ACCP guidelines for an expert witness.
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Biomedical subjects
Publications and source records attributed to T A Neff.
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The effects of various antileukemic agents on DNA replication associated with the nuclear matrix were investigated in CCRF-CEM leukemia cells. Residual nuclear matrices were prepared by sequential treatment of nuclei with 1.5 M NaCl, DNase I, and Triton X-100 and contained 1-5, 10, and 37% of the total nuclear DNA, protein, and phospholipid, respectively. In control cells pulse-labeled for 45 s with [3H]thymidine, the specific activity of nascent DNA was four-fold greater in the nuclear matrix fraction relative to the specific activity of the high salt-soluble (nonmatrix) DNA fraction. Pulse-labeling and reconstitution experiments indicated that this enrichment of newly replicated DNA on the nuclear matrix did not result from aggregation of nascent DNA with the matrix. A 2-h incubation of tumor cells with either 0.1 microM teniposide (VM-26), 0.2 microM VM-26, or 0.5 microM amsacrine (m-AMSA) reduced the relative specific activity of nascent DNA on the nuclear matrix by 59, 61, and 54%, respectively, compared to control cells. In contrast hydroxyurea and cytosine arabinoside, at concentrations that markedly inhibited total nuclear DNA synthesis, did not decrease the relative specific activity of newly replicated DNA on the matrix. The results provide evidence that the antiproliferative effects of the DNA topoisomerase II inhibitors, VM-26 and m-AMSA, are localized on the nuclear matrix of CCRF-CEM leukemia cells.
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A mechanical lung was used to evaluate the pressure and flow characteristics of four demand and two continuous flow intermittent mandatory ventilation (IMV) systems. The amount of negative pressure required to initiate inspiratory flow and peak expiratory resistance were measured. The inspiratory pressure required to initiate flow in the demand mode was also compared to pressures generated in the assist mode. In addition, the peak expiratory resistance was measured with four commercially available exhalation valves. Results showed that the ventilator manometer measuring internal machine pressures significantly underestimated the amount of negative pressure required to open the demand valve (p less than 0.01). There are major differences in the flow and pressure characteristics among demand and continuous flow IMV systems. Systems that impose high inspiratory elastic threshold loads and expiratory flow resistive loads may have a deleterious effect on the mechanics of breathing, and thereby limit weaning success and eventually impair the recovery of certain patients in respiratory failure. The basic methodology, especially the simple technique of inserting an aneroid manometer in line next to a patient's ET tube, for measuring proximal negative inspiratory force (NIF test) can be easily applied to any and all ventilators at any practitioner's individual institution.
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Thirteen years' experience with home oxygen for patients with advanced chronic obstructive pulmonary disease are reviewed. Home oxygen is safe and relieves pulmonary hypertension and elevated RBC mass in some, but not all patients. Marked clinical improvement is the most important result of long-term home oxygen use, including reduced hospitalizations and return to gainful employment for a few patients. Chronic compensated carbon dioxide retention is well tolerated and adaptive in cases of severe chronic airflow obstruction. New oxygen concentrators are effective in correcting hypoxemia and may make home oxygen administration more convenient and less expensive.
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In a patient with tuberculosis and acute renal failure related to administration of therapeutic rifampin, treatment was discontinued for five weeks. It was reinstituted three weeks later. Unlike other patients previously described, the expected adverse renal reaction occurred only gradually and without symptoms, although tubular and glomerular disease developed. Also unique was a striking deposition of immunoglobulin about the tubules. This finding, in association with interstitial nephritis and tubular glycosuria, is similar to an experimental autologous renal disease mediated by antibody to tubular basement membrane.
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Three cases of delayed development of pleural effusion under tension, 20 to 30 years after therapeutic pneumothorax, are described. A sudden increase in dyspnea and the radiographic findings of increasing opacity, a change from hypovolemia to hypervolemia of the hemithorax, and mediastinal shift should alert one to this delayed complication. Careful thoracentesis to decompress intrapleural tension effusion can relieve the dyspnea and improve hypoxemia. The potential risks of creating excessive negative intrapleural pressure are presented.
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Eight patients developed grand mal seizures during intravenous theophylline therapy. None had a history of neurologic disorder, and all were acutely ill with severe pulmonary or cardiovascular disease, or both. Serum theophylline concentrations obtained within 1 hour of the seizure ranged from 25 mug/ml to 70mug/ml, with a mean value (53 plus or minus 4.8 mug/ml) more than twice the upper limit of the recommended therapeutic concentration. This serum theophylline concentration was greater than the concentration found in a group of patients with less severe drug-related symptoms (35 plus or minus 1.8 mug/ml, P less than 0.01). A third group of patients without drug-related symptoms had a mean theophylline serum concentration of 19 plus or minus 2.0 mug/ml, which was less than that found in either group with toxicity symptoms (P less than 0.05). Factors predisposing to the high serum concentrations in the patients with seizures were both higher drug dosage, compared with the other groups (P less than 0.01), and hepatic dysfunction, which was more common in both groups with drug-related symptoms.