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Biomedical subjects

M Brown

Publications and source records attributed to M Brown.

At least 145 records · Page 8Linked to original sources
PubMed2000

Food restriction suppresses muscle growth and augments osteopenia in ovariectomized rats.

We examined effects of 4 wk of food restriction on ovariectomy-related changes in muscle, bone, and plasma insulin-like growth factor I (IGF-I). Female Sprague-Dawley rats (7 mo old) were assigned to freely eating groups: sham-operated (Sham), ovariectomized (Ovx-AL), and estrogen (estradiol)-replaced Ovx (Ovx+E(2)). Ovx rats were also pair fed with Sham (Ovx-PF) or weight matched with Sham by food restriction (Ovx-FR). Ovx-AL and Ovx-PF rats had similar estrogen status and body weight; therefore, the groups were combined (group: Ovx). After treatment, body weight was approximately 10% greater in Ovx than in Sham rats (P < 0.05), and muscle weight-to-body weight ratios were comparable among all groups. Bone mineral contents of whole tibiae in Ovx-FR and Ovx were approximately 15% (P < 0.05) and approximately 6% lower than in Sham rats (P < 0.05), respectively. Plasma IGF-I was approximately 30% higher in Ovx than in Sham (P < 0.05) but was similar between Sham and Ovx-FR. IGF-I was highly correlated with body weight and muscle mass. Within non-estrogen-replaced Ovx rats, IGF-I explained approximately 19% of variance in bone mineral content after accounting for variance attributable to body weight. Findings suggest that estrogen acts indirectly on skeletal muscle and bone in rats through regulation of body growth by factors such as IGF-I.

Animals↗
PubMed2000

Web-based education and support for patients on the cardiac surgery waiting list.

We assessed the effectiveness of two methods of patient education, a printed manual and a Website, provided to patients waiting for cardiac surgery. The four-phase study was conducted over two and a half years, and included urban and rural subjects in Vancouver and the interior of British Columbia. The Website was based on the specially developed patient education manual. A pilot evaluation study was carried out to assess the features of the Website and to ensure it was 'user-friendly', after which it was revised. The two education methods were evaluated using both qualitative and quantitative studies. Findings supported the feasibility and viability of both formats. The Web-based format demonstrated two additional benefits over the print-based format, namely increased social support and decreased anxiety. Other findings included the perception of increased support, lifestyle changes and more positive attitudes towards the impending surgery.

Adult↗
PubMed2000

Predictors of patient response to pulmonary thromboendarterectomy.

OBJECTIVE: We sought to identify imaging features that help predict surgical success in patients undergoing thromboendarterectomy. MATERIALS AND METHODS: Thirty-nine consecutive patients who underwent pulmonary angiography and thromboendarterectomy during 1995 and 1996 were included. Thirty-four underwent helical CT angiography. Measurements of postoperative pulmonary vascular resistance were compared with preoperative imaging features and preoperative pulmonary vascular resistance. RESULTS: The best imaging indicators of a relatively high postoperative pulmonary vascular resistance were the extent of small vessel disease identified on CT angiograms as segments with abnormal perfusion but normal segmental arteries (p = 0.005) and the extent of central disease (p = 0.015). Combined with preoperative pulmonary vascular resistance, these features had a strong correlation with postoperative outcome (p = 0.0005). Segmental arterial disease seen on both conventional angiography and CT angiography correlated poorly with surgical outcome. CONCLUSION: In patients with chronic thromboembolic pulmonary hypertension, CT angiographic evidence of extensive central vessel disease and limited small vessel involvement indicates a favorable surgical outcome.

Adolescent↗
PubMed2000

Relationships between plantar flexor muscle stiffness, strength, and range of motion in subjects with diabetes-peripheral neuropathy compared to age-matched controls.

STUDY DESIGN: Descriptive study to compare relationships between muscle performance measures in 2 subject groups. OBJECTIVES: To determine the relationships between plantar flexor (PF) muscle stiffness, strength (concentric peak torque), and dorsiflexion (DF) range of motion (ROM) in subjects with diabetes who have peripheral neuropathy (n = 17, 10 men, 7 women; age = 58 +/- 11 years) and age-matched controls (n = 17, 10 men, 7 women; age = 62 +/- 6 years). BACKGROUND: The relationships between muscle stiffness, strength, and joint ROM have not been clearly established. Furthermore, the effect of neuromuscular pathology on these relationships is unknown. METHODS AND MEASURES: PF stiffness and strength measurements were obtained with an isokinetic dynamometer. DF ROM was measured with a goniometer. A Pearson correlation matrix was constructed for each subject group using stiffness, strength, and ROM variables. The percent contribution of passive torque to total torque was computed at 2 joint angles. RESULTS: In subjects with diabetes and peripheral neuropathy (DM-PN) peak concentric PF torque was positively correlated with passive torque at 5 degrees DF (r = 0.77), Stiffness #1 (r = 0.58), and Stiffness #2 (r = 0.50). The percentage of passive PF torque at 5 degrees DF was greater in subjects with DM-PN, compared to control subjects (29.3 +/- 9.4% versus 12.6 +/- 5.9%). CONCLUSIONS: The positive correlation between PF stiffness and strength, and the greater percentage of passive PF torque in subjects with DM-PN suggest that patients with decreased strength may use passive torque to maximize total torque. Therefore, treatment methods designed to decrease stiffness should be used cautiously.

Aged↗
PubMed2000

SB-253514 and analogues; novel inhibitors of lipoprotein-associated phospholipase A2 produced by Pseudomonas fluorescens DSM 11579. I. Fermentation of producing strain, isolation and biological activity.

Two new classes of inhibitors of LpPLA2 have been identified in fermentations of Pseudomonas fluorescens. The two structurally isomeric series differ in the geometry of closure of the bicyclic carbamate and comprise a range of compounds varying only in length of their lipophilic sidechain. The most abundant species were extracted from the cells and purified by silica and C18 chromatography. Members of the more stable class were shown to be potent and selective competitive inhibitors of LpPLA2.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2000

The sensitivity and specificity of self-reported symptoms in individuals with traumatic brain injury.

In this study, self-reported symptoms (cognitive, physical, behavioural/affective) from the TIRR Symptom Checklist are compared across six panels: 135 individuals with mild TBI, 275 with moderate/severe TBI, 287 with no disability, 104 with spinal cord injury, 197 who are HIV positive and 107 who had undergone liver transplantation. Participants with TBI and SCI were at least 1 year post-injury. Individuals with TBI reported significantly more symptoms than other panels. Symptom reports in the TBI panels were independent of demographic variables (gender, education, income, ethnicity, age), as well as time since injury and depression. Five of the 67 symptoms were found to be sensitive/specific to TBI in general; 25 symptoms were sensitive/specific to mild TBI (23 were cognitive, one physical and one behavioural/affective). Implications of these results in terms of current debates about the 'reality' of symptom reports in individuals with mild TBI are discussed, as well as implications for using symptom checklists for TBI screening.

Activities of Daily Living↗
PubMed2000

Cost-effectiveness of childhood immunization reminder/recall systems in urban private practices.

OBJECTIVE: To assess cost and cost-effectiveness of immunization reminder/recall systems in the private sector. METHODS: A manual postcard system (mail) was compared with a computer-based telephone system (autodialer) and control. Costs included time costs and the cost of equipment and supplies. The cost per child and the incremental cost of the intervention relative to control were computed. Cost-effectiveness ratios were computed for return visits and for immunizations delivered. RESULTS: The average cost per child was $2.28 for the mail group and $1.47 for the autodialer group. The incremental visit cost relative to the control was higher for the mail group ($9.52) than for the autodialer group ($3.48). The autodialer was more cost-effective in delivering immunizations: $4. 06 per extra immunization (autodialer) versus $12.82 (mail). CONCLUSIONS: Excluding start-up costs, the autodialer system was most cost-effective. Including autodialer equipment costs, the autodialer system is more cost-effective only for larger practices.

Cost-Benefit Analysis↗
PubMed2000

Flow cytometry: principles and clinical applications in hematology.

The use of flow cytometry in the clinical laboratory has grown substantially in the past decade. This is attributable in part to the development of smaller, user-friendly, less-expensive instruments and a continuous increase in the number of clinical applications. Flow cytometry measures multiple characteristics of individual particles flowing in single file in a stream of fluid. Light scattering at different angles can distinguish differences in size and internal complexity, whereas light emitted from fluorescently labeled antibodies can identify a wide array of cell surface and cytoplasmic antigens. This approach makes flow cytometry a powerful tool for detailed analysis of complex populations in a short period of time. This report reviews the general principles in flow cytometry and selected applications of flow cytometry in the clinical hematology laboratory.

Blood Cells↗
PubMed2000

Expression of a subset of steroid receptor cofactors is associated with progesterone receptor expression in meningiomas.

The predominance of meningiomas in females, their accelerated growth during the luteal phase of the menstrual cycle and during pregnancy, and the association between meningiomas and breast cancer have led to a number of studies examining the potential role of steroids on the growth of meningiomas. There are numerous discrepancies in the literature about the mitogenic effects of steroids on meningiomas in both in vitro and in vivo models. The aim of this study was to examine the expression of three steroid receptor coactivators, along with progesterone receptor and estrogen receptor in meningiomas. This additional regulatory layer may explain the heterogeneity of hormone responses observed in these tumors. Using Western blot analysis and immunohistochemistry, we demonstrate the expression of the steroid coactivators steroid receptor cofactor (SRC-1), amplified in breast cancer protein (AIB1), and transcriptional intermediary factor 2 (TIF2) in 81, 76, and 76% of meningiomas, respectively. The expression of SRC-1 and TIF2 is significantly related to progesterone but not to estrogen receptor expression. In contrast, seven normal brain specimens were positive for TIF2 and SRC-1 but negative for AIB1. One leptomeningeal specimen was positive for AIB1, SRC-1, and progesterone receptor. The differential expression of steroid receptor coactivators may explain the differential response of these tumors to hormonal therapy.

Adolescent↗
PubMed2000

Establishing stable test performance in tests from the Behavioral Assessment and Research System (BARS).

Research to identify adverse effects in humans chronically exposed to neurotoxic substances in the workplace or environment typically assesses people at one point in time in a cross-sectional study. The most widely used strategy employs performance measures taken from a single point in time and compares these with either performance of a control group or established normative data. However, multiple comparison points of the same people on the same test allow the dissection of acute--from chronic--exposure effects, among other important questions. When performance measures are used from multiple points in time, within-subject deviations are examined. For either research design, the goal is to minimize the effects of practice and to obtain stable performance on a test. Demographic variables such as age, education, and cultural background or ethnicity influence performance on neurobehavioral tests. These variables may also influence the development of stable performance. Different populations may have different learning curves so that stable performance on a test is achieved with different amounts of practice. This is especially important when making comparisons across groups that may not have equivalent backgrounds. The performance of three groups, English-speaking adults, Spanish-speaking adolescents, and Spanish-speaking migrant adolescents, was examined. Each group completed a battery of neurobehavioral tests from the Behavioral Assessment and Research System (BARS) during four sessions. Repeated measures ANOVAs were used to investigate performance across time. Tests measuring motor performance produced stable performance from the first session. More complex tasks that involved attention and memory showed a practice effect across sessions.

Adolescent↗
PubMed1999

Design and synthesis of potent non-polyglutamatable quinazoline antifolate thymidylate synthase inhibitors.

The synthesis is described of a series of analogues of the potent thymidylate synthase (TS) inhibitor, N-[4-[N-[(3,4-dihydro-2, 7-dimethyl-4-oxo-6-quinazolinyl)methyl]-N-prop-2-ynylamino]-2-f luorob enzoyl]-L-glutamic acid (4, ZM214888), in which the glutamic acid moiety is replaced by homologous amino acids and alpha-amino acids where the omega-carboxylate is replaced by acylsulfonamides and acidic heterocycles. In general these modifications when compared to 4 gave compounds with increased potency as inhibitors of isolated TS and as cytotoxic agents against murine tumor cell lines. The new compounds require transport by the reduced folate carrier for entry into cells but are not converted intracellularly into polyglutamated species. Agents with this profile are expected to show activity against tumors that are resistant to classical antifolates due to low expression of folylpolyglutamate synthetase. The analogue (S)-2-[4-[N-[(3,4-dihydro-2, 7-dimethyl-4-oxo-6-quinazolinyl)methyl]-N-prop-2-ynylamino]-2-f luorob enzamido]-4-(1H-1,2,3,4-tetrazol-5-yl)butyric acid (35, ZD9331) has been selected as a clinical development candidate and is currently undergoing phase I studies.

Animals↗
PubMed1999

Role of mitochondrial lactate dehydrogenase and lactate oxidation in the intracellular lactate shuttle.

To evaluate the potential role of mitochondrial lactate dehydrogenase (LDH) in tissue lactate clearance and oxidation in vivo, isolated rat liver, cardiac, and skeletal muscle mitochondria were incubated with lactate, pyruvate, glutamate, and succinate. As well, alpha-cyano-4-hydroxycinnamate (CINN), a known monocarboxylate transport inhibitor, and oxamate, a known LDH inhibitor were used. Mitochondria readily oxidized pyruvate and lactate, with similar state 3 and 4 respiratory rates, respiratory control (state 3/state 4), and ADP/O ratios. With lactate or pyruvate as substrates, alpha-cyano-4-hydroxycinnamate blocked the respiratory response to added ADP, but the block was bypassed by addition of glutamate (complex I-linked) and succinate (complex II-linked) substrates. Oxamate increased pyruvate (approximately 10-40%), but blocked lactate oxidation. Gel electrophoresis and electron microscopy indicated LDH isoenzyme distribution patterns to display tissue specificity, but the LDH isoenzyme patterns in isolated mitochondria were distinct from those in surrounding cell compartments. In heart, LDH-1 (H4) was concentrated in mitochondria whereas LDH-5 (M4) was present in both mitochondria and surrounding cytosol and organelles. LDH-5 predominated in liver but was more abundant in mitochondria than elsewhere. Because lactate exceeds cytosolic pyruvate concentration by an order of magnitude, we conclude that lactate is the predominant monocarboxylate oxidized by mitochondria in vivo. Mammalian liver and striated muscle mitochondria can oxidize exogenous lactate because of an internal LDH pool that facilitates lactate oxidation.

Animals↗