PubMed Health⌕ Search

Biomedical subjects

D M Finkelstein

Publications and source records attributed to D M Finkelstein.

At least 55 records · Page 3Linked to original sources
PubMed1995

Phase II study of paclitaxel in patients with extensive-disease small-cell lung cancer: an Eastern Cooperative Oncology Group study.

PURPOSE: To evaluate the efficacy and safety of paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ), a novel diterpene plant product in the treatment of previously untreated patients with extensive-disease small-cell lung cancer (SCLC). PATIENTS AND METHODS: Patients with extensive-disease SCLC received paclitaxel 250 mg/m2 intravenously over 24 hours every 3 weeks. Nonresponders or partial responders, who received the maximum number of cycles (n = 4) of paclitaxel received salvage chemotherapy that consisted of etoposide (VP-16) 120 mg/m2 intravenously over 45 minutes on days 1, 2, and 3, and cisplatin 60 mg/m2 intravenously as a short infusion on day 1. Cycles were repeated every 3 weeks. RESULTS: Of 36 patients entered onto the study, 34 and 32 patients were assessable for toxicity and response, respectively. No complete responses (CRs) were observed. Eleven patients (34%) had a partial response (PR) and six (19%) had stable disease (SD). In three of six patients categorized as having SD, there was greater than 50% tumor shrinkage. However, no 4-week follow-up measurements were made, so these could not be considered PRs, in part because patients received salvage chemotherapy by study design. In this trial, induction and salvage chemotherapy resulted in a response (two CRs and 15 PRs) (53%) in 17 patients. The estimated median survival duration was 43 weeks. Dose-limiting toxicity was leukopenia, with 19 patients (56%) having grade 4 leukopenia. The numbers of patients who experienced other grade 4 toxicities were as follows: pulmonary, three (9%); liver, two (6%); cardiac, one (3%); thrombocytopenia, one (3%); metabolic, one (3%); stomatitis, one (3%); and allergic reaction, one (3%). Four additional patients had grade 3 leukopenia and one patient (3%) died of sepsis (grade 5 toxicity). CONCLUSION: Paclitaxel is an active new agent in the treatment of SCLC. Further investigation of this agent in combination with other active agents is appropriate.

Adult↗
PubMed1994

Analysing survival in the presence of an auxiliary variable.

A primary endpoint of AIDS trials is the length of survival. Often there is auxiliary information available on measures of disease progression, which significantly alter the risk of mortality. This paper explores the use of this information in obtaining a refined estimate of survival, and a test based on this estimate. The methods are applied to an AIDS clinical trial, and results of simulations are provided which compare the approach to standard methods for survival analysis.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Designing phase II studies of chemotherapy for HIV infection using CD4 as an end-point.

OBJECTIVE: To provide information that will be helpful in designing AIDS clinical trials that use CD4 as an end-point. DESIGN: Meta-analysis of randomized AIDS clinical trials comparing zidovudine and placebo. SETTING: Tertiary care. PATIENTS: Eight hundred and twenty-seven patients with HIV infection. INTERVENTIONS: Treatment with zidovudine at various dosages compared with placebo. MAIN OUTCOME MEASURE: Differences in the log-ratio CD4 count. RESULTS: The mean difference in the log-ratio CD4 count divided by its standard deviation varied from 0.31 to 0.76 depending on the study. Of the variation in CD4 count 63% is short-term variation. CONCLUSION: Trials of 12 weeks duration can be used to test for the effect of a new drug on CD4 counts. Testing combination therapies may require somewhat longer trial periods. The sample size for clinical trials can be reduced by replicating baseline and follow-up measurements. Trials of new agents should test for an increase in CD4 over baseline. Such trials will require between 25 and 190 patients per arm depending on the patient population. Trials that compare combinations to standard therapies will require between 32 and 235 patients per arm depending on disease stage and prior therapy of study participants.

AIDS-Related Complex↗
PubMed1993

Influence of implantable cardioverter-defibrillators on the long-term prognosis of survivors of out-of-hospital cardiac arrest.

BACKGROUND: Survivors of out-of-hospital cardiac arrest not associated with acute myocardial infarction are at high risk for recurrent cardiac arrest and sudden cardiac death. The impact of the implantable cardioverter-defibrillator on long-term prognosis in these patients is uncertain. METHODS AND RESULTS: Three hundred thirty-one survivors of out-of-hospital cardiac arrest (age, 56 +/- 13.7 years) underwent electrophysiologically guided therapy. Implantable defibrillators were placed in 150 patients (45.3%), and 181 patients (54.7%) received pharmacological and/or surgical therapy alone. Left ventricular ejection fraction was 35.2 +/- 16.6% in defibrillator recipients and 45.3 +/- 18.2% in nondefibrillator patients. Median patient follow-up was 24 months in the defibrillator group and 46 months in the nondefibrillator group. In a proportional hazards model, the independent predictors of total cardiac mortality were left ventricular ejection fraction of less than 0.40 (relative risk, 4.55; 95% confidence interval, 2.44 to 8.33; P = .0001), absence of an implantable defibrillator (relative risk, 2.70; confidence interval, 1.41 to 5.00; P = .017), and persistence of inducible sustained ventricular tachycardia (relative risk, 1.84; 95% confidence interval, 0.97 to 3.49; P = .045). The 1- and 5-year probabilities of survival free of cardiac mortality in patients with left ventricular ejection fraction of less than 0.40 were 94.3% and 69.6% with a defibrillator and 82.1% and 45.3% without a defibrillator, respectively. For patients with left ventricular ejection fraction of 0.40 or more, the 1- and 5-year probabilities of survival free of cardiac mortality were 97.7% and 94.6% with a defibrillator and 95.4% and 86.9% without a defibrillator, respectively. CONCLUSIONS: In survivors of out-of-hospital cardiac arrest, the implantable defibrillator is associated with a reduction in cardiac mortality, particularly in patients with impaired left ventricular function.

Anti-Arrhythmia Agents↗
PubMed1993

Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. Eastern Cooperative Oncology Group.

PURPOSE: This prospective randomized cooperative group study was conducted in patients with neoplastic meningitis treated with intrathecal methotrexate or thiotepa to assess response rates and survival, prognostic factors, and the toxicity of these regimens. PATIENTS AND METHODS: Fifty-nine adults with nonleukemic malignancies, performance status of 0 to 3, and positive CSF cytologies were assigned to receive intrathecal methotrexate (10 mg) or thiotepa (10 mg) twice weekly. Radiation, was administered to mass lesions and/or symptomatic sites and appropriate systemic therapy was given concomitantly. RESULTS: Fifty-two patients were assessable. Most were female (79%), nonambulatory (77%), had been pretreated with radiation (52%) and chemotherapy (77%), and had evidence of systemic disease (65%). Most primary cancers were of the breast (48%), lung (23%), or lymphatics (19%). Treatment arms were well balanced, except that more patients randomized to methotrexate had breast cancer (61% v 33%) and were without evidence of systemic cancer (21% v 4%). No patient had important neurologic improvement with therapy, and 75% deteriorated neurologically within 8 weeks of initiating therapy. Survival ranged from 4 days to 110.5+ weeks. Median survival for patients receiving methotrexate was 15.9 weeks and 14.1 weeks for patients treated with thiotepa. Factors predictive of shorter survival included progressive systemic disease (P = .0005), poor performance status (P = .03), and significant cranial nerve palsies (P = .02). Although serious toxicities were similar, mucositis (P = .04) and neurologic complications (P = .008) were more common in patients who received methotrexate. CONCLUSION: The efficacy and overall toxicities of intraventricular methotrexate and thiotepa seem similar and neither reverses fixed neurologic deficits. Early diagnosis and treatment and new therapeutic approaches are needed to improve the outcome for patients with neoplastic meningitis.

Aged↗
PubMed1993

A proportional hazards model for truncated AIDS data.

An important source of information on the latency period for AIDS is the data from individuals infected by contaminated blood transfusion. However, a difficulty in the analysis and interpretation of these data is that information is available only on individuals who are infected and develop the disease prior to some specific time. In this paper, we propose an approach to the analysis of such data under a proportional hazards model. The proposed approach allows testing for group effects in the presence of multiple explanatory variables.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Determinants of accrual of women to a large, multicenter clinical trials program of human immunodeficiency virus infection. The AIDS Clinical Trials Group.

To determine factors influencing the enrollment of women in a large multicenter human immunodeficiency virus (HIV) clinical trials program in the United States, we analyzed enrollment and demographic data of the AIDS Clinical Trials Group (ACTG) during the period 1987-90. Women comprised 6.7% of 11,909 ACTG participants enrolled in 1987-90. Women entering ACTG trials were significantly more likely to be white (48.5%) and less likely to have ever used i.v. drugs (22.6%) than U.S. women reported to have AIDS (26.5% were white; 51.0% had ever used i.v. drugs, p < 0.0001). In a multiple logistic regression model, specific attributes of individual trials did not influence enrollment of women with the exception that trials that targeted asymptomatic persons had greater enrollment of women. There was wide variation among research units in the percentage of women enrolled (1.0-37.5%), and evidence of significant regional variation in the ability of units to recruit available women. Units with female principal or coprincipal investigators had more than twice the percentage of female enrollment as units headed by men (10.8 vs. 5.3%, p < 0.001). Enrollment of women in a large HIV clinical trials program was low and appeared to be influenced more by demographic and geographic factors that attributes of specific trials. An apparent positive influence of female leadership on the enrollment of women warrants further study.

Acquired Immunodeficiency Syndrome↗
PubMed1992

A controlled trial of trimethoprim-sulfamethoxazole or aerosolized pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. AIDS Clinical Trials Group Protocol 021.

BACKGROUND: Pneumocystis carinii pneumonia (PCP) continues to be the most common index diagnosis in the acquired immunodeficiency syndrome (AIDS), but it is not clear which of several available agents is the most effective in preventing a recurrence of PCP. METHODS: We conducted a comparative, open-label trial in 310 adults with AIDS who had recently recovered from an initial episode of PCP and had no treatment-limiting toxic effects of trimethoprim-sulfamethoxazole or pentamidine. All the patients were treated with zidovudine and were randomly assigned to receive either 800 mg of sulfamethoxazole and 160 mg of trimethoprim once daily or 300 mg of aerosolized pentamidine administered every four weeks by jet nebulizer. The participants were followed for a median of 17.4 months. RESULTS: In the trimethoprim-sulfamethoxazole group (n = 154) there were 14 recurrences of PCP, as compared with 36 recurrences (including 1 extrapulmonary recurrence) in the aerosolized-pentamidine group (n = 156). The estimated recurrence rates at 18 months were 11.4 percent with trimethoprim-sulfamethoxazole and 27.6 percent with pentamidine (P < 0.001). The risk of a recurrence (adjusted for initial CD4 cell count) was 3.25 times higher in the pentamidine group (P < 0.001, 95 percent confidence interval, 1.72 to 6.16). There were no significant differences between the groups in survival or in hematologic or hepatic toxicity. Crossovers from trimethoprim-sulfamethoxazole to aerosolized pentamidine were more common than the reverse (27 vs. 4 percent), partly because of the study protocols for the management of leukopenia. There were 19 serious bacterial infections in the trimethoprim-sulfamethoxazole group and 38 in the pentamidine group. The time to a first bacterial infection was significantly greater for those assigned to trimethoprim-sulfamethoxazole (P = 0.017). CONCLUSIONS: In patients with AIDS who are receiving zidovudine, trimethoprim-sulfamethoxazole is more effective than aerosolized pentamidine in conventional doses for the prevention of recurrent pneumocystis infection.

AIDS-Related Opportunistic Infections↗
PubMed1992

Computer-based interview for screening blood donors for risk of HIV transmission.

OBJECTIVE: To test the ability of a computer-based interview to detect factors related to the risk of the human immunodeficiency virus (HIV) among potential blood donors and to determine donor reactions to the use of the interview. DESIGN: A comparison of the rate of detection of HIV-related factors elicited by a computer interview with that obtained by standard American Red Cross procedures for assessment of donor suitability, including a randomized crossover trial in which the order of the two methods was reversed. Information obtained by the computer was not available to influence the use of blood components for transfusion. SETTING: The computer interview was administered to donors at an American Red Cross blood donor center and at a mobile blood drive at a hospital. SUBJECTS: Consecutive sample of 294 male and female blood donors 18 to 75 years of age. MAIN OUTCOME MEASURES: Subjects' responses to the computer-based interview as well as responses to the standard Red Cross written questionnaires and face-to-face interviews were used for donor assessment. RESULTS: The interview took an average of 8 minutes to complete. From among 272 donors who provided complete data, the computer identified 12 donors who reported either behaviors associated with a risk of HIV acquisition or symptoms compatible with the acquired immunodeficiency syndrome; none of these donors had been so identified either by routine written questionnaires or by face-to-face interviews used to screen potential blood donors. Only one of the 12 identified donors used the confidential unit exclusion procedure to prevent use of his donated unit. The rate of elicitation of HIV-related factors by the computer interview was 12 (4.4%) of 272 (95% confidence interval [CI], 2.3% to 7.6%), compared with two (0.13%) of 1536 (95% confidence upper bound, 0.28%) using the standard Red Cross procedure (P less than .0001). Tests for antibodies to HIV were negative in blood samples from all of the 272 subjects studied. The subjects enjoyed the computer interview and judged it to be more private than the standard donor assessment method. They also predicted that donors would be more honest with the computer interview than with a human interviewer. CONCLUSIONS: Computer-based screening elicits more HIV-related factors in the health histories of blood donors than do the standard questionnaire and interviewing methods currently in use. Computer-based screening is also acceptable to blood donors.

Adolescent↗
PubMed1992

Justification for evaluating new anticancer drugs in selected untreated patients with extensive-stage small-cell lung cancer: an Eastern Cooperative Oncology Group randomized study.

BACKGROUND: Studies have shown that response to a given chemotherapy in previously untreated patients with extensive-stage small-cell lung cancer is superior to that in patients previously treated with other regimens. This finding raises the question of whether it is necessary and ethical to study the effects of new anticancer agents in untreated patients. Such studies appear to be the best test for drug development, but there has been no evaluation of whether survival of untreated patients, whose cancer is sensitive to established drugs, is adversely affected in trials of new drugs. PURPOSE: This randomized study of untreated patients with extensive-stage small-cell lung cancer was designed (a) to compare the survival of patients treated with either effective standard chemotherapy or an investigational anticancer drug as initial therapy and (b) to evaluate response rates and toxic effects of such therapies. METHODS: Eighty-six patients were randomly assigned to receive, as initial therapy, either the standard CAV regimen--cyclophosphamide (1000 mg/m2), doxorubicin (50 mg/m2), and vincristine (1.4 mg/m2) every 3 weeks--or the phase II drug menogaril (200 mg/m2) every 4 weeks. Treatment after induction therapy varied, depending on patient response, but nonresponders and those with disease progression received salvage chemotherapy--etoposide (120 mg/m2 on days 1, 2, and 3) and cisplatin (60 mg/m2 on day 1), repeated every 3 weeks. RESULTS: Of the 43 patients on CAV, 42% responded (eight complete responses and 10 partial responses); 5% of the 43 on menogaril responded (two partial responses) (P = .0001). Twelve (22%) of 54 patients responded to salvage chemotherapy (five complete responses and seven partial responses). Within 3 months from start of treatment, twelve patients died--3 patients in the CAV group and nine patients in the menogaril group (P = .12). The estimated median survival was 37 weeks with menogaril and 45 weeks with CAV (P = .28). At 6 months, survival was 76.7% for the CAV group and 67.4% for the menogaril group. At 12 months, survival rates were 24.4% and 27.9%, respectively. Confidence intervals (95%) for the differences between the proportions surviving in the two groups were -9%-28% at 6 months and -25%-14% at 12 months. Use of CAV resulted in significantly higher occurrence of severe and life-threatening treatment-related complications (P = .002). CONCLUSION: The confidence intervals for the differences in survival are too wide to conclude that evaluation of a new drug in untreated patients with extensive-stage small-cell lung cancer is or is not harmful. The data do suggest, however, that use of this study design may have no adverse effect on survival.

Antineoplastic Agents↗
PubMed1992

Evaluation and management of the drooling patient.

Drooling, or sialorrhea, may appear to be a most mundane problem but in fact can be a condition with a wide spectrum of etiologies. Unhappily, drooling also may lead to several unfortunate medical and psychosocial outcomes for the affected patient. The senior author (WSC) has had a 13 year interest in the treatment of drooling patients. This paper is essentially a distillation of the experience gained in managing these patients. Since 1979 he has participated in a team (which includes an otolaryngologist, a dentist and a speech pathologist) that attends these patients and makes recommendations in a consensus fashion. This team concept, as well as historical and physiologic background material, will be discussed below.

Adult↗
PubMed1991

Effect of culture media on lymphokine-activated killer effector phenotype and lytic capacity.

We compared the ability of murine lymphokine-activated killer (LAK) cells grown in either a serum-supplemented "standard" medium (alpha MEM plus fetal calf serum) or a serum-free medium (AIM-V) to lyse a range of tumour targets. LAK cells grown in either of the media killed a cultured murine tumour line (YAC-1 lymphoma) well and spared syngeneic "self" cells (concanavalin-A-stimulated splenocytes). However, a striking difference was noted in the ability of LAK cells grown in alpha MEM plus fetal calf serum (as opposed to AIM-V) to kill "modified self" cells (trinitrophenol-modified concanavalin A blasts); LAK cells grown in the former always killed modified self cells better than those grown in the latter. This pattern held under a broad range of experimental manipulations and was found to be related to a relative increase in CD3-bearing LAK cells grown in the standard medium. These data suggest that the two media cannot be used interchangeably. This conclusion may have clinical implications for the use of LAK cells, as animal studies have been done using LAK cells generated in serum-containing medium and clinical studies have used LAK cells generated in serum-free medium.

Animals↗
PubMed1991

Bleeding time prolongation and bleeding during infusion of recombinant tissue-type plasminogen activator in dogs: potentiation by aspirin and reversal with aprotinin.

Thrombolytic therapy is associated with a bleeding tendency that may be exacerbated by adjunctive antiplatelet agents. The effect of recombinant tissue-type plasminogen activator (rt-PA) alone or in combination with aspirin on serial measurements of template bleeding time, ex vivo platelet aggregation and coagulation factors and the frequency of bleeding was studied in dogs. During infusion of rt-PA (15, 30 or 60 micrograms/kg per min for 90 min), a dose-related increase in bleeding time was observed. In a randomized blinded study of 25 dogs, the baseline bleeding time (mean +/- SD) was 3.5 +/- 1 min in control animals and 4 +/- 2 min after oral aspirin (15 mg/kg body weight). Infusion of rt-PA (15 micrograms/kg per min for 90 min) prolonged the bleeding time to a maximum of 15 +/- 12 min. In contrast, combined aspirin and rt-PA therapy produced an increase to greater than 30 min during infusion, reverting to 13 +/- 10 min within 2 h after cessation of infusion. Recurrent continuous bleeding from incision sites occurred in one of six dogs given aspirin alone, two of seven given rt-PA alone and all six dogs given both aspirin and rt-PA (p = 0.02). Bleeding time greater than 9 min correlated significantly with bleeding frequency (p less than 0.0001), with a sensitivity of 100% and a specificity of 87%. Intravenous bolus injection of aprotinin (20,000 kallikrein inhibitor units/kg body weight) in six dogs given both rt-PA and aspirin produced a decrease in bleeding time from greater than 30 min to 9.5 +/- 9 min and resulted in cessation of bleeding. Thus, bleeding and bleeding time prolongation in this canine model are potentiated by a marked interactive effect of rt-PA and aspirin that is rapidly reversible. Template bleeding times may provide a useful quantitative index for monitoring the bleeding tendency associated with thrombolytic therapy.

Animals↗
PubMed1991

Delayed central nervous system myelination in the sudden infant death syndrome.

This study was designed to assess whether development of the central nervous system (CNS) is delayed in victims of the sudden infant death syndrome (SIDS). We selected the parameter of myelination because it is a continuously changing and readily accessible marker of CNS development in the SIDS age-range. We assessed myelination blindly in 61 SIDS and 89 autopsy controls. In 62 sites the degree of myelination was visually graded in myelin-stained histological sections on an ordinal scale of 0-4 using the inferior cerebellar peduncle as an internal standard of degree 3. Cases were stratified by postconceptional age at death and SIDS and controls were compared with respect to myelin degree at each site. Significantly delayed myelination (p less than 0.05) occurred in the SIDS group in 25 of the 62 sites examined. Hypomyelination affected fiber systems in which myelination is initiated before or after birth and which myelinate with different tempos and preferentially affect pyramidal and cerebellar (somatomotor) and prefrontal-temporal-limbic (visceromotor) systems. Hypomyelination was not associated with individual clinicopathologic variables in the SIDS group. Somatic growth and brain weight were significantly greater in SIDS than controls. Therefore, we suggest that SIDS is associated with a developmental CNS disorder. Although delayed CNS myelination most likely shares a common antecedent with sudden death and is not its cause, the role of somato- and viscero-motor systems in central cardiorespiratory control and arousal warrants further analysis in SIDS.

Birth Weight↗
PubMed1991

Unilateral otosclerosis and noise-induced occupational hearing loss.

The interaction between noise-induced hearing loss and otosclerosis remains unclear and controversial. In the present study, the effect of chronic noise exposure was examined in 31 patients with unilateral otosclerosis. Consideration was given to hearing loss at specific frequencies, the influence of age, and the effect of the size of the air-bone gap. A small, though statistically significant, protective effect of otosclerosis was demonstrated at 4 kHz. This effect was maintained despite advancing age. An apparent inverse relationship was found between the amount of hearing loss and the size of the air-bone gap at 4 kHz, but multiple linear regression analysis suggested that this finding was contaminated by age effects.

Adult↗
PubMed1991

Modeling the effect of dose on the lifetime tumor rate from an animal carcinogenicity experiment.

The proportion of tumor-bearing animals in a chronic bioassay is often used as a basis for assessing risk at human exposure levels that are below the experimental range. However, such a crude experimental tumor rate can be biased by dose-related differences in the nontumor mortality. To adjust tumor rates for competing mortality, Kodell, Gaylor, and Chen (1986, Biometrics 42, 867-873) propose a standardized tumor rate, calculated separately in each dose group from dose-specific estimates of the tumor prevalence and mortality functions. This paper extends the approach of Kodell et al, by developing a method of modeling the standardized rate as a function of dose. An advantage of this approach is that it leads to estimates that are monotone in dose. In addition, by modeling the lifetime risk as a function of dose directly, it is possible to obtain estimates for the risk at dose levels outside the experimental range, such as for low-dose extrapolation, and estimation of the "tumorigenic dose 50" (TD50). A semiparametric model is developed, as well as the nonparametric alternative of isotonic regression. Simulations are provided to show the relative bias and precision of the two approaches to that of Kodell et al.

Animals↗