Biomedical subjects

D Zelterman

Publications and source records attributed to D Zelterman.

At least 19 recordsLinked to original sources

PubMed2000

Granulocyte-macrophage colony-stimulating factor priming plus papillomavirus E6 DNA vaccination: effects on papilloma formation and regression in the cottontail rabbit papillomavirus--rabbit model.

A cottontail rabbit papillomavirus (CRPV) E6 DNA vaccine that induces significant protection against CRPV challenge was used in a superior vaccination regimen in which the cutaneous sites of vaccination were primed with an expression vector encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine that induces differentiation and local recruitment of professional antigen-presenting cells. This treatment induced a massive influx of major histocompatibility complex class II-positive cells. In a vaccination-challenge experiment, rabbit groups were treated by E6 DNA vaccination, GM-CSF DNA inoculation, or a combination of both treatments. After two immunizations, rabbits were challenged with CRPV at low, moderate, and high stringencies and monitored for papilloma formation. As expected, all clinical outcomes were monotonically related to the stringency of the viral challenge. The results demonstrate that GM-CSF priming greatly augmented the effects of CRPV E6 vaccination. First, challenge sites in control rabbits (at the moderate challenge stringency) had a 0% probability of remaining disease free, versus a 50% probability in E6-vaccinated rabbits, and whereas GM-CSF alone had no effect, the interaction between GM-CSF priming and E6 vaccination increased disease-free survival to 67%. Second, the incubation period before papilloma onset was lengthened by E6 DNA vaccination alone or to some extent by GM-CSF DNA inoculation alone, and the combination of treatments induced additive effects. Third, the rate of papilloma growth was reduced by E6 vaccination and, to a lesser extent, by GM-CSF treatment. In addition, the interaction between the E6 and GM-CSF treatments was synergistic and yielded more than a 99% reduction in papilloma volume. Finally, regression occurred among the papillomas that formed in rabbits treated with the E6 vaccine and/or with GM-CSF, with the highest regression frequency occurring in rabbits that received the combination treatment.

Animals↗

PubMed1999

Follow-up recommendations for patients with American Joint Committee on Cancer Stages I-III malignant melanoma.

BACKGROUND: Guidelines for follow-up of melanoma patients are not established. In 1987, a follow-up protocol was instituted at the Yale Melanoma Unit to improve upon the detection of disease recurrence in patients with American Joint Committee on Cancer Stage I-III cutaneous melanoma. The follow-up protocol consists of a patient education program and a surveillance schedule based on stage of disease. METHODS: The authors retrospectively reviewed the records of 373 patients who were seen and followed according to the surveillance protocol in the Yale Melanoma Unit between January 1988 and December 1994 to determine 1) the time interval between the initial visit and recurrence; 2) the most common method of detecting recurrences; 3) whether the surveillance schedule or the patient detects more recurrences, i.e., asymptomatic recurrences versus symptomatic recurrences; 4) whether there is any survival difference between asymptomatic and symptomatic recurrences. RESULTS: The 5-year overall survival rates for Stage I, II, and III patients were 95%, 72%, and 52%, respectively. Of the 78 recurrences, 44 (56%) were detected by physician-directed surveillance examinations and 34 (44%) by patients. Most recurrences were found within the first (47%) or second (32%) year of follow-up. The estimated 6-month hazard rates for death or recurrence were 0.0044, 0.0088, and 0.0278 for Stage I, II, and III patients, respectively. The group of asymptomatic patients with recurrence had a survival advantage over the symptomatic recurrence group. In addition, patients with locoregional recurrence had better survival than those with distant recurrence. CONCLUSIONS: Although many recurrences arise rapidly and are recognized early by patients, in this study more than half were found by surveillance examinations before symptoms were manifest. Based on the hazard ratio for recurrences, the authors recommend the following surveillance schedules in addition to the patient education program for detection of recurrences: 1) Stage I, annually; 2) Stage II, every 6 months for Years 1-2 and annually thereafter; 3) Stage III, every 3 months for Year 1, every 4 months for Year 2, and every 6 months for Years 3-5; 4) at Year 6 and beyond, all patients should have surveillance annually, due to the risk of late recurrence and/or metachronous multiple primaries.

Adolescent↗

PubMed1999

Functional activity of murine CD34+ and CD34- hematopoietic stem cell populations.

The transmembrane glycoprotein CD34 is expressed on human hematopoietic stem cells and committed progenitors in the bone marrow, and CD34-positive selection currently is used to isolate bone marrow repopulating cells in clinical transplantation protocols. Recently, CD34- hematopoietic stem cells were described in both humans and mice, and it was suggested that CD34+ murine bone marrow cells may lack long-term reconstituting ability. In this study, the long-term repopulating ability of CD34+Lin- vs CD34-Lin- cells was compared directly using syngeneic murine bone marrow transplantation. Highly purified populations of CD34+Lin- and CD34-Lin- cells each are able to reconstitute bone marrow, confirming that both populations contain hematopoietic stem cells; however, the number of hematopoietic stem cells in the CD34+Lin- fraction is approximately 100-fold greater than the number in the CD34-Lin- fraction. In competitive repopulation experiments, CD34+ stem cells are better able to engraft the bone marrow than are CD34- cells. CD34+Lin- cells provide both short- and long-term engraftment, but the CD34-Lin- cells are capable of only long-term engraftment. Ex vivo, the CD34+Lin- stem cells expand over 3 days in culture and maintain the ability to durably engraft animals in a serial transplant model. In contrast, when CD34-Lin- cells are cultured using the same conditions ex vivo, the cell number decreases, and the cells do not retain the ability to repopulate the bone marrow. Thus, the CD34+Lin- and CD34-Lin- cells constitute two functionally distinct populations that are capable of long-term bone marrow reconstitution.

Animals↗

PubMed1999

Neutropenic infections in 100 patients with non-Hodgkin's lymphoma or Hodgkin's disease treated with high-dose BEAM chemotherapy and peripheral blood progenitor cell transplant: out-patient treatment is a viable option.

A retrospective analysis was performed on 100 patients with non-Hodgkin's lymphoma (NHL, n = 75) or Hodgkin's disease (HD, n = 25) who underwent peripheral blood progenitor cell transplant (PBPCT) following high-dose chemotherapy (HDCT) with BCNU, etoposide, cytarabine and melphalan (BEAM) between March 1994 and June 1997. Following PBPCT and until engraftment all patients received oral ciprofloxacin and fluconazole, patients with positive Herpes simplex virus serology received acyclovir and 91 patients received filgrastim. The median days of neutropenia and days to an absolute neutrophil count (ANC) >500/mm3 were 6 and 9, respectively. Febrile neutropenia occurred in 68 patients. Gram-positive bacteremia occurred in 14 patients. No gram-negative infections, invasive fungal infections, intensive care visits or deaths occurred during the period of neutropenia or in the first 30 days following transplant. In multivariate logistic regression the risk of development of any infection was associated only with the duration of neutropenia (P = 0.02) and the risk of bacteremia was associated only with the number of CD34+ cells infused (P = 0.046). Among 49 patients treated in the outpatient setting, 14 (28%) were never admitted. High-dose chemotherapy with BEAM supported by PBPCT, prophylactic antibiotics and filgrastim resulted in a low incidence of infections and no acute mortality. WBC engraftment occurred rapidly allowing for a predictable course during which lengthy hospital stays and amphotericin therapy could be avoided.

Adult↗

PubMed1999

Cyclophosphamide, cytosine arabinoside and TBI as a conditioning regimen for allogeneic bone marrow transplantation in patients with leukemia.

This is a prospective study designed to determine the toxicity, efficacy and antileukemic effect of high-dose cytosine arabinoside (ara-C), cyclophosphamide and total body irradiation (TBI) as a myeloablative regimen prior to allogeneic bone marrow transplantation for patients with hematologic malignancies. Fifty-eight patients with hematologic malignancies were treated with cyclophosphamide, high-dose ara-C and total body irradiation (TBI) followed by allogeneic bone marrow transplantation. Fifty patients had good prognosis disease and eight had poor prognosis disease. Cyclosporine and short-course methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. The conditioning regimen consisted of ara-C 3000 mg/m2 twice a day x six doses on days -7, -6, and -5; cyclophosphamide 1800 mg/m2 on days -4 and -3; and TBI 1400 cGy midline dose at 5 cGy/min in eight total fractions administered twice a day on days -4, -3, -2, and -1. The bone marrow was infused on day 0 (zero). Toxicity related to the conditioning regimen was comparable to that reported with other conditioning regimens, except for diarrhea which appears to be more frequent. The actuarial survival at 1 year was 69% (58-82) and at 5 years was 54% (42-69) with the numbers in parentheses representing the 95% confidence interval of the Kaplan-Meier estimate. After a median follow-up of 28 months, 31 of 58 (53%) patients are alive without evidence of disease. Only four of the 58 patients (7%) have relapsed. Cyclophosphamide, ara-C and TBI is a safe and effective myeloablative regimen for patients with leukemia. The overall relapse rate in our study was 7% with a median follow-up of 28 months and appears to be lower than relapse rates reported in other series. This is probably due to the added antileukemic effect of ara-C. This regimen should be compared with other myeloablative regimens in a controlled study.

Adolescent↗

PubMed1999

Downregulation of p27KIP1 and Ki67/Mib1 labeling index support the classification of thyroid carcinoma into prognostically relevant categories.

The cyclin-dependent kinase inhibitor p27KIP1 has been proposed as a valuable prognostic indicator for a variety of human neoplasms. Immunohistochemical reactivity for p27KIP1 and the proliferation marker Ki67/Mib1 were investigated in 90 thyroid carcinomas of follicular cell origin. The neoplasms were divided into three prognostic groups on the basis of their morphologic features: group 1, well-differentiated papillary or follicular carcinomas with favorable pathologic features (43 papillary carcinomas and 4 minimally invasive follicular carcinomas); group 2, papillary or follicular carcinomas with unfavorable pathologic features (21 poorly differentiated carcinomas and 2 papillary carcinomas, tall cell variant); and group 3, undifferentiated, or anaplastic, carcinomas. p27KIP1 expression (p = 0.007) and Ki67/Mib1 labeling index (p = 0.02) showed a strong correlation with the subdivision of the thyroid carcinomas in the three prognostic groups with a significant linear trend for tumors with low p27KIP1 (p = 0.002) and high Ki67/Mib1 labeling index (p = 0.005) to segregate into the unfavorable categories (groups 2 and 3). Low p27KIP1 expression, but not cellular proliferation, was related to adverse prognostic factors, such as large tumor size (p = 0.03) and extrathyroidal extension (p = 0.01), but the correlation was not independent of the subdivision in the three groups. Low p27KIP1 expression (p = 0.03) and high proliferative rate (p = 0.02) were associated with poor survival, reflecting the close association between patient morbidity and mortality rates and tumor differentiation. No significant association could be seen between p27KIP1 or cellular proliferation and clinicopathologic parameters (e.g., age, sex, tumor size, extrathyroidal extension, vascular invasion, lymph node metastases, distant metastases, tumor stage, and survival rate) within any of the groups, or the histologic diagnosis of papillary versus follicular carcinoma irrespective of their degree of differentiation. Modulation of p27KIP1 and cellular proliferation patterns in thyroid carcinoma correlate with tumor differentiation and support the morphologic classification of thyroid carcinoma into prognostically relevant categories.

Adenocarcinoma, Follicular↗

PubMed1999

Assessment of cardiac and pulmonary function in adult patients with Hodgkin's disease treated with ABVD or MOPP/ABVD plus adjuvant low-dose mediastinal irradiation.

We evaluated the long-term effects of combined modality therapy (CMT) with adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) or mechlorethamine, vincristine, prednisone, procarbazine (MOPP)/ABVD plus adjuvant low-dose (< 30 Gy) involved-field radiation therapy (LDRT) on cardiac and pulmonary functions in adult patients with Hodgkin's disease (HD). Adjuvant LDRT (mean dose, 2340 cGy) to the mediastinum was administered to 24 patients after chemotherapy with MOPP/ABVD (n = 10) and ABVD (n = 14). The mean doses of doxorubicin and bleomycin were 233 mg/m2 and 92 IU/m2, respectively. Cardiac and pulmonary function tests were performed in all patients and, when available, were compared with pretreatment studies. After a median follow-up of 6.3 years, none of the patients had cardiac or pulmonary symptoms. A 4.7% overall decrease in left ventricular ejection fraction (LVEF) was observed (p = 0.03), but only one patient had a mildly decreased LVEF (47%). Diastolic function, LVEF, and left ventricular volume remained within the normal range in the other 23 patients. Mild pulmonary function study abnormalities occurred in 8 of 24 patients, 6 of whom were cigarette smokers. There were no significant changes in total lung capacity and forced vital capacity (FVC) values, but there was a 3% overall decrease in FEV1/FVC ratio (p = 0.05). In adult patients with HD, adjuvant LDRT after chemotherapy with ABVD or MOPP/ABVD did not result in a significant incidence of permanent pulmonary or cardiac toxicity after more than 6.3 years of median follow-up. Further studies are warranted to fully evaluate the impact of such therapy on cardiopulmonary function.

Adolescent↗

PubMed1998

Assessment of pulmonary and cardiac function after high dose chemotherapy with BEAM and peripheral blood progenitor cell transplantation.

BACKGROUND: Limited information is available regarding the cardiac and pulmonary effects of high dose chemotherapy (HDCT) and autologous peripheral blood progenitor cell (PBPC) transplantation. METHODS: The authors evaluated cardiac and pulmonary function after BEAM (BCNU 300 mg/m2, etoposide 400 mg/m2/day x 3 days, cytosine arabinoside 200 mg/m2/day x 4 days, and melphalan 140 mg/m2), HDCT, and PBPC transplantation in 26 patients with non-Hodgkin's lymphoma or Hodgkin's disease. Therapy prior to BEAM included doxorubicin (25 patients), bleomycin (6 patients), and mediastinal irradiation (4 patients). All patients had pulmonary function tests (PFTs) and equilibrium radionuclide angiography before and at a median of 57 weeks after transplantation. RESULTS: Prior to high dose therapy, 8 patients had abnormal PFTs, including 6 with a diffusing capacity of the lung for carbon monoxide (DLCO) <70% of predicted value. At the time of reevaluation after HDCT, all patients included in the study were in complete remission, and none had received additional therapy after transplantation. At a median of 77 weeks after transplantation, none of the patients had cardiac or pulmonary symptoms. Moreover, there were no significant changes in total lung capacity, forced vital capacity, forced expiratory volume in 1 second/forced vital capacity, DLCO, or left ventricular ejection fraction values when compared with baseline studies. CONCLUSIONS: The authors concluded that HDCT with BEAM and PBPC transplantation did not result in significant cardiac or pulmonary toxicity, even in patients with borderline pretransplantation PFT values. Further studies of patients undergoing HDCT and PBPC transplantation are needed.

Adult↗

PubMed1998

Discrete distributions for use in twin studies.

We describe several new discrete distributions motivated by the study of longevity in twins. All individuals both living and dead at a given age are randomly paired. The univariate distribution models the number of these pairs where both individuals are alive. If there is a positive association to longevity in twins, then we would expect to see an excessive number of twin pairs both alive at older ages relative to the number of living individuals. We obtain Poisson and normal approximations to the exact distribution. Multivariate distributions are developed to allow for simultaneous and conditional inference at different ages. Odds-ratio parameter models provide a measure of the association of longevity within twin pairs. These models indicate an excessive number of identical twin pairs both alive after age 60 in a cohort of twins born between 1870 and 1880 in Denmark. Monozygotic twins are contrasted with dizygotic twins to separate the genetic and environmental contributions to the similarity in longevity among twins.

Adult↗

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↗