5-HT3 Receptor-independent Inhibition of the Depolarization-induced 86Rb Efflux from Human Neuroblastoma Cells,TE671, by Ondansetron

The 5-HT₃-receptor antagonist, ondansetron, has been shown to have positive effects in selected in-vivo models of memory impairment and anxiety. The exact mechanisms underlying such bioactivities are unknown. In the present work, an ⁸⁶Rb efflux bioassay was used to show that ondansetron has a unique ability to block voltage-gated potassium channels in TE671 human neuroblastoma cells. This intrinsic potassium-channel-blocking (KCB) property is relatively weak (IC50 20 (M), but is not shared by other 5-HT₃-receptor ligands including zatosetron, MDL 72222, LY 278, 584, zacopride, 1-phenylbiguanide, and ICS 205–930 (tropisetron). Pre-incubation of the target neuroblastoma cells with several 5-HT-receptor ligands including 5-hydroxytryptamine, 8-OH-DPAT, ketanserin, 2-methyl-5-HT, as well as a number of potent 5-HT₃ agonists and antagonists and two selective neurotoxins, failed to abolish the KCB action of ondansetron. A preliminary structure-activity relationship analysis indicates that the KCB activity of ondansetron is almost entirely attributable to its structural nucleus, 2,3-dihyro-9-methyl-4(lH)-carbazolone. It is hypothesized that the KCB action of ondansetron is mediated through receptors other than 5-HT₃ receptors. The KCB activity of ondansetron may be a significant factor in the in-vivo cognition-enhancing activities of this compound, conceivably due to depolarization of the hippocampal synaptic membranes and a consequent augmentation of neurotransmission.     

Prevalence of mental illness and its impact on the use of home care and nursing homes: a population-based study of older adults in Manitoba.

OBJECTIVES: To determine the prevalence of mental illness in older adults and its effect on home care and personal care home (PCH) use. METHODS: Using nonidentifying administrative records (fiscal years 1997-1998 to 2001-2002) from the Population Health Research Data Repository housed at the Manitoba Centre for Health Policy, we determined the 5-year period prevalence for individuals aged 55 years and over (119 539 men and 145 752 women) for 3 mental illness categories: cumulative mental disorders (those having a diagnosis of depression, anxiety disorder, personality disorder, schizophrenia, and [or] substance abuse), any mental illness, and dementia. We calculated age-specific and age-adjusted rates of home care and PCH use and the prevalence of mental illness in PCH residents. RESULTS: From the group aged 55 to 59 years to the group aged 90 years or older, the prevalence of mental illness increased with the population's age. The prevalence of any mental illness rose from 32.4% to 45.0% in men and from 42.6% to 51.9% in women, and dementia prevalence rose from 2.0% to 33.6% in men and from 1.3% to 40.3% in women. The age-adjusted annual rates of open home care cases per 1000 population aged 55 and older varied by mental illness grouping (no mental disorder, 57 for men and 91 for women; cumulative mental disorders, 162 for men and 191 for women; dementia, 300 for men and 338 for women). The age-adjusted rates of PCH use per 1000 population aged 75 years and older also varied by mental illness grouping (no mental disorder, 53 for men and 78 for women; cumulative mental disorders, 305 for men and 373 for women; dementia, 542 for men and 669 for women). Among patients admitted to (or resident in) a PCH in 2002-2003, 74.6% (87.1%) had a mental illness, and 46.0% (69.0%) had dementia. CONCLUSIONS: Mental illness affects the use of home care and nursing homes profoundly. Individuals with dementia used home care at 3 times the rate of those having no mental illness diagnosis, and they used PCHs at 8 times the rate.     

Sympathetic skin response in scleroderma.

Examination of the sympathetic skin response (SSR) was performed in 32 patients with systemic sclerosis, morphea and mixed connective tissue disease displaying scleroderma-like features. The control group consisted of 26 healthy subjects and 12 patients with other skin diseases and asymmetrical cutaneous changes. Right and left median and tibial nerves were stimulated successively and the responses were recorded from the palms and soles simultaneously. SSR abnormalities (delayed latency, decrease and/or asymmetry of amplitude, absent response) were observed in 68.8% of the patients, most frequently in linear scleroderma. An amplitude asymmetry of the responses from upper extremities was the most characteristic pattern of abnormalities. There was no correlation between the SSR and the localization, degree and character (inclurated oedema, atrophy, sclerosis) of skin changes, the duration of the disease, symptoms of the disorder of the autonomic nervous system symptoms (vasomotor and/or sudomotor) and the changes in capillaroscopy. All patients with slow motor conduction and sensor conduction velocities (MCV and SCV) had lower SSR amplitude and the patients with prolonged skin sensory chronaxy had more often delayed latency. The results revealed presence of disturbances of the autonomic nervous system in all varieties of scleroderma, both systemic and localized forms, even without any other signs of autonomic dysfunction.     

Clinical trial of a prevention and treatment protocol for skin breakdown in two nursing homes.

OBJECTIVE: Our objective was to assess the effectiveness of skin care protocols, including a body wash and skin protectant, on skin breakdown in 2 nursing homes. DESIGN: This was a quasi-experimental pretest/posttest design study.Setting and subjects Adult residents (n = 136) of 2 skilled nursing homes consented to participate in this study. Seventy percent were women; the sample average age of 82 years. INSTRUMENTS: A researcher-designed data recording form documented resident demographics, incidence and type of skin breakdown or pressure ulcer, presence of urinary or fecal incontinence, and assessment of the effectiveness of body wash and skin protectant. METHODS: Baseline data on prevalence of pressure ulcers and skin protocol were collected weekly for a 3-month period followed by a week-long educational program by the researchers about skin care and the body wash and skin protectant. During the 3-month trial with the body wash and skin protectant incorporated into routine care, research assistants recorded resident data weekly and researchers again assessed prevalence and incidence of pressure ulcers and skin breakdown weekly. RESULTS: Incorporation of a body wash and skin protectant into a skin care prevention and early intervention protocol in 2 nursing homes documented a decrease in skin breakdowns from 68 pre-intervention to 40 postintervention; the decrease in agency B was statistically significant. There was a statistically significant decrease in stage I and II pressure ulcer incidence overall (pre-intervention = 19.9%, postintervention = 8.1%). Nurses evaluated the body wash and skin protectant as effective for 98% of the time used. CONCLUSION: Implementation of a protocol for skin care along with staff education, including the prophylactic use of a body wash and skin protectant, reduced the incidence of skin breakdown, including pressure ulcers and perineal dermatitis, in 2 long-term care facilities.     

Congenitally corrected transposition of the great arteries and aortic coarctation--an uncommon association.

Congenitally corrected transposition of the great arteries, L-TGA, is a rare abnormality accounting for less than 0.5% of clinically apparent congenital heart disease. Age at time of diagnosis and survival rate are variable and depend mostly on associated anomalies. The authors present a clinical case of a twenty-four-year-old woman in whom, in a routine echocardiogram, congenitally corrected transposition of the great arteries and aortic coarctation were diagnosed, an unusual association. They describe the results of complementary exams (echocardiography, chest X-ray, electrocardiogram and cardiac angiography) that they believe to be useful for the correct diagnosis of this clinical situation. Additionally, the authors make a brief review of the literature relevant to the case.     

Paired Epstein-Barr virus (EBV)-negative and EBV-converted Burkitt lymphoma lines: stimulatory capacity in allogeneic mixed lymphocyte cultures

Epstein-Barr virus (EBV)-negative Burkitt lymphoma lines (BLE-) and their in vitro EBV-converted sublines (BLEc), obtained by infection with the P3HRI and B95-8 strains of EBV, were compared for their capacity to induce T-lymphocyte proliferation in allogeneic mixed lymphocyte cultures (MLC). Regardless of the virus strain used for conversion, the BLEc lines induced a considerably stronger primary MLC response than their EBV-negative parentals. Only the BLEc lines were able to maintain T-lymphocyte proliferation in repeated stimulations. The low proliferative response observed in cultures stimulated with BLE- cells was not due to the generation of suppressor cells or to the release of inhibitory factors. The increased stimulatory capacity of BLEc lines was unrelated to changes in expression of MHC class-I and class-II antigen, or of B-cell activation markers, and was not due to the reactivation of EBV-specific memory T cells, since lymphocytes from EBV-seropositive and seronegative donors responded similarly. The results indicate that the capacity of BL cells to elicit cellular immune responses may be influenced by their EBV-carrying status.