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Biomedical subjects

B Langholz

Publications and source records attributed to B Langholz.

At least 55 records · Page 3Linked to original sources
PubMed1992

Empirical Bayes methods for testing associations with large numbers of candidate genes in the presence of environmental risk factors, with applications to HLA associations in IDDM.

Standard regression models for disease incidence data can be used to test for associations between a disease and measured genetic and environmental factors and their interactions. Complications arise when the gene is not observed, requiring segregation and linkage analysis approaches, or when the candidate gene(s) are found to be highly polymorphic, as in the HLA region. We propose a Bayesian approach to the latter problem, in which the log relative risks for all alleles at a given locus are taken to be independent and exchangeable, assuming there is no preferential zygotic assortment and negligible recombination. Multi-locus problems can be addressed either by adding exchangeable interaction terms or by adopting a multivariate prior for haplotype effects. Some simulations based on our current work on family studies of IDDM are discussed.

Alleles↗
PubMed1991

Transurethral microwave hyperthermia: an alternative treatment for prostadynia?

A total of 15 patients with severe symptoms of prostadynia who were refractory to therapy were treated with transurethral microwave hyperthermia (TUHT) in a phase I trial. All patients had pain as the predominant symptom, 9 (60%) patients gave a history of psychological problems while frequency, urgency, dysuria, nocturia, and impotence were less common symptoms. Treatment consisted of TUHT at 915 MHz given weekly for 5 weeks with a total of 68 treatment sessions and a mean of 4.5 treatments per patient. Each treatment lasted for 60 minutes. The aim was to increase the temperature measured on the urethral surface to greater than or equal to 44 degrees C. T mean for all sessions was 45.5 degrees C. In 91% of treatments, the temperature was greater than or equal to 44 degrees C. Treatment was well tolerated in 87% patients and acute toxicity was mild. Of the 15 patients treated, 2 (13%) did not complete the treatment course due to discomfort during TUHT. Good treatment response, manifested by complete pain relief and a decrease in dysuria, was noted in 7 (47%) patients. A higher (greater than or equal to 46 degrees C) treatment temperature correlated well with good response, P less than .01. Similarly, relief of pain correlated well with the absence of a history of psychological problems, P less than .01. A decrease of obstructive micturition problems was noted in 5 of the 7 patients who had this upon presentation. This study showed evidence of therapeutic activity with the use of TUHT in patients with prostadynia refractory to therapy. The response obtained was limited to less than one-half of the patients. Complete pain relief was obtained in 4 (27%) patients. It is of interest to note that patients who had major benefit did not show evidence of psychological problems and were able to tolerate higher treatment temperatures. The latter could suggest a temperature-related response.

Adult↗
PubMed1991

Generalization of normal discriminant analysis using Fourier series density estimators. Transfusion Safety Study Group.

In this paper we examine the efficiency of a generalization of the traditional normal linear (LDA) or quadratic (QDA) discriminant analysis. This procedure (the generalized discriminant analysis, GDA) replaces each normal density used in the traditional classification rule by a Fourier series density estimator which 'adjusts' the normal density if the data deviate markedly from normality (for example, heavily skewed or multimodal). We derive the GDA in both the univariate and multivariate situations. In a simulation study for the univariate situation, we evaluate the relative efficiency of the GDA. In addition, we demonstrate the performance of the GDA through a series of multivariate applications. We conclude that if the distributions of the data do not deviate markedly from normality, the GDA is as efficient as the LDA or QDA. On the other hand, if either of the distributions deviates from normality, then the GDA, which performs as a semiparametric discriminant procedure, is more efficient than the LDA or QDA.

Antigens, Differentiation↗
PubMed1991

Treatment results of stereotactic interstitial brachytherapy for primary and metastatic brain tumors.

A total of 41 stereotactic interstitial brain implants in 39 patients were performed for recurrence after teletherapy (recurrence implant), or as part of initial treatment in conjunction with teletherapy (primary implant). Implanted tumors consisted of malignant gliomas (33), other primary brain tumors (3), and single metastatic lesions (3). All patients were temporarily implanted with Ir-192 using a coaxial catheter afterloading system; two patients were implanted twice. Survival post-implant for glioblastoma multiforme (GBM), 13 patients, was 10 months whether implanted primarily or for recurrence. Mean time to recurrence, measured from initiation of teletherapy to implantation, was 10 months. Twenty patients with anaplastic astrocytoma (AA) had a median survival post-implant of 23 months for primary implants (7 patients) and 11 months for recurrence implants (13 patients). Mean time to recurrence, measured from initiation of teletherapy to implantation, was 19 months. Three patients (9%) of the evaluable group required reoperation for symptomatic mass effect, all with initial diagnosis of AA. Survival for this subgroup was 14, 22, and 32 months post-implantation. Using stereotactic techniques, interstitial brachytherapy of brain tumors was technically feasible with negligible acute morbidity and mortality, and appeared to offer limited prolongation of control for a subset of patients with recurrent malignant gliomas. The role of this modality in primary treatment for malignant gliomas needs to be further defined by prospectively randomized trials.

Adolescent↗
PubMed1991

Radiotherapy following radical prostatectomy in patients with adenocarcinoma of the prostate.

From 1973 to 1986, 160 patients with adenocarcinoma localized to the prostate were treated with radical prostatectomy and pelvic lymphadenectomy. In 78 (49%) patients more advanced stage of disease was found at surgery and they received local pelvic irradiation (RT). This consisted of 45 Gy for microscopic and 55 Gy for macroscopic residual disease. RT was given at 1.8 Gy a day, using the four-field "box" technique with the 23 MV X ray beam. Pelvic lymph node metastases were found in 28 (36%) patients who, in addition to RT, received systemic therapy: 20 with cyclophosphamide alone, 4 combined with 5-Fluorouracil, and 4 patients received DES. The 5- and 10-year overall actuarial survival was 95 and 77%, respectively, and the 5- and 10-year disease-free survival was 58 and 43%, respectively. Recurrent tumor was found in 34 (44%) patients. Of these 34 patients, 32 (94%) had distant metastatic tumor and 2 (6%) had local recurrence in the pelvis. The presence of metastatic disease in pelvic lymph nodes had clinical significance since it influenced disease-free survival and the incidence of tumor recurrence. The 10-year disease-free survival for the 50 patients with no lymph node metastases was 51%, as compared to 28% for the 28 patients with such metastases, p = 0.001. Similarly, recurrent tumor was found in 28% of the former and 68% of the latter patients, p = 0.002. Other important parameters predicting recurrence were: clinical stage, p = 0.018, histological grade, p = 0.013, and Gleason's grade, p = 0.002. This treatment program was very well tolerated and of low toxicity. There was no surgical mortality. Surgical complications were seen in 10 (13%) patients including: minor in 5 and major in 5. At 1 year, 77% of the patients remained continent, while 10% had mild stress incontinence. Of the remaining 13% only 3 (4%) patients had severe incontinence (greater than 5 pads daily). RT toxicity was mild with 38% experiencing diarrhea. Severe toxicity was seen in 2 (3%) patients who, early in the study, developed scrotal and lower extremity edema. Severe chemotherapy complications were seen in 1 (4%) patient who had severe neutropenic sepsis. Postoperative radiotherapy is a well tolerated, safe and effective treatment in patients who have microscopic or macroscopic residual tumor following radical prostatectomy.

Adenocarcinoma↗
PubMed1991

Management of carcinoma of the esophagus: the role of radiotherapy.

This is an analysis of treatment results over a 23-year period in 241 patients with carcinoma of the esophagus. The treatment for unresectable patients was external beam radiotherapy (EBRT) alone (mean dose 55 Gy) in 137 (57%) combined with brachytherapy (mean dose 50 + 40 Gy) in 46 (19%), and chemotherapy alone in 3 (1%) patients. In the 55 resectable patients, treatment was resection alone in 9 (4%), and combined with radiotherapy (mean dose 43 Gy) in 46 (19%) patients. The 1-, 2-, and 5-year survival for the 241 patients was 36, 15, and 5%, respectively (median 38 weeks). The 5-year survival was 18% for radiotherapy (RT)-surgery (S) patients, 11% for EBRT with brachytherapy, 2% for EBRT alone, and 0% for patients who had S alone, p less than 0.001. Survival correlated well with initial performance status, treatment, stage of disease, tumor size, radiation dose, and degree of response, p less than 0.001, but not with tumor location in the esophagus and patients' race and sex, p = 0.44. Serious complications occurred in 5 (2%) patients treated with RT alone and in 4 (7%) patients treated with S alone or combined with RT. The leading cause of death was persistent or recurrent tumor in the chest found in 39% patients.

Adult↗
PubMed1991

Regional hyperthermia in patients with recurrent genitourinary cancer.

During a 6-year period, 53 patients with advanced tumors of the genitourinary tract were treated in Phase I protocols with deep regional hyperthermia in combination with irradiation (83%) or in combination with chemotherapy (11%). Primary tumors included those of bladder in 22 patients (41%), prostate in 20 patients (37%), kidney in 9 patients (17%), and ureter testicle or adrenal in 3 patients (5%). The majority (77%) had prior definitive therapy and had experienced treatment failure, and 11% had clinically important distant metastases. Treatment consisted of deep regional hyperthermia (mean of 4 sessions). In addition, 44 patients (83%) received irradiation (mean dose 39.2 Gy). The 1- and 3-year actuarial survival was 60% and 56%, respectively. Patients with carcinoma of the prostate had a 1- and 3-year survival of 82%. Complete response was observed in 7 patients (13%), partial response in 8 (15%), and nominal response in 13 (25%). Complete and partial response correlated well with histology of the tumor (adenocarcinoma), radiation dose (greater than 50 Gy), primary site (prostate, kidney), and treatment (hyperthermia-radiotherapy combination), (p = 0.02). There was no such correlation between response and thermal dose (p = 0.13). The treatment tolerance was good in 79% of patients. Treatment toxicity was limited to acute side effects, including pain during hyperthermia (47%), tachycardia greater than 140/min (7%), and blister formation in the treated area (4%). Phase II studies in previously untreated patients with locally advanced tumors of bladder, prostate, and kidney are needed for evaluation of the role of deep regional hyperthermia in the management of these cancers.

Actuarial Analysis↗
PubMed1991

Efficiency of cohort sampling designs: some surprising results.

Cohort sampling designs are proposed which one would intuitively expect to be more efficient than nested case-control sampling. Two of these designs start with a nested case-control sample and distribute controls to sampled risk sets other than those for which they were picked. The third design has the goal of maximizing the number of distinct persons in a nested case-control sample. Simulation results show surprisingly little gain, and more often a loss in efficiency of these new designs relative to nested case-control sampling. This is due to the sampling-induced covariance between score terms. We conclude that the often stated intuition that nested case-control sampling does not make good use of sampled individuals' covariate histories is false.

Analysis of Variance↗
PubMed1990

Treatment of uterine sarcomas.

During a 21-year period, 66 patients with uterine sarcomas were treated at California Medical Center. Histological diagnoses were mixed mesodermal sarcoma in 32 patients (48%), leiomyosarcoma in 24 (36%), and endometrial stromal sarcoma in 10 (15%) patients. The majority of patients (73%) had Stage I tumors. The treatment consisted of surgery alone in 27 (41%), surgery in combination with radiation therapy in 36 (55%), and radiation therapy alone in three (4%) patients. The overall 1-, 2-, and 5-year actuarial survival was 74%, 57%, and 38%, respectively. The 1-, 2-, and 5-year actuarial survival for the 27 surgery alone patients was 73%, 50%, and 25%, which compared with 75%, 61%, and 44% for the 36 surgery plus radiation therapy patients (P = 0.12). The disease-free survival was better for the surgery plus radiation therapy patients, as compared with the surgery alone group (38% vs. 18% at 5 years, P = 0.081). The 5-year survival by histology was 70% for the 10 endometrial stromal sarcoma patients, 40% for the 24 leiomyosarcoma patients, and 23% for the 32 mesodermal sarcoma patients (P = 0.064). As expected, survival depended on the stage of disease (P less than 0.0001). Treatment failure was observed in 35 (53%) patients, which included 9 (14%) with failure in the pelvis. There was no difference in the incidence of failure among patients in the three treatment groups and also in the three histologic groups. There was, however, a significant difference in the incidence of pelvic failure between surgery alone and surgery plus radiation therapy patients. In the 27 surgery alone patients, nine (33%) relapsed in the pelvis, whereas none of the 36 surgery plus radiation therapy patients had locoregional failure, P less than 0.0001. Adjuvant radiation therapy is an important treatment in the management of patients with sarcoma of the uterus.

Adult↗
PubMed1990

Bivariate survival models for analysis of genetic and environmental effects in twins.

Classic methods in genetics for the analysis of binary attributes, based on an assumption of a "threshold" on a normally distributed latent variable called "liability," estimate the strength of genetic and environmental effects from differences in correlations between relatives of differing genetic relatedness. Two problems that are not easily addressed by these methods are the need to take the age of onset into account (particularly in chronic diseases in which incidence rates vary considerably with age and the lengths of time at risk can vary between individuals) and the desirability of incorporating measured covariates (genetic or environmental). The standard methods of cohort analysis used in epidemiology allow for both of these features, but until recently have been restricted to independent individuals. Recent developments in survival analysis have extended the widely used "proportional hazards" model of Cox by the addition of latent variable, epsilon, reflecting the shared susceptibility of related subjects because of their shared genes or shared environment. We show how this approach can be combined with more traditional models of gene-environment interaction to allow the main effects of measured genetic markers and environmental variables to be estimated, as well as the residual variance of genetic and environment and their interactions. The approaches are applied to a cohort of female twin births in Sweden from 1886 to 1958, linked with the Swedish cancer registry from 1961 to 1982.

Adult↗
PubMed1990

Nested case-control and case-cohort methods of sampling from a cohort: a critical comparison.

The recently developed case-cohort method of sampling from a cohort is compared with the nested case-control method. Corrected asymptotic relative efficiency results show that the case-cohort design for single "disease" outcomes offers less improvement for intervention trials for which there is no random censoring than originally suggested. Furthermore, simulation results indicate that if there is moderate random censoring or staggered entry, the case-cohort method can do substantially worse than the nested case-control method.

Case-Control Studies↗
PubMed1990

Episcleral radioactive plaque therapy: initial clinical experience with 56 patients.

Between 1983 and 1987, 56 patients with choroidal melanoma were treated at the University of Southern California with episcleral plaque (RPT). There were 29 female and 27 male patients, with a mean age of 59 years. Tumor stage at diagnosis was T2 in 18 (32%) and T3 in 38 (68%) patients. The tumor height ranged from 2.9 to 15 mm (mean 6.8 mm). Radial dimensions ranged from 5 to 25 mm (mean 13.2 mm), and circumference ranged from 7 to 23 mm (mean 12.3 mm). Most (77%) patients had posteriorly located tumors, including 18% that were juxtapapillary. Custom-designed gold plaques were utilized in this study. Radioactive isotopes used were 125I for 26 procedures or 192Ir for 31 procedures. A total of 56 patients were treated, with one patient having two procedures. Radiation doses at the tumor apex ranged from 29.8 to 165.4 Gy (mean 94.5 Gy), with the dose at 5-mm depth ranging from 70.5 to 430 Gy (mean 161.5 Gy). Follow-up ranged from 29 to 57 months (mean 39 months). The overall 4-year survival was 96%, with a 91% incidence of free-of-disease progression at 4 years. The majority (84%) of patients experienced a decrease in tumor height, with 27 (48%) patients having greater than 50% decrease. Increase in tumor height was noted in 5 (9%) and no change in 4 (7%) patients. Useful vision (greater than 5/200) was observed in 59% of patients, including 21% who had improved vision. Metastatic tumor occurred in 5 (9%) patients, with a mean time to metastases of 14 months. There was a good correlation between radial tumor dimension and metastatic disease, p less than 0.001. Treatment complications were observed in 34 (61%) patients, with cataract and retinopathy being the most common. Enucleation was performed in 11 (20%) patients, with a mean time to enucleation of 14.5 months. Causative factors for enucleation were treatment complications in 6 and tumor progression in 5 patients. Enucleations were required primarily in patients with tumors greater than 8 mm in height (p = 0.009). Improved RPT techniques with three-dimensional dosimetry are needed to reduce the overall incidence of treatment complications. Adjuvant hyperthermia is being investigated in an attempt to improve tumor control in patients with larger tumors.

Adult↗
PubMed1990

Survival models for familial aggregation of cancer.

It has recently been shown that the relative risks of the order of 2 to 4 that are frequently found for cancer among relatives of affected cases are unlikely to be explainable by shared environmental risk factors. Classical methods of epidemiological analysis are not well suited to such analysis because they assume that the outcomes of each individual are independent. Classical methods of genetic analysis, on the other hand, are limited in their handling of environmental factors and variable ages of onset. The recent development of random effects models for survival analysis, however, appears to bridge this gap. Specifically, a proportional hazards model is postulated for the effects of measured covariates and of one or more components of frailty that are unmeasured but assumed to have some common distribution and known covariance structure within each family. From these assumptions, the posterior expectation of the hazard for each individual can be derived, given the covariate value and the observed and expected disease history of the family. These are then treated as known in a standard partial likelihood analysis; this is essentially a form of expectation-maximization algorithm. However, this does not provide a valid estimate of the covariance matrix because it fails to take account of the variability in the estimates of the frailties; an alternative approach using the imputation-posterior algorithm is suggested. This paper describes extensions of this approach to multivariate frailty distributions, modifications for application to pedigree and case-control studies, some simulation results, and applications to studies of breast cancer in twins and of lung cancer in relation to family smoking habits.

Adenocarcinoma↗
PubMed1989

Regional hyperthermia for advanced tumors: a clinical study of 353 patients.

A Phase I study using deep regional hyperthermia (HT) with an annular phased array was conducted in 14 U.S. medical centers from 1980 through 1986. There were 353 patients whose average age was 57 years. All patients had advanced recurrent or persistent tumors. Prior frequently complex, multimodality anti-cancer therapy was received by 71% of the patients. Gastrointestinal adenocarcinoma was present in 146 (41%) patients, genitourinary tumors in 86 (24%), soft tissue sarcomas in 46 (13%), malignant melanoma in 21 (6%) and 15% had other tumors. The sites treated included: pelvis 55%, abdomen 21%, liver 14%, thorax 6%, and other sites 3%. All patients received deep regional HT with an average frequency of 55 MHz. A total of 1412 HT treatments was administered to these 353 patients with an aim to increase the temperature in the volume of interest to greater than 42 degrees C for greater than or equal to 30 minutes. Thermal dose (TD in equivalent minutes at 42.5 degrees C) was less than 50 in 104 (29%), greater than or equal to 50 less than 100 in 30 (11%), greater than or equal to 100 in 26 (7%), and greater than 200 in 34 (10%). The remaining 150 (42%) patients had TD = 0. In addition to HT, 260 (74%) received radiotherapy (RT). RT was given at 180 or 200 cGy daily with an average total dose of 33.4 Gy. A total of 42 (12%) patients were given chemotherapy (CT) with HT, and 15 (4%) CT + HT + RT/HT alone was given to 47 (13%) patients. Complete response (CR) was obtained in 35 (10%) and partial response (PR) in 59 (17%) patients. CR was 12% in patients who received RT, vs 2% in those who did not receive it, p = 0.003. Radiation dose was an important factor influencing response, p less than 0.001. Thermal dose was not an important parameter influencing tumor response. A duration of CR ranged from 4 to 73 weeks with an average duration of 31 weeks and the median duration of 28 weeks. The overall 2-year survival was 13% with the median survival of 42 weeks. Patients with CR and PR had a 2 year survival of 41%, and a median survival of 71 weeks. This compared with 8% 2-year survival and 24 weeks median survival in patients who did not have CR or PR, p less than 0.001. Of the patients presenting with significant pain, 62% had complete or partial pain relief.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1989

Interstitial microwave hyperthermia combined with iridium-192 radiotherapy for recurrent tumors.

From 1985 through 1987, 44 tumors in 39 patients with recurrent cancer were treated with interstitial microwave hyperthermia (HT) combined with interstitial 192Ir radiotherapy (RT). All patients had unresectable and previously treated tumors (mean RT dose 57.6 Gy). Diagnoses were squamous cell carcinoma in 27 (62%), adenocarcinoma in 11 (25%), melanoma in 5 (11%), and soft tissue sarcoma in 1 (2%) site. Interstitial RT dose was from 25 to 50 Gy (mean 38.3 Gy). The first HT session was scheduled immediately before the loading of 192Ir, and the second was scheduled following its removal. Each session lasted 45-60 min at therapeutic temperature (42.5 degrees C). Complete response (CR) was obtained in 28 (64%) sites and partial response (PR) in 15 (34%) sites. None of the CR patients had local recurrence. Tumor volume was the most important factor influencing CR (p less than 0.001). The treated site, radiation dose, and thermal dose were not significant factors for CR (p = 0.03). The overall median survival was 39 weeks, with a 2-year survival of 22%. The treatment was well tolerated, with two patients developing focal skin necrosis.

Actuarial Analysis↗
PubMed1989

Deep regional hyperthermia of the liver. A clinical study of 49 patients.

From 1981 to 1986, six medical centers participated in feasibility studies of radiofrequency deep regional hyperthermia (HT) in the treatment of hepatic metastases. A total of 49 patients, 32 men and 17 women, were treated with an annular phased array. Colon was the primary site in 74% of the patients, and adenocarcinoma was the diagnosis in 80%. More than one half of the patients had been treated previously. This included chemotherapy (CT) in 17 patients and radiotherapy (RT) in 10 patients, with a mean RT dose of 24 Gy. Upper abdominal pain was the dominant presenting symptom in 53% of patients. In the study, treatment was administered as follows: 14 (28%) patients received HT alone, 17 (35%) received HT + RT, 14 (28%) received HT + CT, and 4 (8%) received HT + RT + CT. A total of 157 HT treatments was administered at a mean frequency of 55 MHz and a mean power of 780 watts. The number of HT sessions ranged from 1 to 8, with a mean of 3.2 treatments per patient. Temperature was monitored continuously throughout each treatment session. The treatment aim was to reach and maintain a temperature of 42.5 degrees C for 30 min. In practice, owing to the difficulty in reaching this temperature, an equivalent (lower) temperature from 40 to 42 degrees C was used, extending the duration of treatment sessions to 45-60 min. Thermal dose was defined as the number of minutes at 42.5 degrees C or its equivalent. In 21 (43%) patients, a temperature less than 40 degrees C was obtained and thermal dose = 0. Thermal dose was less than or equal to 50 in 17 (35%) patients, greater than 50 less than or equal to 100 in 7 (14%), and greater than 100 in 4 (8%). RT was given at a daily dose of 1.8 Gy to a total of less than 20 Gy in 14 patients, greater than 20 less than or equal to 30 Gy in 6, and greater than 30 Gy in 1. CT consisted of 5-Fluorouracil by way of Hepatic Artery Infusion (HAI) in 9 patients, i.v. cisplatin in 5, and doxorubicin HAI in 3. Objective tumor regression (CR + PR) was seen in 6 (12%) patients. An additional 10 (20%) patients had less than 50% greater than 25% tumor regression, and 10 (20%) had complete or partial pain relief. The median duration of CR and PR was 26 weeks.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗