Aripiprazole for the treatment of psychoses in institutionalized patients with Alzheimer dementia: a multicenter, randomized, double-blind, placebo-controlled assessment of three fixed doses.

OBJECTIVE: To assess the efficacy and safety of aripiprazole for psychosis associated with Alzheimer dementia (AD). METHODS: In this double-blind, multicenter study, 487 institutionalized patients with psychosis associated with AD were randomized to placebo or aripiprazole, 2, 5 or 10 mg/day. Primary efficacy assessment was the mean change from baseline to week 10 on the Neuropsychiatric Inventory-Nursing Home (NPI-NH) version Psychosis Subscale score. Secondary measures included NPI-NH Total, Clinical Global Impression-Severity of Illness (CGI-S), Brief Psychiatric Rating Scale (BPRS) Core and Total, and the Cohen-Mansfield Agitation Inventory (CMAI) scores. RESULTS: Aripiprazole 10 mg/day showed significantly greater improvements (mean change [2 x SD]) than placebo on the NPI-NH Psychosis Subscale (-6.87 [8.6] versus -5.13 [10.0]; F = 6.29, df = 1, 422, p = 0.013 by analysis of covariance [ANCOVA]); CGI-S (-0.72 [1.8] versus -0.46 [1.6]; F = 4.68, df = 1, 419, p = 0.031 [ANCOVA]); BPRS Total (-7.12 [18.4] versus -4.17 [21.6]; F = 4.72, df = 1, 399, p = 0.030 [ANCOVA]); BPRS Core (-3.07 [6.9] versus -1.74 [7.8]; F = 7.30, df = 1, 407, p = 0.007 [ANCOVA]); CMAI (-10.96 [22.6] versus -6.64 [28.6]; F = 5.23, df = 1, 410, p = 0.023 [ANCOVA]), and NPI-NH Psychosis response rate (65 versus 50%; chi(2) = 5.52, df = 1, p = 0.019 [CMH]). Aripiprazole 5 mg/day showed significant improvements versus placebo on BPRS and CMAI scores. Aripiprazole 2 mg/day was not efficacious. Cerebrovascular adverse events were reported: aripiprazole 2 mg/day, N = 1; 5 mg/day, N = 2; 10 mg/day, N = 4; placebo, N = 0. No deaths in any group (aripiprazole 2 mg/day, 3%; 5 mg/day, 2%; 10 mg/day, 7%; placebo, 3%) were considered to be treatment-related. CONCLUSION: Aripiprazole 10 mg/day was efficacious and safe for psychosis associated with AD, significantly improving psychotic symptoms, agitation, and clinical global impression. However, clinicians should be aware of the safety considerations of atypical antipsychotic uses in this population.     

Daughters caregiving for hispanic and non-hispanic alzheimer patients: Does ethnicity make a difference?

This study assessed Cuban-American Hispanic and White non-Hispanic daughters who were major caregivers for their mothers suffering from Alzheimer's Disease. Although patients in both ethnic groups did not differ in their level of cognitive and functional impairment, Cuban-American Hispanic patients were significantly more likely to be living in their daughters' homes while the White non-Hispanic patients resided in institutional settings. Caregivers were equivalent in their knowledge and utilization of community services, but Cuban-American daughters were significantly more aware of financial aid resources. Cuban-American patients were significantly more depressed than their White non-Hispanic counterparts with daughters showing similar but nonsignificant trends. The impact of cultural factors on caregiving is discussed.     

Protein malnutrition alters the distribution of Fc gamma R+ (T gamma) and Fc mu R+ (T mu) T lymphocytes in experimental pulmonary tuberculosis.

Inbred, strain 2 guinea pigs were given isocaloric diets containing either 30% (control diet) or 10% (low-protein diet) ovalbumin and infected 4 weeks later by the respiratory route with virulent Mycobacterium tuberculosis. By using an Fc receptor rosette assay, the proportions of T lymphocytes bearing Fc receptors for immunoglobulin G (T gamma cells) or immunoglobulin M (T mu cells) were quantified in blood and lymphoid tissues taken postinfection. A significant elevation in the proportion of the putative suppressor T subset (T gamma) in the blood of protein-deprived guinea pigs was observed at all intervals postinfection. Conversely, the levels of the putative helper T subset (T mu) in the bronchotracheal lymph nodes draining the site of virulent infection in malnourished animals were significantly reduced. Diet did not influence T gamma or T mu cells in the spleens. Diet-induced loss of purified protein derivative-specific T-cell functions in tuberculosis may be associated with alterations in the proportions of or the balances between T gamma and T mu subsets.     

Dietary protein deficiency and Mycobacterium bovis BCG affect interleukin-2 activity in experimental pulmonary tuberculosis.

Inbred strain 2 guinea pigs were vaccinated with Mycobacterium bovis BCG or were left unvaccinated. They were maintained for 6 weeks on defined, isocaloric diets containing either 30% (control animals) or 10% (animals receiving low protein) ovalbumin as the sole protein source. Animals were challenged by the respiratory route with a low dose of virulent M. tuberculosis H37Rv and killed 4 weeks later. Protein-malnourished animals were not protected by previous vaccination with BCG. Lymphocytes isolated from various tissues were tested in vitro for proliferative responses to mitogen (concanavalin A) and antigen (purified protein derivative [PPD]), production of interleukin-2 (IL-2), and response to exogenous recombinant IL-2 (rIL-2). Protein-malnourished guinea pigs responded only weakly to PPD skin tests, and their blood and lymph node lymphocytes exhibited impaired proliferation when cultured with PPD in vitro. IL-2 levels were consistently low in cultures of stimulated blood and spleen lymphocytes from protein-deprived animals. BCG vaccination of nutritionally normal guinea pigs, on the other hand, induced significantly more IL-2 production by PPD- and concanavalin A-stimulated lymphocytes. The addition of exogenous mouse rIL-2 (40 and 80 U/ml) in vitro to PPD-stimulated blood and lymph node cells from nonvaccinated, protein-deprived guinea pigs resulted in no improvement of the proliferative response. Previous vaccination of malnourished guinea pigs did not consistently enhance the response of PPD-stimulated lymphocytes to added rIL-2. Dietary protein deficiency and BCG vaccination appear to modulate antigen-driven cellular immunity in animals with tuberculosis by altering the production of, and the response to, IL-2 by PPD-stimulated lymphocytes.     

Melanin pigmentation in mammalian skin and its hormonal regulation

Cutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory control by multiple agents interacting via pathways activated by receptor-dependent and -independent mechanisms, in hormonal, auto-, para-, or intracrine fashion. Because of the multidirectional nature and heterogeneous character of the melanogenesis modifying agents, its controlling factors are not organized into simple linear sequences, but they interphase instead in a multidimensional network, with extensive functional overlapping with connections arranged both in series and in parallel. The most important positive regulator of melanogenesis is the MC1 receptor with its ligands melanocortins and ACTH, whereas among the negative regulators agouti protein stands out, determining intensity of melanogenesis and also the type of melanin synthesized. Within the context of the skin as a stress organ, melanogenic activity serves as a unique molecular sensor and transducer of noxious signals and as regulator of local homeostasis. In keeping with these multiple roles, melanogenesis is controlled by a highly structured system, active since early embryogenesis and capable of superselective functional regulation that may reach down to the cellular level represented by single melanocytes. Indeed, the significance of melanogenesis extends beyond the mere assignment of a color trait.     

Uncemented press-fit total knee arthroplasty

Nineteen total knee arthroplasties in 16 patients were performed using a new prosthesis designed specifically for uncemented, press-fit fixation without any provision for tissue ingrowth. This design may be suited for use in patients with juvenile rheumatoid arthritis, postseptic knees, failed total knee arthroplasties with large bone stock deficiencies, and young, active, overweight individuals. Preservation of bone stock is possible because the fixation stems are nails rather than larger cement pegs, removal for revision is easier without cement, sequestration of microbes within cement cannot occur, and bone graft may be continually loaded with this type of prosthesis. Pain relief, discarding crutch support, operative blood loss, and corrective alignment were equivalent to results obtained with cemented arthroplasty. Seventeen of the 18 knees available for review (average follow-up period, 3 years, 7 months; range of follow-up period, 2 years, 10 months to 4 years, 11 months) were pain-free. Range of motion averaged -2 degrees of extension to 101 degrees of flexion. Ambulation was unrestricted and unsupported in the majority of patients. Radiographic evaluation showed the development of increased bone density under the tibial plateau as well as a sclerotic line at the ends of the femoral and tibial stems. This observation gives support to the theory that multiple microtrabecular fractures with healing form a new supportive "subchondral bone plate." There was one incidence of tibial subsidence. Prosthesis migration and loosening were not observed.     

Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: a randomized, double-blind trial. Risperidone Study Group

BACKGROUND: We report the findings from the first large, double-blind, placebo-controlled study conducted to evaluate the efficacy and safety of risperidone in the treatment of psychotic and behavioral symptoms in institutionalized elderly patients with dementia. METHOD: 625 patients (67.8% women; mean age = 82.7 years) with DSM-IV diagnoses of Alzheimer's disease (73%), vascular dementia (15%), or mixed dementia (12%) and significant psychotic and behavioral symptoms were included. Each patient was randomly assigned to receive placebo or 0.5 mg/day, 1 mg/day, or 2 mg/day of risperidone for 12 weeks. The primary outcome measure was the Behavioral Pathology in Alzheimer's Disease rating scale (BEHAVE-AD). RESULTS: The study was completed by 70% of the patients. Baseline Functional Assessment Staging scores were 6 or 7 in more than 95% of the patients, indicating severe dementia. At endpoint, significantly greater reductions in BEHAVE-AD total scores and psychosis and aggressiveness subscale scores were seen in patients receiving 1 and 2 mg/day of risperidone than in placebo patients (p = .005 and p < .001, respectively). At week 12, 0.5 mg/day of risperidone was superior to placebo in reducing BEHAVE-AD aggression scores (p = .02). More adverse events were reported by patients receiving 2 mg/day of risperidone than 1 mg/day. The most common dose-related adverse events were extrapyramidal symptoms, somnolence, and mild peripheral edema. The frequency of extrapyramidal symptoms in patients receiving 1 mg/day of risperidone was not significantly greater than in placebo patients. CONCLUSION: Risperidone significantly improved symptoms of psychosis and aggressive behavior in patients with severe dementia. Results show that 1 mg/day of risperidone is an appropriate dose for most elderly patients with dementia.     

In Vivo Antiplaque Effect of Three Edible Toothpastes

Objectives: The objective of this study was to analyse the antibacterial and antiplaque activity of three edible toothpastes with the widest worldwide distribution: KidScents™, which contains essential oils; Browning B&B™, with medicinal plants; and Wysong Probiodent™, which contains probiotics. Study Design: The study group was formed of twenty healthy volunteers (dental students) with a good oral health status. Using a balanced randomisation system, all volunteers performed toothbrushing with four products (the three edible toothpastes and water) at intervals of one week. Bacterial vitality in the saliva was analysed by epifluorescence microscopy and plaque regrowth was evaluated using the Turesky-Quigley-Hein plaque index. Results: Bacterial vitality in the saliva was significantly higher after toothbrushing with water (positive control) than with the three toothpastes (P=0.002, P=0.003 and P<0.001, respectively). The plaque index was significantly higher after using these three toothpastes than after toothbrushing with water (P=0.047, P=0.032 and P<0.001, respectively). Conclusions: The three edible toothpastes analysed have some antimicrobial activity but favour plaque regrowth. Key words:Edible toothpaste, dental plaque, oral bacteria.