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Biomedical subjects

M Fisher

Publications and source records attributed to M Fisher.

At least 253 records · Page 14Linked to original sources
PubMed1996

Modulation of pulsatile GH release through a novel receptor in hypothalamus and pituitary gland.

Hormone replacement should provide a serum hormone profile similar to that found in normal physiology. This is generally impractical because hormones are usually released episodically and therefore require frequent administration. However, rather than replacing the hormone directly, in theory, one could administer a mimic or amplifier of the pulse generator that controls pulsatile release of the particular hormone. Using growth hormone (GH) as a paradigm we sought such a mimetic that would provide episodic GH release when administered by the oral route. A GH secretagogue MK0677, is described that has these ideal properties; following oral administration MK0677 amplifies episodic GH release. Mechanistically, it synergizes with growth hormone releasing hormone (GHRH) through a receptor and signal transduction pathway distinct from that of GHRH and is a functional antagonist of somatostatin (SRIF). MK0677 also acts on the arcuate nucleus and appears to stimulate GHRH release. By using 35S-MK0677, a new G-protein coupled receptor for MK0677 was characterized in the plasma membrane fraction of pituitary and hypothalamic tissue. The receptor is present in very low abundance and couples to phospholipase C. Other ligands selective for this receptor also cause synchronization of well-defined pathways leading to GH release. Repeated oral treatment of dogs once daily with MK0677 initiates amplified pulsatile GH release accompanied by increases in IGF-1 that are sustained. The unique biological properties of MK0677 and other synthetic ligands that bind to the same receptor force us to predict that these ligands mimic a naturally occurring hormone that regulates pulsatile GH release. Understanding the regulatory mechanisms involved in this paradigm has broad implications for the control of pulsatile rhythms in the endocrine system.

Amino Acid Sequence↗
PubMed1995

New magnetic resonance techniques for acute ischemic stroke.

Neuroimaging was revolutionized by the development of computed tomography (CT) and standard T1- and T2-weighted magnetic resonance imaging (MRI). Magnetic resonance imaging and CT can adequately distinguish hemorrhage from infarction and depict ischemic stroke 12 to 24 hours after onset. However, during the critical initial hours after the onset of ischemic stroke, these imaging technologies do not adequately demonstrate the location and extent of infarction. Diffusion-weighted MRI and perfusion imaging, as well as advances in magnetic resonance spectroscopy, will enhance our ability to evaluate ischemic stroke shortly after onset. Some of the uses of MRI techniques are as follows: (1) Diffusion-weighted imaging can depict the location and extent of the ischemic lesion as soon as a stroke patient is available for examination. (2) Perfusion imaging evaluates blood flow within the brain's microvasculature and can reveal regions of perfusion deficits corresponding to major vascular territories. (3) Magnetic resonance spectroscopy evaluates metabolic abnormalities associated with focal brain ischemia by specific biochemical measurements. These MRI techniques will rapidly provide important information to clinicians about ischemia, guiding diagnosis and helping in the development of acute stroke interventions to improve outcome.

Brain Ischemia↗
PubMed1995

An amplified chemiluminescent assay for the detection of alkaline phosphatase.

An amplification assay for the measurement of alkaline phosphatase has been combined with a luminescent end point using the luminol-peroxidase system to produce the first enzyme-amplified chemiluminescent assay based on the principle of prosthetogenesis. This assay is both quantitative and extremely sensitive. When the assay was used to detect alkaline phosphatase in solution, the detection limit was 0.4 amol in a 5-min assay. The interassay variance ranged from 4 to 20% and 7 to 19% across the dynamic range of the assay for a chemiluminescent assay and an enhanced chemiluminescent assay, respectively, employing two different preparations of luminol.

Alkaline Phosphatase↗
PubMed1995

Reversal of heparin anticoagulation by recombinant platelet factor 4 in humans.

BACKGROUND: Protamine is used to reverse the anticoagulant effects of heparin, but it can have important side effects. Platelet factor 4 (PF4) is a protein found in platelet alpha granules that binds to and thereby neutralizes heparin. We evaluated the safety and effectiveness of intravenous recombinant PF4 to neutralize heparin anticoagulation after cardiac catheterization in a phase 1, open-label trial. METHODS AND RESULTS: The study group consisted of 18 patients having diagnostic cardiac catheterization. Heparin (5000 U) was given after vascular access was obtained. In the first 12 patients, additional heparin was given at the conclusion of the procedure so that all patients had activated coagulation times > 300 seconds before rPF4 was given. Three patients each received 0.5, 1.0, 2.5, or 5.0 mg/kg rPF4 over a period of 3 minutes at the conclusion of the catheterization procedure. In 6 additional patients, extra heparin was not given at the conclusion of the procedure, and 1.0 mg/kg rPF4 was given. Hemodynamic measurements, cardiac output, and serial blood tests were performed 5, 10, 20, and 30 minutes after rPF4 and then into the next 24 hours. There were no serious side effects in any patient, despite transient rPF4 levels as high as 14,870 ng/mL in the patients receiving 5.0 mg/kg. One patient receiving 2.5 mg/kg had a slight transient rise in liver enzymes possibly related to the rPF4. There were no important hemodynamic effects of rPF4 administration at any dose used. Doses of 2.5 and 5.0 mg/kg were uniformly effective in reversing the anticoagulant effect of heparin. At lower doses, rPF4 neutralized the effects of heparin in most but not all patients. Pharmacokinetic analysis suggested a monophasic and one-compartment clearance of the PF4-heparin complex. No neutralizing factors to rPF4 were detected in the samples collected 7 days after dosing. CONCLUSIONS: rPF4, in doses ranging from 0.5 to 5.0 mg/kg over 3 minutes, had no serious side effects. Given in sufficient amounts, rPF4 can completely and rapidly reverse the anticoagulant effects of heparin.

Cardiac Catheterization↗
PubMed1995

Recurrent syncope of unknown origin: value of permanent pacemaker insertion.

We studied the outcome of permanent pacing in those with a history suggestive of Stokes-Adams attacks but no electocardiographic evidence of bradyarrhythmia. Of 11 patients who fulfilled pre-defined inclusion criteria, over a mean follow-up period of 5.4 years, seven patients were free of symptoms and two were much improved following pacing. We suggest that in those with a clinical history of frequently recurrent Stokes-Adams attacks and a normal electrocardiogram, pacemaker insertion may be a reasonable course of action.

Adams-Stokes Syndrome↗
PubMed1995

Stated and unstated reasons for visiting a high school nurse's office.

PURPOSE: To determine the presenting complaints of students visiting a high school nurse's office and seek associations between specific presenting complaints and psychosocial problems. METHODS: One hundred eighty-six students visiting the school nurse in a suburban high school were surveyed with a questionnaire developed by the investigators. Categorical data were compared utilizing chi-square or Fisher's Exact Test. Associations were determined by the Kruskal-Wallis Test. RESULTS: Headaches (25%), infections (17%), stomach aches (12%), and dizziness or tiredness (12%) were the most common presenting complaints. Students indicated that "not sleeping well" and "stress" were two factors that most frequently played a role in their visits. Most students wanted either to rest or await going home; few were interested in receiving medical care or talking to the nurse. Specific complaints of headache, dizziness or tiredness, and no specific symptom were associated (p < .05) with not sleeping well, family problems, stress, school problems and depression. CONCLUSIONS: Complaints of headache, dizziness or tiredness, and no specific symptoms may be used as markers for exploring possible psychosocial problems underlying a visit to the school nurse. If school nurses are to address psychosocial issues, they will need to look beyond stated reasons to unstated reasons for visits. Ways to achieve this expanded level of care are discussed.

Adolescent↗
PubMed1995

Delayed treatment with intravenous basic fibroblast growth factor reduces infarct size following permanent focal cerebral ischemia in rats.

Basic fibroblast growth factor (bFGF) is a polypeptide that supports the survival of brain cells (including neurons, glia, and endothelia) and protects neurons against a number of toxins and insults in vitro. This factor is also a potent dilator of cerebral pial arterioles in vivo. In previous studies, we found that intraventricularly administered bFGF reduced infarct volume in a model of focal cerebral ischemia in rats. In the current study, bFGF (45 micrograms/kg/h) in vehicle, or vehicle alone, was infused intravenously for 3 h, beginning at 30 min after permanent middle cerebral artery occlusion by intraluminal suture in mature Sprague-Dawley rats. After 24 h, neurological deficit (as assessed by a 0- to 5-point scale, with 5 = most severe) was 2.6 +/- 1.0 in vehicle-treated and 1.5 +/- 1.3 in bFGF-treated rats (mean +/- SD; N = 12 vs. 11; p = 0.009). Infarct volume was 297 +/- 65 mm3 in vehicle- and 143 +/- 135 mm3 in bFGF-treated animals (p = 0.002). During infusion, there was a modest decrease in mean arterial blood pressure but no changes in arterial blood gases or core or brain temperature in bFGF-treated rats. Autoradiography following intravenous administration of 111In-labeled bFGF showed that labeled bFGF crossed the damaged blood-brain barrier to enter the ischemic (but not the nonischemic) hemisphere. Whether the infarct-reducing effects of bFGF depend on intraparenchymal or intravascular mechanisms requires further study.

Animals↗
PubMed1995

Spreading waves of a reduced diffusion coefficient of water in normal and ischemic rat brain.

Using echo planar diffusion-weighted magnetic resonance imaging, we measured three-dimensional changes in the apparent diffusion coefficient (ADC) of water in eight contiguous coronal slices, encompassing the entire rat brain, before and after local cortical stimulation. We applied chemical (potassium chloride application; n = 6) and mechanical (needle stab; n = 4) stimulations to the right posterior parietal rat cortex. In all animals in which potassium chloride or the needle stab was applied, a region of decreased ADC values to a mean of 0.45 +/- 0.03 x 10(-5)cm2/s occurred. These reduced ADC levels appeared in the posterior parietal cortex within 1 min after cortical stimulation and the change recovered within 1 min. Then a ripple-like movement of similar changes developed across the unilateral cortex. This change was localized to the cortex and no significant ADC changes occurred in subcortical structures. The propagating speed of this movement was 3.4 +/- 0.5 mm/min. These findings are compatible with spreading depression as observed electrophysiologically. Similar ADC changes occurred in areas distinct from the ischemic lesion in 3 of 12 animals subjected to focal cerebral ischemia. This magnetic resonance method could detect spreading ADC decline if it occurred in human diseases including brain ischemia.

Animals↗
PubMed1995

Diffusion weighted imaging for acute cerebral infarction.

The diagnosis of acute cerebral ischemia remains difficult. Computed tomography and magnetic resonance tomography are not specific at early time points. Diffusion imaging a new technique for magnetic resonance imaging was introduced in experimental studies and shown to have much earlier sensitivity for acute ischemic infarction. Diffusion imaging demonstrated early hyperintensities within minutes after ischemic onset and correlated well with post-mortem studies of the final infarct size. On the basis of molecular motion of water, hyperintensities during ischemia on diffusion imaging are most likely related to the development of ischemia induced cytotoxic edema and to slower diffusional motion. Experimental treatment and reperfusion studies with diffusion imaging demonstrated lesion reversal in vivo. Continuous monitoring after induction of ischemia enables an in vivo demonstration of the evolution of the ischemic lesion. Quantitative analysis of the apparent diffusion coefficient may enable the differentiation of infarcted tissue in the core of the lesion from reversibly damaged tissue. Preliminary clinical studies demonstrated a superior sensitivity of diffusion imaging compared with T2-weighted imaging. Clinicians may be able in the near future to image early stroke and to assess therapy when the stroke is still evolving.

Acute Disease↗