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Biomedical subjects

C Williams

Publications and source records attributed to C Williams.

At least 199 records · Page 11Linked to original sources
PubMed1998

Nitrogen mustard up-regulates Bcl-2 and GSH and increases NTP and PCr in HT-29 colon cancer cells.

We hypothesized that unexplained increases in nucleoside triphosphates (NTP) observed by 31P magnetic resonance spectroscopy (MRS) after treatment of tumours by DNA-damaging agents were related to chemotherapy-induced up-regulation of the bcl-2 gene and DNA damage prevention and repair processes. To test this hypothesis, we treated HT-29 cells with 10(-4) M nitrogen mustard (HN2) and performed sequential perchloric acid extractions in replicate over 0-18 h. By reference to an internal standard (methylene diphosphonic acid), absolute changes in 31P-detectable high-energy phosphates in these extracts were determined and correlated with changes in bcl-2 protein levels, cell viability, cell cycle, apoptosis and total cellular glutathione (GSH) (an important defence against DNA damage from alkylating agents). After HN2 administration, bcl-2 protein levels in the HT-29 cell line rose at 2 h. Cell viability declined to 25% within 18 h, but apoptosis measured using fluorescence techniques remained in the 1-4% range. Increased cell division was noted at 4 h. Two high-energy interconvertible phosphates, NTP (P < or = 0.006) and phosphocreatine (PCr) (P < or = 0.0002), increased at 2 h concurrently with increased levels of bcl-2 protein and glutathione. This study demonstrates that bcl-2 and glutathione are up-regulated by HN2 and links this to a previously unexplained 31P MRS phenomenon: increased NTP after chemotherapy.

Adenosine Triphosphate↗
PubMed1998

Caudal epidurals: the whoosh test.

Caudal epidural injection is a simple procedure that carries a low risk of complications. The whoosh test (injection of air into the caudal epidural space with simultaneous auscultation over the thoracolumbar spine) has been recommended as an aid to correct needle placement. A 1-year prospective study, using fluoroscopic imaging to identify needle position, was conducted to compare the sensitivity and specificity of the whoosh test with that of clinical impression alone in assessing correct needle placement in the caudal space. Of 131 patients studied, correct needle placement was achieved in 121 on the first attempt (92%). Clinical impression alone had a sensitivity of 94% and a specificity of 20%. The whoosh test had a sensitivity of 80% and a specificity of 60%. The whoosh test is superior to clinical judgment in detecting incorrect caudal needle placement.

Air↗
PubMed1998

Influence of fluid intake pattern on short-term recovery from prolonged, submaximal running and subsequent exercise capacity.

The aim of this study was to examine if the pattern of fluid intake with a carbohydrate-electrolyte solution during 4 h recovery from prolonged, submaximal running would influence the subsequent endurance capacity. Seven well-trained athletes aged 19.8 +/- 0.3 years (mean +/- s(mean)) took part in the study, which had university ethical committee approval. They ran at 70% VO2 max on a level treadmill for 90 min (T1), or until volitional fatigue, whichever came first, on two occasions, at least 7-10 days apart. Four hours later, the subjects ran at the same speed for as long as possible (T2), as a measure of their endurance capacity. During the 4 h rehydration recovery period, the runners were allowed to drink a carbohydrate-electrolyte solution (6.9% Lucozade-Sport; sodium, 24 mmol l(-1); potassium, 2.6 mmol l(-1); calcium, 1.2 mmol l(-1); osmolality, 300 mOsm kg(-1)) ad libitum on one occasion. On the other occasion, the volume of the same fluid was prescribed from calculations of the body mass loss during T1 (2.6% of pre-exercise body mass). All subjects completed the 90 min run during T1 on both trials. However, during T2, in the prescribed intake trial, the exercise time to exhaustion was 16% longer (P< 0.05) than during T2 in the ad libitum trial (69.9 +/- 9.1 vs 60.2 +/- 10.2 min). Although there was no difference between conditions in the total volume ingested (1499 +/- 155 vs 1405 +/- 215 ml), the volume of carbohydrate-electrolyte solution ingested in the fourth hour of the rehydration recovery period was greater in the prescribed intake trial than in the ad libitum trial (258 +/- 52 vs 78 +/- 34 ml; P< 0.05). The amount of glucose ingested in this period during the prescribed intake trial was also greater than during the ad libitum trial (17.8 +/- 3.6 vs 5.4 +/- 2.4 g; P< 0.05). There was a higher blood lactate concentration at the start of T2 in the prescribed intake trial than in the ad libitum trial (1.12 +/- 0.20 vs 0.94 +/- 0.09 mmol l(-1); P< 0.05), but there were no differences in blood glucose, plasma insulin, free fatty acid concentrations or urine volume between trials. The results of this study suggest that drinking a prescribed volume of a carbohydrate-electrolyte solution after prolonged exercise, calculated to replace the body fluid losses, restores endurance capacity to a greater extent than ad libitum rehydration during 4 h of recovery, even though the total volumes ingested were the same between trials.

Adult↗
PubMed1998

Mutation analysis of UBE3A in Angelman syndrome patients.

Angelman syndrome (AS) is caused by chromosome 15q11-q13 deletions of maternal origin, by paternal uniparental disomy (UPD) 15, by imprinting defects, and by mutations in the UBE3A gene. UBE3A encodes a ubiquitin-protein ligase and shows brain-specific imprinting. Here we describe UBE3A coding-region mutations detected by SSCP analysis in 13 AS individuals or families. Two identical de novo 5-bp duplications in exon 16 were found. Among the other 11 unique mutations, 8 were small deletions or insertions predicted to cause frameshifts, 1 was a mutation to a stop codon, 1 was a missense mutation, and 1 was predicted to cause insertion of an isoleucine in the hect domain of the UBE3A protein, which functions in E2 binding and ubiquitin transfer. Eight of the cases were familial, and five were sporadic. In two familial cases and one sporadic case, mosaicism for UBE3A mutations was detected: in the mother of three AS sons, in the maternal grandfather of two AS first cousins, and in the mother of an AS daughter. The frequencies with which we detected mutations were 5 (14%) of 35 in sporadic cases and 8 (80%) of 10 in familial cases.

Angelman Syndrome↗
PubMed1998

Psychosocial determinants of alcohol use among minority youth living in public housing developments.

Youth residing in low income, inner city, public housing developments might be extremely vulnerable to psychosocial risk factors associated with alcohol use. In this study, we developed and tested a model of alcohol etiology with 624 African-American and Hispanic 7th graders residing in public housing developments. The students completed questionnaires concerning their alcohol use, social influences on their drinking, their drinking attitudes and knowledge, their psychosocial skills, and demographic and behavioral control information. Logistic regression analyses indicated that social influences from adults, friends, and family members predicted alcohol use. Individual psychosocial characteristics, e.g., drinking refusal, lowered the odds of drinking. These findings imply that effective prevention approaches targeting minority urban youths residing in public housing developments should provide them with an awareness of social influences to drink, correct misperceptions concerning the prevalence of drinking, and train them in relevant psychosocial skills.

Adolescent↗
PubMed1998

Current or recent proton pump inhibitor therapy markedly impairs the accuracy of the [14C]urea breath test.

BACKGROUND: There are increasing indications for assessing Helicobacter pylori status by non-invasive means in dyspeptic patients. There is also increasing use of proton pump inhibitor therapy for dyspeptic disease. AIMS: To determine the effect of proton pump inhibitor therapy on the accuracy of the [14C]urea breath test. PATIENTS: [14C]Urea breath tests were performed in 20 H. pylori-positive and 13 H. pylori-negative dyspeptic patients before commencing omeprazole and after 4 weeks of treatment with 40 mg/day and then 6 months of treatment with 20 mg/day. Further studies were done in H. pylori-positive patients to examine the time course of the onset and resolution of the effect observed. RESULTS: False negative results occurred in 45% of the H. pylori-positive subjects after 4 weeks of omeprazole 40 mg/day and in 28% after 6 months of 20 mg/day. False positive results occurred in 15% of the H. pylori-negative subjects after 4 weeks of omeprazole 40 mg/day. In the H. pylori-positive subjects time course studies showed increasing suppression of the breath test result over the first 2-4 weeks of treatment. It took a similar time for the breath test result to recover after stopping treatment. There was no significant change in H. pylori IgG serology in the H. pylori-positive patients after 7 months of omeprazole treatment. CONCLUSIONS: Proton pump inhibitor therapy markedly impairs the accuracy of the [14C]urea breath test and, in particular, produces a high proportion of false negative results. The effect is dose related and may persist for 2-4 weeks after stopping therapy. Patients should be carefully questioned about recent proton pump inhibitor therapy before accepting a negative breath test result as reliable.

Anti-Ulcer Agents↗
PubMed1998

Mapping of epitopes exposed on intact human immunodeficiency virus type 1 (HIV-1) virions: a new strategy for studying the immunologic relatedness of HIV-1.

To study the antigenic conservation of epitopes of human immunodeficiency virus type 1 (HIV-1) isolates of different clades, the abilities of human anti-HIV-1 gp120 and gp41 monoclonal antibodies (MAbs) to bind to intact HIV-1 virions were determined by a newly developed virus-binding assay. Eighteen human anti-HIV MAbs, which were directed at the V2, V3 loop, CD4-binding domain (CD4bd), C5, or gp41 regions, were used. Nine HIV-1 isolates from clades A, B, D, F, G, and H were used. Microtiter wells were coated with the MAbs, after which virus was added. Bound virus was detected after lysis by testing for p24 antigen with a noncommercial p24 enzyme-linked immunosorbent assay. The anti-V3 MAbs strongly bound the four clade B viruses and viruses from the non-B clades, although binding was weaker and more sporadic with the latter. The degrees of binding by the anti-V3 MAbs to CXCR4- and CCR5-tropic viruses were similar, suggesting that the V3 loops of these two categories of viruses are similarly exposed. The anti-C5 MAbs bound isolates of clades A, B, and D. Only weak and sporadic binding of all the viruses tested with anti-CD4bd, anti-V2, and anti-gp41 MAbs was detected. These results suggest that V3 and C5 structures are shared and well exposed on intact virions of different clades compared to the CD4bd, V2, and gp41 regions.

Antibodies, Monoclonal↗
PubMed1998

Effect of a carbohydrate-electrolyte drink on endurance capacity during prolonged intermittent high intensity running.

OBJECTIVE: To examine the effect of a carbohydrate-electrolyte solution on endurance capacity during prolonged intermittent running. METHODS: Nine subjects (eight men and one woman) ran to exhaustion on a motorised treadmill on two occasions separated by at least 10 days. After an overnight fast, they performed repeated 15 second bouts of fast running (at 80% Vo2MAX for the first 60 minutes, at 85% Vo2MAX from 60 to 100 minutes of exercise, and finally at 90% Vo2MAX from 100 minutes of exercise until exhaustion), separated by 10 seconds of slow running (at 45% Vo2MAX). On each occasion they drank either a water placebo (P) or a 6.9% carbohydrate-electrolyte (CHO) solution immediately before the run (3 ml/kg body mass) and every 20 minutes thereafter (2 ml/kg body mass). RESULTS: Performance times were not different between the two trials (112.5 (23.3) and 110.2 (21.4) min for the P and CHO trials respectively; mean (SD)). Blood glucose concentration was higher in the CHO trial only at 40 minutes of exercise (4.5 (0.6) v 3.9 (0.3) mmol/1 for the CHO and P trials respectively; p < 0.05), but there was no difference in the total carbohydrate oxidation rates between trials. CONCLUSION: These results suggest that drinking a 6.9% carbohydrate-electrolyte solution during repeated bouts of submaximal intermittent high intensity running does not delay the onset of fatigue.

Adult↗
PubMed1998

Eradicating Helicobacter pylori reduces hypergastrinaemia during long-term omeprazole treatment.

BACKGROUND: Both proton pump inhibitor drug treatment and Helicobacter pylori infection cause hypergastrinaemia in man. AIMS: To determine whether eradicating H pylori is a means of reducing hypergastrinaemia during subsequent proton pump inhibitor treatment. METHODS: Patients with H pylori were randomised to treatment with either anti-H pylori or symptomatic treatment. One month later, all received four weeks treatment with omeprazole 40 mg/day for one month followed by 20 mg/day for six months. Serum gastrin concentrations were measured before and following each treatment. RESULTS: In the patients randomised to anti-H pylori treatment, eradication of the infection lowered median fasting gastrin by 48% and meal stimulated gastrin by 46%. When gastrin concentrations one month following anti-H pylori/symptomatic treatment were used as baseline, omeprazole treatment produced a similar percentage increase in serum gastrin in the H pylori infected and H pylori eradicated patients. Consequently, in the patients in which H pylori was not eradicated, median fasting gastrin concentration was 38 ng/l (range 26-86) at initial presentation and increased to 64 ng/l (range 29-271) after seven months omeprazole, representing a median increase of 68% (p < 0.005). In contrast, in the patients randomised to H pylori eradication, median fasting gastrin at initial presentation was 54 ng/l (range 17-226) and was unchanged after seven months omeprazole at 38 ng/l (range 17-95). CONCLUSION: Eradicating H pylori is a means of reducing the rise in gastrin during subsequent long term omeprazole treatment. In view of the potential deleterious effects of hypergastrinaemia it may be appropriate to render patients H pylori negative prior to commencing long-term proton pump inhibitor treatment.

Adult↗
PubMed1998

Case-control study of salmeterol and near-fatal attacks of asthma.

BACKGROUND: A case-control study was undertaken to investigate the hypothesis that the use of the long acting beta agonist salmeterol increases the risk of a near-fatal attack of asthma. METHODS: The cases comprised admissions to the intensive care unit (ICU) for asthma in 14 major hospitals within the Wessex region in 1992. For each of the cases four age-matched controls were selected from asthma admissions to the same hospital during the same period. Information on prescribed drug therapy for the 48 cases and 185 controls was collected from the hospital admission records. RESULTS: The patients admitted to the ICU had greater chronic asthma severity and had generally been prescribed more asthma drugs than the control admissions to hospital. The relative risk of a near-fatal attack of asthma in patients prescribed inhaled salmeterol was 2.32 (95% CI 1.05 to 5.16), p = 0.04. However, the salmeterol relative risk decreased to 1.42 (95% CI 0.49 to 4.10), p = 0.52 when the analysis was restricted to the more chronically severe patients (those in the subgroup of patients with a hospital admission for asthma in the previous 12 months). These findings suggest that the increased unadjusted relative risk with salmeterol is predominantly due to confounding by severity--that is, the increased relative risk is due to patients with more severe asthma (at greatest risk of a near-fatal asthma attack) being preferentially prescribed salmeterol. This interpretation is supported by the finding in this study that, within the control group (selected from the population of asthmatics requiring hospital admission), salmeterol was preferentially prescribed to the most severe patients (a threefold greater prescription of salmeterol to control patients if they had been admitted to hospital in the 12 months prior to the index admission). There was no increased risk of a near-fatal attack of asthma in patients prescribed a beta agonist by metered dose inhaler (OR 0.75 (95% CI 0.31 to 1.78), p = 0.51). In contrast, the relative risks for beta agonists delivered by nebulisation (OR 3.86 (95% CI 1.99 to 7.50), p < 0.001) and oral theophylline (OR 2.45 (95% CI 1.26 to 4.78), p < 0.01) were increased and did not markedly decrease when the analysis was restricted to the more severe asthmatic subjects. CONCLUSIONS: Although these findings are not conclusive, particularly because of the small numbers involved in some subgroup analyses, they suggest that the use of salmeterol by patients with chronic severe asthma is not associated with a significantly increased risk of a near-fatal attack of asthma. If a near-fatal asthma attack is considered to be an intermediate step in a process by which a severe attack of asthma may become fatal, these results would suggest that salmeterol is unlikely to be associated with an increased risk of death, at least by this mechanism.

Adolescent↗
PubMed1998

Use of dexamethasone and granisetron in the control of delayed emesis for patients who receive highly emetogenic chemotherapy. National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To evaluate the roles of granisetron and dexamethasone for emesis control on days 2 through 7 after the administration of cisplatin in doses of 50 mg/m2 or greater to patients who had not previously received chemotherapy. PATIENTS AND METHODS: Four hundred thirty-five eligible and assessable patients were randomized to one of two arms in a double-blind fashion: arm A; granisetron 3 mg intravenous (i.v.) plus dexamethasone 10 mg i.v. prechemotherapy followed by granisetron 1 mg orally at 6 and 12 hours, then granisetron 1 mg orally and dexamethasone 8 mg orally twice daily on days 2 through 7 (219 patients); arm B; as in arm A but with placebo substituted for granisetron on days 2 through 7 (216 patients). All patients completed diaries in which episodes of emesis and severity of nausea were recorded. RESULTS: The addition of granisetron on days 2 through 7 had no discernable impact on nausea and vomiting during this period. CONCLUSION: The administration of a 5-hydroxytryptamine3, receptor (5-HT3) antagonist, in this case granisetron, after 24 hours conferred no benefit. This negative result needs to be assessed in light of conflicting literature, but at present it does not appear that the routine use of these drugs in this setting is justified.

Antiemetics↗
PubMed1998

Maturational change in the cortical response to hypoperfusion injury in the fetal sheep.

A characteristic of perinatal encephalopathies are the distinct patterns of neuronal and glial cell loss. Cerebral hypoperfusion is thought to be a major cause of these lesions. Gestational age is likely to influence outcome. This study compares the cortical electrophysiologic and histopathologic responses to hypoperfusion injury between preterm and near term fetuses. Chronically instrumented 0.65 (93-99-d, n = 9) and 0.9 (119-133-d, n = 6) gestation fetal sheep underwent 30 min of cerebral hypoperfusion injury. The parasagittal cortical EEG and impedance (measure of cytotoxic edema) responses plus histologic outcome (3 d) were compared. The acute rise in impedance was similar in amplitude, but the onset was delayed (5.0 +/- 0.7 versus 9.1 +/- 1.1 min, p < 0.05) in the preterm fetuses relative to those near term. In contrast the extent of the secondary rise was reduced (p < 0.01) and peaked earlier in the preterm fetuses (19.8 +/- 1.0 versus 40.5 +/- 3.5 h, p < 0.01). Both groups had a similar fall in EEG spectral edge frequency. The preterm fetuses had a milder loss of EEG intensity at 72 h (-7.7 +/- 1.5 versus -12.8 +/- 0.9 dB, p < 0.05). At both ages there was a predominantly parasagittal cortical distribution of damage with a similar pattern of neuronal loss in the thalamus and striatum. There was extensive selective neuronal loss within the upper layers of the cortex in those near term. In contrast the preterm fetuses developed subcortical infarcts (p < 0.05). The cortical response to injury altered during the last trimester. The results suggest the severity of the delayed phase of cortical neuronal injury and selective neuronal loss increased near term. In contrast, the preterm fetuses had a more rapidly evolving injury leading to necrosis of the subcortical white matter.

Animals↗
PubMed1998

Human muscle glycogen metabolism during exercise. Effect of carbohydrate supplementation.

Carbohydrate (CHO) ingestion during exercise, in the form of CHO-electrolyte beverages, leads to performance benefits during prolonged submaximal and variable intensity exercise. However, the mechanism underlying this ergogenic effect is less clear. Euglycaemia and oxidation of blood glucose at high rates late in exercise and a decreased rate of muscle glycogen utilisation (i.e. glycogen 'sparing') have been proposed as possible mechanisms underlying the ergogenic effect of CHO ingestion. The prevalence of one or the other mechanism depends on factors such as the type and intensity of exercise, amount, type and timing of CHO ingestion, and pre-exercise nutritional and training status of study participants. The type and intensity of exercise and the effect of these on blood glucose, plasma insulin and catecholamine levels, may play a major role in determining the rate of muscle glycogen utilisation when CHO is ingested during exercise. The ingestion of CHO (except fructose) at a rate of > 45 g/h, accompanied by a significant increase in plasma insulin levels, could lead to decreased muscle glycogen utilisation (particularly in type I fibres) during exercise. Endurance training and alterations in pre-exercise muscle glycogen levels do not seem to affect exogenous glucose oxidation during submaximal exercise. Thus, at least during low intensity or intermittent exercise, CHO ingestion could result in reduced muscle glycogen utilisation in well trained individuals with high resting muscle glycogen levels. Further research needs to concentrate on factors that regulate glucose uptake and energy metabolism in different types of muscle fibres during exercise with and without CHO ingestion.

Beverages↗