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Biomedical subjects

A Hill

Publications and source records attributed to A Hill.

At least 145 records · Page 8Linked to original sources
PubMed1995

Failure of macrophage activation in experimental obstructive jaundice: association with bacterial translocation.

Bacterial translocation from the gastrointestinal tract and macrophage activation are central to current theories of sepsis. The relevance of both in obstructive jaundice is unclear. The effect of bile duct ligation for 7 days on bacterial translocation to mesenteric lymph nodes and on macrophage activation in a rat model was examined. Compared with an incidence of zero in sham-ligated controls, bile-duct ligated rats had a 67 per cent incidence of Gram-negative colonization of mesenteric lymph nodes. This was associated with a significant (P < 0.001) decrease in macrophage tumour necrosis factor, superoxide anion and nitric oxide production compared with that in sham controls. Spontaneous bacterial translocation occurs in experimental obstructive jaundice and is associated with marked suppression of macrophage activation. This suggests a mechanism whereby jaundiced patients may be more susceptible to persistent infection but relatively protected against uncontrolled sepsis.

Animals↗
PubMed1995

Characterization of two Epstein-Barr virus epitopes restricted by HLA-B7.

We have identified two epitopes for Epstein-Barr virus specific cytotoxic T lymphocytes (CTL) restricted by the common allele HLA-B7. They are EBNA 3C 881-9 (QPRAPIRPI) and EBNA 3A 379-387 (RPPIFIRRL). The epitopes conform well to the recently described motif for HLA-B7-binding peptides (Huckzo et al., J. Immunol. 1993. 151:2572). Titration of the peptides in CTL assays and detergent lysate binding assays revealed that extending the peptides at either the N or C terminus did not reduce their affinity for HLA-B7. This behavior contrasted with HLA-B51, which binds peptides with a similar motif to B7, and has identical amino acid residues at sites expected to form the "F" pocket of the peptide-binding groove. HLA-B51 also bound the peptide EBNA 3C 881-9, but was unable to bind peptides extended at the C terminus.

Amino Acid Sequence↗
PubMed1995

Effects of resistance training on regional and total bone mineral density in premenopausal women: a randomized prospective study.

This study was designed to assess the effects of 18 months of resistance exercise on regional and total bone mineral density (BMD) and soft tissue lean mass (STL) in premenopausal women aged 28-39 randomly assigned to an exercise or control group. Twenty-two exercise and 34 control subjects completed the 18-month training study. All subjects were previously inactive and untrained women. Initial, 5-, 12- and 18-month assessments were made of total and regional BMD and total and regional STL using dual energy X-ray absorptiometry. All subjects consumed a 500 mg/day elemental calcium supplement throughout the study. Initial Ca intake without supplement averaged 1,023 mg/day in total sample. Serum levels of bone osteocalcin and dietary assessments using 12 randomly assigned days of diet records were also completed. Muscular strength was assessed from both 1 repetition maximum (RM) testing of 10 weightlifting exercises and by peak torque for hip abduction/adduction and knee extension/flexion. Training increased strength by 58.1% based on 1 RM testing and by 33.8% based on isokinetic testing at 18 months versus baseline. BMD increased significantly above baseline at the lumbar spine for the exercise group at 5 months (2.8%), 12 months (2.3%), and 18 months (1.9%) as compared with controls. Femur trochanter BMD increased significantly (p < 0.05) in the exercise group at 12 months (1.8%) and 18 months (2.0%) but not at 5 months (0.7%) as compared with controls. No changes in total BMD, arm BMD, or leg BMD were found. There was a 20% increase in BGP in the exercise group as compared with controls at 5 months and this difference was maintained throughout the study. For STL, significant increases for total, arm, and leg were found at 5, 12, and 18 months for the exercise group versus control ranging from 1-6% over baseline. These results support the use of strength training for increasing STL and muscular strength with smaller but significant regional increases in BMD in the premenopausal population.

Absorptiometry, Photon↗
PubMed1995

AM630, a competitive cannabinoid receptor antagonist.

AM630 (iodopravadoline), a novel aminoalkylindole, has been found to attenuate the ability of a number of cannabinoids to inhibit electrically-evoked twitches of the mouse isolated vas deferens. It did not block the inhibitory effects of morphine or clonidine on the twitch response. AM630 behaved as a competitive antagonist of CP 55,940, WIN 55,212-2, anandamide and (R)-(+)-arachidonyl-1'-hydroxy-2'-propylamide (AM356), producing rightward shifts in the log concentration response curves of these cannabinoid receptor agonists that were concentration-dependent, essentially parallel and not accompanied by any decrease in the size of maximal response. AM630 also produced concentration-dependent, parallel rightward shifts in the log concentration-response curve of delta 9-THC. However, these shifts were accompanied by a decrease in the maximal response. AM630 was markedly more potent as an antagonist of delta 9-THC and CP 55,940 (Kd = 14.0 and 17.3 nM respectively) than as an antagonist of WIN 55,212-2, AM356 or anandamide (Kd = 36.5, 85.9 and 278.8 nM respectively). These differences in dissociation constant imply that the mouse vas deferens may contain more than one type of cannabinoid receptor. The data also indicate that the receptors for which AM630 has the highest affinity may not be CB1 cannabinoid receptors as the CB1 selective antagonist, SR141716A, is known to be equally potent in attenuating the inhibitory effects of CP 55,940 and anandamide on the twitch response of the mouse vas deferens.

Animals↗
PubMed1995

Antibodies to measles, mumps and rubella in UK children 4 years after vaccination with different MMR vaccines.

Persistence of antibodies 4 years after vaccination with measles, mumps and rubella (MMR) vaccine from three different manufacturers was compared in 475 children who received a single injection of vaccine when aged 12-18 months. Antibodies to measles and mumps were measured using a plaque reduction neutralisation assay; rubella antibodies were measured by radial haemolysis and latex agglutination. Children given MMR vaccine containing the Urabe mumps strain were less likely to be antibody negative than those given the Jeryl Lynn mumps strain (39/266, 15% vs 39/204, 19%, p = 0.048). However, the relatively high proportions in both groups without detectable mumps neutralising antibody suggests the probable need for a second dose in order to achieve mumps elimination. No significant differences were found in the proportions with detectable antibody to measles between vaccines containing the Schwarz and the Enders-Edmonston strains. Overall, only 3% of vaccinees were without detectable measles antibody, although a further 28% had a level below 200 mille International Units, the putative protective level for clinical measles. Geometric mean titres (GMTs) to measles were twofold higher in girls vaccinated after than before 14 months of age; GMTs in boys were intermediate and showed no age effect. Over 99% of vaccinees were seropositive to rubella, confirming the excellent immunogenicity of the RA 27/3 rubella strain and the potential for elimination of rubella with a single dose strategy.

Antibodies, Viral↗
PubMed1995

The role of coping in adjustment to phantom limb pain.

Research has indicated that the way individuals cope with pain may influence pain, and physical and psychological adjustment. The present study assessed the relationship between coping strategy use and adjustment in amputees with phantom limb pain (PLP). Coping strategies were measured using the Coping Strategies Questionnaire (CSQ) and their relationship with adjustment was examined using both composite scores and individual strategy scores. The results indicated that the relationship between coping and adjustment was primarily explained by the use of strategies within the 'Helplessness' factor of the CSQ. A clearer picture of coping strategy use was gained from examining individual strategies rather than the composite measures. Catastrophizing explained the largest proportion of variance in pain report (26%), while increasing behavioral activity and hoping or praying strategies explained a smaller proportion of the variance (3% and 1%, respectively). Catastrophizing also explained a large proportion of the variance in physical and psychosocial dysfunction (11% and 22%), while hoping or praying strategies accounted for only a small proportion of the variance in physical dysfunction (3%), and re-interpreting pain sensations accounted for a small proportion of the variance in psychosocial dysfunction (3%). The findings in this study have important clinical implications in that coping strategy use was associated with increased, rather than decreased, levels of pain and disability. However, since the reported use of coping strategies in the present study was low, further research, perhaps utilizing other measures of coping, is required to clarify these findings.

Adaptation, Psychological↗
PubMed1995

Epirubicin, cisplatin and infusional 5-fluorouracil (5-FU) (ECF) in hepatobiliary tumours.

Hepatobiliary tumours are rare, often present late and have a poor prognosis, with no current effective systemic therapy available. This study aimed to evaluate the activity and toxicity of epirubicin, cisplatin and continuous infusional 5-fluorouracil (5-FU) (ECF) in patients with these tumours. From March 1991 to November 1993, 25 patients with advanced biliary tumours and 7 with hepatoma were treated with epirubicin 50 mg/m2 and cisplatin 60 mg/m2 intravenously (i.v.) day 1, each given every 21 days and 5-FU 200 mg/m2/day given as a continuous 24 h i.v. infusion throughout the treatment course. 8 of the 20 (40%) evaluable patients with biliary tumours responded. Median duration of response was 10 months. 2 of the 7 (29%) patients with hepatoma responded. The regimen was well tolerated with minimal haematological and non-haematological toxicity. This novel regimen is active in advanced hepatobiliary tumours.

Adult↗
PubMed1995

Clinical aspects of perinatal hypoxic-ischemic brain injury.

Perinatal hypoxic-ischemic cerebral injury is a significant cause of neurological morbidity and mortality in childhood. It is often difficult to determine the precise timing of such injury. Data from epidemiological and neuropathological studies have identified several maternal and fetal risk factors that seem to be associated with suspected prenatal brain injury. Hypoxic-ischemic cerebral injury that originates earlier in gestation may result in few, if any, clinical abnormalities during the newborn period. Clinical abnormalities may also be difficult to recognize in the premature newborn, and greater reliance must be placed on other adjunctive investigations, eg, neuroimaging. In contrast, term infants who sustain acute, intrapartum hypoxic-ischemic insult of sufficient magnitude to result in long-term sequelae invariably show recognizable encephalopathy during the newborn period. A combination of clinical data and adjunctive investigations during the neonatal period is a powerful predictive tool for long-term outcome.

Birth Injuries↗
PubMed1995

Adjuvant chemotherapy for oesophagogastric cancer with epirubicin, cisplatin and infusional 5-fluorouracil (ECF): a Royal Marsden pilot study.

Previous trials of adjuvant chemotherapy for oesophagogastric cancer have shown only modest or no improvement in survival. However, the regimens used in these studies produce low response rates in patients with advanced disease. ECF is a new regimen which results in higher response rates and may therefore be more effective in the adjuvant setting. Twenty-nine patients who had undergone a potentially curative resection for oesphagogastric carcinoma were treated with ECF [epirubicin 50 mg m-2 and cisplatin 60 mg m-2 for 18 weeks]. The median age was 52.5 years. Three patients had oesophageal tumours, 14 had tumours of the oesophagogastric junction (OGJ) and 12 had gastric tumours. All were adenocarcinomas apart from one undifferentiated carcinoma. One patient had stage I disease, nine stage II, 17 stage II and two stage IV. The mean number of chemotherapy cycles per patient was 5.2 (range 2-8). The median follow-up was 8.4 months (1.5-36.3 months). Eleven patients relapsed during follow-up (38%). One patient had an anastomotic recurrence and ten patients distant metastases. Overall 3 year survival was 61.5% (95% confidence interval 42-79); 3 year survival in stage II was 50% (21.2-86.3) and in stage III 65.6% (40-86). Chemotherapy was well tolerated, with grade 3/4 toxicity as follows: leucopenia 13.5%, nausea and vomiting 10%, diarrhoea 3.5%, infection 3.5% and thrombocytopenia 3.5%. There were no treatment-related deaths. We conclude that ECF can be administered safely as adjuvant treatment to patients with surgically resected gastro-oesophageal carcinoma. The results, especially in patients with stage III disease, are encouraging and support the investigation of this regimen within a prospective randomised trial.

Adenocarcinoma↗
PubMed1995

Evaluation of safety and efficacy of 3TC (lamivudine) in patients with asymptomatic or mildly symptomatic human immunodeficiency virus infection: a phase I/II study.

In a phase I/II study, 7 levels of 3TC therapy (from 0.5 to 20.0 mg/kg/day) were studied in 104 asymptomatic and mildly symptomatic human immunodeficiency virus-infected patients with CD4 cell counts < or = 400 x 10(6)/L. Mild and transient episodes of diarrhea, headache, fatigue, nausea, and abdominal pain were the most frequent events reported. No dose-limiting toxicities were observed. Small and transient increases in CD4 cell counts were detected during the first 4 weeks of treatment. These were followed by progressive declines during prolonged therapy. Sustained decreases in beta 2-microglobulin, neopterin, and p24 antigen levels were seen over the 52-week study. There was no consistent dose-response correlation for any surrogate marker. Penetration of 3TC into cerebrospinal fluid (CSF) was in the same range as reported for ddC and ddI; the mean CSF-to-serum ratio was 0.06. These findings indicate that 3TC exhibits an excellent safety profile and has antiretroviral activity at the dosages studied.

Adult↗
PubMed1995

Cisplatin and protracted venous infusion 5-fluorouracil (CF)--good symptom relief with low toxicity in advanced pancreatic carcinoma.

PURPOSE: The combination of protracted venous infusion (PVI) 5-FU with moderate dose cisplatin was evaluated in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Sixty-three patients with locally advanced or metastatic disease were treated with cisplatin (60 mg/m2 every 21 days) and PVI 5-FU (300 mg/m2/day) for a maximum of 24 weeks. All patients had histologically/cytologically confirmed tumour. Radiological response was assessed by CT scanning and toxicity, performance status and symptomatic response were assessed 3 weekly. RESULTS: The objective response rate was 16% with two radiological complete responses. The median survival was 7.6 months with a 1-year survival of 33% and a median progression-free survival of 6.6 months. Patients who had local disease only had a median survival of 14.8 months with a 1-year survival of 52%. Thirty-four percent of patients had an improvement in performance status on treatment and specific symptom response rates were weight loss 71%, dysphagia 100%, nausea and vomiting 70%, pain 60%, anorexia 50%, and reflux 81%. Chemotherapy was well tolerated with grade 3 or 4 toxicity being nausea/vomiting 5%, diarrhoea 7%, infection 4%, stomatitis 2%, plantar palmar syndrome 2%, anaemia 14%, leucopenia 5, neutropenia 10% and thrombocytopenia 8%. CONCLUSIONS: The CF regimen provides good symptomatic palliation with low toxicity in patients with advanced pancreatic cancer.

Adenocarcinoma↗
PubMed1995

Phase I/II study of 3TC (lamivudine) in HIV-positive, asymptomatic or mild AIDS-related complex patients: sustained reduction in viral markers. The Lamivudine European HIV Working Group.

OBJECTIVE: To evaluate the efficacy of 3TC (lamivudine), a synthetic nucleoside analogue that inhibits HIV reverse transcriptase in vitro, as treatment for HIV-positive, asymptomatic or mild AIDS-related complex patients. DESIGN: Open-label, multinational and multicentre, non-comparative, escalating dose study. METHODS: Patients who meet the selection criteria (n = 104) were enrolled in three European countries. Ten to 15 patients were included at each of the six dose levels of 3TC (0.5, 1.0, 2.0, 4.0, 8.0, 12.0 and 20.0 mg/kg daily in two divided doses every 12 h). Virological parameters--immune-complex dissociation (ICD) assay for HIV p24 antigenaemia, plasma HIV RNA load, whole blood assay and cellular viraemia--were evaluated at weeks 0, 4, 12 and 24. RESULTS: Sustained reductions in HIV RNA load and in ICD p24 antigen levels were observed and maintained over the 12-week assessment period. Greater reductions were noted at higher doses but this trend did not reach statistical significance. In 38 patients, reductions of cell viraemia were significantly greater at 4 weeks for patients treated at higher doses of 3TC. CONCLUSION: These virological data show that 3TC is a potent inhibitor of HIV replication in HIV-positive, asymptomatic or mild ARC patients as assessed by ICD p24 antigenaemia, plasma HIV RNA load and cell viraemia.

AIDS-Related Complex↗
PubMed1995

Royal Marsden phase III trial of fluorouracil with or without interferon alfa-2b in advanced colorectal cancer.

PURPOSE: Phase II studies have shown that the combination of interferon alfa-2b (IFN) and fluorouracil (5-FU) is active in patients with metastatic colon cancer. This study was designed to investigate whether treatment with the combination of IFN and 5-FU could improve the response rate, duration of response, or survival compared with treatment with 5-FU alone. PATIENTS AND METHODS: Patients with histologically confirmed advanced colorectal cancer were randomized to receive 5-FU 750 mg/m2/d by continuous infusion for 5 consecutive days followed by weekly bolus 5-FU 750 mg/m2 either with or without IFN 10 MU subcutaneously three times weekly. Treatment was continued until disease progression or unacceptable toxicity for up to 12 months. RESULTS: Radiologic response was observed in 26 of 106 assessable patients (25%): 10 of 52 (19%) in the group that received 5-FU plus IFN (all partial responses [PRs]) and 16 of 54 (30%) in the 5-FU-alone group (three complete responses [CRs] and 13 PRs) (P = .21). There was similarly no significant difference between the two groups in progression-free survival (median, 3 months), 1-year survival, or overall survival (median, 8 months). However, patients who received IFN did experience significantly more toxicity in the form of leukopenia (P = .013), lymphopenia (P = .01), depression (P = .014), and alopecia (P = .002), and were significantly more likely to be withdrawn due to adverse events (P = .003). There were four toxic deaths, all of which occurred in patients who had received IFN. CONCLUSION: At the doses and schedules used in this study, IFN affords no benefit to 5-FU in terms of response and survival and significantly increases toxicity for patients with advanced colorectal cancer.

Adult↗
PubMed1995

Antibiotic prophylaxis for bacterial meningitis: overuse and uncertain efficacy.

BACKGROUND: There is little evidence supporting the efficacy of prophylactic antibiotics in preventing secondary cases of bacterial meningitis, and recent guidance extended the use of prophylactic antibiotics amongst children who attend pre-school groups. METHODS: We examined the volume of rifampicin prescribed, and that recommended to contacts of cases of meningococcal and Hib meningitis in Somerset over a three-year period using case note records of the Consultant for Communicable Disease Control (CCDC) and PACT data. RESULTS: There was evidence of excessive prescribing over and above that recommended by the CCDC. CONCLUSIONS: Excessive prescribing increases the chance of serious drug side effects and the development of antibiotic resistance. It is suggested that both meningitis contacts and information about early symptoms of meningitis, as well as an explanation of the rationale behind the prescribing of antibiotic prophylaxis to contacts. This may reduce the likelihood of unnecessary prescribing and subsequent complications.

Adult↗
PubMed1995

Oxidative stress is present in atherosclerotic peripheral arterial disease and further increased by diabetes mellitus.

OBJECTIVE: Atherosclerosis, which is associated with increased oxidative stress, may be widespread and more advanced in both complicated and uncomplicated diabetics than in healthy, age-matched non diabetic controls. The development of microangiopathy and the early development of microangiopathy and the early development of macroangiopathy which occurs in diabetes have unclear aetiology. We have previously shown an increase in the products of free radical activity in conventional atherosclerosis and this study has considered whether there us a further increase in this oxidative stress in diabetics. EXPERIMENTAL DESIGN: We measured oxidation by free radicals as lipid peroxides (malondialdehyde) and plasma thiols in 19 insulin dependent diabetic patients with retinopathy or microproteinuria but no clinical evidence of large vessel disease, 19 non diabetic patients with obstructive peripheral arterial disease confirmed by angiography and 19 asymptomatic matched healthy control subjects. PATIENTS: The patients were recruited from either the local diabetic or vascular surgery clinics. RESULTS: There were significant increases in oxidative stress in diabetic patients compared to control subjects with increased malondialdehyde 9.2 mumol/l (7.1-11.2) versus 7.65 mumol/l (5.4-9.6, p < 0.01 Mann Whitney test) and reduced plasma thiols 458 mumol/l (294-595) versus 506 mumol/l (433-589, p < 0.05). Those non-diabetic patients with obstructive peripheral arterial disease also had significantly increased malondialdehyde levels at 8.4 mumol/l (6.5-10.1, p < 0.05) and reduced plasma thiols 435 mumol/l (361-462, p < 0.05) compared to controls. The difference between patients with conventional atherosclerotic peripheral arterial disease and those with additional diabetes was significant for malondialdehyde (p < 0.05). CONCLUSIONS: These data confirm the oxidative stress that exists in atherosclerotic peripheral arterial disease and suggest that diabetic patients with microangiopathy have an increase in this oxidative stress which may contribute to their early development of atherosclerosis.

Adult↗
PubMed1994

Epidemiology of meningococcal disease and a community outbreak in Somerset.

We describe the epidemiology of meningococcal disease in Somerset and a community outbreak in one district. Fifty-seven cases of meningococcal disease occurred in residents of Somerset between 1 May 1990 and 30 April 1993 (incidence 4.7/100,000/year), of whom six died. Thirteen of the cases occurred in one local authority area in a six month period from 1 November 1992 to 30 April 1993; an incidence of 26.6/100,000/year. Twenty-seven patients were given benzyl-penicillin before admission to hospital. General practitioners were significantly more likely to give benzylpenicillin to patients with rashes. The proportion that received prophylaxis tended to increase after a press release was issued and general practitioners were advised. The number of cases was too small to demonstrate the protective effect of early administration of benzylpenicillin. In five cases the consultant in communicable disease control was not informed for over 12 hours. Thirty-seven of the 48 index cases for whom information was available received rifampicin prophylaxis before discharge from hospital.

Adolescent↗