Biomedical subjects
Publications and source records attributed to J Howard.
Thirty-one patients with advanced head and neck cancer were treated with 4'-epidoxorubicin. Three of 25 evaluable patients with squamous cell carcinoma and two of three with minor salivary gland carcinoma had partial remissions. Four patients received cumulative doses of 680-1270 mg/m2; none developed clinical heart failure.
Fifty-nine patients with HLA-B27 positive ankylosing spondylitis were HLA genotyped to look for immunogenetic differences between patients with associated peripheral arthritis and those with disease limited to the axial skeleton. An association was found between the peripheral arthropathy and 2 antigens, HLA-A11 and HLA-DR7 at the p less than 0.05 level. Complementation between these 2 alleles and HLA-B27 occurred in both the cis and trans positions. Four patients with peripheral arthritis had a rare HLA-B27 haplotype (HLA-B27, HLA-DR7) which was not found in the group with axial disease alone.
Parents seldom seek help directly for infant mental health problems. Parents enter the health care system seeking advice for identified or presumed biological problems in their infants. Many of these biological problems, however, have major psychosocial components of importance to infant mental health. It is important that physicians deal directly with the psychosocial issues and avoid converting them into biological medical problems unintentionally. Three common types of problems and appropriate methods of management are discussed to ensure special recognition and effective handling by the physician of psychosocial problems and the promotion of mental health. The problems discussed are the following: Infants seen with defined medical conditions that generally have associated psychosocial problems including child abuse. Infants seen who have fully recovered from critical illnesses but are considered "at risk" for later developmental disability. Infants seen with normal variations of behavior that are misinterpreted by their parents or physicians as due to a medical problem. In infancy medical and psychosocial issues are so closely interwoven that it is critical that physicians learn to recognize the major psychosocial consequences of primary medical problems and the medical manifestations of primary psychosocial problems and their management.
The dose from heavy ion beams has been calculated using a one-dimensional transport theory and evaluated for 670 MeV/ amu 20Ne beams in water. The result is presented so as to be applicable to arbitrary ions for which the necessary interaction data are known. The present evaluation is based on the Silberberg - Tsao fragmentation parameters augmented with light fragment production from intranuclear cascades, recently calculated nuclear absorption cross sections, and evaluated stopping power data. Comparison with recent experimental data obtained at the Lawrence Berkeley Laboratory reveals the need for more accurate fragmentation data.
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Thirty-five patients with advanced malignant melanoma were treated with 4'-epi-doxorubicin iv once every 3 weeks. Most patients had not received prior chemotherapy and had good performance status. Three partial remissions and three minor regressions were observed. All patients experienced myelosuppression, but other toxic effects were minimal. 4'-Epi-doxorubicin has limited therapeutic activity in this disease.
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The dose distribution of carbon ion beams was modified to cover 14 cm peak width using a ridge filter suitable for clinical application. The results of cell survival as a function of depth of penetration of carbon ions and the mouse skin (foot) response at the proximal-, mid-, and distal-peak positions using four daily fractions are reported. The objective of these studies is to verify whether the dose distribution in the peak region is properly compensated to produce uniform biological effect. The implications of the shape of the dose distribution in the peak region to radiotherapy application are discussed.
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4-Demethoxydaunorubicin (4-DMDR), an anthracycline analogue available in i.v. and p.o. form, has shown significant antitumor activity in murine tumor models while producing less cardiac toxicity than doxorubicin at equimyelotoxic doses. Phase I and clinical pharmacology studies of the i.v. and p.o. preparation were performed. With i.v. 4-DMDR, consistent myelosuppression was observed at a dose of 15 mg/sq m at a median Day 15; mild nausea and vomiting were observed in 9% of all treatment courses. In patients given p.o. 4-DMDR, myelosuppression occurred at median Day 14 in 10 of 12 patients given 50 mg/sq m. Nausea and vomiting occurred in 25% of all treatment courses, and dividing the dose over 3 days did not decrease the incidence. Alopecia occurred in 13% of evaluable patients treated with the i.v. preparation and 30% of evaluable patients treated p.o. No stomatitis was observed with either preparation, and no patient developed clinical signs of congestive heart failure. Pharmacokinetic studies were performed with both preparations and revealed prolonged plasma levels of the 13-hydroxy metabolite 4-DMDR-ol. The suggested starting dose for Phase II studies is 12.5 mg/sq m given every 21 days for i.v. 4-DMDR with dose escalation by 2.5 mg/sq m in the absence of myelotoxicity. For p.o. 4-DMDR, the suggested starting dose is 40 mg/sq m given every 21 days with escalation by 10 mg/sq m if no myelotoxicity is observed.
Survival of colony-forming units-spleen (CFU-S) was measured after single doses of photons or heavy charged particles from the BEVALAC. The purposes were to define the radiosensitivity to heavy ions used medically and to evaluate relationships between relative biological effectiveness (RBE) and dose-averaged linear energy transfer (LET infinity). In in vitro irradiation experiments. CFU-S suspensions were exposed to 220 kVp X rays or to 20Ne (372 MeV/micron) or 40Ar (447 MeV/micron) particles in the plateau portion of the Bragg curve. In in vivo irradiation experiments, donor mice from which CFU-S were harvested were exposed to 12C (400 MeV/micron). 20Ne (400 or 670 MeV/micron), or 40Ar (570 MeV/micron) particles in Bragg peaks spread to 4 or 10 cm by spiral ridge filters. Based on RBE at 10 survival, the maximum RBE of 2.1 was observed for 40Ar particles characterized by an LET infinity of approximately 100 keV/micron. Lower RBEs were determined at lower or higher estimated values of LET infinity and ranged from 1.1 for low energy 40Ar particles to 1.5-1.6 for low energy 12C and 20Ne. The responses of CFU-S are compared with responses of other model systems to heavy charged particles and with the reported sensitivity of CFU-S to neutrons of various energies. The maximum RBE reported here, 2.1 for high energy 40Ar particles, is somewhat lower than values reported for fission-spectrum neutrons, and is appreciably lower than values for monoenergetic 0.43-1.8 MeV neutrons. Low energy 12C and 20Ne particles have RBEs in the range of values reported for 14.7 MeV neutrons.
Rubella vaccination of children in the United States has resulted in a shift in the age of affected and susceptible individuals toward older age groups. In an effort to reduce the incidence of congenital rubella syndrome, the American Academy of Pediatrics and the Advisory Committee on Immunization Practices have recommended rubella vaccine for all male and female medical personnel who might contract and spread rubella to pregnant women. A survey of hospitals and outpatient practices in Little Rock, Arkansas, revealed extremely low compliance with the recommendation, suggesting the need for further education or legislation on rubella immunization for health care personnel.
Plasmodium falciparum DNA was prepared from cells cultured in vitro in human erythrocytes. The P. falciparum DNA was mixed with a tritium-labeled Escherichia coli DNA standard, and the kinetics of reassociation were measured using hydroxyapatite chromatography. It was found that the P. falciparum genome size is equal to 3.8 . 10(8) nucleotide pairs, and that a repetitive component is present which contains about 10% of the DNA. The average repetition frequency in this component is 95 copies of each sequence.
The Aspirin Myocardial Infarction Study (AMIS) was a double-blind placebo-controlled trial to test the effect of aspirin on the survival of 4524 people who had experienced a prior heart attack. Shortly before their closeout visits, 400 of the participants were randomly selected to be interviewed concerning their perceptions of their treatment assignments; 380 were actually interviewed. A bare majority (52)% correctly identified their study therapy, 28% mistakenly named the alternative treatment, 13% declined to guess, and 7% specified extraneous substances. According to the proposed formula for evaluating the patient blind, only 24% of the sample made "informed" guesses regarding their therapy, while the remainder guessed in an uninformed way or not at all. Those who tested their capsules (usually be taste) showed proportionately more correct responses than the nontesters. Correctness also varied with the reasons for the subjects' guesses (e.g., side effects). Among the sample as a whole, most people were only moderately or less than moderately certain their guess was correct. Even among those who were in fact correct, only 18% were absolutely certain of their choice.
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To evaluate the complaint of exertional dyspnea in asbestos-exposed shipyard workers, pulmonary function tests were performed at rest and during exercise on 90 subjects with pleural plaques. We divided the subjects into four groups based on resting pulmonary function studies. Group I subjects (eight) had a restrictive defect; group II subjects (30) had an obstructive defect; group III subjects (six) had an isolated reduction in diffusing capacity; and group IV subjects (46) had a normal study. Subjects with a restrictive defect demonstrated minor physiologic abnormalities during exercise. Subjects with an obstructive defect demonstrated abnormalities consistent with their obstructive defect. Subjects in groups III and IV demonstrated an abnormally elevated wasted ventilation fraction, which may be an early indicator of interstitial disease due to asbestos exposure. We believe exercise testing was a useful tool in excluding the presence of significant functional exercise limitation due to asbestos exposure in the majority of subjects and also in disclosing some physiologic abnormalities in some of the subjects in our study.
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