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Biomedical subjects

R Sherwood

Publications and source records attributed to R Sherwood.

At least 37 records · Page 2Linked to original sources
PubMed1999

Plasma tryptophan and trait aggression.

Many studies have reported correlations between measures of aggression and indices of serotonergic function, but most have studied patient or offender populations and relatively few have investigated plasma concentrations of the serotonin precursor tryptophan. This study investigates the relationship between plasma concentrations of tryptophan and trait hostility, depression and anxiety in male healthy volunteers. Sixty-seven healthy male volunteers gave blood samples and completed trait questionnaires. Plasma tryptophan was positively correlated with the Buss-Durkee Hostility Inventory Total score and Motor Aggression subscale, but not with the Attitudinal Hostility subscale or with trait anxiety or depression. In conclusion, there is evidence for an association between high concentrations of plasma tryptophan and aggressive behaviour in men, presumably mediated by some aspect of central serotonergic function, which seems unlikely to be explained by high trait anxiety or depression.

Adult↗
PubMed1998

Psychomotor performance: investigating the dose-response relationship for caffeine and theophylline in elderly volunteers.

OBJECTIVE: The aim of the study was to investigate the dose-response relationship for psychomotor performance, caffeine and theophylline in healthy elderly volunteers. METHODS: In a randomized, double-blind, placebo-controlled, six-period cross-over study we compared the effect of three doses of theophylline (predicted peak concentrations of 3, 6 mg. 1(-1) and 12 mg . 1(-1), two doses of caffeine (predicted peak concentrations of 4.5 mg. 1(-1) and 9 mg. 1 (-1) and placebo on ten healthy elderly volunteers. Psychomotor performance was measured using a continuous attention task, symbol digit substitution test and choice reaction time. Subjective effects were assessed using visual analogue scales. Following drug administration, subjects received the test battery at 30-min intervals, up to 150 min. Maximum and mean effects from baseline on each variable were included in the analysis. RESULTS: Significant improvement on the continuous attention task was seen at the lowest concentration of caffeine and theophylline used, while at higher concentrations there was a non-significant trend towards placebo scores. There was little effect of either drug on the subjective effects measured by visual analogue scales. CONCLUSION: Caffeine and theophylline increase psychomotor performance measures of attention at low plasma concentrations in healthy elderly volunteers. This effect is not increased by higher drug concentrations and there is trend towards a return to placebo scores. The lack of effect of both caffeine and theophylline on subjective measures is consistent with previous studies of caffeine in the elderly.

Aged↗
PubMed1998

Correlation of endothelium-dependent and -independent vasodilatation with liver function tests during prolonged perfusion of the rat liver.

Twelve male Wistar rats were anaesthetized with pentobarbitone (3 mg 100g(-1) i.p.), the livers were excised and perfused in vitro through the hepatic artery and portal vein at constant flow rates of 0.32+/-0.01 (mean+/-S.E.) and 0.98+/-0.03 ml min(-1) g liver(-1), respectively. The tone of the preparation was raised by methoxamine (7.5 x 10(-6) M). Responses to mid-range doses of acetylcholine (-11 log mol) and sodium nitroprusside (-9 log mol) produced submaximal degrees of vasodilatation (-log mol ED50 = 12.18+/-0.08) and (-log mol ED50 = 9.95+/-0.23), respectively, which did not subside until 5.5 h of perfusion. These did not coincide with the increase in activities of lactic acid dehydrogenase (LDH) and aspartate serine transaminase (AST) activity at 2.5 h, which were indicative of hepatocellular mitochondrial and cytoplasmic damage, respectively. Vascular responses suggested that there was little deterioration in endothelial or smooth muscle function in the hepatic artery up to 5 h perfusion. This model can be reliably used to investigate endothelium-dependent and -independent vasodilators in vascular pharmacological studies of the rat liver although some minimal increases may occur in AST and LDH activity before hemodynamic changes appear at 5.5 h.

Acetylcholine↗
PubMed1998

The release of free prostate specific antigen into the circulation during transurethral resection of the prostate: kinetics and interaction with serum protease inhibitors.

OBJECTIVE: To determine the nature and extent of the release of prostate specific antigen (PSA) and its interaction with its plasma protein-derived inhibitors after transurethral resection of the prostate (TURP). MATERIALS AND METHODS: Twenty-three consecutive patients undergoing routine TURP for benign prostatic hyperplasia had blood samples taken pre-operatively and then post-operatively at 8-hourly intervals for 24 h. Further samples were obtained at 48 and 72 h post-operatively. Serum free and total PSA were determined by immunofluorometric assay. The major plasma protein inhibitors for PSA were also determined by immunoassay. RESULTS: The mean free and total PSA fractions increased significantly post-operatively with levels greatest immediately after surgery. There was also a gradual increase in the complexed PSA fraction, reaching a peak at 48 h. The concentration of the major serum inhibitors of PSA (alpha-1-antichymotrypsin and alpha-2-macroglobulin) also declined immediately after surgery. CONCLUSION: Increases of serum total PSA in patients after TURP are caused by increases in the free PSA fraction. The exponential decline in free PSA concentrations is consistent with the complexing of PSA with its protease inhibitors present in the plasma. The formation of this complex suggests that the free PSA released into the circulation at the time of TURP is the enzymatically active form.

Humans↗
PubMed1998

Central cooling effects in patients with hypercholesterolaemia.

1. A prospective study has been carried out, and 68 patients with hypercholesterolaemia have been investigated to study the effects of central cooling on serum lipid levels. 2. Central cooling was obtained by the exposure of the whole body to cold water. All patients were trained to gradually reduce the water temperature from 22 to 14 degrees C and to increase the time of exposure from 5 to 20 min over a period of 90 days. The 33 male and 35 female patients were aged between 40 and 60 years at entry with total cholesterol of 6.0 mmol/l or greater and low-density lipoprotein (LDL)-cholesterol of 4. 0 mmol/l or greater. Thyroid-stimulating hormone, free thyroxine (FT4), total T3, total cholesterol, LDL-cholesterol, high-density lipoprotein (HDL)-cholesterol, triacylglycerols and total fat mass (determined by dual-energy X-ray absorptiometry scan) were obtained at baseline and after 3 months treatment with hydrotherapy. 3. Central cooling obtained by hydrotherapy results in a median fall in tympanic temperature from 0.2 degrees C (P<0.001) to 0.8 degrees C (P<0.001). We have observed in these patients a significant reduction in total cholesterol (-0.2 mmol/l, P=0.006) and LDL-cholesterol (-0.2 mmol/l, P=0.004). Serum FT4 level was higher than baseline results in 30 of these hypercholesterolaemic patients (15.5 pmol/l to 17.3 pmol/l) and there was no significant change in serum thyroid-stimulating hormone and total T3. 4. In conclusion, in our patients with hypercholesterolaemia we have observed a significant reduction of total cholesterol and LDL-cholesterol after body temperature regulation.

Adult↗
PubMed1997

Effects of the dihydropyridine calcium channel blocker amlodipine on ventricular and atrial protein synthesis in an aortic constriction model of hypertension and, following chronic treatment, in the left ventricle of SHR rats.

The dihydropyridine calcium channel blocking agent amlodipine is an effective anti-hypertensive agent and its use (in doses of 5 or 10 mg/day/kg body weight) was investigated in male Wistar rats with hypertension induced by aortic constriction. Controls were sham-operated and pair-fed. At the end of the study, rates of protein synthesis were measured with radiolabelled phenylalanine to calculate fractional rates of protein synthesis (ks), absolute rates of protein synthesis (Vs) and synthesis rates relative to RNA (kRNA). After 30 days of aortic constriction, weights of the left ventricle and left atrium were significantly increased by hypertension. The weights of the right ventricle and right atrium were relatively unaffected. Hypertension was accompanied by significant increases in the protein and RNA contents of the left ventricle and left atrium. The contractile and non-contractile protein contents were also increased in the left ventricles of hypertensive rats as were total proteins and total RNA. In the myofibrillary fraction, ks decreased. The right ventricle and right atrium were generally unaffected except for a decline in mixed protein ks. Many of these changes in hypertension were ameliorated by treatment with amlodipine, particularly at the higher dose (i.e. 10 mg/kg body weight/day) implicating an effect on protein metabolism. In the left ventricle these included amelioration of the increases in mixed and contractile proteins, total RNA contents, mixed Vs and Vs for sarcoplasmic and stromal proteins. The ameliorating effects of amlodipine were moderate in the left atrium. Furthermore, amlodipine also retarded the hypertension-induced reduction in right ventricule rates of protein synthesis. Although the preceding study emphasises the preventative aspects of amlodipine's efficacy, an additional study was carried out in SHR rats to ascertain the applicability for regression per se. Amlodipine (10 mg/kg/body weight) therapy for 30 weeks caused regression of LV mass, total protein, RNA and DNA contents. We conclude that amlodipine, is an efficient agent in ameliorating the hypertension-induced changes in protein metabolism in an aortic constriction model.

Amlodipine↗
PubMed1997

Intestinal tolerability of nitroxybutyl-flurbiprofen in rats.

BACKGROUND: Nitric oxide derivatives of non-steroidal anti-inflammatory drugs (NSAIDs) are thought to be much less ulcerogenic than their parent compounds. AIM: To compare the effect and potency of flurbiprofen and nitroxybutyl-flurbiprofen to uncouple mitochondrial oxidative phosphorylation (an early pathogenic event in NSAID enteropathy), increase intestinal permeability (transitional stage), and cause macroscopic small intestinal damage. METHODS: In vitro uncoupling potency was assessed using isolated coupled rat liver mitochondria and in vivo by electron microscopy of rat small intestinal mucosa (two hours after the drugs). A dose-response study with flurbiprofen (single doses of 5, 10, 20, and 40 mg/kg) and equimolar doses of nitroxybutyl-flurbiprofen was performed; assessing their effect on intestinal permeability (at 18-20 hours), with 51Cr EDTA, and the number of pointed (< 5 mm) and longitudinal (> 5 mm) small intestinal ulcers at 24 hours. RESULTS: Flurbiprofen, but not nitroxybutyl-flurbiprofen, stimulated coupled respiration in vitro. Both drugs, however, uncoupled in vivo; in the case of nitroxybutyl-flurbiprofen possibly because hydrolysis of its ester bond released free flurbiprofen. Intestinal permeability was uniformly and equally increased with both drugs compared with controls. The number of small intestinal ulcers, pointed and longitudinal, was significantly reduced with nitroxybutyl-flurbiprofen apart from the number of longitudinal ulcers with the highest dose. CONCLUSIONS: These studies show that nitroxybutyl-flurbiprofen is associated with significantly less macroscopic damage in the small intestine than flurbiprofen but was associated with mitochondrial damage in vivo and caused similar increases in permeability of the small intestine, suggesting that its beneficial effect is on the later pathogenic stages of the damage.

Animals↗
PubMed1997

Megakaryocyte ploidy and platelet changes in human diabetes and atherosclerosis.

Altered platelet morphology and function have been reported in patients with diabetes. They are likely to be associated with the pathological processes and increased risk of vascular disease seen in these patients. Mean platelet volume (MPV), platelet count, and megakaryocyte (MK) ploidy (DNA content) were measured in (1) nondiabetics with normal coronary arteries, (2) nondiabetics with coronary artery atherosclerosis, (3) diabetics without evidence of vascular complications, and (4) diabetics with vascular disease. The platelet count (+/- SD) was increased in all groups but only significantly in the diabetics with vascular disease (236 +/- 65 versus 250 +/- 54 versus 257 +/- 64 versus 295 +/- 90 [P < or = .05] x 10(9)/L, for groups, I, II, II, and IV, respectively). The MPV was significantly increased in patients with atherosclerosis (7.0 +/- 0.4 versus 8.0 +/- 1.2 [P < or = .05] versus 7.2 +/- 0.9 versus 8.1 +/- 0.9 [P < or = .05] IL). Geometric mean MK ploidy was significantly increased in all groups compared with controls (16 +/- 1.5 versus 18.7 +/- 1.8 [P < or = .05] versus 19.8 +/- 1.6 [P < or = .05] versus 20.1 +/- 2.7 [P < or = .05]). Furthermore, some patients with vascular disease and/or diabetes had a modal ploidy shift from 16 (the normal mammalian modal ploidy) to 32, with a concomitant reduction of MKs in the 8 and 16 ploidy classes. This shift was seen particularly in the diabetics with vascular disease (P = .007). Interleukin-6 (IL-6) levels were measured and were elevated in patients with atherosclerosis; the highest levels were found in the diabetic patients (0.7 +/- 0.9 versus 5.3 +/- 5.5 [P < or = .05] versus 2.5 +/- 2.8 versus 6.7 +/- 5.5 [P < or = .05] ng/L). In the diabetic patients with atherosclerosis, fibrinogen levels were also increased (2.85 +/- 0.76 versus 3.34 +/- 1.32 versus 2.43 +/- 1.50 versus 5.59 +/- 1.72 [P < or = .05] g/L). Furthermore, IL-6 levels correlated with MK ploidy (r = .45, P = .009) and fibrinogen levels (r = .5, P = .0001). This study demonstrates that patients with vascular disease, particularly diabetics, have an altered MK ploidy distribution, showing a shift toward higher ploidy in association with an increased platelet mass (count x volume). Changes in platelets in diabetes probably reflect MK changes, which themselves are a response to systemic change.

Aged↗
PubMed1996

Troponin T release with warm and cold cardioplegia.

Cardiac troponin T (cTnT) levels were measured in 41 patients undergoing elective coronary artery surgery. Twenty-one patients received continuous warm antegrade blood cardioplegia to maintain asystole whilst 20 patients received antegrade cold blood cardioplegia intermittently. Serum levels of cTnT were determined preoperatively and at 0, 6, 12 and 18 h postbypass. Peak cTnT levels and total cTnT release (calculated from the area under the curve postoperatively) were found to be significantly higher (p < 0.05: Mann-Whitney) when cold cardioplegic solutions were used. Continuous warm cardioplegia results in lower cTnT release than intermittent cold blood cardioplegia suggesting that the former may provide better myocardial preservation.

Aged↗
PubMed1995

Screening for fetal trisomy 21 in the first trimester of pregnancy: maternal serum free beta-hCG and fetal nuchal translucency thickness.

The aim of this prospective study was to measure the contribution of maternal serum free beta-human chorionic gonadotropin (beta-hCG) in a screening program for fetal trisomy 21 based on fetal nuchal translucency in the first trimester of pregnancy. The maternal serum was collected at the time of the ultrasound scan and assayed without knowledge of the nuchal translucency measurement or karyotype. A total of 2529 pregnancies were examined (normal group, n = 2427; trisomy 21 group, n = 102). Maternal serum free beta-hCG was significantly associated with gestational age and maternal weight. In the trisomy 21 group the free beta-hCG was significantly higher than in the normals, being above the 95th centile in 29% of the cases. There was no significant association between the deviation from the mean for free beta-hCG and nuchal translucency thickness in either the normal or the trisomy 21 groups. When maternal serum free beta-hCG was added to a model based on maternal age and fetal nuchal translucency thickness, the detection rate for trisomy 21 was increased from 80% to 85%.

Adolescent↗
PubMed1993

Biochemical markers of bone turnover in women with surgically treated carcinoma of the breast.

Biochemical markers of bone turnover were measured in fasting urine and blood samples obtained from 38 postmenopausal women with previous surgical treatment of breast cancer combined with adjuvant chemotherapy, tamoxifen, or placebo. Significantly elevated urinary pyridinoline as nmol mmol-1 creatinine (47.5 and 42.5 in tamoxifen and placebo treated patients compared with 26.3 in normal controls, both P < 0.001) and deoxypyridinoline (11.9 and 10.5 compared with 6.3, P < 0.001 and P = 0.002 respectively) were found with unchanged urinary hydroxyproline, serum alkaline phosphatase and procollagen I carboxyterminal peptide (PICP). These findings suggest enhanced bone resorption resulting from the humoral osteoclast activating effect of the previous breast cancer or underlying carcinoma recurrence. Alternatively the raised pyridinium excretion might indicate an altered crosslinking composition of bone collagen. No specific effect on bone metabolism was found with tamoxifen treatment as all measured parameters were similar in both tamoxifen ex-users and non-users. This confirmed the safety of tamoxifen therapy with respect to bone.

Aged↗
PubMed1993

Personality subgroups in an inpatient Vietnam veteran treatment program.

Millon Clinical Multiaxial Inventory personality profiles of 250 male inpatient Vietnam veterans were examined to locate subgroups within that population. Using a hierarchical cluster analysis to form relatively homogeneous groups, four clusters were identified which accounted for 98% of the population. Three clusters had Millon profiles suggestive of a stress reaction and one cluster had a profile indicative of an antisocial adjustment. As measured by a PTSD subscale of the Minnesota Multiphasic Personality Inventory two clusters are high stress groups and two clusters are lower stress groups. The two Millon personality profiles in the high stress category were an 8-2-1/6 group and a 2-8-1-3 group. The lower stress groups had profiles of /8-2 and 6/8-5. The high stress groups are considered Posttraumatic Stress Disorder groups and the lower stress groups are considered nonPosttraumatic Stress Disorder groups.

Adult↗
PubMed1992

A national model of faculty development in addiction medicine.

Increasing the number of faculty with expertise in addiction medicine is one of the challenges facing the medical community in the 1990s. To meet this challenge, the Society of Teachers of Family Medicine created a faculty development course to increase the expertise of family practice faculty involved in teaching residents. The authors describe the development, implementation, and consequences of the five-day intensive course that was taught to 165 participants at ten sites in 1990. The participants' self-reporting before and three months after the course showed significant increases in the numbers of participants who taught addiction medicine in eight of 11 clinical situations. The authors conclude that the course represents a model of faculty development in addiction medicine that is applicable to other specialties and health professions.

Evaluation Studies as Topic↗
PubMed1992

Administration of human recombinant insulin-like growth factor-I to patients following major gastrointestinal surgery.

OBJECTIVE: The aim was to study the pharmacokinetic parameters and biological activity of a single dose of human recombinant IGF-I (rhIGF-I) administered to patients following major gastrointestinal surgery. DESIGN: A double blind placebo controlled externally randomized study of 30 patients; the study commencing 24 hours after major colonic or gastric surgery. MEASUREMENTS: After a baseline blood sampling day, IGF-I (40 micrograms/kg by single subcutaneous dose, n = 20) or placebo (n = 10) was administered and serum and urine samples collected over the ensuing 72 hours. Serum IGF-I, IGF-II, IGF binding proteins (IGFBP-1, IGFBP-3), GH and insulin were measured by radioimmunoassay. Serum IGF bioactivity was assessed using a validated porcine cartilage bioassay. Serum and urinary electrolytes were measured by standard methodology. RESULTS: Serum immunoreactive IGF-I levels peaked at 4 hours following injection of IGF-I (1.09 +/- 0.12 U/ml mean +/- SEM), remained elevated for 15 hours and returned to basal levels by 24 hours after injection. IGF bioactivity was increased by 57% 6 hours after IGF-I injection. Mean levels of IGFBP-1 and IGFBP-3, IGF-II and GH were unaffected by IGF-I administration. Insulin levels were suppressed at 30 minutes following injection of IGF-I compared with the placebo group (16.9 +/- 3.0 mU/I vs 32.3 +/- 7.1, P = 0.02); thereafter, there were no differences in insulin levels. The mean change in serum creatinine following IGF-I (-6.3 +/- 3.0 mmol/l) was significantly different from that in the control group (+7.2 +/- 6.2, P = 0.03). Creatinine clearance rose from a mean of 71.6 +/- 7.5 ml/min to 83.2 +/- 7.6 ml/min after IGF-I treatment (P = 0.02). In the IGF treated patients, cholesterol levels consistently fell (-0.20 +/- 0.05 mmol/l); this was not observed in the placebo group (+0.20 +/- 0.14, P = 0.006). Basal serum potassium levels in the IGF treatment group (4.1 +/- 0.1 mmol/l) fell to 3.8 +/- 0.1 at 4 hours (P = 0.002) and 3.6 +/- 0.1 at 10 hours (P = 0.001) returning to a level of 4.0 +/- 0.1 (P = 0.293) at 24 hours after injection. There were no other observed differences in serum or urinary electrolytes or serum free fatty acids and triglycerides. Pharmacokinetic parameters derived from baseline adjusted IGF-I measurements revealed a slow absorption of the administered dose with a Tmax of 5.0 +/- 0.43 hours and an elimination half-life of 10.8 +/- 1.2 hours. The computed volume of distribution was 0.33 +/- 0.05 I/kg and the clearance on average 25 ml/min. CONCLUSION: A single subcutaneous dose of IGF-I normalized circulating IGF-I levels in post-operative patients, was well tolerated and without side-effects. IGF bioactivity was increased and associated with a fall in serum cholesterol, potassium and creatinine levels and a rise in creatinine clearance. Further long-term studies are now required to assess the anabolic effects of rhIGF-I in this type of patient group.

Aged↗