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Biomedical subjects

M Fisher

Publications and source records attributed to M Fisher.

At least 145 records · Page 8Linked to original sources

The effect of submaximal exercise on recovery hemodynamics and thermoregulation in men and women.

Five women and 5 men were studied to examine the effects of submaximal exercise on thermoregulatory and hemodynamic variables during recovery in two environments: (a) control (C), 22 degrees C, 33% rh; and (b) hot humid (H), 32 degrees C. The participants exercised on a cycle ergometer at 60% of peak oxygen consumption for 35 min prior to 90 min of seated recovery. Sessions were identical, except for environment. Variables evaluated (p < .05) were: core temperature (TR), mean skin temperature (Ts), sweat rate (SR), heart rate (HR), stroke index (SI), cardiac index (CI), forearm blood flow (FBF), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Men and women exhibited similar patterns of TR, Ts, and SR in both environments. Ts and SR (collapsed means for gender) were higher in the H than in the C. DBP was higher in men than in women throughout recovery in both environments. With combined means for gender, HR was higher in the H than in the C. CI, SI, FBF, and SBP were similar in both environments and returned to baseline within 15 min into recovery. These data suggest that heat dissipation during extended recovery was accomplished with similar contributions of cutaneous vasodilation and sweating in M and F. Furthermore, the moderate exercise level did not influence hemodynamics beyond 15 min of recovery in either environment.

Adolescent↗

Endothelin-1 enhances plasminogen activator inhibitor-1 production by human brain endothelial cells via protein kinase C-dependent pathway.

The effects of endothelin-1 (ET-1) on the production of plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (t-PA) by human brain-derived endothelial cells in culture were studied. At 100 nmol/L, ET-1 increased PAI-1 production by 88+/-6% within 72 hours, and increased PAI-1 mRNA expression within 1 hour of stimulation; there was no significant effect on t-PA production. PAI-1 activity was also examined and found to increase with ET-1 treatment. Suboptimal concentrations of ET-1 and tumor necrosis factor-alpha (TNF-alpha) acted synergistically to increase PAI-1 production. ET-1 activated protein kinase C and cAMP-dependent protein kinase pathways within 3 to 5 minutes of treatment, with the peak at 10 minutes. Activation of protein kinase C by phorbol-12-myristate-13-acetate (PMA) resulted in increased PAI-1 production, whereas activation of the cAMP-dependent protein kinase by forskolin or dibutyryl cAMP (dBu-cAMP) significantly decreased PAI-1 production. However, simultaneous activation of protein kinase C by PMA and cAMP-dependent protein kinase by dBu-cAMP only slightly attenuated PMA-induced PAI-1 increase. Inhibition of protein kinase C by GF-109213X abolished the effects of ET-1. These results demonstrate that ET-1 and TNF-alpha function synergistically to induce procoagulant activity of brain endothelial cells in a process that involves a protein kinase C-dependent pathway.

Brain↗

Spontaneous hyperthermia and its mechanism in the intraluminal suture middle cerebral artery occlusion model of rats.

BACKGROUND AND PURPOSE: The intraluminal suture middle cerebral artery occlusion (MCAO) model is increasingly used in experimental stroke studies. The purposes of this study were to determine whether (1) spontaneous hyperthermia occurs after different periods of MCAO in this model, (2) hypothalamic injury contributes to hyperthermia, and (3) hyperthermia increases infarct volume after permanent MCAO. METHODS: Rats were subjected to 60, 90, and 120 minutes of transient MCAO (n=8 per group), permanent MCAO (n=8 per group, 5 groups), and permanent hypothalamic occlusion, in which an occluder was inserted 15 to 15.5 mm to block only the hypothalamic branch from the internal carotid artery (n=4) with the use of the intraluminal suture MCAO method. In one group undergoing permanent MCAO, the body temperature was maintained at 37 degrees C throughout the experiment. In another group (n=4) undergoing 90 minutes of temporary MCAO, diffusion- and perfusion-weighted imaging were performed to document the in vivo ischemic changes in the hypothalamus. Body temperature was measured hourly for 12 hours. At 24 hours (12 hours in 2 permanent MCAO groups), triphenyltetrazolium chloride staining was used to verify ischemic hypothalamic injury and to calculate corrected infarct volumes. RESULTS: Spontaneous hyperthermia (>39 degrees C) occurred in the 120-minute group, all permanent MCAO groups, and the hypothalamic occlusion group but not in the 60-minute or the 90-minute groups. Hypothalamic infarction was found in 1 rat each in the 60-minute and 90-minute groups, 6 of the 8 rats in the 120-minute group, 37 of the 40 rats in the permanent occlusion groups, and all 4 rats in the hypothalamic occlusion group. After 90 minutes of transient MCAO, the decreased cerebral blood flow and apparent diffusion coefficient values in the hypothalamic region during occlusion recovered fully 2 hours after reperfusion. The corrected infarct volumes were identical in all permanent occlusion groups. CONCLUSIONS: The intraluminal suture MCAO lasting for >/=2 hours induces spontaneous hyperthermia that is associated with hypothalamic injury, and delayed spontaneous hyperthermia does not increase infarct volume after permanent intraluminal suture MCAO.

Analysis of Variance↗

Synergistic effects of a combination of low-dose basic fibroblast growth factor and citicoline after temporary experimental focal ischemia.

BACKGROUND AND PURPOSE: Basic fibroblast growth factor (bFGF) and citicoline (cytidine 5'-diphosphate choline, an endogenous compound that stabilizes membrane function) have demonstrated neuroprotective effects after focal cerebral ischemia. Both agents are candidates for future stroke therapy in humans. For evaluation of synergistic effects of bFGF and citicoline, a low-dose combination of both compounds was tested against each compound alone and placebo. METHODS: Four groups of Sprague-Dawley rats (n=12 per group) underwent 90 minutes of focal cerebral ischemia with the use of the suture model of middle cerebral artery occlusion. Animals were randomly and blindly assigned to one of the following treatment groups: placebo, low-dose citicoline (250 mg/kg IP daily for 4 days), low-dose bFGF (10 microg/kg per hour IV for 3 hours), and the combination of both (250 mg/kg citicoline and 10 microg/kg per hour bFGF). Triphenyltetrazolium chloride staining was used after 4 days to determine postmortem infarction. Neurological scores were assessed on a daily basis. RESULTS: The premature mortality rate was 41.7% in the placebo and citicoline groups, 33.3% in the bFGF group, and 25% (P=NS) in the combination group. The mean neurological score on day 4 was 3.1+/-1.6 (placebo), 3.1+/-1.6 (citicoline), 2.9+/-1.5 (bFGF), and 2.4+/-1.4 (combination) (P=NS). The mean volume of infarction was significantly reduced in the combination group (136. 5+/-25.4 mm3) versus placebo (172.6+/-48.9 mm3; P=0.036, Fisher test), versus citicoline alone (186.0+/-35.7 mm3; P=0.005, Fisher test), and versus bFGF alone (176.0+/-49.2 mm3; P=0.023, Fisher test). CONCLUSIONS: These results demonstrate synergistic effects of a low-dose combination of the growth factor bFGF and citicoline after temporary experimental focal cerebral ischemia and furthermore support the effectiveness of a combination treatment regimen for the management of acute stroke.

Animals↗

Nicotine increases plasminogen activator inhibitor-1 production by human brain endothelial cells via protein kinase C-associated pathway.

BACKGROUND AND PURPOSE: Smoking both increases stroke risk and reduces the risk of thrombolysis-associated intracerebral hemorrhage. Plasminogen activator inhibitor-1 (PAI-1) is a major regulator of fibrinolysis; elevation of PAI-1 is associated with an increased risk of thrombotic disorders. We studied the effect of nicotine, an important constituent of cigarette smoke, on PAI-1 production by human brain endothelial cells. METHODS: Adult human central nervous system endothelial cells (CNS-EC) were used for tissue culture experiments. We analyzed culture supernatant for PAI-1 protein and measured PAI-1 mRNA (by Northern blot analysis) and protein kinase C (PK-C) activity. RESULTS: Nicotine at 100 nmol/L increased PAI-1 protein production and mRNA expression by CNS-EC. After 72 hours of exposure to nicotine, the concentration of secreted PAI-1 in the cell supernatant was increased 1.90+/-0.2 fold compared with untreated cells. PAI-1 mRNA also increased approximately twofold. Inhibition of PK-C completely abolished this effect. Nicotine had no effect on the concentration of tissue plasminogen activator. CONCLUSIONS: Nicotine increases brain endothelial cell PAI-1 mRNA expression and protein production via PK-C-dependent pathway. These findings provide new insights into why smoking may be associated with predisposition to thrombosis and inversely associated with intracerebral hemorrhage after therapeutic tissue plasminogen activator therapy.

Adult↗

Transforming growth factor-beta mediates astrocyte-specific regulation of brain endothelial anticoagulant factors.

BACKGROUND AND PURPOSE: Astrocytes are potent regulators of brain capillary endothelial cell function. Recently, astrocytes were shown to regulate brain capillary endothelial expression of the fibrinolytic enzyme tissue plasminogen activator (tPA) and the anticoagulant thrombomodulin (TM). To study the mechanism of this process, we examined the hypothesis that astrocyte regulation of endothelial tPA and TM is mediated by transforming growth factor-beta (TGF-beta). METHODS: Brain capillary endothelial cells were grown in blood-brain barrier models. We examined astrocyte-endothelial cocultures, endothelial monocultures, and astrocyte-conditioned media (ACM) for the expression of TGF-beta. We also incubated endothelial cells with ACM to determine the role of TGF-beta. Following 24 hours of incubation, we assayed for tPA and TM mRNA, as well as tPA and TM activity. RESULTS: Astrocyte-endothelial cocultures and ACM exhibited significantly higher levels of active TGF-beta than brain endothelial monocultures and endothelial cells grown in nonconditioned media, respectively. Brain endothelial cells incubated with ACM exhibited reduced tPA and TM mRNA and activity. Treatment with exogenous TGF-beta produced dose-dependent reductions in tPA and TM. The effects of ACM on both tPA and TM were blocked by TGF-beta neutralizing antibody. CONCLUSIONS: These data indicate that TGF-beta mediates astrocyte regulation of brain capillary endothelial expression of tPA and TM.

Animals↗

Insulin lispro for the treatment of type 2 diabetes.

Tight control can prevent complications in type 2 diabetes, and many patients will require insulin therapy to achieve this. Newer insulin formulations may offer some advantages with regard to patient convenience and a reduction in hypoglycaemia.

Adult↗

Sex role charactersitics of males in nursing.

Sex role stereotypes are widely held concepts that attribute unique sets of characteristics to each sex. The feminine sex role stereotype coupled with the nature of nursing work, renders the profession more appropriate for females. Due to the pressures imposed by hegemonic masculinities, it is perceived that male nurses, as a consequence of their biological sex, are unable to possess the feminine sex role. A survey design was used to ascertain differences in sex role identity between male and female nurses in a contemporary Australian work force. The short form of the Bem Sex Role Inventory (BSRI) was distributed to 98 nurses to determine their perceived sex role identity. There was no significant difference between male and female nurses in masculine and feminine scores, and sex type categories. The results of this preliminary investigation supports the view that a significant proportion of male nurses see themselves having the personal attributes synonymous with the feminine sex role.

Female↗

Adolescent health assessment and promotion in office and school settings.

Issues of health assessment and health promotion for adolescents have received increased attention during the past decade with the publication of several national and international guidelines for health assessment and a more intense examination of "what works and what doesn't work" in the area of health promotion. In this chapter, history and definitions of adolescent health assessment are reviewed, a synopsis of currently available office guidelines is provided, data regarding health screening and promotion in clinical practice are presented, and issues of health screening and education in school settings are discussed.

Adolescent↗

Do your nurses delegate effectively?

Read how to build a work environment that combines your organization's policies and standards, legal regulations, and nurses' expertise into a safe delegation system with positive impact.

Clinical Competence↗

Higher rates of coronary angiography and revascularization following myocardial infarction may be associated with greater survival in the United States than in Canada. The CARS Investigators (Coumadin/Aspirin Reinfarction Study).

BACKGROUND: Significant differences are known to exist between the United States and Canada with respect to coronary catheterization and intervention. In a post hoc analysis, it was hypothesized that these differences may have the greatest impact on outcome in patients at risk for recurrent events such as those following myocardial infarction (MI). PATIENTS AND METHODS: The hypothesis was tested in a nonrandomized comparison of the catheterization and revascularization patterns for patients following acute MI in 7029 patients in the United States and 1774 patients in Canada who participated in the Coumadin/Aspirin Reinfarction Study (CARS). CARS tested the effectiveness of low dose warfarin in combination with acetylsalicylic acid (ASA) versus ASA alone in reducing cardiovascular morbidity and mortality. RESULTS: Before study enrollment (median day 7 to 8), 84.5% of the American patients underwent coronary angiography compared with only 7.7% in Canada (P<0.01). CARS patients in the United States underwent significantly more frequent angioplasty during their hospital admission before study enrollment than their Canadian counterparts (55.8% versus 3.0%, respectively, P<0.01), and there was a more frequent use of intravenous heparin among American CARS patients (96% versus 88%, respectively, P<0.01) but less frequent administration of thrombolytic therapy (44% versus 49%, respectively, P<0.01). For follow-up of up to 32 months, American CARS patients had significantly fewer primary events (cardiovascular deaths, nonfatal MI, nonfatal ischemic stroke) than Canadian patients. Cumulative estimate of a primary end point comparing American with Canadian patients was, respectively, 2.0% versus 3.1% at one month, 8.0% versus 11.3% at one year and 11.6% versus 15.0% at two years. Thus, time to the primary event was significantly longer in American patients (P=0.0001). All-cause mortality estimates at 12 months were 2.2% and 4.0%, respectively, for the American and Canadian CARS subgroups. When management for the index MI (ie, angiography and angioplasty) is included in the model, the risk of death for Canadian versus American subgroups of CARS is not statistically different (0.9, 95% CI 0.6 to 1.2, P=0.40). CONCLUSION: Among study participants, American patients experienced a better outcome than Canadian patients, which may be attributable to more aggressive management based on early coronary angiography and angioplasty. However, angioplasty before study enrollment in American patients may have resulted in enrollment of lower risk patients. This selection bias limits the scope of the comparison.

Aged↗

American Academy of Pediatrics. Committee on Adolescence. Contraception in adolescents.

The risks and negative consequences of adolescent sexual intercourse are of national concern, and promoting sexual abstinence is an important goal of the American Academy of Pediatrics. In previous publications, the American Academy of Pediatrics has addressed important issues of adolescent sexuality, pregnancy, sexually transmitted diseases, and contraception. The development of new contraceptive technologies mandates a revision of this policy statement, which provides the pediatrician with an updated review of adolescent sexuality and use of contraception by adolescents and presents current guidelines for counseling adolescents on sexual activity and contraceptive methods.

Adolescent↗

Vegan pregnancy.

Explore the source record for details and available documents.

Calcium, Dietary↗

Rat brain capillary thrombomodulin: structure and function.

The anticoagulant transmembrane glycoprotein thrombomodulin (TM) is expressed at the luminal surface of vascular endothelial cells. Recently, we showed that TM antigen and TM mRNA are expressed in brain microvessels in several species and that brain capillaries have the capability to activate protein C. The activation of protein C in brain microcirculation was greatly impaired by major stroke risk factors in rats due to downregulation of TM. In this study, a partial sequence of TM was determined from TM mRNA from brain capillaries examined in brain capillaries of the rat, a species that provides a useful model to investigate stroke mechanisms in relation to brain hemostasis. The predicted deduced amino acid sequences for rat TM were compared with other TM sequences. Particularly high homology (77-100%) among functional domains of the protein, i.e., the epidermal growth factor repeats (EGFRs) 1-6 and the transmembrane region, was observed between mice and rats. Somewhat less degree of homology was observed for bovine and human EGFRs 1-6, while the homology of the transmembrane region was 92-96%. All cysteine residues were conserved among the TM sequences, and specific amino acids previously suggested to be essential for activation of protein C by thrombin TM were highly conserved. We conclude that the highly conserved mRNA and protein sequences may reflect a similar anticoagulant role of TM in brain endothelial and systemic vascular endothelial cells across different species.

Amino Acid Sequence↗