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Biomedical subjects

A J Fisher

Publications and source records attributed to A J Fisher.

5 recordsLinked to original sources

Crystallization and preliminary data analysis of Flock House virus.

Flock House virus, purified from infected cultured Drosophila cells, crystallizes into three different forms under identical growth conditions. Two crystal forms grow in the trigonal space group R3, both with equivalent cell constants a = 323.6 A, alpha = 61.7 degrees. The difference between the two trigonal crystal forms is 1.1 degrees in the orientation of the virus particle as determined from the rotation function. Early crystal setups grew in one form, while recent crystals grew in the other form. The third space group, which accounts for 5% of the observed crystals and grows with both trigonal forms, is orthorhombic I222 with cell parameters a = 416.7, b = 332.1, c = 351.2 A. The trigonal crystal forms contain one virion per unit cell and the orthorhombic form contains two particles per cell. All three crystal forms diffract X-rays to 2.8 A resolution.

Animals

Effects of chronic hypoxia on capillary flow and hematocrit in rat skeletal muscle.

The cremasteric microcirculation was studied in rats exposed to chronic hypoxia. Control male weanling Sprague-Dawley rats (n = 8) were raised for 42-49 days at 752 mmHg. Hypoxic rats (n = 9) were reared for 3 days at 551 mmHg, 4 days at 461 mmHg, 3 days at 371 mmHg, and 31-38 days at 311 mmHg (6,000 m). Red blood cells labeled with fluorescein isothiocyanate were injected. The exposed cremaster was observed using fluorescence microscopy. Rats acutely breathed 10, 21, and 30% O2 spontaneously in random order. Hypoxia-adapted animals had greater (P less than 0.01) red cell flux (10.6 +/- 1.0 vs. 5.7 +/- 0.4/s), capillary hematocrits, capillary-to-systemic hematocrit ratios (0.42 +/- 0.02 vs. 0.33 +/- 0.02), and reduced red cell spacing (11.4 +/- 1.3 vs. 22.3 +/- 2.0 microns) than controls under 21% O2. Chronically hypoxic rats also demonstrated significantly (P less than 0.05) larger capillary diameters (6.52 +/- 0.04 vs. 6.15 +/- 0.06 microns) and greater perfused (135 +/- 5 vs. 94 +/- 3 mm/mm3) and anatomic (182 +/- 5 vs. 151 +/- 8 mm/mm3) microvessel length-densities at 21% O2. Results were generally similar for 10 and 30% O2. Bulk capillary blood flow was significantly (P less than 0.01) greater in controls (2.75 +/- 0.32 vs. 1.87 +/- 0.12 pl/s) only under 30% O2. Our experiments demonstrate that numerous physiological, in addition to anatomic, alterations can occur in the cremasteric microcirculation in response to chronic hypoxia.

Adaptation, Physiological

Cytarabine-induced cerebellar syndrome: case report and literature review.

High-dose cytarabine (HDARAC) therapy is an effective regimen in treating refractory leukemias. A typical regimen is cytarabine 3 g/m2 iv over one to three hours q 12h for a total of 8 to 12 doses. This case report illustrates the neurotoxicity unique to HDARAC. The patient received two cycles of HDARAC over the course of a ten-week period. During the first treatment, dysarthria and ataxia were seen after completion of the patient's eighth and final dose of HDARAC. These symptoms resolved over a period of five days. Six weeks later a more severe syndrome of dysarthria and ataxia developed during a second cycle of treatment. These symptoms worsened over 24 hours despite discontinuation of therapy, then gradually decreased in severity but persisted until his death two months later. The neurotoxicity seen with HDARAC is dose-related and has occurred in up to 60 percent of treated patients. The incidence of cerebellar toxicity approaches 30 percent, with irreversible ataxia reported in up to 16.7 percent. Because the cerebellar toxicity may be worsened by continuation of therapy after initial onset of symptoms, prompt termination of HDARAC is recommended.

Cerebellar Diseases

Glottic cancer. Surgical salvage for radiation failure.

Radiation therapy is a well-established treatment for early squamous cell carcinoma of the glottic larynx. However, the management of patients suspected to have persistent or recurrent disease may present both diagnostic and therapeutic dilemmas, particularly when laryngeal edema persists months after conclusion of radiation therapy. We reviewed the outcome of 212 patients with T1s, T1, and T2NOMO carcinoma of the glottic larynx who had been treated for cure with radiation therapy, with surgical salvage reserved for radiation failures. Twenty-four patients (11%) had recurrences after radiation therapy, 13 (59%) of whom had successful salvage by surgery. The five-year, recurrence-free survival in this series was 92% for T1s and T1 and 69% for T2. We conclude that T1s, T1, T2NOMO carcinoma of the glottic larynx is effectively managed by radiation therapy and surgical salvage for radiation failure. Total laryngectomy usually was necessary for surgical salvage.

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