Biomedical subjects
M Fisher
Publications and source records attributed to M Fisher.
Coated charcoal assay of unsaturated iron-binding capacity.
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Voluntary health insurance for the disadvantaged.
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The problem of associating coagulase-negative staphylococci with disease.
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A local authority contraceptive clinic: a survey of its effectiveness.
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Further evolution toward effective therapy for acute ischemic stroke.
The effective treatment of acute ischemic stroke remains an important goal of modern medicine and substantive advances are occurring. Recently, thrombolytic therapy with tissue-type plasminogen activator was approved for selected patients with acute ischemic stroke when therapy is started within 3 hours of onset. Streptokinase therapy for acute ischemic stroke has not been shown to be effective and is associated with an increased risk of hemorrhage, although it was not evaluated as early after stroke onset as tissue-type plasminogen activator. Various types of neuroprotective interventions are effective in animal models, but none has yet been proven effective in patients. In the future, combinations of thrombolytic and neuroprotective drugs may be used to attempt maximum rates of recovery after acute ischemic stroke. For combination therapy to achieve its maximum potential, patients with acute ischemic stroke will have to be carefully selected and treated.
Diagnosis of macrosomia in the postdates population: combining sonographic estimates of fetal weight with glucose challenge testing.
OBJECTIVE: To evaluate the test characteristics of sonographic estimation of fetal weight in the detection of macrosomia in nondiabetic postdates patients as a function of maternal glucose value measured after glucose challenge testing performed at 24-28 weeks of gestation. METHODS: At or beyond 41 weeks' gestation, 656 nondiabetic patients had sonographic estimation of fetal weight. Receiver-operator characteristic curve analysis was used to define the glucose value at which an optimal number of macrosomic fetuses could be identified. The test characteristics of sonography in the prediction of macrosomia in the two populations defined by that cut-off value were evaluated. RESULTS: A glucose level of 120 mg/dL (6.6 mM) was identified as the optimal cutoff for prediction of birth weight > or = 4,000 g. In the group with a glucose level > or = 120 mg/dL, sonographic estimation of fetal weight in the detection of macrosomia offered a sensitivity, specificity, and positive and negative predictive values of 63%, 91%, 71%, and 86%, respectively. In those with glucose level <120 mg/dL, sonography demonstrated a sensitivity, specificity, and positive and negative predictive values of 65%, 89%, 60%, and 91%, respectively. CONCLUSIONS: In postdates nondiabetic patients, routine glucose challenge testing performed early in pregnancy has limited ability to improve the test characteristics of sonography to predict macrosomia. The positive predictive value of sonographically suspected macrosomia increases from 60-71% in patients whose glucose level was > or = 120 mg/dL (P = 0.002).
Pharmacokinetics and pharmacodynamics of nifedipine in patients at steady state.
The pharmacokinetics and associated pharmacodynamics of nifedipine were studied at steady state in 12 patients with angina pectoris who were receiving nifedipine 10-40 mg tid. After dosing, serum nifedipine concentrations rose rapidly and decayed in a log-linear fashion. The mean (+/- SEM) maximum serum concentration (Cmax) after dose normalization, and the time to Cmax (tmax) were 115 +/- 7 ng/mL and 0.72 +/- 0.13 hr, respectively. The mean area under the plasma concentration-time curve per 10-mg dose was 304 +/- 34 hr-ng/mL. The average elimination rate constant was 0.205 +/- 0.016 hr, and the harmonic mean elimination half-life was 3.4 hr (range, 2.5-4.9 hr). Heart rate increased (5-6 beats/min, P less than .05) from baseline for up to one hour after dose, while mean diastolic blood pressure decreased (6-15 mm Hg, P less than .05) for up to four hours. Cardiac output was increased (1.1-2.8 L/min, P less than .05), and calculated total systemic resistance (3.8-6.3 mm Hg/L/min, P less than .05) was decreased for the entire dosing interval after nifedipine dosing. Hysteresis plots for heart rate and mean diastolic blood pressure showed a time lag between changes in serum nifedipine concentrations and heart rate, but not between serum nifedipine concentrations and blood pressure. Changes in cardiac output did not correlate with serum nifedipine concentrations. The steady-state kinetic and dynamic parameter values in patients with angina pectoris in this study were similar to those found in healthy volunteers or hypertensive patients after acute nifedipine administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Determination of focal ischemic lesion volume in the rat brain using multispectral analysis.
Multispectral (MS) analysis was used to determine the ischemic lesion volume in the rat brain after permanent middle cerebral arterial occlusion. MS analysis used a four-dimensional MS model consisting of an estimate of the average apparent diffusion coefficient of water (ADC(av)), T2, proton density, and perfusion. Four classification methods were investigated: (a) multivariate gaussian (MVG); (b) k-nearest neighbor (k-NN); (c) k-means (KM); and (d) fuzzy c-means (FCM). MVG and k-NN classifiers are supervised methods requiring labeled training data to characterize the stroke lesion. Unsupervised classifiers (KM, FCM) do not require previous statistics or labeled training data, resulting in potentially greater clinical usefulness. All MS methods provided significant correlation with postmortem findings beyond the use of ADC(av) alone (partial correlation given the ADC(av) estimate: MVG, .66; k-NN, .75; KM, .68; FCM, .70). This study demonstrates that MS analysis provides an improved estimate of ischemic lesion volume over that obtained from ADC alone.
Remifentanil in the horse: identification and detection of its major urinary metabolite.
Remifentanil (4-methoxycarbonyl-4-[(1-oxopropyl)phenylamino]-1-piperidinepropionic acid methyl ester) is a mu-opioid receptor agonist with considerable abuse potential in racing horses. The identification of its major equine urinary metabolite, 4-methoxycarbonyl-4-[(1-oxopropyl)phenylamino]-1-piperidinepropionic+ ++ acid, an ester hydrolysis product of remifentanil is reported. Administration of remifentanil HCl (5 mg, intravenous) produced clear-cut locomotor responses, establishing the clinical efficacy of this dose. ELISA analysis of postadministration urine samples readily detected fentanyl equivalents in these samples. Mass spectrometric analysis, using solid-phase extraction and trimethylsilyl (TMS) derivatization, showed the urine samples contained parent remifentanil in low concentrations, peaking at 1 h. More significantly, a major peak was identified as representing 4-methoxycarbonyl-4-[(1-oxopropyl)phenylamino]-1-piperidinepropionic+ ++ acid, arising from ester hydrolysis of remifentanil. This metabolite reached its maximal urinary concentrations at 1 h and was present at up to 10-fold greater concentrations than parent remifentanil. Base hydrolysis of remifentanil yielded a carboxylic acid with the same mass spectral characteristics as those of the equine metabolite. In summary, these data indicate that remifentanil administration results in the appearance of readily detectable amounts of 4-methoxycarbonyl-4-[(1-oxopropyl)phenylamino]-1-piperidinepropionic+ ++ acid in urine. On this basis, screening and confirmation tests for this equine urinary metabolite should be optimized for forensic control of remifentanil.
Clenbuterol in the horse: confirmation and quantitation of serum clenbuterol by LC-MS-MS after oral and intratracheal administration.
Clenbuterol is a beta2 agonist/antagonist bronchodilator, and its identification in post-race samples may lead to sanctions. The objective of this study was to develop a specific and highly sensitive serum quantitation method for clenbuterol that would allow effective regulatory control of this agent in horses. Therefore, clenbuterol-d9 was synthesized for use as an internal standard, an automated solid-phase extraction method was developed, and both were used in conjunction with a multiple reaction monitoring liquid chromatography-tandem mass spectrometry (LC-MS-MS) method to allow unequivocal identification and quantitation of clenbuterol in 2 mL of serum at concentrations as low as 10 pg/mL. Five horses were dosed with oral clenbuterol (0.8 microg/kg, BID) for 10 days, and serum was collected for 14 days thereafter. Serum clenbuterol showed mean trough concentrations of approximately 150 pg/mL. After the last dose on day 10, serum clenbuterol reached a peak of approximately 500 pg/mL and then declined with a half-life of approximately 7 h. Serum clenbuterol declined to 30 and 10 pg/mL at 48 and 72 h after dosing, respectively. By 96 h after dosing, the concentration was below 4 pg/mL, the limit of detection for this method. Compared with previous results obtained in parallel urinary experiments, the serum-based approach was more reliable and satisfactory for regulation of the use of clenbuterol. Clenbuterol (90 microg) was also administered intratracheally to five horses. Peak serum concentrations of approximately 230 pg/mL were detected 10 min after administration, dropping to approximately 50 pg/mL within 30 min and declining much more slowly thereafter. These observations suggest that intratracheal administration of clenbuterol shortly before race time can be detected with this serum test. Traditionally, equine drug testing has been dependent on urine testing because of the small volume of serum samples and the low concentrations of drugs found therein. Using LC-MS-MS testing, it is now possible to unequivocally identify and quantitate low concentrations (10 pg/mL) of drugs in serum. Based on the utility of this approach, the speed with which new tests can be developed, and the confidence with which the findings can be applied in the forensic situation, this approach offers considerable scientific and regulatory advantages over more traditional urine testing approaches.
Report from the International Study Group on Implantable Insulin Delivery Devices.
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Computer diagnosis of the acutely ill patient with fever and a rash.
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Relation of diet to LDL cholesterol, VLDL cholesterol, and plasma total cholesterol and triglycerides in white adults. The Lipid Research Clinics Prevalence Study.
The association of diet with low density lipoprotein cholesterol (LDL-C) and total triglycerides, as well as with total and very low density lipoprotein cholesterol (VLDL-C), was investigated in a random sample of 4374 white participants aged 20 to 59 years seen by the Lipid Research Clinic Prevalence Study. Carbohydrate and total calories were negatively associated with LDL-C. There was also a statistically significant positive association of LDL-C with the percentage of total calories from fat. These three findings are generally consistent with what other cross-sectional studies have reported for the relation of diet with total cholesterol levels. The only diet variables significantly related to triglyceride levels in both men and women were the percentage of calories from fats, particularly polyunsaturated fatty acids (PFA), the P/S ratio, and the number of grams of PFA per day, all of which were inversely associated with the level of this lipid.
Focal cerebral ischemia distal to a cerebral aneurysm in hereditary hemorrhagic telangiectasia.
Neurologic complications in patients with Hereditary Hemorrhagic Telangiectasia (HHT) occur as a consequence of a variety of vascular malformations. One type of intracranial malformation, saccular aneurysm, has recently been appreciated as a potential source of ischemic cerebrovascular disease on the basis of aneurysm to artery emboli. We report a patient with HHT and an unruptured saccular intracranial aneurysm presenting with ischemic vascular events.
A double blind trial of naloxone in the treatment of acute stroke.
Naloxone has been reported to have potential benefit in the treatment of stroke. We evaluated the effect of naloxone in a double-blind trial conducted with 15 stroke patients whose deficits ranged from 8 to 60 hours in duration. All but one patient sustained a cerebral infarction. Neurologic function was assessed before and five minutes after each of two injections given to each patient in a double-blind fashion. The injections consisted of naloxone (0.4 mg in 3 patients and 4.0 mg in 12 patients) and saline. Prior to the trial, samples of plasma were obtained for determination of immunoreactive beta-endorphin for each patient. Four patients showed minimal improvement following injection of naloxone, while five patients exhibited a slightly greater improvement following saline injection. There were no significant elevations of plasma beta-endorphin among stroke patients. We conclude that naloxone may not have a significant therapeutic role for stroke in the clinical setting.
Selective thromboxane inhibition: a new approach to antiplatelet therapy.
Antiplatelet drugs as exemplified by aspirin are used frequently to prevent stroke. Aspirin inhibits the formation of both the potent platelet aggregator, thromboxane A2 and the potent anti-aggregator, prostacyclin. Another approach to the inhibition of platelet aggregation might involve selective suppression of thromboxane formation. We report our experience in swine with UK-38,485, a drug which selectively inhibits thromboxane formation. The rationale and potential uses of UK-38,485 in the in vivo prevention of platelet aggregation and for the therapy of cerebrovascular disease are discussed.