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Biomedical subjects

G Goodman

Publications and source records attributed to G Goodman.

At least 55 records · Page 3Linked to original sources
PubMed1994

The beta-carotene and retinol efficacy trial (CARET) for chemoprevention of lung cancer in high risk populations: smokers and asbestos-exposed workers.

CARET is a multicenter, two-armed, double-masked randomized chemoprevention trial in Seattle, Portland, San Francisco, Baltimore, Connecticut, and Irvine, to test whether oral administration of beta-carotene (30 mg/day) plus retinyl palmitate (25,000 IU/day) can decrease the incidence of lung cancer in high risk populations, namely, heavy smokers and asbestos-exposed workers. The intervention combines the antioxidant action of beta-carotene and the tumor suppressor mechanism of vitamin A. As of April 30, 1993, CARET had randomized 1,845 participants in the 1985-1988 pilot phase plus 13,260 "efficacy" participants since 1989; of these, 4,000 are asbestos-exposed males and 11,105 are smokers and former smokers (44% female). Accrual is complete everywhere except Irvine, which was the last center added (1991), and the safety profile of the regimen to date has been excellent. With 14,420 smokers, 4,010 asbestos-exposed participants, and 114,100 person-years through February 1998, we expect CARET to be capable of detecting a 23% reduction in lung cancer incidence in the two populations combined and 27, 49, 32, and 35% reductions in the smokers, female smokers, male smokers, and asbestos-exposed subgroups, respectively. CARET is highly complementary to the alpha-tocopherol-beta-carotene study in Finland and the Harvard Physicians Health Study (beta-carotene alone) in the National Cancer Institute portfolio of major cancer chemoprevention trials.

Aged↗
PubMed1994

Dermabrasion using tumescent anesthesia.

BACKGROUND: Dermabrasion is a very useful and versatile technique. However, it suffers from side effects and difficulties that limit its popularity among operating dermatologic surgeons and the public. OBJECTIVE: To show that it is possible to eliminate the need for chlorofluorocarbons, improve the standard dermabrasion technique, decrease the healing time, improve its side effect profile, and reduce risks to the operating surgeon. METHODS: Tumescent fluid containing dilute Xylocaine, bicarbonate, and epinephrine in saline was infiltrated before coarse wire brush dermabrasion. Eutectic mixture of local anesthetic (EMLA) was also used topically. The first 14 patients dermabraded by this method are reported on here. Their healing, progress, side effects, and results are described. A patient questionnaire was completed by 12 of the patients who describe the procedure and results from the patient's viewpoint. RESULTS: The procedure was found to be effective in producing anesthesia, eliminating the use of freezing the skin, and limiting the necessity for sedatives, narcotics, and other anesthesia. It gives a firm surface to dermabrade against, makes the procedure more rapid and technically easier, and produces less splatter and therefore less risk for the surgeon. The results subjectively and objectively would appear to be at least as good as standard techniques. The healing in this small sample would appear to be faster both to reepithelialization and to reestablishment of normal color. There was only one case of transient hyperpigmentation lasting less than 1 week. Otherwise there were no cases of pigmentary or scarring side effects. CONCLUSION: Tumescent dermabrasion is safe, effective, and has many benefits over traditional methods.

Acne Vulgaris↗
PubMed1994

Mercury inhalation poisoning and acute lung injury in a child. Use of high-frequency oscillatory ventilation.

Acute mercury inhalation poisoning is a rare cause of acute lung injury. It is commonly fatal in the young child because of progressive pulmonary failure. We describe a 3-month-old infant who survived this insult with the use of high-frequency oscillatory ventilation. This form of support may be an option in the patient with severe adult respiratory distress syndrome (ARDS) or air leak syndromes.

High-Frequency Ventilation↗
PubMed1994

Development of infant botulism in a 3-year-old female with neuroblastoma following autologous bone marrow transplantation: potential use of human botulism immune globulin.

Infant botulism is a rare disease caused by the release of toxin produced in the intestinal tract by Clostridium botulinum. The disease primarily affects infants under 1 year of age. We report a 3-year-old child with stage IV neuroblastoma who developed symptoms of progressive motor weakness, bulbar palsy and respiratory failure 42 days after autologous BMT. The diagnosis of infant botulism was established by identifying botulism toxin in the stool. Human botulism immune globulin (HBIG) was administered. Following the diagnosis, the patient made significant recovery over the next 7 weeks and was successfully extubated from mechanical ventilation. However, her neuroblastoma eventually recurred and she subsequently died of progressive disease. Although the etiology of the development of infant botulism in this case following autologous BMT still remains unclear, alteration of the intestinal microbial environment from gut sterilization and laminar airflow room isolation or, alternatively, immune suppression during pre- and post-autologous BMT and activation of endogenous spores may have contributed to the development of this disease. The use of HBIG in children with botulism over 1 year of age may be beneficial.

Bone Marrow Transplantation↗
PubMed1992

Interferon-gamma induced by administration of recombinant interleukin-2 to patients with cancer: kinetics, dose dependence, and correlation with physiological and therapeutic response.

The administration of recombinant interleukin-2 as an i.v. bolus at dose levels of from 1 to 30 MIU/m2 to patients with cancer induces easily measurable serum interferon-gamma levels of 1 to 500 U/ml. After a lag of 1 h, interferon-gamma rises to a maximum at 4 h and then slowly decreases. The peak values are poorly correlated with the dose of interleukin-2, and thus must be also be dependent on other factors. Successive administration of interleukin-2 typically increases the peak level of interferon-gamma fourfold, but does not diminish the lag period. Peak levels of interferon-gamma are also increased by concurrent administration of interferon-beta with interleukin-2. Continuous i.v. infusion of 1.5 to 20 MIU/m2 of interleukin-2/day results in interferon-gamma levels of 1 to 7 U/ml. Hypotension, which is characteristically associated with interleukin-2 administration, is correlated with interferon-gamma levels in only some patients. There was no apparent correlation between tumor regression and serum interferon-gamma levels.

Blood Pressure↗
PubMed1992

Comparison of the dependence of the TD50 on maximum tolerated dose for mutagens and nonmutagens.

The relationship between the minimum TD50 (i.e., the TD50 measured at the most sensitive site) and the maximum dose administered (maxD) in rodent carcinogenicity bioassays was investigated separately for mice and rats. The relationship between log(1/TD50) and log(1/maxD) was analyzed as a function of (1) mutagenicity and (2) the statistical significance cutoff for selecting the minimum TD50 values. For rat bioassays, the variance of log(1/TD50) is larger and the correlation of log(1/TD50) with log(1/maxD) is weaker for mutagens than for nonmutagens, suggesting that the relationship between minimum TD50 and MTD is, in general, stronger for nonmutagens than for mutagens. The difference in correlation does not depend on the TD50 statistical significance cutoff, but the difference in variance is not significant for the most stringently selected dataset. For mouse bioassays, no significant mutagen/nonmutagen differences in log(1/TD50) variance are found. A significantly weaker correlation of log(1/TD50) with log(1/maxD) for mutagens in comparison to nonmutagens occurs only for the dataset with minimum TD50 chosen at the least stringent level, suggesting that this difference may be due to chance variation. We also looked for changes in correlation and regression parameters as a function of mutagenic potency in Salmonella; the variance of log(1/TD50) and its correlation with log(1/maxD) are not found to vary in a consistent manner. Taken as a whole, our results indicate that (1) mutagenicity is a determinant of the TD50/maxD relationship in rats and (2) any effect that mutagenicity may exert on the TD50/maxD relationship in mice is unimportant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Monte Carlo simulation of rodent carcinogenicity bioassays.

In this paper we describe a simulation, by Monte Carlo methods, of the results of rodent carcinogenicity bioassays. Our aim is to study how the observed correlation between carcinogenic potency (beta or 1n2/TD50) and maximum tolerated dose (MTD) arises, and whether the existence of this correlation leads to an artificial correlation between carcinogenic potencies in rats and mice. The validity of the bioassay results depends upon, among other things, certain biases in the experimental design of the bioassays. These include selection of chemicals for bioassay and details of the experimental protocol, including dose levels. We use as variables in our simulation the following factors: (1) dose group size, (2) number of dose groups, (3) tumor rate in the control (zero-dose) group, (4) distribution of the MTD values of the group of chemicals as specified by the mean and standard deviation, (5) the degree of correlation between beta and the MTD, as given by the standard deviation of the random error term in the linear regression of log beta on log (1/MTD), and (6) an upper limit on the number of animals with tumors. Monte Carlo simulation can show whether the information present in the existing rodent bioassay database is sufficient to reject the validity of the proposed interspecies correlations at a given level of stringency. We hope that such analysis will be useful for future bioassay design, and more importantly, for discussion of the whole NCI/NTP program.

Animals↗
PubMed1991

Lead risks.

Explore the source record for details and available documents.

Child↗
PubMed1991

Quantitative prediction of human cancer risk from rodent carcinogenic potencies: a closer look at the epidemiological evidence for some chemicals not definitively carcinogenic in humans.

The existence of rodent carcinogens for which at least one epidemiological study found no evidence of human carcinogenicity has been claimed to provide evidence of the poor predictivity of rodent bioassays (F. K. Ennever, T. J. Noonan, and H. S. Rosenkranz (1987). Mutagenesis 2, 73-78). We have performed quantitative comparisons of the rodent and human carcinogenic potencies for these same chemicals. Starting with the rodent TD50 at the most sensitive site, we derived a predicted human incidence for the degree of exposure and duration of follow-up corresponding to the most comprehensive epidemiological study available, and then we compared the predicted incidence with the observed incidence. If a chemical produced no statistically significant increase in cancer at any site in the exposed population, consistency with rodent results is inferred if the minimum rodent TD50 is sufficiently high that no attributable cases would have been expected under the actual conditions of human exposure and follow-up. For 18 of the 22 chemicals examined, the human evidence is consistent with the predictions based on the rodent bioassay results. For two chemicals, dichlorobenzidine and ethylene thiourea, there is not enough epidemiological information to make a useful comparison with rodent bioassay data. For the two remaining chemicals, actinomycin D and vinylidene chloride, the human evidence is inconsistent with the predictions. But the conditions of the rodent bioassay of actinomycin D were inappropriate for the comparison, and for vinylidene chloride the human exposure dose and duration were uncertain; either chemical might yet demonstrate consistency with the rodent results in future epidemiological studies.

Algorithms↗
PubMed1991

A phase I study including pharmacokinetics of polyethylene glycol conjugated interleukin-2.

A more soluble formulation of recombinant interleukin-2 with a prolonged half-life would allow alternate routes or schedules of administration and enhance patient comfort. The covalent attachment of polyethylene glycol to recombinant interleukin-2 provides an analog with preclinical data suggesting those desired characteristics while maintaining biologic activity. This is the report of a phase I study in which we sought to determine the maximum tolerated dose of polyethylene glycol interleukin-2, observe biologic activity, and confirm the prolonged half-life in vivo. Sixty-six patients were entered into the study during 19 months. Polyethylene glycol interleukin-2 was administered intravenously once a week over 15 minutes. The maximum tolerated dose was 20 x 10(6) U/M2. The pattern of toxicity was quite similar to that of the parent compound. Four patients had evidence of tumor regression (three partial remission; one minor response). The pharmacokinetic data confirmed a 10- to 20-fold prolongation in half-life compared with recombinant interleukin-2. No neutralizing antibodies were detected. This study provides sufficient impetus for the ongoing phase II studies of polyethylene glycol interleukin-2.

Adult↗
PubMed1991

Anaerobic work and power output during cycle ergometer exercise: effects of bicarbonate loading.

Eight trained male cyclists who competed regularly in track races, were studied under control, alkalotic (NaHCO3) and placebo (CaCO3) conditions in a laboratory setting to study the effect of orally induced metabolic alkalosis on 60 s anaerobic work and power output on a bicycle ergometer. Basal, pre- and post-exercise blood samples in the three conditions were analysed for pH, pCO2, pO2, bicarbonate, base excess and lactate. All blood gas measurements were within normal limits at basal levels. There were significant differences in the amount of work produced, and in the maximal power output produced by the cyclists in the experimental condition when compared to the control and placebo conditions (P less than 0.01). The post-exercise pH decreased in all three conditions (P less than 0.05) and post-exercise pCO2 increased significantly in the alkalosis trial (P less than 0.01). In the alkalotic condition, the pre-exercise base excess and HCO3- levels were both higher (P less than 0.05) than the basal levels, suggesting that the bicarbonate ingestion had a significant increase in the buffering ability of the blood. Post-exercise lactate levels were significantly higher (P less than 0.05) after the alkalotic trial when compared to the other two conditions, immediately post-exercise and for the next 3 min. Post-exercise lactate levels were higher than basal or pre-exercise levels (P less than 0.001). This was true immediately post-exercise and for the next 5 min. The results of this study suggest that NaHCO3 is an effective ergogenic aid when used for typically anaerobic exercise as used in this experiment. We feel that this ergogenic property is probably due to the accelerated efflux of H+ ions from the muscle tissue due to increased extracellular bicarbonate buffering.

Adult↗
PubMed1991

CARET, the beta-carotene and retinol efficacy trial to prevent lung cancer in asbestos-exposed workers and in smokers.

CARET is a two-armed, double-blind, randomized chemo-prevention trial to test the hypothesis that oral administration of beta-carotene 30 mg/day plus retinyl palmitate 25,000 IU/day will decrease the incidence of lung cancer in high-risk populations: heavy smokers and asbestos-exposed workers who have smoked. The agents combine anti-oxidant and nuclear tumor suppressor mechanisms. Fastidious monitoring for possible side effects is facilitated by inclusion of a Vanguard population. As of 31 December 1990, 6,105 participants of the 18,000 needed have been randomized in the trial. Efficacy results are expected in 1999.

Aged↗