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J Franklin

Publications and source records attributed to J Franklin.

At least 73 records · Page 4Linked to original sources

Interleukin-2-based immunotherapy for the treatment of metastatic renal cell carcinoma: an analysis of 203 consecutively treated patients.

PURPOSE: This article analyzes the long-term results of 203 consecutive patients with metastatic renal cell carcinoma who were treated with various recombinant interleukin-2 (rIL-2) -based immunotherapy regimens, and describes factors that may influence response to therapy and long-term survival. PATIENTS AND METHODS: The response and survival of 203 patients with metastatic renal cell carcinoma treated consecutively between July 1987 and October 1995 at the UCLA Medical Center Kidney Cancer Program with rIL-2-based immunotherapy were analyzed. Patients were divided into four groups: (1) no prior nephrectomy (n = 24), (2) nephrectomy > 6 months prior to rIL-2 therapy (n = 76), (3) nephrectomy < or = 6 months prior to rIL-2 therapy (n = 47), and (4) nephrectomy followed by treatment with rIL-2 and tumor-infiltrating lymphocytes +/- interferon-alpha (n = 56). Response and survival for each of these patient groups and survival per response to therapy were compared. RESULTS: The overall median survival for all patients was 18 months, and survival at 1, 2, and 3 years after therapy was 61%, 40%, and 31% percent, respectively. A total of 12 patients (6%) achieved a complete response, and all were alive at 3 years. Of 36 patients (18%) who achieved a partial response and 41 patients (20%) with stable disease, 3-year survival was 37% and 50%, respectively. The survival of patients with a partial response or stable disease was significantly better than that of patients who exhibited progressive disease. Patients with nephrectomy > 6 months prior to rIL-2 therapy had a 46% 3-year survival rate, compared with a 9% 3-year survival rate for patients with nephrectomy < or = 6 months prior to rIL-2 therapy and a 4% 3-year survival rate for patients with no nephrectomy. Patients treated with tumor-infiltrating lymphocytes had a 38% 3-year survival rate, which was also significantly better than patients treated with nephrectomy < or = 6 months prior to rIL-2 therapy or with no nephrectomy. CONCLUSION: This analysis demonstrated that rIL-2-based therapy offers a significant survival benefit to patients with advanced metastatic renal cell carcinoma, compared with historical controls. Furthermore, we have shown that nephrectomy > 6 months prior to rIL-2 therapy and nephrectomy followed by treatment with tumor-infiltrating lymphocytes/rIL-2 +/- interferon-alpha was associated with the greatest survival benefit. Tumor response to rIL-2-based therapy and time from nephrectomy to treatment were the most important predictors of survival. Randomized studies in a large group of patients are needed to confirm these observations.

Adult↗

Absence of germline p53 mutations in familial lymphoma.

p53, a tumor suppressor gene, is frequently mutated in sporadic human cancer, and inherited mutations in p53 predispose to the early onset of cancer. p53 mutations occur frequently in sporadic lymphoma, and, in mice deficient for p53, lymphoma is the most common type of malignancy. Families with an increased incidence of lymphoma have been described, suggesting an inherited predisposition to lymphoma in these circumstances. To determine whether the predisposition to lymphoma in these families results from germline mutations in p53, we analysed exons 4-11 of the p53 gene in 35 individuals from 19 lymphoma-prone kindreds. We found no germline p53 mutations in any of the individuals tested. However, p53 expression assessed by immunohistochemistry, which suggests mutation, was observed in 35% of the tumor samples from the familial Hodgkin's disease cases and in 13% of the familial non-Hodgkin's lymphoma cases. These results suggest that p53 mutations do not play a critical role in heritable susceptibility to lymphoma. p53 may act by different, non-mutation related mechanisms in this setting, or be involved in late events in the pathogenesis of these tumors.

Adolescent↗

Lymphocyte predominant Hodgkin's disease--a workshop report. European Task Force on Lymphoma.

Since lymphocyte predominant Hodgkin's disease (LPHD) may comprise more than one entity, diagnostic criteria, clinical features, and treatment strategies are still being controversially discussed. Thus, in December 1994 a multinational project on lymphocyte predominant Hodgkin's disease was initiated by the European Task Force on Lymphoma. This project is aimed at clarifying the clinical and histopathological spectrum of LPHD, as well as its relation to T-cell- rich B-cell lymphoma and classical types of HD. 525 paraffin blocks and clinical data of 478 patients from 16 international centres were submitted. At the Third International Symposium on Hodgkin's Lymphoma in Cologne, 232 of these cases were discussed by an expert panel. The preliminary results are presented here. Most cases of LPHD were reclassified into nodular paragranuloma (NP) and lymphocyte rich classical HD. In both groups, a considerable number of cases with atypical features was observed. Few cases of NHL were found among the cohort. LPHD was generally treated according to common standards for HD. The whole group of LPHD did not have a better prognosis than NS; whereas early stage NP did perform better than early stage NS (data from the German Hodgkin's Lymphoma Study Group). There is however a striking discrepancy between good survival and the frequent relapses observed in NP which needs to be elucidated.

Hodgkin Disease↗

Systematic reviews.

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Databases, Bibliographic↗

The European Organization for Research and Treatment of Cancer breast cancer-specific quality-of-life questionnaire module: first results from a three-country field study.

PURPOSE: To construct a breast cancer-specific quality-of-life questionnaire (QLQ) module to be used in conjunction with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and to test its reliability and validity cross-culturally. PATIENTS AND METHODS: Module construction took place after the EORTC guidelines for module development. The module--the QLQ-BR23--consists of 23 items covering symptoms and side effects related to different treatment modalities, body image, sexuality, and future perspective. This module was tested in 170 Dutch, 168 Spanish, and 158 American cancer patients at two points in time. The timing for the Dutch and Spanish patients was before and during treatment with radiotherapy or chemotherapy. For the American patients, the questionnaire was administered at admission at the breast clinic and 3 months after the first assessment. RESULTS: Multitrait scaling analysis confirmed the hypothesized structure of four of the five scales. Cronbach's alpha coefficients were, in general, lowest in Spain (range; .46 to .94) and highest in the United States (range; .70 to .91). On the basis of known-groups comparisons, selective scales distinguished clearly between patients differing in disease stage, previous surgery, performance status, and treatment modality, according to expectation. Additionally, selective scales detected change over time as a function of changes in performance status and treatment-induced change. CONCLUSION: These results lend support to the clinical and cross-cultural validity of the QLQ-BR23 as a supplementary questionnaire for assessing specific quality-of-life issues relevant to patients with breast cancer.

Adult↗

Alcohol abuse.

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Adolescent↗

A casemix for mental health services: the development of the mental health and substance abuse components of the Australian national diagnosis-related groups.

OBJECTIVE: To describe the development of the mental health and substance abuse sections of the version of the Australian casemix system, Australian national diagnosis-related groups 3 (AN-DRG 3), released in July 1995. METHOD: The guiding principles and data sources used to construct the mental health and substance abuse components of AN-DRG 3 are described by the group who undertook that task. The group used data sets of patients separating from hospitals throughout Australia, and from hospitals in South Australia, to examine the capacity of existing and revised diagnosis-related groups (DRGs) to predict patients' lengths of hospital stay. They also reviewed the lists of conditions allowed as complicating and comorbid conditions within the AN-DRG system. RESULTS: A variety of recommendations were made including: moving organic mental disorder DRGs to a neuroscience area of the AN-DRG; completely reorganising the mental health section of the casemix; creating a number of narrowly defined DRGs covering areas such as schizophrenia, major affective disorders, anxiety disorders and eating disorders, while allowing for a limited number of more heterogenous DRGs and simplifying substance abuse DRGs into groups covering alcohol and other substances, and differentiating intoxication and withdrawal from abuse and dependency. CONCLUSIONS: A casemix dialect based on clinical diagnosis, which describes mental health and substance abuse problems in terms which should be familiar to clinicians, has been developed. Its applications and limitations are briefly discussed.

Australia↗

Infection of human endothelial cells with Epstein-Barr virus.

Interleukin-6 (IL-6) promotes growth and tumorigenicity of Epstein-Barr virus (EBV)-immortalized B cells, and is abnormally elevated in the serum of solid organ transplant recipients who develop EBV-positive posttransplant lymphoproliferative disease (PTLD), but not in control transplant recipients. Endothelial cells derived from PTLD lesions were found to secrete spontaneously high levels of IL-6 in vitro for up to 4 mo. We examined possible mechanisms for sustained IL-6 production by endothelial cells. Here, we show that EBV can infect endothelial cells in vitro. After 3-4 wk incubation with lethally irradiated EBV-positive, but not EBV-negative cell lines, a proportion of human umbilical cord-derived endothelial cells (HUVECs) expressed in situ the EBV-encoded small RNAs (EBER). Southern blot analysis after polymerase chain reaction showed EBV DNA in HUVEC that had been incubated with lethally irradiated EBV-positive cells, but not in the controls. Exposure of HUVECs to lethally irradiated EBV-positive but not EBV-negative cell lines induced IL-6 production that was sustained for up to 120 d of culture. These studies identify endothelial cells as targets for EBV infection and raise the possibility that this infection may be important in the life cycle and pathology of EBV.

Base Sequence↗

The investigation of Epstein-Barr viral sequences in 41 cases of Burkitt's lymphoma from Egypt: epidemiologic correlations.

BACKGROUND: Epstein-Barr virus (EBV) is associated with many human neoplasms, including Burkitt's lymphoma (BL). Endemic BL in central Africa is more often EBV-associated than BL in the United States, where seroconversion for EBV occurs somewhat later than in Africa. Therefore, the EBV association rate in BL may correlate more with the socioeconomic status of the population studied, which influences the age of EBV seroconversion, than with such factors as malaria, which may relate to the overall higher incidence rate in endemic regions. METHODS: Forty-one patients with BL in Egypt, which differs both climatically and racially from central African countries (i.e., Kenya, Uganda) where BL is endemic, were analyzed. All biopsies were evaluated for EBV-encoded RNAs (EBER1) by RNA in situ hybridization, analyzed for p53 protein expression using the monoclonal antibody D07, and immunophenotyped using a panel of monoclonal antibodies that included L26 (CD20), Leu 22 (CD43), and A6 (CD45RO). Twelve cases were evaluable for EBV subtype by polymerase chain reaction with EBV-specific primers. RESULTS: The median age at diagnosis was 9 years (range, 2-22 years). The biopsy site was extranodal in 29 patients and nodal in 12 patients. All 41 cases were documented as B-cell neoplasms. A hybridization signal for EBER1 RNA was identified in greater than 95% of the neoplastic cells in 30 of 41 cases (73%), whereas no signal was observed in 11 cases (27%). Epstein-Barr virus subtype 1 was found in 10 patients, subtype 2 in two patients. Immunostaining for p53 was observed in greater than 5% of the neoplastic cells in 9 of 37 cases (24%). No significant correlation was observed between EBV positivity and sex, biopsy site, or p53 immunostaining. CONCLUSIONS: The prevalence of EBV in BL from Egypt is slightly lower than in BL in endemic regions, but significantly higher than in sporadic BL. Epstein-Barr virus positivity probably reflects the socioeconomic status of the patient population, and age at seroconversion. The prevalence of EBV subtype 1 suggests that immunodeficiency does not play a role in Egyptian Burkitt's lymphoma, in contrast to endemic Burkitt's lymphoma, in which holoendemic malaria is thought to contribute to immunodeficiency, a higher incidence rate, and the observed prevalence of subtype 2.

Adolescent↗

Development and validation of a scale for rating mood states of psychiatric inpatients.

OBJECTIVE: The authors assessed reliability and validity of a scale developed for use with inpatients on a mood disorders unit. The scale is used to rate a patient's mood along a quantitative continuum from -5, depressive stupor, through 0, euthymic, to 5, full mania. The scale lists behaviors that constitute criteria for each rating point. Mixed states and idiosyncratic behavior can also be assessed. METHODS: Assessment of the scale's reliability and validity was based on data for 53 psychiatric inpatients. The scale's reliability was assessed by comparing nurses' ratings. Validity was assessed by comparing nurses' ratings with patients' self-ratings using previously validated self-report instruments as well as a patient self-report version of the scale. RESULTS: Interrater reliability for the instrument was high (r = .84). Estimates of validity obtained using patient self-report measures ranged from .54 to .85. CONCLUSIONS: The psychometric properties of the scale are comparable to and in some cases are superior to those reported for instruments that include more items and that take longer to complete.

Adult↗

DSM-III-R disorders, social factors and management of school attendance problems in the normal population.

Eighty 13-15-year-old children who failed to attend one of four schools for more than 40% of a term, without good reason, were studied. A systematic schedule (C.A.P.A.) was used in interviewing parents and children. Twenty-five had DSM-III-R Disruptive Behaviour Disorders and 15 had Anxiety/Mood Disorders. Truancy was associated with the former and school refusal with the latter but both often occurred without any Disorder. Fourteen children had neither school refusal nor truancy. Compared to controls, poor attenders came from materially disadvantaged homes. School refusal with anxiety disorders rarely received psychiatric treatment. Non-disturbed absentees were not usually dealt with appropriately.

Absenteeism↗

Annual economic costs attributable to cigarette smoking in Texas.

The costs attributable to smoking in Texas continue to rise. The most recent estimates show more than $4 billion in 1990 can be associated with the direct health-care costs from treatments for disease and the indirect costs associated with mortality and morbidity. The breakdown of these estimates for adults 35 years and older shows 61% of the total costs was due to premature death caused by smoking, 29% due to direct health-care costs, and 9% attributable to indirect morbidity costs, which indicate lost wages caused by smoking-related illness. The 1990 smoking-attributable deaths estimated at 24,600 far exceed the accumulated deaths, 9430 in 1991, caused by auto accidents, homicide, AIDS, alcohol, fires, cocaine, crack, heroin, and morphine. The estimates are prepared by The University of Texas M.D. Anderson Cancer Center Office of the Vice President for Health Policy for the Office of Smoking and Health, Bureau of Chronic Disease Prevention and Control, Texas Department of Health.

Adult↗