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Biomedical subjects

M Sampson

Publications and source records attributed to M Sampson.

At least 37 records · Page 2Linked to original sources

Appropriate insulin regimes for type 2 diabetes: a multicenter randomized crossover study.

OBJECTIVE: To directly compare the rate of hypoglycemia and metabolic control achieved on once-daily ultralente insulin administration with twice-daily NPH insulin administration in patients with type 2 diabetes. Patient treatment satisfaction and quality of life were also examined before and during each treatment. RESEARCH DESIGN AND METHODS: A crossover study was performed involving five centers and 79 patients with type 2 diabetes (fasting blood glucose > 8 mmol/l) with a 2-month run-in followed by two 6-month periods of either NPH or ultralente insulin administration. Patients were managed by a specialist nurse using a dosage adjustment protocol. RESULTS: HbA1c was lower with NPH insulin therapy during each of the 6-month periods (9.7 +/- 0.2 vs. 9.1 +/- 0.3 and 9.8 +/- 0.2 vs. 9.0 +/- 0.3 mmol/l; both P < 0.01). The difference was accounted for by higher evening glucose levels with ultralente insulin (fasting 8.2 +/- 0.3 vs. 8.2 +/- 0.3 mmol/l, 6:00 P.M. 11.5 +/- 0.4 vs. 10.6 +/- 0.4 mmol/l). Despite worse control, the total number of hypoglycemic episodes was greater with ultralente insulin (220 vs. 171), and hypoglycemic episodes requiring third-party assistance occurred almost entirely with ultralente (14 vs. 1). Treatment satisfaction scores increased more with NPH insulin compared with ultralente and rose further upon changing to NPH insulin, but fell upon changing to ultralente insulin. These changes were highly significant (P < 0.001). Diabetes quality of life improved on both regimens. CONCLUSIONS: These data clearly demonstrate the lower hypoglycemia rate, better glucose control, and greater treatment satisfaction accompanying therapy for type 2 diabetes with twice daily NPH compared with once daily ultralente insulin.

Blood Glucose↗

The differential effect of food intake and beta-adrenergic stimulation on adipose-derived hormones and cytokines in man.

We determined whether the physiologic changes that accompany food intake or sympathetic activation by beta-adrenergic stimulation result in alterations in the secretion of leptin, tumor necrosis factor-alpha (TNF alpha), or interleukin-6 (IL-6) by serially sampling sc abdominal adipose interstitial fluid by open-flow microperfusion before and after a standardized meal and in response to isoproterenol (1 micromol/L) delivered locally. Post cibum IL-6 rose up to 5-fold, whereas leptin and TNF alpha secretion did not change; TNF alpha, but not IL-6, correlated positively with indices of lipolysis. Isoproterenol-induced lipolysis was accompanied by a transient 40% reduction in leptin and a parallel 85% elevation of TNF alpha concentration, whereas IL-6 levels did not change; again, TNF alpha correlated positively with lipolysis. These data show that secretion of some, but not all, metabolically relevant polypeptides by adipose tissue is modulated within a short time frame by food or stress stimuli, suggesting a role of these peptides in local autocrine/paracrine or distant endocrine effects on fat metabolism. TNF alpha's close correlation with lipolysis suggests that this cytokine participates in a local positive autocrine feedback loop, potentiating lipolysis and inhibiting insulin's antilipolytic actions. The regulations of adipose leptin, TNF alpha, and IL-6 secretion seem distinct from each other and different in the fed vs. fasting state.

Adipose Tissue↗

Dose reduction during CT scanning in an anthropomorphic phantom by the use of a male gonad shield.

Shielding the radiosensitive gonads during X-ray exposure has been advocated for plain film radiography for many years. In the UK, gonad shields are not widely employed in routine CT scanning, possibly owing to a perceived difficulty in protecting the gonads from a multidirectional X-ray source. The increasing numbers of CT scanners in the UK, with the large doses they deliver to patients, make potential dose reduction methods an important issue. This study measures the dose reduction achievable by shielding the male gonads with a lead wrap-around protection device. The reductions in dose when shielded both from direct radiation and from indirect radiation scattered from local tissues were studied. The use of the device resulted in a statistically significant reduction in the absorbed testicular dose from both direct and scattered radiation, with no increase in the dose measured in surrounding tissues. In three clinically relevant experimental protocols where the testes were not irradiated directly, the testicular absorbed dose from indirect scatter was reduced by 77-93% of the corresponding non-shielded figure. In these three experiments, image quality was unaltered by the use of the shield. A larger dose reduction was obtained when the shield was used to protect the testes from direct irradiation. However, this was achieved at the expense of considerable image degradation from streak artefact that would effectively prevent the clinical use of the device in this setting.

Gonads↗

Vitamin E supplementation and oxidative damage to DNA and plasma LDL in type 1 diabetes.

OBJECTIVE: To determine the effect of 400 IU/day of the antioxidant vitamin E on the susceptibility of plasma LDL and lymphocyte DNA to oxidative damage in type 1 diabetes. RESEARCH DESIGN AND METHODS: We studied 42 patients with type 1 diabetes and 31 age- and sex-matched control subjects in a randomized prospective double-blind placebo-controlled trial by using 400 IU/day of oral vitamin E for 8 weeks. Measurements were made of single-strand breaks in lymphocyte DNA at baseline and after hydrogen peroxide-induced stress (comet assay) and of copper-induced LDL oxidization and plasma antioxidant profiles. RESULTS: Plasma LDL and lymphocyte DNA were more resistant to induced oxidative change in the type 1 diabetes group than in control subjects. Vitamin E supplementation reduced LDL oxidizability in the control subjects but not in the type 1 diabetes group and had no effect on oxidative DNA damage in either group. The type 1 diabetes group had a significantly poorer plasma antioxidant profile with lower mean serum concentrations of alpha-tocopherol and most carotenoids than control subjects. CONCLUSIONS: Plasma LDL and lymphocyte DNA appear to be more resistant to oxidative change in type 1 diabetic subjects than in control subjects, and there was no evidence of oxidatively induced DNA or LDL change in type 1 diabetes. This study does not support the hypothesis of oxidative damage in these patients, and a dose of vitamin E (400 IU/day) that reduced LDL oxidative susceptibility in control subjects did not do so in patients with type 1 diabetes.

Administration, Oral↗

Spinal abscess of Haemophilus paraphrophilus. A case report.

STUDY DESIGN: A case of paraspinal abscess formation from Haemophilus paraphrophilus is presented. OBJECTIVES: To describe a case of paraspinal abscess formation from H. paraphrophilus, a fastidious commensal organism of the mouth and pharynx. A precise bacteriologic identification can be difficult; techniques for such identification are discussed. SUMMARY OF BACKGROUND DATA: Spinal abscess caused by H. paraphrophilus is unusual and can be very difficult to diagnose. METHODS: The etiology, clinical presentation, technical examinations, and treatment are reviewed. RESULTS: Prolonged antibiotic treatment was curative, although surgery was considered. CONCLUSIONS: Bacteriologic diagnoses in these rare infections are difficult. Antibiotic therapy was curative in the patient described.

Abscess↗

Treatment of Alzheimer's disease with sabeluzole: functional and structural correlates.

Sabeluzole, a new benzothiazole derivative, has been shown to be neurobiologically active preclinically and clinically appears to exert beneficial effects on memory. In this study, sabeluzole (5 or 10 mg twice daily vs. placebo) was investigated in patients with probable Alzheimer's disease over 1 year, with assessments of cognitive performance and structural changes. Cognitive performance was measured using the Alzheimer's Disease Assessment Scale periodically during treatment. Potential structural correlates in the frontal horn, caudate, third ventricle and hippocampal regions were examined by obtaining computerized tomographic (CT) images before and after treatment. Patients receiving sabeluzole evidenced greater stability than did placebo-treated patients in some cognitive measures. CT measures showed no significant changes from baseline, but some weak associations were found between relative preservation of cognitive function and smaller structural declines in the third ventricle and hippocampus. Cognitive outcome measures suggest that sabeluzole may have potential in slowing the cognitive deterioration of Alzheimer's disease. Furthermore, the method used to explore potential benefits on a morphologic level, although negative in this study, could yet have potential.

Aged↗

Positive interference in lithium determinations from clot activator in collection container.

We describe positive interference with the ion-selective electrode determination of lithium (Lytening 2Z analyzer; Dade) when blood is collected in a 10-mL plain red-top plastic Vacutainer Plus Tube (Becton Dickinson) containing a silica clot activator and silicone surfactant (prod. no. 36-7820). We evaluated both the original tube (blue-labeled) and a new tube formulated to contain less silicone surfactant (striped-labeled). We determined that the interference is from either the silica clot activator or the silicone surfactant used to fix the silica to the tube and is inversely related to the volume of blood in the tube. Long-term intermittent exposure of the Li ion-selective electrode to the silica clot activator or surfactant results in decreased Li values--in terms of both the positive interference by the silica clot activator or surfactant and the actual Li determinations. Moreover, this long-term interference with the Li ion-selective electrode for patient's specimens is undetected by the Dade control material (QCLytes).

Blood Coagulation↗

Assessment of monoethylglycinexylidide as measure of liver function for patients with chronic viral hepatitis.

The liver metabolizes lidocaine by oxidative deethylation to form monoethylglycinexylidide (MEGX), an analyte proposed as an index of liver function. We determined MEGX and lidocaine serum concentrations with the TDx (Abbott Laboratories) at baseline and 15, 30, 60, and 90 min after the intravenous administration of lidocaine (1 mg/kg), analyzing specimens from 12 apparently healthy volunteers and 40 patients with chronic viral hepatitis diagnosed by liver biopsy and serum tests. The patients were grouped on the basis of the histology activity index. The following laboratory tests were performed on serum specimens from all subjects: albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin, and prothrombin time. The results showed no significant difference among the four groups for the concentrations of MEGX, lidocaine, and lidocaine/MEGX at the four time points. However, the concentrations of ALB, ALT, AST, AST/ALT, and prothrombin time were substantially different among the four groups. Thus, we conclude that assay of MEGX in our patients with chronic viral hepatitis did not contribute to the assessment of liver function when compared with apparently healthy volunteers and traditional tests of liver function.

Adult↗

Impaired vascular reactivity in insulin-dependent diabetes mellitus is related to disease duration and low density lipoprotein cholesterol levels.

OBJECTIVES: This study sought to examine whether endothelial function is impaired in the large vessels of asymptomatic young adults with insulin-dependent diabetes and whether endothelial dysfunction is related to duration or control of diabetes, small-vessel disease or other vascular risk factors. BACKGROUND: Endothelial dysfunction is an early event in atherosclerosis, and large-vessel atherosclerotic disease is the major cause of morbidity and mortality in diabetes. METHODS: We compared 80 young adults with insulin-dependent diabetes (15 to 40 years old; mean [+/- SD] diabetes duration 13 +/- 8 years) with 80 matched nondiabetic control subjects. Using high resolution vascular ultrasound, we measured brachial artery responses to reactive hyperemia (with increased flow causing endothelium-dependent dilation) and sublingual glyceryltrinitrate (causing endothelium-independent dilation). RESULTS: Flow-mediated dilation was significantly impaired in diabetic subjects (5.0 +/- 3.7% vs. 9.3 +/- 3.8% in control subjects, p < 0.001). The ratio of flow-mediated dilation to glyceryltrinitrate-induced dilation was significantly lower in the diabetic subjects (p < 0.02), indicating that impaired dilation to increased flow was out of proportion to the impairment of the glyceryltrinitrate response in these subjects (15.6 +/- 5.6% vs. 19.7 +/- 6.6% in control subjects, p < 0.001). On multivariate analysis, flow-mediated dilation was inversely related to both duration of diabetes (r = -0.26, p < 0.05) and low density lipoprotein (LDL) cholesterol levels (r = -0.38, p < 0.005). CONCLUSIONS: Vascular reactivity is impaired in the systemic arteries of asymptomatic young adults with insulin-dependent diabetes and may represent early large-vessel disease. The degree of impairment is related to the duration of diabetes, and these patients appear particularly vulnerable to damage from LDL cholesterol, even at levels considered acceptable in nondiabetic subjects.

Adolescent↗

Utility of clinical trial batteries in the measurement of Alzheimer's and Huntington's dementia.

Tests used as outcome measures in clinical trials of antidementia agents are not typically employed as part of diagnostic evaluations, and little information exists as to the sensitivity of these tests in terms of either differentiating demented patients from normal individuals or in distinguishing dementias of various types and etiologies. Sensitivity to mild dementia and sensitivity to impairment of various neuropsychological domains are, however, prerequisites for valid use of an instrument as an outcome measure in this context. The present study was undertaken to directly compare six different tests (three traditional psychometric tests and three clinical trial batteries) in terms of their sensitivity to detect and distinguish between mild dementia in patients with either Alzheimer's disease (n = 15) or Huntington's disease (n = 15), when compared to normal controls (n = 15). Tests included the Mattis Dementia Rating Scale, the Mini-Mental State Examination, the Wechsler Memory Scale-Revised, the Alzheimer's Disease Assessment Scale-Cognitive Subscale, the Computerized Drug Research (CDR) Cognitive Assessment System, and the Repeatable Battery for the Assessment of Dementia (RBAD). All of the tests were roughly equivalent in terms of their ability to discriminate normal subjects from mildly demented patients. Only the CDR and RBAD, however, were able to reliably discriminate between the two patient groups. The results are discussed in terms of the applicability of these tests as outcome measures for clinical trials in dementing disorders.

Adult↗

Ambulatory blood pressure profiles and plasminogen activator inhibitor (PAI-1) activity in lean women with and without the polycystic ovary syndrome.

OBJECTIVE: Hyperinsulinaemic women with the polycystic ovary syndrome (PCOS) may be at increased risk of vascular disease later in life, mediated by blood pressure or lipid abnormalities or by elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1) activity. PAI-1 may also be involved in ovarian follicle development and ovarian connective tissue remodelling. We measured plasma PAI-1 activity and 24-hour ambulatory blood pressure records in women with and without PCOS. DESIGN: Cross-sectional study of three groups. PATIENTS: Twenty-four non-obese women with a classic ovarian ultrasound appearance of PCO and extreme menstrual disturbance (Group 1), 26 matched controls with a normal menstrual cycle and an ultrasound appearance of PCO (Group 2) and 10 matched controls with a normal menstrual cycle and normal ovarian ultrasound (Group 3). MEASUREMENTS: Twenty-four hour ambulatory blood pressure recordings (Spacelabs 90207), ovarian ultrasonography, fasting plasma insulin and glucose, plasma PAI-1 activity, HDL and total cholesterol, triglycerides, gonadotrophins and testosterone. Family history of premature vascular disease. RESULTS: Median fasting plasma insulin was significantly higher in Group 1 (45.8 pmol/l, range 12.9-161.9) than in Group 2 (28.1 pmol/l; range 13.6-91; P < 0.05) or Group 3 (26.0 pmol/l; range 13.5-63.3; P < 0.05). There were no differences between groups in 24-hour, daytime or night-time ambulatory blood pressure measurements, and no relation between plasma insulin and any blood pressure variable. Mean plasma PAI-1 activity was higher in Group 1 (10.0 +/- 7.1 AU/l) than in Group 2 (6.0 +/- 4.6 AU/l; P < 0.05) or Group 3 (5.1 +/- 3.5 AU/l; P = 0.06). There was a significant independent direct relation between fasting plasma insulin and PAI-activity (r = 0.41, R2 = 0.154; F1,59 = 11.38; P = 0.001). Groups did not differ in parental history of premature vascular disease, or in mean HDL or fasting triglyceride levels. CONCLUSIONS: The only measurable vascular risk factor associated with hyperinsulinaemia and menstrual disturbance in non-obese women with PCOS is an elevated plasma PAI-1 activity. These women did not differ from controls in ambulatory blood pressure profiles, lipid measurements or in a parental history of premature vascular disease. PAI-1 and plasminogen are involved in ovarian follicle maturation and the present finding suggests a biologically plausible link between hyperinsulinaemia, anovulation and vascular risk in PCOS.

Adult↗

Cognitive and quantified electroencephalographic correlates of cycloserine treatment in Alzheimer's disease.

Cycloserine acts as a potent and selective modulator of the N-methyl-D- aspartate (NMDA) receptor-associated glycine recognition site, which may be a possible mechanism for this compound's positive effects on memory formation and retrieval processes in animals. Studies in normal human volunteers have shown that cycloserine can have significant positive effects on cognitive processing in the elderly and can ameliorate memory deficits induced by subcutaneously administered scopolamine. Based on this profile, a double-blind, placebo controlled, parallel group (three drug dosages) study was conducted as part of a larger study to assess the efficacy and safety, as well as the cognitive and central nervous system (CNS) impact, of 6 months of cycloserine treatment in patients (N = 40) with probable dementia of the Alzheimer type (DAT). The Cognitive Drug Research Computerize Assessment System (CDR System) served as the primary outcome measure of efficacy. CNS activity was assessed using quantified electroencephalography (QEEG). Safety measures included adverse effects documentation and analysis of blood chemistry/hematology. Cycloserine proved to be a safe agent in this population at the doses given but failed to show any statistically significant effects in the areas of cognition and global clinical ratings and did not indicate significant CNS activity on QEEG. These findings suggest that cycloserine has no measurable therapeutic effect on Alzheimer's disease at the doses given.

Aged↗

Development studies of Aurelia (jellyfish) ephyrae which developed during the SLS-1 mission.

Aurelia polyps (scyphistomae) and ephyrae were exposed to microgravity for nine days aboard the space shuttle during the SLS-1 mission. During strobilation, polyps segment transversely and each segment develops into an ephyra. Polyps were induced to strobilate at 28 degrees C, using iodine or thyroxine, at L(Launch)-48h, L-24h, and L+8h. Ephyrae developed in the groups tested in space and on Earth. The number of ephyrae formed per polyp was slightly higher in the L+8h groups as compared with those induced at L-24h and L-48h. On Earth, iodine is used by jellyfish to synthesize jellyfish-thyroxine (Jf T4), needed for ephyra production. Since iodine-treated polyps strobilated and formed ephyrae in space, it appears that jellyfish can synthesize Jf-T4 in space. Indeed, two groups of polyps not given inducer formed ephyrae [correction of ephryae] in space, presumably due to enhanced Jf-T4 synthesis, utilization or accumulation. Some ephyrae that formed in space were also fixed in space on Mission Day (MD) 8; others were fixed post-flight. Examination of living ephyrae with the light microscope and fixed ones with the Scanning and Transmission Electron Microscopes revealed that those which developed in space were morphologically very similar to those which developed on Earth. Quantitation of arm numbers determined that there were no significant differences between space and Earth-developed ephyrae. Pulsing abnormalities, however, were found in greater numbers (18.3%) in space-developed ephyrae than in Earth-developed controls (2.9%). These abnormalities suggest abnormal development of the graviceptors, the neuromuscular system, or a defect in the integration between these systems in apparently microgravity-sensitive animals.

Animals↗

Size isn't important; the Forrest Unit.

The early success of breast screening in the UK is encouraging, and has been achieved by cooperation between multidisciplinary teams working together in large screening units. Future market forces may serve to disintegrate this arrangement with the resulting emergence of smaller, self-sufficient units. Winchester's 'first round' screening results suggest that with appropriately trained team members, such units can provide a convenient, high quality local service without compromising cancer detection.

Breast Neoplasms↗