Incidence and prevalence of dementia in elderly adults with mental retardation without down syndrome

Rates of dementia in adults with mental retardation without Down syndrome were equivalent to or lower than would be expected compared to general population rates, whereas prevalence rates of other chronic health concerns varied as a function of condition. Given that individual differences in vulnerability to Alzheimer's disease have been hypothesized to be due to variation in cognitive reserve, adults with mental retardation, who have long-standing intellectual and cognitive impairments, should be at increased risk. This suggests that factors determining intelligence may have little or no direct relationship to risk for dementia and that dementia risk for individuals with mental retardation will be comparable to that of adults without mental retardation unless predisposing risk factors for dementia are also present.     

A cognitive-behavioral weight reduction program in the treatment of obstructive sleep apnea syndrome with or without initial nasal CPAP: a randomized study

BACKGROUND AND PURPOSE: To evaluate (a) whether an active weight reduction strategy based on the cognitive-behavioral approach and an initial very-low-calorie diet might lead to short- and long-term weight loss and alleviation of OSAS; and (b) whether the results of this intervention could be enhanced by combining it with nasal continuous positive airway pressure (CPAP) treatment during the first 6 months. PATIENTS AND METHODS: Thirty-one obese male symptomatic sleep apnea patients underwent a 2-year weight reduction program with total follow-up of 36 months from baseline. The mean age (+/-SD) was 49.1+/-7.9 years, body mass index 43.8+/-5.4, and oxygen desaturation index (ODI4) 51.3+/-31.1. The patients were randomized to CPAP (17 patients) and non-CPAP groups (14 patients). RESULTS: The mean weight loss was 19.1+/-10.2 kg (14% of the original weight) for the whole group at 6 months, 18.3+/-13.2 (13%) at 12 months and 12.6+/-14.7 kg (9%) at 24 months. Excellent or good treatment results, as defined in terms of an ODI4 (average number of oxygen desaturation events p/h>4% from baseline) reduction of at least 50% from the baseline, were seen in 61% of patients at 6 months and were still observable in 42% of patients at 24 months. The correlations between changes in weight and in ODI4 were 0.59 (P<0.01) at 6 months, 0.68 (P<0.01) and 0.75 (P<0.01) at 24 months. Adding CPAP treatment to the weight reduction therapy for the first 6 months did not result in greater weight loss or diminution of desaturation indices (without CPAP) at any time point. One year after the termination of the program the mean weight loss was 6.6+/-12.9 kg, and 42% of patients still showed at least 5% weight loss as compared with their original weight. CONCLUSION: Satisfactory weight loss associated with improvement of OSAS could be achieved by means of a cognitive-behavioral weight loss program. Adding CPAP in the initial phase of the weight reduction program did not result in significantly greater weight loss.     

Lifestyle and late effects after poliomyelitis. A risk factor study of two populations

BACKGROUND: Patients with polio often experience new symptoms (muscle weakness, pain, fatigue and respiratory problems) many years after the acute disease. This study examined possible interactions between lifestyle factors (overweight, physical inactivity, smoking) and late polio with new symptoms. METHODS: A total of 148 patients hospitalized for acute polio in 1950-1954 at Haukeland University Hospital, Norway and 128 patients, hospitalized for acute polio in 1958 at Tartu University Hospital, Estonia responded to a mailed questionnaire regarding lifestyle and late polio with new symptoms. Multiple regression analysis, two samples t-test and chi-square analysis were undertaken. RESULTS: Mean body mass index (BMI) and percentage of smokers did not differ in the two cohorts, while polio patients were physically less active in Estonia. The physically active patients in both cohorts had significantly lower odds for experiencing polio-related late muscle pain (OR = 0.21; 95% CI = 0.08-0.55) and fatigue (OR = 0.32; 95% CI = 0.14-0.75). With increasing age the patients had significantly higher odds for experiencing new muscle weakness (OR = 1.03; 95% CI = 1.00-1.07), fatigue (OR = 1.04;95% CI = 1.01-1.07) and breath shortness (OR = 1.04; 95% CI = 1.00-1.07). CONCLUSION: Physically inactive patients are at a higher risk for late polio-related symptoms. An active lifestyle should be recommended for patients with polio sequels.     

Working Group report 4: exposure assessment for biological agents

This Working Group was assembled to review and evaluate methods currently used to estimate work site exposures to biological agents and to present recommendations on suitable measurement strategies. The current state of exposure assessment was evaluated for environments with organic dust including agriculture, composting, sewage and waste treatment processing, peat moss harvesting and handling, cotton and textile processing, greenhouse work, and grass seed processing. Methods for measurement of microbial contaminants in indoor environments were also considered. Important methods are emerging that use quantitative PCR for assessment of microbial agents. Difficulties exist with optimization of extraction to yield contaminant-free DNA without significant DNA loss. Advances in assays for microbial agents (e.g., endotoxin and glucans) as well as allergens have increased the utility of exposure assessment for these agents. A crucial area for further development is international harmonization of methodologies to reduce interlaboratory variability and to facilitate establishment of exposure guidelines. Endotoxin exposure assessment using the Limulus amebocyte lysate method is a high priority for harmonization because of its importance as a pulmonary inflammatory agent in many occupational settings.     

"Viagra stories": challenging 'erectile dysfunction'

Medical approaches to sexual difficulties prioritise the physical aspects of sexuality over other aspects, locating 'disorders' primarily in the anatomy, chemistry or physiology of the body. In accordance with this perspective on sexual matters, physicians look to physical interventions (for example, hormones, drugs, and surgery) to treat any 'abnormalities'. Following the discovery of popular--and profitabl-e-sexuopharmaceuticals such as sildenafil citrate (Viagra) for the treatment of erectile difficulties affecting men, the medical model has gained increasing influence in the domain of sexual health and well-being. However, while medical definitions of--and interventions related to--sexual difficulties are underpinned by an understanding of a 'universal' body (that is, an essential biological body that transcends culture and history), and by the categorisation of the normal and the pathological, the accounts of users of Viagra, and their sexual partners, do not necessarily support such understandings. In some cases, the experiences and perspectives of those affected by erectile difficulties directly challenge the reductionist model of sexuality and sexual experience espoused by medicine. In this paper, we report on a New Zealand study investigating the socio-cultural implications of Viagra, involving 33 men and 27 women discussing the impact of erectile difficulties and Viagra use within relationships. The diverse experiences of participants are discussed in relation to two key issues: the notion of 'sexual dysfunction' itself; and the idea of drugs such as Viagra acting as a 'quick fix' for sexual difficulties affecting men. We argue that the existence of a range of Viagra 'stories' disrupts a simplistic mechanistic portrayal of the male body, male sexuality and 'erectile disorder'.     

Assessing the competence of practicing physicians in New Zealand, Canada, and the United Kingdom: progress and problems

Members of the public expect practicing physicians to be competent. They expect poorly performing physicians to be identified and either helped or removed from practice. "Maintenance of professional standards" by continuing education does not identify the poorly performing physician; assessment of clinical performance is necessary for that. Assessment may be responsive-ie, following a complaint- or periodic, either for all physicians or for an identified high-risk group. A thorough review using a range of tools is appropriate for a responsive assessment but is not practical for periodic assessment for all. A single, valid, reliable, and practical screening tool has yet to be devised to identify physicians whose practice is suboptimal. Further, articulate commentators are concerned about the harm that too-intensive scrutiny of professional performance may cause. We conclude that high performance by all physicians throughout their careers cannot be fully ensured, but it is nonetheless the responsibility of licensing bodies to use reasonable methods to determine whether performance remains acceptable. Such methods should be shown scientifically to be accurate, valid, and reliable for practicing physicians. Such an approach is likely to encourage the agreement and cooperation of the profession. To do less risks losing the trust of the public.     

Blinding decreased recruitment in a prevention trial of postmenopausal hormone therapy

PURPOSE: To compare the effect of blind design (active drug and placebo) and nonblind design (active drug and no treatment) on recruitment. SETTING: A primary prevention trial with postmenopausal hormone therapy in Estonia. METHODS: Women who were eligible and willing to participate on the basis of the questionnaire survey were randomized into blind and nonblind groups. Recruitment rates are based on record keeping, and reasons for participating were requested in the first-year follow-up. RESULTS: The recruitment was 30% higher in the nonblind group: of the 4,295 women invited, 37% (95% confidence interval CI=35-39%) in the blind group and 48% (95% CI=46-49%) in the nonblind group were recruited. In both groups, once randomized, most of the losses were women who did not attend the first clinical examination: 49% (blind; 95% CI=47-51%) and 40% (nonblind; 95% CI=38-42%). The rest were found ineligible or lost their interest during clinical examinations. The reasons for joining the trial were relatively similar in the two groups. CONCLUSIONS: Blinding decreased women's interest in joining a long-term preventive trial. Women's reasons for joining the trial were not influenced by blinding.     

Cancer cells as targets for lentivirus-mediated gene transfer and gene therapy

Lentiviruses have been used as gene transfer vectors for almost 10 years and their utility has been demonstrated in a variety of different applications. However, their value in cancer gene therapy has not been studied thoroughly. Here we show that VSV-G pseudotyped HIV-1-based lentiviruses are efficient vectors for human tumor cells in vitro and in vivo. Lentiviral gene transfer efficiency was demonstrated by transducing 42 different cell lines, representing 10 different human tumor types. It was shown that most of the cell lines were good or excellent targets for lentiviral transduction, allowing 50-95% gene transfer efficiency. These results were comparable to those obtained with an E1/E3 deleted, serotype 5 adenovirus vector. Analysis of lentivirus vector structure revealed that virus particles devoid of HIV-1 accessory proteins appeared to be more efficient, but the presence of enhancing elements cPPT and WPRE did not play a major role in transduction efficiency to four different human tumor cell lines. However, their effect on the gene expression level in these cells was apparent. To examine the impact of lentiviral gene expression level on suicide gene therapy approach, human osteosarcoma cells were transduced with lentivirus- or adenovirus vectors carrying the fusion gene HSV-TK-GFP and exposed to ganciclovir. Cell viability analysis after the treatment revealed that both vector types induced similar level of cytotoxicity, suggesting that lentiviral expression of a suicide gene is adequate for tumor cell destruction. Finally, in vivo transduction studies with subcutaneous tumors showed that lentivirus vectors can yield similar gene transfer efficiency than adenovirus vector, despite three orders of magnitude lower titer of the lentiviral preparation. In conclusion, these data show that lentiviruses are efficient gene transfer vehicles for human tumor cells and justify their use in further preclinical cancer gene therapy studies.     

Antioxidant defense mechanisms in human neutrophils

Neutrophils have a short half-life and high tendency to undergo apoptosis. One feature that may influence these characteristics is the antioxidant/oxidant balance of these cells. There are few studies on the levels of antioxidant enzymes in human neutrophils. We have analyzed by immunohistochemistry of paraffin-embedded cells and from cytospin preparations the most important antioxidant proteins in human neutrophils, and compared their levels with those in blood monocytes. Neutrophils showed moderate to high catalase, weak to moderate extracellular superoxide dismutase, and weak copper zinc superoxide dismutase and gamma-glutamylcysteine synthetase immunoreactivities. There were no detectable levels of manganese superoxide dismutase, thioredoxin, and heme oxygenase 1. Some differences were observed between the samples prepared by embedding in paraffin or by cytospin. These results, in combination with a recent study from this laboratory, suggest that a prominent feature in neutrophils is their high catalase activity but lower level of glutathione-dependent antioxidant enzymes. The differences in antioxidant profiles in neutrophils and monocytes may have important effects on the life span of human neutrophils, in both healthy and diseased tissues.