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Biomedical subjects

M Bednar

Publications and source records attributed to M Bednar.

10 recordsLinked to original sources
PubMed2001

A Phase I/II study of weekly paclitaxel and 3 days of high dose oral estramustine in patients with hormone-refractory prostate carcinoma.

BACKGROUND: The maximum tolerated dose (MTD) and efficacy of weekly 1-hour paclitaxel with 3 days of high dose oral estramustine were evaluated in patients with hormone-refractory prostate carcinoma. METHODS: Patients enrolled in cohorts of three received two cycles of six weekly treatments with 1 week of rest: Cohort I received paclitaxel 40 mg/m2 and estramustine 600 mg/m2, and Cohorts II-IV received paclitaxel 60 mg/m2, 75 mg/m2, or 90 mg/m2, respectively, and estramustine 900 mg/m2. Toxicity was assessed weekly, and response was measured by serum prostate specific antigen (PSA), abdominal computed tomography scans, and bone scans at Week 13. RESULTS: Eighteen patients were enrolled, with 12 in Cohorts III and IV. Four patients did not complete treatment. Grade 3 toxicity included one patient with nausea and diarrhea in Cohort III and one patient each with neutropenia and edema followed by Grade 4 thromboembolism in Cohort IV. Grade 1-2 anemia or myelotoxicity were not observed; 3 patients had neuropathy, 5 patients had hair loss, and 8 patients had gastrointestinal symptoms. A decline in the serum PSA level > or = 50% occurred in none of three patients, one of three patients, four of six patients, and four of six patients in Cohorts I-IV, respectively. An intent-to-treat analysis showed responses in 9 of 18 patients (50%) in Cohorts I-IV, with 9 of 15 responders (60%) in Cohorts II-IV. Seven patients achieved declines in serum PSA levels > 75%. The median duration of PSA response was 16.7 weeks. Response was observed in one of three patients with measurable disease. CONCLUSIONS: The MTD for 1-hour weekly paclitaxel was 90 mg/m2 with 3 days of 900 mg/m2 estramustine. Hematologic and neurotoxicity were reduced markedly, and gastrointestinal symptoms were ameliorated, but thromboembolic events were unaffected. PSA response rates were within the expected 60% range for these agents.

Administration, Oral↗
PubMed2001

In vivo determination of available brachioradialis excursion during tetraplegia reconstruction.

The brachioradialis muscle is a common donor in tetraplegia reconstruction. The purpose of this study was to determine the available excursion of the brachioradialis during graduated release of its insertion sites. Fourteen extremities in 10 patients with cervical spine injuries underwent surgical reconstruction for restoration of hand function using the brachioradialis as a donor for one of the restored movements. At the time of surgery the brachioradialis was exposed along the forearm and a wire was inserted into the muscle followed by excitation with a biphasic, asymmetrical, charge-balanced waveform. A 12-Hz frequency and 20-mA current were used to stimulate the muscle while the pulse duration was varied between 0 and 200 milliseconds to achieve maximum contraction. Average brachioradialis excursion after incision of the radial styloid insertion site was 8 mm and 14 mm after mobilization to the musculotendinous junction. Further release of the fascial connections and mobilization of the muscle belly increased the excursion to an average of 61 mm. The increase in excursion after fascial release and muscle mobilization was significant and should be performed to obtain maximum available excursion.

Adolescent↗
PubMed2001

Peripheral neuropathy in the hands of diabetic patients with lower extremity amputations.

One hundred unilateral ambulatory lower extremity amputees underwent sensibility testing of their remaining foot and right hands to determine if the magnitude of peripheral neuropathy present in the feet of patients with diabetes was of greater magnitude than that in their hands. Testing was performed with a series of Semmes-Weinstein monofilaments. Ninety-one of the subjects were male, and 9 were female. Sixty-five were diabetic, 40 required insulin. The magnitude of peripheral neuropathy was compared between the hands and feet of patients with and without diabetes, and between insulin-dependent and non-insulin-dependent diabetics. There was a slight trend to a more severe degree of insensitivity in the feet as compared with the hands in each of the individual groups. There was no statistically significant difference when comparing hand and foot sensibility in any of the comparison groupings. The quantitative amount of peripheral neuropathy appears to affect the hands and feet of diabetics in a similar "stocking-glove" fashion. The results of this screening gives further support to the concept of prophylactic foot care programs in diabetics with peripheral neuropathy to decrease the risk for the development of foot ulcers, which are often the precursor of eventual lower extremity amputation.

Aged↗
PubMed1998

Evaluation of cerebral vasospasm after early surgical and endovascular treatment of ruptured intracranial aneurysms.

OBJECTIVE: To document the influence of the treatment modality (early surgery versus early endovascular treatment) on measures of cerebral vasospasm in a nonrandomized series of 156 patients treated within 72 hours of aneurysmal subarachnoid hemorrhage. METHODS: The following parameters were prospectively collected in a computerized data base and retrospectively analyzed for association with vasospasm-related ischemic infarctions: 1) Hunt and Hess (H&H) grade, 2) Fisher grade, 3) highest mean cerebral blood flow velocity (CBFVMAX) and maximum percent change in mean CBFV (%deltaCBFV) as recorded by transcranial Doppler ultrasound, 4) incidence of repeat subarachnoid hemorrhage, 5) incidence of delayed ischemic neurological deficits, 6) incidence of delayed ischemic infarctions, and 7) Glasgow Outcome Scale score. RESULTS: Forty-one patients (26.3%) suffered ischemic infarctions. The ischemic infarction rate was correlated with higher H&H grade (P = 0.002), higher Fisher grade (P = 0.05), higher CBFVMAX (P < 0.001) and %deltaCBFV (P = 0.01), occurrence of repeat subarachnoid hemorrhage, occurrence of delayed ischemic neurological deficits, and endovascular treatment (P = 0.02). CONCLUSION: The infarction rate was higher with endovascular treatment versus surgery (37.7 versus 21.6%), as a result of a skewed Fisher Grade 4 infarction pattern in the endovascular treatment group versus the surgery treatment group (66.7 versus 24.5%). We suspect that unremoved subarachnoid/intracerebral clots contributed to the higher infarction rate with endovascular treatment. When patients with Fisher Grade 4 and H&H Grade V were excluded from analysis, the difference in infarct incidence between the treatment groups no longer reached statistical significance (Fisher Grades 1-3, P = 0.49; H&H Grades I-IV, P = 0.96).

Adult↗
PubMed1997

Hand infections in the diabetic patient.

Between 1984 and 1994, 23 diabetic patients were admitted to a university hospital/Department of Veterans Affairs (DVA) Medical Centre with a primary or secondary diagnosis of hand infection. We also identified 726 patients admitted to all DVA Medical Centres during the years 1989 through 1994 with co-diagnoses of diabetes mellitus and hand infection. Contrary to previously published literature, most diabetic hand infections are non-specific, confined to the soft tissues, and respond to broad spectrum parenteral antibiotic therapy. When surgery is necessary, most patients do not require amputation.

Adult↗
PubMed1987

Traumatic intraspinal pneumocele.

Traumatic intraspinal pneumocele (TIP) is a radiologic finding in which air is visualized within the spinal canal on routine cervical spine x-rays following a head injury. TIP may be the initial radiologic evidence of a severe central nervous system injury. The presence of TIP will alert a physician to the severity of the head injury, as well as the need for further radiologic investigations.

Air↗
PubMed1986

Studies of anaerobic and aerobic glycolysis in Saccharomyces cerevisiae.

Glucose metabolism was followed in suspensions of Saccharomyces cerevisiae by using 13C NMR and 14C radioactive labeling techniques and by Warburg manometer experiments. These experiments were performed for cells grown with various carbon sources in the growth medium, so as to evaluate the effect of catabolite repression. The rate of glucose utilization was most conveniently determined by the 13C NMR experiments, which measured the concentration of [1-13C]glucose, whereas the distribution of end products was determined from the 13C and the 14C experiments. By combining these measurements the flows into the various pathways that contribute to glucose catabolism were estimated, and the effect of oxygen upon glucose catabolism was evaluated. From these measurements, the Pasteur quotient (PQ) for glucose catabolism was calculated to be 2.95 for acetate-grown cells and 1.89 for cells grown on glucose into saturation. The Warburg experiments provided an independent estimate of glucose catabolism. The PQ estimated from Warburg experiments was 2.9 for acetate-grown cells in excellent agreement with the labeled carbon experiments and 4.6 for cells grown into saturation, which did not agree. Possible explanations of these differences are discussed. From these data an estimate is obtained of the net flow through the Embden-Meyerhof-Parnas pathway. The backward flow through fructose-1,6-bisphosphatase (Fru-1,6-P2-ase) was calculated from the "scrambling" of the 13C label of [1-13C]glucose into the C1 and C6 positions of trehalose. Combining these data allowed us to calculate the net flux through phosphofructokinase (PFK). For acetate-grown cells we found that the relative flow through PFK is a factor of 1.7 faster anaerobically than aerobically.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerobiosis↗
PubMed1985

Nafazatrom-induced salvage of ischemic myocardium in anesthetized dogs is mediated through inhibition of neutrophil function.

The effects of nafazatrom on leukocyte function in vitro and in vivo were related to its ability to salvage ischemic myocardium in an occlusion-reperfusion model of myocardial injury in the anesthetized dog. Nafazatrom (0.4-75 microM) produced dose-related inhibition in vitro of neutrophil aggregation, superoxide anion generation, arachidonic acid metabolism, and, to a lesser extent, the release of beta-glucuronidase. In contrast, nafazatrom (0.4-37.5 microM) did not substantially influence platelet aggregation or the platelet metabolism of arachidonic acid. In vivo nafazatrom (10 mg/kg, po) reduced infarct size from 58 +/- 3% of the risk area (mean +/- SEM, n = 9) in control dogs to 23 +/- 2% of the risk area (n = 9, P less than 0.01). Nafazatrom also reduced the incidence of accompanying arrhythmias. Nafazatrom-induced myocardial salvage was not associated with any hemodynamic changes; moreover, it was independent of platelets, since thrombocytopenia did not prevent nafazatrom from exerting a protective effect. Measurements of the neutrophil-specific myeloperoxidase enzyme in ischemic myocardium indicate that the smaller infarct size in dogs treated with nafazatrom is accompanied by diminished leukocyte infiltration. Thus, the ability of nafazatrom to inhibit neutrophil function in vitro and cell infiltration in vivo may underly its myocardial-protective effects.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMedDate not supplied

Neutrophil depletion suppresses 111In-labeled platelet accumulation in infarcted myocardium.

Platelets and neutrophils accumulate rapidly in infarcted myocardium. Although antineutrophil agents reduce the size of the infarcted area, this is not observed with antiplatelet drugs. The possibility that myocardial ischemia-induced platelet deposition was secondary to a neutrophil-mediated event was assessed by injecting prostacyclin-washed autologous 111In-labeled platelets and measuring the amount of radioactivity in different regions of the heart following 90-min occlusion of the left anterior descending coronary artery followed by reperfusion for periods up to 5 h. Platelet deposition during the reperfusion phase was linear with time and similar to the time course of neutrophil accumulation. There was a transmural distribution of radioactivity across the myocardium where the "zone" between infarcted and risk regions, called the "interface," greater than infarct greater than risk greater than normal. Neutropenia (21 +/- 2% control levels), induced with specific sheep anti-dog neutrophil antiserum, had minimal effects on platelet aggregation ex vivo, but significantly reduced platelet accumulation in the ischemic myocardium following 5-h reperfusion and abolished the transmural platelet distribution. These results suggest that myocardial platelet deposition is secondary to a neutrophil-mediated event in this occlusion-reperfusion model of myocardial injury. Interactions between platelets and neutrophils at the site of tissue damage may influence the process of myocardial ischemic injury.

Animals↗