Biomedical subjects

D Zelterman

Publications and source records attributed to D Zelterman.

At least 19 recordsLinked to original sources

PubMed1997

Dose-escalation and pharmacodynamic study of topotecan in combination with cyclophosphamide in patients with refractory cancer.

PURPOSE: Based on preclinical data that demonstrated synergy between alkylating agents and topoisomerase (topo) I poisons, we determined the maximum-tolerated dose (MTD) of topotecan, using a 5 day bolus schedule, that could be given in combination with a single, fixed dose of cyclophosphamide. Pharmacodynamics of this combination were explored by analyzing biochemical effects of treatment in peripheral-blood mononuclear cells (PBMCs). PATIENTS AND METHODS: Patients with refractory cancer were treated with cyclophosphamide 600 mg/m2 on day 1, followed by topotecan given as a 30-minute infusion for 5 consecutive days. Cycles were repeated every 3 weeks. Once the MTD was defined, granulocyte colony-stimulating factor (G-CSF) was added to the regimen in an attempt to escalate further the dose of topotecan. Plasma concentrations of topotecan were determined during the first treatment cycle by high-performance liquid chromatography. PBMCs were sampled at baseline and throughout the 5-day treatment period for analysis of topo I protein concentrations and to determine drug-induced DNA fragmentation. RESULTS: Twenty-six patients were treated with topotecan at doses that ranged from 0.5 mg/m2/d to 1.2 mg/ m2/d for a total of 74 cycles. Reversible neutropenia was dose-limiting, with mild to moderate suppression of the other blood-cell elements commonly occurring. Transfusions of RBCs and platelets were required in 24% and 7% of treatment cycles, respectively. The most prominent nonhematologic toxicities were fatigue and weight loss. Compared with previously published data in which topotecan was administered alone, cyclophosphamide did not appear to alter the pharmacokinetics of topotecan. Significant increases in topo I concentration were identified in PBMCs following the administration of cyclophosphamide on day 1 and there was a significant decrease in topo 1 during the 5-day course of treatment (P < .01, sign test). DNA fragmentation as a result of drug treatment was identified in 11 of 15 (73%) cycles analyzed. CONCLUSION: For previously treated patients, the recommended dose of topotecan in this schedule is 0.75 mg/m2/d without growth factor support and 1.0 mg/ m2/d if it is administered with G-CSF. Biochemical changes in cells induced by exposure to camptothecins can be measured in vivo and these effects may have important implication in the design of combination therapies and the optimal scheduling of this class of agents.

Adult↗

PubMed1997

Gallium scans in the management of patients with Hodgkin's disease: a study of 101 patients.

PURPOSE: To evaluate the utility of periodic gallium (67Ga) scans in the management of patients with Hodgkin's disease. PATIENTS AND METHODS: From 1990 to 1994, 101 patients treated for Hodgkin's disease (stage I to II, n = 67; stage III to IV, n = 34) had a positive 67Ga scan at the time of diagnosis. Treatment included chemotherapy in 27 patients, radiation therapy in 28, and combined modality therapy in 46. All patients underwent 67Ga scans at the time of diagnosis, near the end or just after treatment, and at periodic follow-up evaluation. RESULTS: After treatment, the 67Ga scan remained positive in four patients and was interpreted as negative in 97. Among the four patients with positive scans, two died of progressive disease and two relapsed. Among the remaining 97 patients with negative 67Ga scans, 16 patients relapsed, including five with stage I to II (7.5%) and 11 with stage III to IV (34.4%) disease. The negative predictive value of posttherapy 67Ga scan was 83.5% for all patients; however, when calculated according to stage, it was 92.4% for patients with stage I to II disease and 64.5% for patients with stage III to IV disease (P < .01). CONCLUSION: A positive 67Ga scan at the end of therapy is rarely seen in patients with Hodgkin's disease and should be considered a manifestation of gross residual disease. However, a negative 67Ga scan after therapy had a significantly lower predictive value in patients with stage III to IV disease compared with stage I to II disease. The predictive value of 67Ga scans, as well as newer imaging studies, should be analyzed according to pretreatment stage.

Adolescent↗

PubMed1997

A 40-year analysis of 265 gastric carcinoids.

OBJECTIVES: Gastric carcinoid tumors were previously regarded as rare, benign neoplasms. Few data are available on the epidemiology of this lesion. METHODS: We have analyzed the End Results Group (1950-1969), the Third National Cancer Survey (1969-1971) and the Surveillance, Epidemiology, and End Results (SEER, 1973-1991) databases of the National Cancer Institute. The three files consist of 8305 carcinoid cases collectively, including 265 gastric carcinoids. RESULTS: The percentage of gastric carcinoids among all gastric malignancies has increased from 0.3% to 0.54%. The black:white ratio declined from 0.36 to 0.17 as well as the male:female ratio from 0.9 to 0.57. The age-adjusted incidence rates have increased in white females but are much higher for the black population. Gastric carcinoids are associated with other malignant neoplasms in 7.8% of cases. The 5-yr survival rates for localized lesions, with regional and with distant metastases, were 48.6%, 39.9%, and 10%, respectively. CONCLUSIONS: Gastric carcinoids have increased in incidence over the last 20 yr. This may represent either improved diagnostic techniques, increased awareness, or a real change in incidence. Poor 5-yr survival rates indicate that gastric carcinoid tumors exhibit an aggressive biological behavior.

Age Distribution↗

PubMed1997

Log-linear modeling with the negative multinomial distribution.

We develop a negative multinomial sampling plan in which observed cell counts are positively correlated. We show that maximum likelihood estimates of cell means are the same as those found under independent Poisson sampling. There is no maximum likelihood estimate for the shape parameter in general. We propose an estimate of the shape parameter based on the mean and quantiles of Pearson's chi-squared statistic. These techniques are applied to models of cancer incidence for three cities in Ohio and longitudinal health care utilization by a group of senior citizens.

Aged↗

PubMed1996

Tuberculosis in physicians: compliance with surveillance and treatment.

BACKGROUND: Physicians have historically shown poor compliance with tuberculosis (TB) skin testing and treatment after infection. Studies showed that nearly one half of physicians had positive skin test results, but one half to two thirds of physicians with negative tuberculin skin test results did not undergo annual skin testing despite significant exposure to patients with TB. Compliance with chemoprophylaxis after skin test conversion was worse; only 8% to 10% of physicians with a positive tuberculin skin test result received antituberculous therapy. The Centers for Disease Control and Prevention published guidelines on prevention of tuberculosis transmission recommending that all health care workers (including physicians) comply with regular skin testing and get appropriate follow-up care. The Occupational Safety and Health Administration has adopted the guidelines as part of its strategy to prevent occupationally acquired TB. OSHA's requirement provided the opportunity to study the effect on physicians of hospital-wide attempts to apply those guidelines. No previous study has looked at the differences in compliance between physicians in training, full-time staff physicians, and part-time staff (associate physicians). Understanding these differences will enable the hospital's administration to target efforts to improve compliance with TB surveillance and medical therapy after skin test conversion. METHODS: Two hundred eighty-four physicians (189 staff physicians, 65 resident physicians, and 30 associate physicians) responded to a questionnaire that asked about demographic and professional characteristics, current status of tuberculin skin test results, and follow-up of physicians with positive skin test results. RESULTS: We found that 71% of resident and full-time physicians were current in their tuberculin skin test status, whereas 66% of associate physicians were up to date. Thirteen percent of the resident and full-time physicians had positive TB skin test results, compared with 20% of associate physicians. Female physicians had a lower prevalence of positive skin test results than did male physicians. The departments of pathology, surgery, and pediatrics had the highest prevalence of positive test results, followed by radiology, emergency medicine, and obstetrics and gynecology. Family practice and internal medicine were among the departments with the lowest prevalence of positive skin test results. Physicians obtained their skin tests from multiple sources and had their test results interpreted in multiple facilities; hence, the test procedure was not uniform. Compliance with disease prophylaxis was 55% among the resident physicians with positive Mantoux test results, 44% among the full-time staff physicians, and only 17% among the associate physicians. More than half of the physicians with positive Mantoux test results remained untreated. CONCLUSION: Physicians have unique issues in complying with TB surveillance that need to be specifically addressed by hospitals in light of guidelines enforceable by the Occupational Safety and Health Administration. Resident physicians were the most compliant with TB surveillance and treatment after infection. Staff and associate staff physicians had poor compliance with treatment. Although this study shows some improvement when compared with prior studies on physician compliance, hospital follow-up and enforcement may be necessary to bring about significant behavioral change among physicians.

Adult↗

PubMed1996

Second solid tumors in patients with Hodgkin's disease cured after radiation or chemotherapy plus adjuvant low-dose radiation.

PURPOSE: Late solid tumors (STs) are a significant cause of morbidity and mortality in long-term survivors of Hodgkin's disease. To investigate the carcinogenic potential of two different therapeutic approaches, we measured the relative risk (RR) of STs in patients with early-stage disease cured after primary full-dose (approximately 40 Gy) radiation therapy (RT) and in patients with advanced disease who were treated with chemotherapy followed by low-dose (15 to 30 Gy) involved-field radiation (CMT). PATIENTS AND METHODS: Because therapy-induced STs generally begin after a latency period of 5 to 10 years, we restricted our analysis to patients treated before 1986 who achieved durable remissions. Patients who required salvage chemotherapy or who died of Hodgkin's disease were excluded from analysis. The RR of STs was calculated by dividing the observed number of cases by the expected number in a matched population from the Connecticut Tumor Registry. The actuarial incidence of STs was also measured. RESULTS: A total of 197 patients formed the RT group and 116 the CMT group. The median follow-up period in the RT group was 12.8 years, versus 13.5 years in the CMT group. The overall RR of STs in the CMT group was 1.5 (95% confidence interval [CI], 0.6 to 3.5; P = .122). There were no cases of lung or breast cancer. In the RT group, the overall RR of STs was 3.3 (95% CI, 2.0 to 5.3; P < .001). There were seven cases of lung cancer (RR = 10.8; 95% CI, 5.3 to 22.2; P < .001) and two cases of breast cancer (RR = 2; 95% CI, 0.6 to 7.4; P = .07). All six benign tumors occurred in the RT group. CONCLUSION: In patients cured by initial treatment for Hodgkin's disease, RT was associated with a statistically significant increase in STs, particularly lung cancer. CMT was not associated with a significant increase in STs. These data may have important implications for the design of newer therapies for early-stage Hodgkin's disease.

Actuarial Analysis↗

PubMed1995

Survival curves subjected to occasional insults.

We describe a parametric family of survival curves which can be used to model time to event data in systems subjected to occasional insults or shocks. Parameters control the location, magnitude, and duration of the effect for each insult. We use these models to describe the survival history of a large cohort of Drosophila that were transferred to new vials on a weekly basis as their nutrient medium deteriorated. A periodic model with fewer parameters exhibits a good fit to the data.

Animals↗

PubMed1994

Prevalence of carotid canal dehiscence in the human middle ear: a report of 1000 temporal bones.

A total of 1000 human temporal bones were used to study the prevalence of carotid canal dehiscence, microdehiscence, and thin bony coverage. Additionally, this study compares the prevalence according to sex and temporal bone age. A carotid canal dehiscence was detected in 77 (7.7%) bones. It was present bilaterally in 23.2% of the paired temporal bones. The prevalence of carotid canal dehiscence decreases with increasing temporal bone age. It was found in 10 (15.9%) bones in the younger than 2 age group, as opposed to 43 (6.3%) bones from the 40 and older group. The concept of microdehiscence of the carotid canal is introduced. A carotid canal microdehiscence was found in 74 (7.4%) bones. Microdehiscences were noted to occur bilaterally in 12.3% of the paired bones. The prevalence of carotid canal microdehiscence also decreases with increasing temporal bone age. It was detected in 7 (11.1%) bones in the younger than 2 age group, in contrast to 51 (7.5%) bones in the 40 and older group. A total of 134 (15.5%) temporal bones were found to have a thin bony coverage, without the presence of a dehiscence or microdehiscence. The prevalence of thin coverage was noted to increase linearly with age. A thin carotid canal was found in 2 (8.3%) bones from the younger than 2 age group, whereas 113 (17.3%) temporal bones from the 40 and older group exhibited this entity. To the best of our knowledge, this is the first systematic study of histologic sections of a large number of temporal bones that looks at these entities.

Adolescent↗

PubMed1994

Piecewise exponential survival curves with smooth transitions.

Several models of a population survival curve composed of two piecewise exponential distributions are developed. In one formulation the hazard rate changes at a point that is an unobservable random variable that varies between individuals. The population hazard function may decrease with age even when all individuals' hazards are increasing. In a second formulation, the population hazard function is modeled directly. Several models are fit to the survival history of a cohort of 5751 highly inbred male Drosophila melanogaster and the British coal mining disaster data.

Animals↗

PubMed1994

Topical CTC-96 accelerates wart growth in rabbits infected with cottontail rabbit papillomavirus.

CTC-96, a cobalt containing complex, was tested as a putative topical therapeutic agent for the treatment of papillomavirus-induced tumors in our cottontail rabbit papillomavirus (CRPV)-rabbit model system. Following experimental infection of domestic rabbits with CRPV, CTC-96 was applied to infection sites twice daily, 5 days a week for a total of 8 weeks. Two levels of concentrations of aqueous CTC-96 were compared to placebo control-treated animals. With increasing dose of CTC-96 we observed tumors earlier, larger, and more often across eight infected sites on each animal.

Administration, Topical↗

PubMed1994

Prevalence of facial canal dehiscence and of persistent stapedial artery in the human middle ear: a report of 1000 temporal bones.

A total of 1000 temporal bones were used to study the prevalence of facial canal dehiscence and of persistent stapedial artery in detail. Of the temporal bones studied, 560 (56%) contained at least one facial canal dehiscence. There was a 76.3% prevalence of bilaterality of this canal wall gap. The most common site of dehiscence was the oval window area. The concept of microdehiscence of the facial canal is introduced. One third of the temporal bones observed had a microdehiscence of the facial canal, usually located at the oval window area (74.9%) and found bilaterally 40% of the time. The authors found a 0.48% prevalence (5 out of 1045) of persistent stapedial artery. This is the first histological study of temporal bones to report a prevalence of this vascular anomaly.

Adolescent↗

PubMed1994

Prevalence of microfissures in the human temporal bone: a report of 1000 temporal bones.

A total of 1000 human temporal bones were studied to determine the prevalence of two microfissures: 1. the one between the facial canal and the vestibule, 2. the microfissure between the round window niche (RWN) and the posterior semicircular canal (PSC). Additionally, this study compares the prevalence according to temporal bone age and sex. The microfissure between the facial canal and the vestibule was observed in 470 (47%) temporal bones, with a bilateral presence of 77.2%. The prevalence of this microfissure increases linearly with age. It was not found in any bone within the 0 to 2 age group. It was present in 3 (7.3%) bones from the 2 to 9 age group, as opposed to 374 (54.8%) bones from the 40 and over group. The microfissure between the RWN and the PSC was detected in 915 (91.5%) temporal bones. This second microfissure was found to be an overwhelmingly bilateral entity. The prevalence of this other microfissure also increases with age. This microfissure was also not present in any temporal bone within the 0 to 2 age group. It was found in 28 (68.3%) bones from the 2 to 9 age group, in contrast to 678 (99.4%) temporal bones from the 40+ group.

Adolescent↗

PubMed1993

Generalized logistic models for low-dose response data.

We discuss a generalization of the logistic response function of the form Pr(y = 1/x) = [1 + exp(- theta - beta'x)]-alpha, where alpha > 0. This function coincides with the usual logistic response when the shape parameter alpha is equal to one. We describe the use of this model for analysing cancer rates in mice for low-dose exposure to a known carcinogen. When estimating the low-dose responses, the errors associated with extrapolation are reduced when a priori knowledge about the rates among unexposed individuals is incorporated into the fitting procedures.

2-Acetylaminofluorene↗

PubMed1993

Symptomatic versus asymptomatic endolymphatic hydrops: a histopathologic comparison.

One of the unanswered questions in Meniere's disease research is the pathophysiology by which the classic symptoms are produced. A histopathological study was undertaken to identify the pathological features of symptomatic endolymphatic hydrops and their relationship to these symptoms. Two groups of temporal bones were examined, compared, and described. The first group was from patients with symptoms of Meniere's disease (n = 29). Temporal bones in the second group were chosen for the presence of endolymphatic hydrops and the absence of otologic symptoms (n = 13). Significant differences were noted in the severity of hydrops, the frequency of membrane ruptures, the endolymphatic duct, and coexistent pathologic conditions. Ruptures were seen in 38% of temporal bones from symptomatic patients and in only 8% of temporal bones from patients with asymptomatic endolymphatic hydrops. Based on this study and a review of the literature, the authors believe that the symptoms and findings of Meniere's disease are explained best on the basis of both chemical and physical mechanisms being operational intermittently and together.

Cochlea↗

PubMed1992

Mechanisms of retraction pocket formation in the pediatric tympanic membrane.

The epidemiological nature of acquired cholesteatoma in children has shown that it occurs more often in the posterosuperior quadrant of the pars tensa and in the pars flaccida. This type of cholesteatoma is rarely seen before the age of 3 years, and serous otitis media is the most important risk factor for its occurrence. In an attempt to present a pathological rationale for these clinical findings, tympanic membranes from 11 temporal bones with purulent otitis media and 13 with serous otitis media were evaluated light microscopically and compared with 14 temporal bones without disease. Ages ranged from newborn to 3 years 6 months. The persistence of mesenchyme and greater inflammatory reaction observed in the pars flaccida and the posterosuperior quadrant of the pars tensa and changes in collagen and elastin observed in purulent otitis media and serous otitis media may represent a pathological rationale for the epidemiological nature of cholesteatoma in children.

Age Factors↗

PubMed1992

Longitudinal study of psychotropic drug use by elderly nursing home residents.

In this longitudinal study of patterns of use of psychotropic drugs by a cohort of elderly nursing home residents (N = 5,752), drug use was examined upon admission, 3 months later, and at discharge/end of study. At each time point, 17% of the cohort used neuroleptics. Half of the subjects discontinued neuroleptics at each time point; however, a similar number were initiated on the drug. Benzodiazepines were used by 21%, 15%, and 15% at each of the three time points, respectively. Twice as many people were taken off benzodiazepines as initiated on them following admission. The 5% rate of antidepressant use was constant across the three time periods, although only half of those who took antidepressants upon admission were also taking them upon discharge/end of study. The amount of change due to discontinuation of these drugs and adjustment in dosage levels challenges the stereotype of the "neglected psychotropic drug user" in nursing homes.

Aged↗

PubMed1992

Inadequate treatment of depressed nursing home elderly.

OBJECTIVE: To determine the prevalence of antidepressant drug treatment among nursing home elderly with major depression. DESIGN: Survey early and late in nursing home stay. SETTING: Sixty Medicaid/Medicare-certified skilled nursing homes. PARTICIPANTS: Admission cohort of 5,752 residents age 65 or older in 1976 through 1983. MEASURES: Chart review by nurse-abstractors of physicians' diagnoses, drug used, and alertness rating. Diagnosis of depression equivalent to DSM-III-R major depression. RESULTS: Of 868 persons with a diagnosis of depression in the medical record, only 10% were treated with antidepressant drugs. More received neuroleptics and benzodiazepines than received antidepressants, but most (52%) received no psychoactive drug at all. A subset of 258 depressed persons had positive notations in their records supporting a mental status rating of "alert and oriented." Of that subset, only 15% received antidepressants. When followed from admission to discharge or end of study the prevalence rate of antidepressant drug treatment increased by 4%. CONCLUSIONS: In the late 1970's and early 1980's, even when the primary care physician made and recorded a diagnosis of depression, most such nursing home residents remained untreated, incorrectly treated, or inadequately treated.

Aged↗

PubMed1992

Morphologic scales and relative distances between lesions identified on Papanicolaou smears.

We fit a Gaussian-type curve to a nonmonotonic transform of initial arbitrarily given scales (pseudoscalar transform) of a two-way discrete classification table by maximizing the likelihood (entropy) and computing morphologic scales of clusters of objects identified by visual judgments. The scales give the relative distance between pairs of categories or states. Morphologic scales of histologic lesions (states) identified on Papanicolaou smears were computed from a confusion matrix consisting of 3,545 matched pairs of observations on Papanicolaou smears and colposcopically directed biopsies available from the Gynecologic Cytology Laboratory, University of Minnesota, between 1985 and 1987. The original (uncollapsed) confusion matrix consisted of eight cytologic categories and histologic states: normal plus atypical benign, reactive atypia (including condylomatous changes); mild, moderate and severe dysplasia; squamous carcinoma in situ; invasive squamous cell carcinoma; and other malignancies. The morphologic scales are expressed numerically, which reflects a degree of confusion between two diagnostic categories or states. Except for malignancies other than squamous cell carcinoma, morphologic scales of histologic states seen from cytology retained the order of clinical severity. We detected a high degree of confusion between severe dysplasia and carcinoma in situ. Malignancies other than squamous cell carcinoma fell between moderate and severe dysplasia. Such a transposition of the scales in this group containing adenocarcinoma was likely due to frequent association of adenocarcinoma with cervical intraepithelial neoplasia. Morphologic scales of cytologic categories seen from histology showed high degrees of confusion and transpositions between mild and moderate dysplasia and between severe dysplasia and carcinoma in situ.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗