Enhanced in vivo cytotoxicity of recombinant human tumor necrosis factor with etoposide in human renal cell carcinoma

Summary The combination of tumor necrosis factor (TNF) and etoposide (ETP) was evaluated for potential cytotoxic efficacy against a human renal cell carcinoma xenograft using an in vivo assay employing an athymic mouse host with tumor implanted a the subrenal capsule site. Both antitumor efficacy (relative survival or RTS) and toxicity (weight loss) of TNF and ETP alone and in combination were evaluated. While TNF and ETP alone were mildly inhibitory (RTS 90% and 71%, respectively), the combination caused marked tumor inhibition (45% of controls). Host toxicity encountered with the combination did not exceed the toxicity associated with ETP alone, suggesting that the therapeutic index may have been augmented. It is concluded that enhanced antitumor activity without substantial augmentation of toxicity is observed with this combination, providing a rationale for further evaluation of tumor necrosis factor-based regimens for the treatment of advanced renal carcinoma.Supported by a Merit Review grant, VA Medical Research Service, Durham, NC 27710, USA     

Physical and Sexual Abuse and their Relation to Psychiatric Disorder and Suicidal Behavior among Adolescents who are Psychiatrically Hospitalized

Adolescents who were psychiatrically hospitalized ( N = 105) were classified as sexually abused, physically abused, both sexually and physically abused, or not abused, and studied to determine the prevalence of suicidal behavior and psychiatric disorders. Self-reports of hopelessness, depression, coping, and self-concept were also examined. No difference in suicidal behavior or psychiatric disorder, based on abuse history, was found, with one exception. Adolescents who were sexually abused, particularly those who experienced the most severe sexual abuse, used negative coping strategies more often than those not sexually abused. Findings suggest that symptomatology of adolescents who are psychiatrically hospitalized does not differ markedly based on history of abuse.     

Quantitative thallium-201 scintigraphy after dipyridamole infusion combined with low level exercise in healthy volunteers

To establish test specific normal limits for quantitative analysis of uptake and washout of ²⁰¹Tl after dipyridamole infusion combined with low level exercise, 20 healthy volunteers were studied with low likelihood of coronary artery disease (CAD) assessed by a stepwise probability analysis based on age, sex, symptoms, resting electrocardiogram, and exercise electrocardiography. Likelihood of CAD in these volunteers was calculated as 1%. After dipyridamole infusion combined with low level exercise, one volunteer complained of headache; no other side effects were observed. There were no chest pain complaints. Maximal hemodynamic changes were achieved during the 6th and 7th min of the test. No ST segment depression was recorded. Visual analysis of the ²⁰¹Tl scintigrams was normal in all volunteers. Mean regional washout at 4 h was 44.37%±2.11%. The regional washout in the 70° LAO view (46.65%±1.10%) was significantly higher than in the anterior and 30° LAO views (43.44%±1.50% and 43.02%±1.45%, respectively). Profiles of uptake and washout of ²⁰¹Tl were different after dipyridamole infusion combined with low level exercise as compared to maximal exercise. Thus, in quantitative analysis of ²⁰¹Tl scintigraphy after dipyridamole infusion in conjunction with low level exercise as applied in the present study, it is mandatory to use normal limits of uptake and washout of ²⁰¹Tl derived from healthy volunteers who underwent the same combined protocol.     

Treatment results among adults with childhood tumors: a 20-year experience

Controversy exists regarding the most appropriate treatment for the rare adult patient who develops a so-called pediatric cancer. We have reviewed our 20-year experience with these patients and analyzed their outcome. A total of 299 patients with rhabdomyosarcoma (106), Wilms' tumor (97), and neuroblastoma (96) were evaluated and treated at Stanford University Medical Center between January 1967 and December 1987. Only 26 of these patients (8.7%) were diagnosed during "adulthood"; their age range was 18-67 years, median 23 years. Wilms' tumor; Five patients presented with Wilms' tumor at age greater than or equal to 18 years; four had unfavorable histology. All underwent multimodality therapy; however, only two have survived, one currently disease-free and one with disease. Neuroblastoma: Five patients presented with neuroblastoma at age greater than or equal to 18 years. Four underwent attempted surgical resection, post-operative irradiation (RT), and chemotherapy (CT); the other received no adjuvant CT. Only two of the five patients survive, both with disease. Rhabdomyosarcoma: Of the 16 adults (greater than or equal to 21 years) with rhabdomyosarcoma, 14 (87%) had advanced Intergroup Rhabdomyosarcoma Study-group disease (eight Group III, six Group IV). All 16 underwent aggressive multimodality therapy. At 10 months-16 years follow-up, only five patients survive, four of whom are apparently cured of their tumor. Neither histologic subtype nor site of presentation were of prognostic value. This series demonstrates that adults with Wilms' tumor, neuroblastoma, or rhabdomyosarcoma have a worse prognosis than do children with the same diagnosis. Possible explanations for this disparity in outcome include different tumor biology, less tolerance for treatment, and different natural history among adults relative to children.     

The CC chemokine receptor 5 delta32 mutation is not associated with inflammatory bowel disease (IBD) in NE England

Inflammatory bowel disease (IBD) is a group of chronic inflammatory diseases of the gastrointestinal tract of unknown aetiology. Evidence of abnormalities in immune regulation and cytokine production in patients with IBD has led to investigations of various immuno-regulatory genes as potential candidate susceptibility loci. Studies using whole genome scanning have highlighted chromosomes 3, 7, 12 and 16. A 32 base-pair deletion in the CC-chemokine receptor-5 gene (CCR5-A32, chromosome 3p21.3) has been associated with susceptibility to IBD. We have investigated CCR5 as a candidate susceptibility gene in 350 patients (251 with ulcerative colitis and 99 with Crohn's disease) and 103 controls using polymerase chain reaction. There were no significant differences in the distribution of CCR5 genotypes or frequencies comparing patients and controls, or associations with extent of colitis. In contrast to preliminary data, these findings suggest no evidence for involvement of this mutation in susceptibility/resistance or disease progression in IBD.     

Prevalence of hearing loss among people aged 65 years and over: screening and hearing aid provision.

The aim of this study was to assess the prevalence of hearing loss among people aged 65 years and over and to offer hearing aids where necessary. The study was carried out in a large health centre practice in Birmingham with a computerized record system. All patients aged 65 years, and a 20% random sample of patients aged 66 years and over were invited for interview. They were questioned about hearing loss and examined audiometrically. All patients with a hearing loss in the better ear of 35 decibels or more over the speech frequencies (0.5-4 kHz) were offered a hearing aid. A total of 322 patients attended (72% of those invited) and of these 34 patients already had a hearing aid. A further 142 patients were identified for whom an aid was recommended and 69 of these accepted. The acceptance rate was higher among men than women (57% compared with 43%). Sixty one patients (19% of those screened) had an asymmetrical hearing loss and of these 24 required consultant assessment; none had serious underlying pathology. There is a large unmet need for hearing aid provision. Simple audiometric assessment in health centres provides an opportunity to meet this need.