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Biomedical subjects

M Fisher

Publications and source records attributed to M Fisher.

At least 307 records · Page 17Linked to original sources
PubMed1994

Effects of acute and repeated intravenous administration of L-692,585, a novel non-peptidyl growth hormone secretagogue, on plasma growth hormone, IGF-1, ACTH, cortisol, prolactin, insulin, and thyroxine levels in beagles.

L-692,585 is a 2-hydroxypropyl derivative of L-692,429, both novel non-peptidyl growth hormone (GH) secretagogues. The effects of single and repeated intravenous administration of L-692,585 on serum or plasma GH and other hormones in beagles were evaluated. In a balanced 8-dog dose-ranging study, compared to the saline control with a mean (+/- S.E.M.) after-dose serum GH peak of 6.1 +/- 1.3 ng/ml, L-692,585 significantly increased (P < 0.05) peak GH concentrations 4.3-fold (32.5 +/- 7.0 ng/ml) at a dose of 0.005 mg/kg, 7-fold (49.4 +/- 10.6 ng/ml) at a dose of 0.02 mg/kg, and 21-fold (134.3 +/- 29.0 ng/ml) at a dose of 0.10 mg/kg. Total GH release, expressed as area under the curve, showed a similar dose-dependent increase. Peak GH levels were recorded at 5 or 15 min after dosing with the levels returning to near baseline by 90 min. Serum cortisol levels were increased above saline control levels in a dose-dependent manner; however, the increases were modest compared to the GH increases. Based on peak responses and total GH release, L-692,585 was 10- to 20-fold and 2- to 2.5-fold more potent than L-692,429 and the growth hormone releasing peptide, GHRP-6, respectively. When L-692,585 was administered once daily for 14 consecutive days at 0, 0.01 or 0.10 mg/kg to each of 6 dogs, peak plasma GH levels and total GH release on days 1, 8 and 15 significantly increased in a dose-dependent manner, and no desensitization was evident.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1994

Quality improvement through use of medication incident reports.

This paper describes the background to the development of a Medication Incident Report pro forma, for use throughout the Liverpool Health Service. This pro forma is used by Medical, Pharmacy and Nursing staff to report prescription, dispensing and administration of medication errors.

Humans↗
PubMed1994

Epibatidine, an alkaloid from the poison frog Epipedobates tricolor, is a powerful ganglionic depolarizing agent.

Epibatidine, a newly discovered alkaloid from the skin of Dendrobatidae frogs, has structural similarities to nicotine. We examined the effects of epibatidine on cardiorespiratory function and ganglionic synaptic transmission. Superior cervical or splanchnic sympathetic nerve discharge (sSND) and phrenic nerve discharge (PND) were recorded along with arterial pressure (AP) in urethane-anesthetized, paralyzed and artificially ventilated rats. Epibatidine administered i.v. at low doses (0.5-2 micrograms/kg) produced a transient increase in AP and sSND, followed by a decrease and return to baseline; this low dose of epibatidine also produced a dose-dependent increase in PND. At high doses (cumulative dose of 8-16 micrograms/kg), epibatidine produced bradycardia, a profound depression in sSND and a transient elimination of PND. After i.v. administration of the ganglionic blocker chlorisondamine (5 mg/kg), AP was still increased by 1 microgram/kg epibatidine (+39 +/- 11 mm Hg). This pressor effect was not altered by pretreatment with the alpha-1 adrenergic antagonist phentolamine (+40 +/- 10 mm Hg); however, it was blocked by additional pretreatment with the vasopressin antagonist [beta-mercapto-beta,beta-cyclopentamethylenepropiony1, O-ET-Tyr2,Val4,Arg8]vasopressin (50 micrograms/kg i.v.; +2 +/- 0.4 mm Hg). Low doses of epibatidine (0.5-2 micrograms/kg) produced firing of postganglionic neurons in a decentralized ganglion preparation and potentiated synaptic transmission; at high doses (cumulative dose of 8-16 micrograms/kg), the alkaloid blocked ganglionic synaptic transmission. These results suggest that epibatidine is a potent agonist of ganglionic nicotinic receptors and that the alkaloid elicits cardiorespiratory effects similar to those of nicotine.

Alkaloids↗
PubMed1993

Defective vasculature in fibronectin-receptor-deficient CHO cell tumors in nude mice.

The level of expression of the alpha 5/beta 1 integrin fibronectin receptor (FnR) strongly affects the growth rate of CHO cell tumors in nude mice. Here we report that alpha 5/beta 1 expression also influences the organization of the tumor vasculature. Tumors formed from CHO clones defective in FnR expression have a leaky vasculature that gives them a hemorrhagic appearance. Tumors from wild-type CHO cells, or from FnR-deficient CHO clones transfected with constructs coding for the alpha 5 integrin subunit, have an intact, non-leaky vasculature. In tumors from FnR-deficient cells, the endothelial lining of blood vessels is sparse, and red cells and plasma proteins can be detected in the tumor parenchyma. In tumors from cells expressing the alpha 5/beta 1 FnR, tumor vessels are circumscribed by a lining of von-Willebrand-factor-positive endothelial cells, and blood cells and proteins are confined to the vessel lumina. Thus, the level of expression of the alpha 5/beta 1 FnR in the tumor parenchymal cells can influence the development of tumor vasculature. Since alpha 5/beta 1 is vital to the organization of the extracellular matrix, one possibility is that altered matrix assembly contributes to the defective vascularization seen in alpha 5/beta 1-deficient tumors.

Animals↗
PubMed1993

Evolving toward effective therapy for acute ischemic stroke.

Acute ischemic stroke is a common, devastating disorder without beneficial therapy. Recent advances concerning the pathophysiology of ischemic brain injury have led to the development of rational pharmacological interventions. Thrombolytic and cytoprotective therapies may be useful and are being evaluated in clinical trials. The design of adequate clinical trials to evaluate these promising therapies has also evolved based on experience. Potential therapy for acute ischemic stroke must be assessed in a large number of patients who are given the intervention within hours of onset using a neurological scoring scale and a disability scale. Several new magnetic resonance imaging technologies are emerging that should allow the clinician to rapidly and accurately identify ischemic brain lesions and to evaluate cerebral perfusion. The availability of potentially efficacious therapies for ischemic stroke evaluated in well-designed clinical trials with magnetic resonance imaging technology, which can also assess therapeutic effects in vivo, should lead to the emergence of therapy to improve the outcome of patients with ischemic stroke in the near future.

Acute Disease↗
PubMed1993

Hypermagnesemic pseudocoma.

We treated a case of iatrogenic hypermagnesemia that clinically mimicked a central brain-stem herniation syndrome. Hypermagnesemia (magnesium level, 9.85 mmol/L [24 mg/dL]) can cause parasympathetic blockade, inducing fixed and dilated pupils, in addition to neuromuscular blockade. Extreme hypermagnesemia can therefore mimic a midbrain syndrome and cause a pseudocomatose state.

Adult↗
PubMed1993

A model for prosthetogenic enzyme amplification assays.

A mathematical model describing the behaviour of a new class of prosthetogenic enzyme amplification assays is described. The predictions of the model are favourably compared with an enzyme amplification assay for alkaline phosphatase. The model is used to kinetically characterise and optimise the enzyme amplification assay.

Alkaline Phosphatase↗
PubMed1993

Bergmann glia require continuous association with Purkinje cells for normal phenotype expression.

Bergmann glia (Bg) respond to the early postnatal Purkinje cell (Pc) death in Lurcher (Lc) mutant mouse cerebellum by down-regulating expression of the enzyme glycerol-3-phosphate dehydrogenase (GPDH). To determine whether glial GPDH expression requires the continued presence of Pcs in adults, we used single intracerebellar injections of kainic acid to kill Pcs in wild-type mice from 7 weeks to 11 months old. Bg at all ages tested responded to Pc loss by down-regulating GPDH expression. To learn whether a high level of GPDH could be reinduced following down-regulation in Lc Bg, we grafted wild-type fetal Pcs into Lc cerebella. The influence of grafted Pcs on GPDH expression is host-age and implant-position dependent. Only Pcs implanted into hosts less than 6 weeks old were later found to be associated with GPDH-positive Bg. Grafted Pcs that migrated into the anterior folia of young hosts were more likely to be associated with GPDH-positive Bg than Pcs migrating to other positions. EM analysis showed that Bg ensheathment of grafted Pcs is thinner and more discontinuous, but qualitatively similar to normal. The results suggest that the interaction between host Bg and grafted Pcs can sustain elevated GPDH expression in Bg that have not yet down-regulated, but is not adequate to reinduce expression in those cells that have.

Age Factors↗
PubMed1993

Apparent diffusion coefficient mapping of experimental focal cerebral ischemia using diffusion-weighted echo-planar imaging.

Diffusion-weighted, echo-planar imaging (EPI) was used to map regional changes in the apparent diffusion coefficient (ADC) during experimental focal ischemia in the rat brain following permanent middle cerebral arterial occlusion (MCAO). Sixteen 64 x 64 diffusion-weighted EPIs were acquired in 32 s with successively increasing amplitudes of the diffusion-sensitive gradient pulses. A linear least-squares regression algorithm was used to fit 15 of the 16 two-dimensional matrices, on a pixel-by-pixel basis, to solve for the slope from which the ADC value was calculated. The correlation coefficient of the fit, R2, was used to filter the final ADC maps, and the ADCs were then scaled appropriately to be displayed in a 256 gray level format. Ranges (bins) of 0.05 x 10(-3) mm2/s were then grouped and color coded to qualify and quantify the evolution of ischemia in the MCA territory. The percentage of area in the ischemic and contralateral hemispheres in seven ADC bins were calculated at 30, 60, and 120 min after MCAO for 10 animals and demonstrated a significant increase in ADC bins below 0.45 x 10(-3) mm2/s and a decrease in bins above 0.50 x 10(-3) mm2/s over time. The postmortem infarct area, as measured by TTC staining, was highly correlated with the portion of the ischemic hemisphere falling below ADC values of 0.55 x 10(-3) mm2/s at 2 h after stroke onset. These studies suggest that focally ischemic brain tissue can be quantitatively subdivided according to ADC values and that ADC values below 0.55 x 10(-3) mm2/s 2 h following ischemia highly predict infarction in a rat permanent occlusion stroke model.

Algorithms↗
PubMed1993

Inhibition of inflammatory cell-mediated myelin oxidation and interleukin-1 beta generation by a 21-aminosteroid, U74500A.

Inflammatory cell-mediated myelin injury may be an important cause of tissue damage in both acute and chronic central nervous system (CNS) disorders. The 21-aminosteroids are novel derivatives of methylprednisolone without obvious glucocorticoid or mineralocorticoid side effects. We evaluated the ability of 21-aminosteroid, U74500A, to inhibit oxidation of rat brain myelin by human polymorphonuclear leukocytes (PMN) and monocytes. Myelin samples, as confirmed by SDS-PAGE, were incubated with PMN or monocytes and 100 microM U74500A or vehicle. Myelin oxidation by both PMN and monocytes was significantly reduced by U74500A. These observations demonstrate that U74500A can inhibit myelin oxidation by inflammatory cells. Additionally, 100 microM U74500A significantly reduced production of interleukin 1-beta by monocytes exposed to myelin. The aminosteroids may be beneficial in CNS disorders where myelin injury by inflammatory cells appears to contribute, such as acute focal ischemia or multiple sclerosis.

Animals↗
PubMed1993

Coronary angiography with 5 French diagnostic catheters may miss an ostial left main stenosis.

Critical ostial left main disease may lead rapidly to sudden death and is, therefore, of paramount importance to diagnose. While the number of cardiac catheterizations is increasing, government and third party reimbursement sources are imposing pressure to perform more studies in an outpatient setting, as the economic resources for medical procedures are shrinking. Outpatient cardiac catheterization requires the patient to ambulate within several hours after the procedure. In order to allow patients to safely ambulate early after their procedures, 5 French catheters are often used (whether the femoral or brachial approach is used) rather than the standard 7 French catheters. We describe a patient with an ostial left main stenosis that was not visualized when coronary arteriography was performed using a diagnostic 5 French catheter. Selective intubation of the left main coronary artery was easily achieved without damping of the pressure tracing. Selective coronary angiography did not demonstrate the ostial stenosis, and there appeared to be a normal amount of contrast refluxing into the aortic root. When the patient returned for an angioplasty and a guiding angiogram was performed with an 8 French catheter, an ostial stenosis was evident with coronary angiography.

Aged↗
PubMed1993

Diffusion and perfusion magnetic resonance imaging studies to evaluate a noncompetitive N-methyl-D-aspartate antagonist and reperfusion in experimental stroke in rats.

BACKGROUND AND PURPOSE: Diffusion magnetic resonance imaging (MRI) can quantitatively detect focal ischemic injury within minutes of onset, and perfusion MRI can evaluate the brain's microcirculation. N-Methyl-D-aspartate (NMDA) antagonists and reperfusion can reduce lesion size in stroke models. We used diffusion and perfusion MRI to evaluate the in vivo effects of a noncompetitive NMDA antagonist, CNS 1102, in a temporary ischemia model. METHODS: Sixteen Sprague-Dawley rats underwent suture occlusion of the middle cerebral artery. Fifteen minutes after occlusion, animals were randomly assigned to treatment with CNS 1102 (n = 10) or placebo (n = 6), receiving a bolus of 1.13 mg/kg at that time and an infusion of 0.785 mg.kg-1.h-1 for the next 165 minutes. The placebo group received a saline bolus and infusion. Diffusion MRI studies by a spin-echo technique were initiated 30 minutes after occlusion and repeated every 30 minutes for the next 3 hours. Perfusion MRI studies were obtained using echo-planar imaging after injection of superparamagnetic iron oxide particles, immediately before and 15 minutes after withdrawal of the occluder at 3 hours after middle cerebral artery occlusion. At 24 hours, the animals were clinically evaluated (scale of 0 to 5) and electively killed, and the brain was stained with triphenyltetrazolium chloride to evaluate infarct size. RESULTS: Diffusion imaging demonstrated markedly reduced ischemic lesion area in the CNS 1102 group during occlusion--10.5 +/- 7.3% (mean +/- SEM) of the ischemic hemisphere (optic chiasm slice) at 30 minutes after occlusion versus 50.0 +/- 2.7% of the hemisphere in controls (P < .02). With reperfusion after 3 hours of temporary ischemia, diffusion imaging documented an additional 29% reduction of the ischemic lesion area in the CNS 1102-treated group (P < .01) compared with the prereperfusion ischemic lesion area, with no change in the placebo group. During occlusion, perfusion imaging demonstrated a relative signal intensity decline of 31.5 +/- 7.7% in controls and 83.4 +/- 7.6% in the CNS 1102 group (P < .005), indicating better perfusion in the latter group. After removal of the occluder, perfusion improved in both groups and was not significantly different. Post mortem infarct volume was 53.8 +/- 20.0 mm3 in the CNS 1102 group and 216.8 +/- 16.1 mm3 in the controls (P < .0001). Clinical outcome at 24 hours was 1.1 +/- 0.4 in the CNS 1102 group and 4.0 +/- 0.5 (scale of 0 to 5) in the controls (P < .005). CONCLUSIONS: This study demonstrates that CNS 1102 reduces early postischemic injury as documented by diffusion MRI and improves perfusion as documented by perfusion MRI and that reperfusion confers additional reduction of ischemic lesion size.

Animals↗