regression coefficients for friends' usage and healthfulness were smaller than those for liking and parental usage for all foods studied.

Adolescent↗

TNF-alpha is a principal cytokine involved in the recruitment of NK cells to liver parenchyma.

Isolated murine splenic NK cells and the cultured murine endothelioma cell line, eEND2, were used to study the effects of cytokines on NK cell/endothelial cell adhesion. Treatment of eEND2 cells with TNF-alpha induced a marked increase (four- to sevenfold) in adherence of NK cells, as compared with control cultures of endothelioma cells or eEND2 cells treated with IL-1 alpha or IL-6. TNF-alpha induction of NK cell adherence to eEND2 was dose dependent with rapid kinetics, reaching a maximum at concentrations between 10 and 1000 U/ml after a 2-h incubation. TNF-alpha treatment of L929 fibroblasts or CL-2 hepatoma cells did not result in increased NK cell adhesion. The concentration range of TNF-alpha that was found to maximally augment NK cell adhesion to eEND2 also induced NK cell chemokinetic activity. The relevance of these in vitro results was subsequently analyzed in vivo. Initial studies confirmed that a single dose of polyinosinic-polycytidylic acid and poly-L-lysine stabilized in carboxymethyl cellulose (poly-ICLC), augmented hepatic NK activity and resulted in a 2.2-fold increase in the number of liver-associated NK cells. Concomitant treatment of mice with a TNF-alpha neutralizing antisera eliminated both the hepatic influx of NK cells and the increase in poly-ICLC-induced liver NK activity. These results suggest that TNF-alpha is a principal cytokine involved in the in vivo recruitment and localization of parenchymal NK cells after treatment with a biological response modifier, and that this regulation seems to occur via alterations in NK cell/endothelial cell interactions.

Animals↗

Time-course of medial and intimal thickening in pig venous arterial grafts: relationship to endothelial injury and cholesterol accumulation.

With use of an established model of pig saphenous vein grafts in the carotid artery, the time-course of the following changes was related: (1) medial and intimal size by morphometry of transverse sections, (2) cell number by deoxyribonucleic acid concentration, (3) cell density by deoxyribonucleic acid concentration per milligram wet weight and by counting nuclei in transverse sections, (4) endothelial morphology by scanning electron microscopy, and (5) cholesterol concentration. In the first week after grafting, medial and intimal thickening occurred associated with an increase in cell number. Between 1 and 4 weeks after grafting, further rapid medial and intimal thickening occurred with no further increase in cell number but with a reduction in cell density, which suggested that cell migration, hypertrophy, and the laying down of extracellular matrix were responsible. Between 4 and 39 weeks after grafting, a slower increase in medial and intimal size occurred, associated with a parallel increase in cell number and no further change in cell density. The endothelium of grafts showed only localized abnormalities, including loss of cells and leukocyte adhesion, either 1 or 4 weeks after grafting. Cholesterol concentration was slightly elevated 1 week after grafting but returned to values similar to those in vein by 4 weeks after grafting. Distention to 600 mm Hg during surgical preparation of vein for grafting resulted in lower graft patency after either 1 or 4 weeks and caused significant medial and endothelial injury. Distention did not, however, affect changes in medial or intimal size, deoxyribonucleic acid, or cholesterol concentration caused by grafting. We conclude that three processes contribute to medial and intimal thickening, namely: (1) an initial phase of rapid smooth muscle cell proliferation, (2) smooth muscle cell migration, hypertrophy, and synthesis of extracellular matrix, and (3) a late phase of slower smooth muscle cell proliferation. The incomplete late suppression of smooth muscle cell proliferation occurs despite regeneration of a morphologically intact endothelium and in the absence of progressive cholesterol accumulation.

Anastomosis, Surgical↗

Distention promotes platelet and leukocyte adhesion and reduces short-term patency in pig arteriovenous bypass grafts.

A pig model of autologous saphenous vein to common carotid artery bypass grafting was developed. An end-to-end anastomotic technique led to lower middle graft and distal turbulence. Saphenous veins were surgically prepared with or without distention at 600 mm Hg, implanted into the arterial circulation, and removed 2 hours later. Medial integrity was then assessed by adenosine triphosphate/adenosine diphosphate concentration ratio, and endothelial integrity, leukocyte and platelet adhesion by scanning electron microscopy. In grafts made with undistended vein adenosine triphosphate/adenosine diphosphate concentration ratio was not significantly lower (3.0 +/- 0.1, n = 32) than in freshly isolated vein (3.3 +/- 0.1, n = 26), endothelial cover was 98% +/- 1%, n = 6, and there was little platelet or leukocyte adhesion. In distended grafts adenosine triphosphate/adenosine diphosphate concentration ratio was reduced to 2.2 +/- 0.2 (n = 7, p less than 0.005), endothelial cover was reduced to 38% +/- 14% (n = 6, p less than 0.001), and there was extensive platelet and leukocyte adhesion to exposed subendothelium. In separate experiments graft patency measured at 1 to 5 weeks was significantly greater (96%, n = 25) when undistended vein was used than when distended vein was used (64%, n = 25, p less than 0.005). The data show that distention leads to medial and endothelial damage and that this is associated with increased platelet and leukocyte adhesion and with reduced early patency.

Adenosine Diphosphate↗

The prevalence of antibiotic resistance in Haemophilus influenzae in Ireland.

From January to April 1988, 36 clinical microbiology laboratories in Northern Ireland and Eire took part in a survey to determine the prevalence of antibiotic resistance in Haemophilus influenzae. All isolates were collected and despatched to a coordinating laboratory where identification was confirmed and antibiotic sensitivity tests repeated. One thousand seven hundred and ninety strains were available for analysis. Of these, 10.9% were resistant to ampicillin (10.2% being beta-lactamase producers), 0.4% to amoxycillin-clavulanate, 2.1% to cefaclor, 3.7% to chloramphenicol, 2.6% to erythromycin, 4.1% to tetracycline, 2.6% to sulphonamide and 5.1% to trimethoprim. One hundred and nine strains (6.3%) were resistant to two or more of the antibiotics tested and 31 (1.7%) exhibited combined resistance to ampicillin, chloramphenicol and tetracycline. The prevalence of resistance to ampicillin and chloramphenicol was higher than had been previously recorded in largescale studies conducted on the British mainland.

Anti-Bacterial Agents↗

The effects of triiodothyronine on cultured neonatal rat cardiac myocytes.

The purpose of this study was to determine whether thyroid hormone could directly affect the phenotypic expression of two isozymic systems [lactate dehydrogenase (LDH) and myosin] and the energy transducing potential of cultured neonatal heart cells. In addition we determined if these biochemical systems developed in culture as they normally do during in vivo post-natal development. Cells were maintained for 14 days in culture medium containing 10% horse serum and Earle's salts. Experimental cultures were supplemented with 10 nmol/l 3,3',5-triiodo-L-thyronine (T3). Hearts used to study in vivo development were excised from rats at the ages of 2 and 14 days post-natal to correspond with the time of isolating and harvesting the cultured heart cells, respectively. Adult hearts were used to represent the final developmental stage. Cultured cardiomyocytes without T3 administered to the culture medium showed no change in the isozymic profiles (myosin and LDH) or in metabolic potential during the 2 week culture period. The T3 treated cultures showed a complete shift to the V1 myosin isozyme. The glycolytic and aerobic metabolic potential [i.e., phosphofructokinase (PFK) and citrate synthase (CS) activities] and the LDH isozyme distribution were unaltered by T3 treatment. During in vivo development a shift toward the V1 myosin and H-LDH isozymes along with an increase in aerobic metabolism occurred in the rat heart. These findings indicate that the development of these selected biochemical systems in cultured cardiac myocytes does not result from an intrinsic myogenetic program and thus must be regulated in vivo by epigenetic factor(s). These results show that T3 has the potential to be the prime determinant of the phenotypic expression of the myosin isoforms, but does not have the potential to be the sole determinant for the expression of the LDH isozymes or the glycolytic (PFK) and aerobic (CS) capacities of cardiac muscle cells.

Aging↗

The prevalence of antibiotic resistance in Haemophilus influenzae in Wales. Report from the Standing Specialist Advisory Group for Microbiology in Wales.

From January to April 1986 all 21 Clinical Microbiology Laboratories in Wales took part in a survey to determine the prevalence of antibiotic resistance in Haemophilus influenzae. All isolates were collected and despatched to a central laboratory where identification was confirmed and antibiotic sensitivity tests repeated. One thousand four hundred and forty strains were available for analysis. Resistance was present in 128 (8.9%) to ampicillin, 23 (1.6%) to cefaclor, 28 (1.7%) to chloramphenicol, 282 (19.6%) to erythromycin, 43 (3.0%) to tetracycline, 90 (6.2%) to sulphonamide and 66 (4.6%) to trimethoprim. One hundred and twenty-one strains (8.4%) were beta-lactamase producers. Thirteen (0.9%) were resistant to four or more antibiotics and included one type b strain isolated from cerebrospinal fluid resistant to ampicillin, chloramphenicol, tetracycline, trimethoprim and sulphonamide. The prevalence of resistance to ampicillin and trimethoprim was higher than that recorded previously in two large studies elsewhere in the United Kingdom. Ampicillin resistance was more common in strains from hospital inpatients than those from general practice.

Drug Resistance, Microbial↗

Preparation of human saphenous vein for coronary artery bypass grafting impairs its capacity to produce prostacyclin.

Prostacyclin production was measured from freshly isolated human saphenous vein and from vein subjected to routine surgical preparation for coronary bypass grafting. Surgical preparation had no effect on spontaneous prostacyclin production but significantly reduced stimulated rates from 16.9(1.1) to 7.1(0.5) pg.min-1 per mg wet weight (n = 27). Stimulated prostacyclin production was not reduced by storage of vein for 2 h at 23 degrees C in blood or saline nor by distension, but it was reduced to 5.0(0.6) pg.min-1 per mg (n = 10) by de-endothelialisation. Reduced prostacyclin production, which might in itself contribute to vein graft occlusion, provides a quantitative biochemical estimate of endothelial integrity.

Aged↗

A surgical preparative technique for coronary bypass grafts of human saphenous vein which preserves medial and endothelial functional integrity.

Measurements of adenosine triphosphate concentration and adenosine triphosphate/diphosphate ratio provided quantitative markers for medial integrity and stimulated (vortex-mixing) prostacyclin production for endothelial function. Freshly isolated vein had an adenosine triphosphate concentration of 470 +/- 60 nmol X gm-1 wet weight and an adenosine triphosphate/diphosphate ratio of 2.50 +/- 0.13; it produced prostacyclin at a rate of 9.3 +/- 1.0 pg X min-1 X mg-1 wet weight. Vein subjected to dissection, proximal anastomosis, and distention with the patient's own arterial pressure had an adenosine triphosphate concentration of 490 +/- 70 nmol X gm-1 wet weight and an adenosine triphosphate/diphosphate ratio of 2.29 +/- 0.13; it produced prostacyclin at a rate of 10.4 +/- 2.2 pg X min-1 X mg-1 wet weight. All values were indistinguishable from those in freshly isolated vein. In vein subjected to dissection, distention at less than 300 mm Hg with patient's heparinized blood, and distal anastomosis, adenosine triphosphate concentration, adenosine triphosphate/diphosphate ratio, and prostacyclin production (5.5 +/- 0.6 pg X min-1 X mg-1 wet weight) were all significantly (p less than 0.001) reduced. These results demonstrated that surgical preparation by first proximal anastomosis preserved both medial and endothelial function.

Adenosine Diphosphate↗

The effect of administration rate on cisplatin-induced emesis.

In an attempt to determine the influence of administration time on cisplatin-induced emesis, 20 adults previously untreated with cisplatin were enrolled into this double-blind study. Twenty patients were randomly assigned to receive high-dose cisplatin (greater than 100 mg/m2) either by a one-hour infusion or by an eight-hour infusion. All patients received antiemetic therapy with metoclopramide 2 mg/kg intravenously one-half hour before cisplatin administration, and 1 1/2, 3 1/2, 5 1/2, and 8 1/2 hours after cisplatin administration. Patients in the eight-hour infusion group experienced significantly fewer emesis episodes than did patients in the one-hour infusion group. The median of emesis episodes in the eight-hour group was one (range, 0 to 2) and in the one-hour group was three (range, 0 to 8). In patients receiving high-dose cisplatin plus metoclopramide, increasing the administration time from one hour to eight hours resulted in a small but significant decrease in emesis episodes. The cisplatin infusion rate should be considered as a variable in cisplatin-antiemetic trials.

Adult↗

Effect of exercise on plasma pyruvate kinase and creatine kinase activity.

Plasma pyruvate kinase (PK) and creatine kinase (CK) were measured in healthy subjects engaging in (a) mild exercise, 30 min on an exercise cycle maintaining a pulse rate of 150/min, (b) moderate exercise, squeezing a ball until exhaustion with a sphygmomanometer cuff inflated above systolic pressure around the arm (max. 2 min) and (c) severe exercise, completing a marathon race. Mild exercise resulted in no change in enzyme levels over 24 h. Moderate exercise produced a small increase in PK but no change in CK. PK activity rose from 35.3 +/- 10 U/l pre-exercise to 41.3 +/- 13 U/l 15 min post-exercise (n = 8, p less than 0.025). Severe exercise (completing a marathon race) resulted in a 3-fold increase in PK from 26 (4-87) U/l pre-race to 69 (21-156) U/l immediately post-race, and also, as expected, an increase in CK from 60 (15-164) U/l to 257 (72-1535) U/l (results are means and ranges, n = 69, p less than 0.001 for both enzymes). Runners showed parallel increases in PK and CK (p less than 0.05 by Spearman rank correlation). The mean post-race activity of CK-MB was less than 5% of total CK but 18 runners had values greater than 6% (mean 4.8, range 1-18). We conclude that PK, like CK, is increased following exercise due to liberation of muscle enzyme. However, only severe exercise is likely to lead to a substantial increase in plasma PK activity and therefore prejudice its clinical usefulness as a diagnostic test.

Adolescent↗

IMV and weaning.

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Humans↗