Growth hormone treatment attenuates age-related changes in hippocampal short-term plasticity and spatial learning.

Downregulation of the growth hormone/insulin-like growth factor-1 (IGF-1)axis is one of the most robust biomarkers of mammalian aging. Reports have suggested that age-related changes in secretion of growth hormone and IGF-1 contribute to the development of some peripheral characteristics of the aged phenotype including decreased bone density and lean body mass. Recent work has focused on the identification of a role for age-related reductions in growth hormone and IGF-1 in the development of cognitive impairments associated with aging. In the current study, we report that aged (30 month-old) Brown Norway x Fisher rats demonstrate impairments in spatial learning compared with adult (10 month-old) animals, and that 4-month treatment with growth hormone (300 microg twice daily) attenuates age-related learning impairments. After 6 months of treatment, we employed an extracellular paired-pulse protocol to investigate age-related changes in hippocampal short-term plasticity, and found that aged rats exhibit significantly increased paired-pulse ratios (PPRs) at an interpulse interval of 50 ms compared with adult rats. Long-term growth hormone administration restored PPRs in aged animals to values comparable to those observed in adult controls. Since the age-related changes observed in PPR may result from decreases in hippocampal inhibitory tone mediated by GABA(A) receptors, we assessed GABA(A) receptor subunit expression by immunoblot analysis. Data revealed significant age-related decreases in GABA(A) receptor alpha-1 subunit expression which were attenuated by growth hormone treatment. However, hippocampal levels of the gamma2 subunit, glutamic acid decarboxylase (GAD)(65), and GAD(67) protein concentrations were not significantly affected by age or growth hormone treatment. In conclusion, we suggest that age-related decreases in growth hormone and IGF-1 contribute to cognitive decline, in part, via alterations in hippocampal short-term plasticity. Changes in plasticity may reflect a shift in the balance of hippocampal inhibitory and excitatory function.

Evaluating the financial impact of clinical trials in oncology: results from a pilot study from the Association of American Cancer Institutes/Northwestern University clinical trials costs and charges project.

PURPOSE: Medical care for clinical trials is often not reimbursed by insurers, primarily because of concern that medical care as part of clinical trials is expensive and not part of standard medical practice. In June 2000, President Clinton ordered Medicare to reimburse for medical care expenses incurred as part of cancer clinical trials, although many private insurers are concerned about the expense of this effort. To inform this policy debate, the costs and charges of care for patients on clinical trials are being evaluated. In this Association of American Cancer Institutes (AACI) Clinical Trials Costs and Charges pilot study, we describe the results and operational considerations of one of the first completed multisite economic analyses of clinical trials. METHODS: Our pilot effort included assessment of total direct medical charges for 6 months of care for 35 case patients who received care on phase II clinical trials and for 35 matched controls (based on age, sex, disease, stage, and treatment period) at five AACI member cancer centers. Charge data were obtained for hospital and ancillary services from automated claims files at individual study institutions. The analyses were based on the perspective of a third-party payer. RESULTS: The mean age of the phase II clinical trial patients was 58.3 years versus 57.3 years for control patients. The study population included persons with cancer of the breast (n = 24), lung (n = 18), colon (n = 16), prostate (n = 4), and lymphoma (n = 8). The ratio of male-to-female patients was 3:4, with greater than 75% of patients having stage III to IV disease. Total mean charges for treatment from the time of study enrollment through 6 months were similar: $57,542 for clinical trial patients and $63,721 for control patients (1998 US$; P =.4) CONCLUSION: Multisite economic analyses of oncology clinical trials are in progress. Strategies that are not likely to overburden data managers and clinicians are possible to devise. However, these studies require careful planning and coordination among cancer center directors, finance department personnel, economists, and health services researchers.

"Naturalization" of the alien hand: case report.

The alien hand syndrome is an involuntary motor phenomenon that occurs infrequently and mostly in stroke patients. A case is reported of a 67-year-old man with left hemiparesis whose hand crept and crawled, especially at night, which caused him to awaken by grasping his collar. The disturbing nocturnal activity of the hand was stilled by placing it in a common oven mitt.

Burkitt cell acute lymphoblastic leukemia with partial expression of T-cell markers and subclonal chromosome abnormalities in a man with acquired immunodeficiency syndrome.

A 45-year-old white male, bisexual, with a 2-year history of acquired immunodeficiency syndrome (AIDS) prodrome, developed a Burkitt cell-like acute lymphoblastic leukemia (ALL). Marker studies of marrow blasts show an unusual and possibly unique pattern, in that an unequivocal monoclonal B cell leukemia, having K-IgM with HLA-DR and B cell subset antigen (BA-1) expression, was superimposed with a mature suppressor T cell marker profile (pan-T, mature T, and suppressor/cytotoxic T antigens). The leukemic blasts were totally negative for terminal deoxynucleotidyl transferase (TdT), human T cell leukemia-lymphoma virus (HTLV) p19 antigen, and other immunoglobulin isotypes. Chromosome analysis of marrow cells disclosed that 70% of the cells had 47,XY, + 12,t(8;14)(q24;q32) chromosome complement, and 30% of the cells had a 47,XY, + 12,dup1q + (q22-31),t(8;14)(q24;q32). The consistent finding of the specific chromosome rearrangement (8/14 translocation) in all abnormal cells suggests that the cells were derived from a common precursor. With regard to the partial T cell marker expression, the significance of these markers in B cell leukemia is unclear, as is their relation to the additional chromosome abnormalities that apparently developed in the process of clonal evolution.

An attempt to influence attitudes towards textured soya protein as an alternative to meat.

The effect of person-to-person discussions, demonstrations and advertising on the attitude of mothers of young families towards textured soya-bean protein products as an alternative to meat has been studied. The results show that person-to-person interviews can influence the attitudes towards textured vegetable protein although some individuals remain resistant to this approach.