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Biomedical subjects

R A Sherwood

Publications and source records attributed to R A Sherwood.

At least 19 recordsLinked to original sources
PubMed2006

The pharmacokinetics of a single rectal dose of paracetamol (40 mg x kg(-1)) in children with liver disease.

BACKGROUND: The aim of our study was to measure the serum paracetamol concentrations achieved following a single rectal loading dose of 40 mg x kg(-1) in children with chronic liver disease. METHODS: We recruited 17 children (3-15 years, 10.6-75 kg) undergoing minor surgical procedures under general anesthesia. Paracetamol was administered at the end of surgery and blood samples were taken for analysis at 2, 3, 4, 6 and 8 h postdose. RESULTS: The mean Cmax of 11.4 mg x l(-1) [coefficient of variation (CV) 66%] was achieved at a Tmax of 2.7 h (CV 42%). The relative bioavailability (F) of the suppository formulation was not estimated, but clearance (Cl/F) estimates 0.73 l x kg(-1) x h(-1) (CV 87%) and time-concentration profiles for these children were similar to the normal pediatric population. CONCLUSIONS: There are currently no biologic markers available for monitoring possible hepatotoxicity in this cohort of patients with liver disease, but our data suggest that a single-dose suppository is a satisfactory analgesic alternative.

Acetaminophen↗
PubMed2005

Prognostic role of cardiac troponin I after percutaneous coronary intervention in stable coronary disease.

OBJECTIVE: To assess the role of cardiac troponin I (cTnI) in predicting outcome after percutaneous coronary intervention (PCI). METHODS AND RESULTS: cTnI was measured immediately before and at 6, 14, and 24 hours after PCI in 316 consecutive patients with stable symptoms and native coronary artery disease. The study end point was the occurrence of major adverse cardiac events (MACE) at 30 days and at 18 months after PCI: death, Q wave myocardial infarction (MI), or repeat revascularisation in hospital. Postprocedural cTnI increased in 31% of patients. The cumulative MACE rate at 18 months was 25% (17.7% due to repeat PCI procedures). There was a significant association between postprocedural cTnI increase and death, Q wave MI, or both (odds ratio (OR) 3.28, 95% confidence interval (CI) 1.7 to 6.4, p = 0.01). Post-PCI cTnI increase had a positive predictive value (PPV) for adverse events at 18 months of 0.47 and a negative predictive value (NPV) of 0.96 (OR 18.9, 95% CI 9.7 to 37, p < 0.0001). The presence of both a postprocedural cTnI rise and a procedural angiographic complication gave a PPV for adverse events of 0.69 and an NPV of 0.92 (OR 22.6, 95% CI 2.6 to 68.6, p = 0.0005). CONCLUSIONS: cTnI increased post-procedurally in one third of this stable patient population undergoing elective PCI and was independently and significantly predictive of an increased risk of adverse events at 18 months, predominantly in the form of repeat PCI.

Aged↗
PubMed2004

Evaluation of neuromuscular symptoms in UK Gulf War veterans: a controlled study.

OBJECTIVES: To determine whether Gulf War veterans with neuromuscular symptoms that included weakness and fatigue had either 1) objective correlates for muscle weakness or fatigue; or 2) any etiologic explanation for such symptoms; and if so, 3) whether such objective measures or etiologic mechanisms were specific to Gulf War service. METHODS: Forty-nine ill Gulf War veterans with more than four neuromuscular symptoms (Gulf-ill) were compared with 26 Gulf-well veterans, 13 symptomatic Bosnian veterans (Bosnia-ill), and 22 symptomatic troops who were not deployed to the Gulf (Era-ill). Quantitative myometry was used to objectively measure weakness and fatigue. Subjects had an ischemic forearm exercise test, a subanaerobic bicycle exercise test, and a muscle biopsy. RESULTS: Quantitative strength and fatigue measures did not correlate with self-perception of weakness or fatigue for any of our groups. No specific muscle biopsy abnormalities were found. There was no defect of adenylate deaminase or glycogenolysis found. Gulf-ill subjects did find the subanaerobic bicycle exercise more effortful and generated significantly higher plasma lactate concentrations compared with Gulf-well subjects. CONCLUSION: Because complaints of weakness and fatigue in unwell servicemen do not correlate with actual weakness or fatigue, explanations for these symptoms must lie outside of the neuromuscular system. Increased lactate production during subanaerobic bicycle exercise reflects mitochondrial inefficiency, but it is unclear whether this reflects mitochondrial damage sustained during Gulf War service or inactivity secondary to ill health.

Biopsy↗
PubMed2002

Primary cultures of prostate cells and their ability to activate carcinogens.

Differences in the incidence of prostate cancer (CaP) amongst different migrant populations point to causative agents of dietary and/or environmental origin. Prostate tissues were obtained following transurethral resection of the prostate (TURP) or radical retropubic prostatectomy. After surgery, TURP-derived or tumour-adjacent tissue fragments were minced in warm PFMR-4A medium (37 degrees C) and suspensions pipetted into collagen-coated petri dishes. Non-adherent material was removed by washing with fresh medium after 12 h. Adhered cells subsequently reacted positively with monoclonal antibodies to prostate specific antigen (PSA). PSA was also detected in the medium. The genotoxicities of the chemical carcinogens 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP), its N-hydroxy metabolite (N-OH-PhIP) and benzo[a]pyrene (B[a]P) in adherent cell populations from different donors (n=8) were examined. Cells were treated in suspension for 30 min at 37 degrees C in the presence of the DNA repair inhibitors hydroxyurea (HU) and cytosine arabinoside (ara-C). DNA single-strand breaks were detected in cells by the alkaline single cell-gel electrophoresis ('Comet') assay and quantified by measuring comet tail length (CTL) in microm. All three carcinogens induced dose-related increases in CTLs (P<0.0001) in cells from four donors 24 h post-seeding. However, in cells from a further two donors the genotoxic effects of PhIP, N-OH-PhIP and B[a]P were much less apparent after 48 h than after 24 h in culture. After 96 h in culture, cells from these donors appeared to be resistant to the comet-forming activity of the compounds. However, B[a]P-DNA adducts were still measurable by (32)P-postlabelling for up to 14 days following a 24-h exposure to 50 microM B[a]P in adhered cells from another two donors. This study shows that primary cultures of cells derived from the prostate can activate members of two classes of chemical carcinogens. Further development may provide a robust model system in which to investigate the aetiology of CaP.

Adult↗
PubMed2002

Folic acid enhances endothelial function and reduces blood pressure in smokers: a randomized controlled trial.

OBJECTIVE: Cigarette smoking is associated with increased plasma homocysteine concentrations, endothelial dysfunction and arterial stiffening. Homocysteine per se induces endothelial dysfunction and arterial stiffening and might account, at least partly, for the vascular abnormalities observed in smokers. We sought to determine whether folic acid supplementation, by reducing plasma homocysteine concentrations, enhanced endothelial function and reduced arterial stiffness in smokers. DESIGN: Double-blind, randomized controlled, parallel-group, trial. SETTING: Academic medical centre. SUBJECTS: A consecutive sample of 24 healthy cigarette smokers (age 37.8 +/- 2.5 years, mean +/- SEM). INTERVENTION: Subjects were randomly assigned to 4-week folic acid 5 mg day-1 or placebo. MAIN OUTCOME MEASURES: The following were measured before and after treatment: (i) peripheral vasoreactivity (forearm arterial blood flow, FABF) during intra-arterial administration of endothelium-dependent (acetylcholine 1.5, 4.5 and 15 microg min-1) and endothelium-independent (sodium nitroprusside 1, 2 and 4 microg min-1) vasodilators; (ii) carotid-femoral pulse-wave velocity (PWV); (iii) blood pressure (BP). RESULTS: Folic acid reduced homocysteine concentrations (10.8 +/- 0.6 vs. 8.2 +/- 0.5 micromol L-1, P < 0.001) and enhanced endothelium-dependent vasodilatation during each acetylcholine infusion rate (ratio between the FABF in the infused and control arm during increasing infusion rates at baseline 1.09 +/- 0.03 vs. 1.41 +/- 0.09 after treatment, P < 0.01; 1.39 +/- 0.07 vs. 1.83 +/- 0.12, P < 0.01; 1.65 +/- 0.16 vs. 2.72 +/- 0.36, P < 0.05) whilst endothelium-independent vasodilatation was unaffected. A significant fall in BP was also observed (mean BP 88 +/- 2 vs. 83 +/- 1 mmHg, P < 0.01). By contrast, PWV did not significantly change (8.4 +/- 0.3 vs. 7.8 +/- 0.4 m s-1). No significant changes in plasma homocysteine concentrations, FABF, BP, and PWV were observed in the placebo group. A multiple regression analysis showed that changes in folic acid plasma concentrations independently predicted both FABF changes during maximal acetylcholine-mediated vasodilatation (P < 0.01) and BP changes (P = 0.01). CONCLUSIONS: Short-term folic acid supplementation significantly enhanced endothelial function and reduced BP in young chronic smokers. These effects were largely independent from the homocysteine lowering effects. Thus, a simple, nontoxic, and relatively inexpensive vitamin intervention might be useful in primary cardiovascular prevention in this high-risk group.

Adult↗
PubMed2001

Changes in brain natriuretic peptide concentrations following open cardiac surgery with cardioplegic cardiac arrest.

Elevated brain natriuretic peptide (BNP) concentration in peripheral blood reflects impaired cardiac ventricular function. We investigated the release pattern of BNP following cardioplegic cardiac arrest during heart surgery. In particular, we sought to discover whether there is an increase in peripheral BNP concentrations following reperfusion of the ischaemic heart. A secondary aim of the study was to investigate whether allopurinol, an anti-oxidant, has any effect on BNP release. A total of 29 patients scheduled for elective coronary artery bypass grafting were recruited, of whom 12 were randomly allocated to receive allopurinol with their pre-medication. Blood specimens were taken at six time points from the indwelling arterial catheter, the first before surgery and the last 2 h following the termination of cardiopulmonary bypass (CPB). BNP was found to decrease markedly when the aortic cross clamp was applied and the heart was isolated from circulation (P=0.0001). There was a slight increase in BNP following cross clamp release and myocardial reperfusion (P=0.04). A more substantial increase occurred with weaning from CPB when ventricular filling occurred (P=0.0015). Only the final BNP value, 2 h after CPB, was elevated compared with baseline (P=0.0013). Allopurinol had no demonstrable effect on changes in BNP.

Aged↗
PubMed2001

Validity of PSA, free/total PSA ratio and complexed/total PSA ratio measurements in men with acute urinary retention.

The reliability of serum prostate specific antigen (PSA) measurements in men with acute urinary retention is unclear. Total PSA, free and complexed PSA were measured, and the free/total (f/t) PSA and complexed/total (c/t) PSA ratios calculated, prior to catheterisation and at 48 and 72 h post-catheterisation in 39 men with acute retention. Subsequent histology showed 12 patients had prostate cancer and 27 benign prostatic hypertrophy. Serum free and total PSA fell following catheterisation, while complexed PSA rose during the first 48 h then subsequently fell. The f/t PSA and c/t PSA ratios provided the best discrimination at 48-72 h with 100% sensitivity and 75-82% specificity.Prostate Cancer and Prostatic Diseases (2001) 4, 167-172.

Journal Article↗
PubMed2001

Serum S100beta protein as a marker of disease activity in patients with malignant melanoma.

The purpose of the study was to evaluate serum S100beta protein as a marker of disease activity in patients with malignant melanoma (MM) and compare it with serum alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). One hundred sixty-four patients with MM, stages I-IV according to the American Joint Committee on Cancer (AJCC), were studied. Recurrent disease was categorized as active (AD) if metastases were evident clinically or with imaging investigations and inactive (ID) if no metastases were apparent at the time of sample collection. The sensitivity and specificity of S100beta, LDH, and ALP for discrimination between AD and ID were calculated using receiver-operating characteristic curve (ROC) analysis. Serum S100beta, LDH, and ALP concentrations were significantly higher in AD compared to ID. Serum S100beta protein was the best discriminator between AD and ID, the areas under the ROC curve being 0.89, 0.71, and 0.70 for S100beta, LDH, and ALP, respectively. Serum S100beta and LDH levels (both p < 0.0001) and serum ALP levels (p = 0.0014) corresponded with the number of metastatic sites involved. Using a cutoff point of 0.20 microg/L for serum S100beta protein, a specificity of 93% with a sensitivity of 68% was obtained for AD in MM. In stage IV disease, S100 was an independent predictor of survival in univariate (p = 0.001; hazard ratio = 1.0156) and multivariate (p = 0.038; hazard ratio = 1.0108) analyses. Serum S100beta protein is a better indicator of disease activity in MM than LDH or ALP and is an independent predictor of survival in stage IV disease.

Adult↗
PubMed2001

Cardioprotective effect of propranolol from alcohol-induced heart muscle damage as assessed by plasma cardiac troponin-t.

BACKGROUND: Heavy alcohol consumption from either long-term misuse or binge drinking is associated with poor cardiac contractility, mitochondrial dysfunction, and ventricular arrhythmias. The aim of this study was to measure circulating cardiac troponin-T as a marker for myocardial damage following acute and chronic alcohol administration. METHODS: In acute studies, male Wistar rats were treated with alcohol (75 mmol/kg body weight, intraperitoneal) and plasma was collected 2.5 hr after alcohol administration for analysis of rat cardiac troponin-T. In addition, rats were pretreated with cyanamide (an inhibitor of acetaldehyde dehydrogenase), various beta-blockers, xanthine oxidase inhibitors, or lisinopril before acute alcohol dosing. In chronic studies, rats were fed alcohol (as 35% of total dietary calories) for 6 weeks. RESULTS: The results of the time course study showed that acute alcohol administration significantly raised plasma cardiac troponin-T levels after 2.5 hr and 6 hr, but not after 24 hr. The effects of alcohol on cardiac troponin-T were potentiated with cyanamide pretreatment. Acute ethanol, alone or with cyanamide pretreatment, decreased systolic blood pressure and increased heart rates. Beta-blocker pretreatment with propranolol reduced the alcohol-induced increase in plasma troponin-T, whereas lisinopril potentiated this effect. The beta-blockers, atenolol and metoprolol, and the xanthine oxidase inhibitors, allopurinol and oxypurinol, were unable to reduce elevated troponin-T. However, pretreatment with the beta-blocker timolol moderated the acute alcohol-induced increase in troponin-T. In the chronic alcohol rat model, no differences were observed between alcohol and control pair-fed rats, suggesting the inducement of tolerance. CONCLUSIONS: In conditions of acute exposure, ethanol-induced lesions are characterized by raised plasma cardiac troponin-T possibly due to beta1 and/or beta2 adrenergic activation.

Adrenergic beta-Antagonists↗
PubMed2000

A comparative investigation into the effect of chronic alcohol feeding on the myocardium of normotensive and hypertensive rats: an electrophoretic and biochemical study.

We investigated whether the imposition of chronic alcohol in hypertension leads to greater biochemical and cellular abnormalities of the myocardium than those arising in normotension. Fifteen-week-old spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were fed ethanol-containing diets for six weeks. Particular attention was focused on the composition of contractile proteins identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), fractional rate of protein synthesis, and synthesis rates relative to RNA (RNA activity) or DNA (cellular efficiency). In addition, myocardial enzymes and adenine nucleotides were measured. In both SHR and WKY rats chronic ethanol caused a general decrease in the contents of all nine contractile proteins with myosin heavy chain predominantly affected. Fractional rates of mixed (i.e., total) and myofibrillary proteins remained unaltered in both WKY rats and SHR, as were cellular efficiencies. The RNA activity was significantly reduced in ethanol-treated SHR but not in WKY rats. In ethanol-treated SHR, cardiac creatine kinase (CK) and malate dehydrogenase (MDH) activities were increased, AMP levels were elevated, whilst ATP levels and the energy charge were reduced. In WKY rats, the only significant change related to increased aspartate aminotransferase activities in response to alcohol feeding. Although there were only subtle differences between the response of the normotensive and hypertensive rats due to ethanol dosage, the reduced ATP levels and increased CK and MDH activities in SHR may reflect a greater susceptibility to ischaemic damage. Reduced contractile protein content, particularly myosin heavy chain, may contribute to contractile defects, a common feature of subclinical and clinical alcoholic cardiomyopathy.

Adenosine Diphosphate↗
PubMed2000

The detection of prostate cells by the reverse transcription-polymerase chain reaction in the circulation of patients undergoing transurethral resection of the prostate.

OBJECTIVE: To determine whether prostate cells are disseminated into the circulation of patients after transurethral resection of the prostate (TURP), as assessed by a reverse transcription-polymerase chain reaction (RT-PCR) assay for prostate specific antigen (PSA) mRNA. PATIENTS AND METHODS: Fifty-one patients, comprising 34 with benign prostatic hyperplasia (BPH) and 17 with prostate cancer who were undergoing routine TURP, had blood samples taken before and 30 min after surgery. The blood mononuclear cell layer was isolated by density-gradient centrifugation and total RNA extracted. Complementary DNA was synthesized by RT of the RNA. The target PSA sequence was amplified by PCR with specific PSA primers and the product detected on agarose-gel electrophoresis with ethidium bromide staining. RESULTS: Five patients (all with prostate cancer) were positive on PSA RT-PCR before surgery and remained positive after TURP. Of the remaining 46 patients, five (11%; three with BPH and two with cancer) changed from a negative to a positive result after TURP. CONCLUSION: In a proportion of patients TURP causes the dissemination of prostate cells into the circulation which are then detectable by RT-PCR of PSA mRNA.

Aged↗
PubMed2000

Serum S-100beta protein is a potential biochemical marker for cerebral oedema complicating severe diabetic ketoacidosis.

CASE REPORT: A 39-year-old man with Type 1 diabetes mellitus was hospitalized with severe diabetic ketoacidosis (DKA). Sixteen hours after admission he suddenly deteriorated having a respiratory then cardiac arrest. A brain computed tomography scan performed 2 h after the respiratory arrest showed severe cerebral oedema. Serial serum samples were stored and analysed for S-100beta protein. The S-100beta protein concentration was initially normal (0.12 microg/l) then rose significantly before the onset of the respiratory arrest (8.5 h = 0.61 microg/l, 14.5 h = 0.9 microg/l, 18 h = 1.6 microg/l, 25.5 h = 3.1 microg/l, 34 h = 4.6 microg/l and44 h = 19.5 microg/l). CONCLUSIONS: In this case of DKA, serum S-100beta concentration rose coinciding with the onset of cerebral oedema, before it became clinically evident. Monitoring serum S-100beta may have a useful role in the management of DKA.

Adult↗
PubMed2000

Comparison of cardiac troponin T and I and CK-MB for the detection of minor myocardial damage during interventional cardiac procedures.

A number of cardiac interventional procedures are available for the treatment of angina, including percutaneous transluminal coronary angioplasty (PTCA), stent insertion and rotational atherectomy (RA). Variable degrees of myocardial cell injury during PTCA and stent insertion have been observed, based on rises in creatine kinase MB isoenzyme (CK-MB) and cardiac troponin T (cTnT) 6-24 h post-procedure. As there are many variations in technique within each procedure it would be helpful to be able to determine objectively the degree of myocardial damage in order to optimize technique. We measured CK-MB, cTnT and cardiac troponin I (cTnI) to ascertain which is the most sensitive marker for minor myocardial damage in this setting. Blood samples were taken both before and 6, 14 and 24h after the procedure in 109 patients (77 men) with angina, 42 of whom had unstable angina. Of the 109 patients, 86 had a stent inserted (21 as a primary stent), nine had PTCA, eight had RA and six intracoronary brachytherapy. Using the manufacturers' recommended cut-offs--CK-MB 4 microg/L, cTnI and cTnT 0.1 microg/L--five patients were excluded from further analysis as all three markers were raised pre-procedure. Post procedure all three markers were in agreement for 68 patients (44 all normal, 24 all raised). Overall, CK-MB was raised in 28 patients, cTnT in 38 and cTnI in 58. In 19 patients CK-MB and cTnT were normal, but cTnI was raised (15 between 0.11 and 0.30 microg/L). cTnI was the most sensitive indicator of minor myocardial damage, but at the recommended cut-off of 0.1 microg/L may be overly sensitive. We await the results of our follow-up study to determine the clinical implications of these small rises in cTnI.

Angina Pectoris↗
PubMed1999

Substance misuse in early pregnancy and relationship to fetal outcome.

UNLABELLED: To establish the frequency of substance misuse in early pregnancy in an urban UK population, 807 consecutive positive pregnancy test urine samples were screened for a range of drugs, including cotinine as an indicator of maternal smoking habits. A positive test for cannabinoids was found in 117 (14.5%) samples. Smaller numbers of samples were positive for other drugs:- opiates (11), benzodiazepines (4), cocaine (3) and one each for amphetamines and methadone. Polydrug use was detected in nine individuals. Only two samples tested positive for ethanol. The proportion with a urine cotinine level indicative of active smoking was 34.3%. The outcome of the pregnancy was traced for 288 subjects. Cannabis use was associated with a lower gestational age at delivery (P < 0.005), an increased risk of prematurity (P < 0.02) and reduction in birth weight (P < 0.002). Whilst maternal smoking was associated with a reduction in infant birth weight (P < 0.05), this was less pronounced than the effect of other substance misuse. CONCLUSION: This study suggests that one in six women in South London are using drugs in early pregnancy and that cannabinoid use is associated with a poorer pregnancy outcome.

Female↗
PubMed1999

Angiogenic peptides in prostatic disease.

OBJECTIVE: To determine the value of measuring serum concentrations of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in patients with benign prostatic hyperplasia (BPH), advanced and localized prostate cancer, and thus assess the role of angiogenesis factors as markers of malignancy and the formation of metastasis. PATIENTS AND METHODS: Serum was obtained from 106 suitable patients who attended a routine clinic during the study period. A histological diagnosis was confirmed for each patient and a bone scan was positive in those with metastatic disease. The level of serum prostate specific antigen (PSA) was measured and the serum concentrations of VEGF and bFGF measured using a quantitative sandwich immunoassay technique. RESULTS: There was a significant difference (1.6-fold) in the serum concentration of bFGF between patients with local and advanced prostate cancer (P=0.006), but there was no significant difference for either of the growth factors between patients with BPH and metastatic prostate cancer (Mann-Whitney test). CONCLUSION: The serum levels of VEGF and bFGF could not be used to distinguish benign from malignant prostatic disease; the serum PSA level is of more value than either, but the serum concentration of bFGF may be of some value in differentiating patients with local and advanced malignancy.

Aged↗
PubMed1999

Lipid profiles in patients with atherosclerotic renal artery stenosis.

BACKGROUND: Atherosclerotic renal artery stenosis (ARAS) is an important cause of renal disease in the elderly, and these patients have a high morbidity and mortality. There are no data on their blood lipid profiles. METHODS: The lipoprotein profiles were examined in patients with proven ARAS and compared with patients matched for age, gender, renal function and presence of diabetes. RESULTS: The profiles did not show any significant difference for apolipoprotein B (control 1.31 +/- 0.39 vs. ARAS 1.24 +/- 0.28; mean +/- SD), cholesterol (control 5.65 +/- 1.28 vs. ARAS 6.12 +/- 1.29), LDL cholesterol (control 3.72 +/- 1.03 vs. ARAS 4.06 +/- 1.18), fibrinogen (control 2.48 +/- 1.39 vs. ARAS 3.29 +/- 1.49), HDL cholesterol (control 1.16 +/- 0.38 vs. ARAS 1.00 +/- 0.26) and triglyceride (control 1.68 +/- 0.80 vs. ARAS 2.32 +/- 1.73) levels between the groups. Surprisingly lipoprotein(a) levels were higher in the control group (0.58 +/- 0.45) vs. ARAS (0.31 +/- 0.21). The most striking abnormality was the markedly lower apolipoprotein A1 levels in the ARAS group (control 2.09 +/- 0.55 vs. ARAS 0.95 +/- 0. 30) and apolipoprotein A1/B ratio (control 1.74 +/- 0.71 vs. ARAS 0. 78 +/- 0.24). CONCLUSION: The lipoprotein abnormality in ARAS mirrors that in other severe vascular diseases. Potential therapeutic interventions in patients with ARAS should consider treatments to modify the apolipoprotein A1 concentration rather than cholesterol alone.

Adult↗