Reduced insulin-induced phosphatidylinositol-3-kinase activation in peripheral blood mononuclear leucocytes from patients with Alzheimer's disease

The epidemiological finding of an increased risk of dementia in patients with diabetes mellitus has raised the hypothesis that a dysfunction of the insulin receptors plays a role in the pathogenesis of Alzheimer's disease (AD). A possible link is suggested by the evidence that the insulin-stimulated phosphatidylinositol-3-kinase (PI-3-K)/phospho-Akt pathway negatively controls the glycogen synthase kinase-3beta. The activation of this enzyme mediates the hyperphosphorylation of the tau protein, a relevant step in the formation of the neurofibrillary tangles associated with AD. We hypothesized that the neurodegeneration associated with AD is related to an impairment of the intracellular signalling stimulated by insulin receptors. To test this hypothesis we assessed the PI-3-K/phospho-Akt pathway following in-vitro challenge with insulin in peripheral blood mononuclear cells from subjects with AD (n = 20) and controls (n = 20). We found that the stimulation of PI-3-K is blunted in patients with AD with respect to control. The reduction did not correlate with the extent of cognitive decline or with scores at neuropsychological tests exploring attention, memory, language or visuospatial abilities. The study supports the hypothesis that an impaired control of glycogen synthase kinase-3beta activity by insulin receptor-mediated signalling plays a role in the pathogenesis of AD, facilitating tau protein phosphorylation and neurofibrillary tangle formation.     

Adolescent quality of life,part II: initial validation of a new instrument

The psychometric properties of the Youth Quality of Life Instrument-Research Version (YQOL-R) perceptual module are presented. Self-reports were obtained from 236 youth aged 12-18 years with mobility disability, attention-deficit hyperactivity disorder, or without self-reported chronic conditions. Item and factor analyses confirmed the hypothesized conceptual model derived from previous qualitative research. The scales of the YQOL-R showed acceptable internal consistency (Cronbach's alpha=0.77-0.96), reproducibility (ICCs=0.74-0.85), expected associations with other constructs, and ability to distinguish between known groups. The YQOL-R showed sufficient validity to encourage further use.     

Probiotic effects on faecal inflammatory markers and on faecal IgA in food allergic atopic eczema/dermatitis syndrome infants

Probiotic bacteria are proposed to alleviate intestinal inflammation in infants with atopic eczema/dermatitis syndrome (AEDS) and food allergy. In such infants we investigated effects of probiotic bacteria on faecal IgA, and on the intestinal inflammation markers tumour necrosis factor-alpha (TNF-alpha), alpha1-antitrypsin (AT), and eosinophil cationic protein (ECP). A total of 230 infants with AEDS and suspected cow's milk allergy (CMA) received in a randomized double-blinded manner, concomitant with elimination diet, Lactobacillus GG (LGG), a mixture of four probiotic strains (MIX), or placebo for 4 wk. Four weeks after treatment, CMA was diagnosed with a double-blind placebo-controlled milk challenge. Faecal samples of 102 infants, randomly chosen for analysis, were collected before treatment, after 4-wk treatment, and on the first day of milk challenge. After treatment, IgA levels tended to be higher in probiotic groups than in the placebo group (LGG vs. placebo, p=0.064; MIX vs. placebo, p=0.064), and AT decreased in the LGG group, but not in other treatment groups. After challenge in IgE-associated CMA infants, faecal IgA was higher for LGG than for placebo (p=0.014), and TNF-alpha was lower for LGG than for placebo, but non-significantly (p=0.111). In conclusion, 4-wk treatment with LGG may alleviate intestinal inflammation in infants with AEDS and CMA.     

70% glucose solution: clinical usefulness for postoperative management of anuric patients

Hemodialysis is necessary for postoperative management of the patients with bilateral renal tumor or chronic renal failure, but taking into account the heavy burden imposed upon the patients, use of postoperative hemodialysis should be kept to the minimum. As one bottle (300 ml) of 70% glucose solution contains 840 cal, two bottles per day (its volume is nearly equal to intensive perspiration) is enough in calorific value. This 70% glucose solution was found useful for the management of patients with acute renal failure. Because the postoperative state of anuric patients is similar to the state of acute renal failure, this time we studied the clinical usefulness of a 70% glucose solution for the postoperative management of these patients. We administered 600 ml of a 70% glucose solution to three postoperative patients, who were operated on for bilateral renal tumor, bilateral renal pelvic tumor, and renal tumor with lung metastasis and who had been on chronic hemodialysis. The rate of blood urea nitrogen increase was very low, and hyperkalemia was not seen. We concluded that a 70% glucose solution was useful to delay the start of hemodialysis and to lessen its frequency, which suggests that it is useful to improve the postoperative course of anuric patients.     

Functional-aesthetic reconstruction of periorbital fractures and defects

Patients with periorbital defects experience social rejection and psychological impairment as a result of their defect. We have developed a procedure to repair the defect which gives aesthetically and functionally satisfactory results. Infraorbital bony reconstruction and reconstruction of the intraorbital anatomical units are performed as primary surgery; supraorbital reconstruction is done secondarily. We make use of implants made of heath-polymerizing prefabricated polymethyl-methacrylate, and have had satisfactory results.     

Asthma, airway inflammation and treatment in elite athletes

Highly trained athletes are repeatedly and strongly exposed to cold air during winter training and to many inhalant irritants and allergens all year round. Asthma occurs most commonly in athletes engaging in endurance events such as cross-country skiing, swimming, or long-distance running. As well as the type of training, a major risk factor is atopic disposition. A mixed type of eosinophilic and neutrophilic airway inflammation has been shown to affect elite swimmers, ice-hockey players, and cross-country skiers. The inflammation may represent a form of repeated thermal, mechanical, or osmotic airway trauma resulting in a healing or remodelling process. Elite athletes commonly use antiasthma drugs to treat exercise-induced bronchial symptoms. Only a few controlled studies have been conducted on the effects of antiasthma drugs on asthma symptoms, bronchial hyperresponsiveness and airway inflammation in elite athletes. Inhaled beta(2)-adrenoceptor agonists are effective against exercise-induced bronchospasm. In contrast, airway inflammation, bronchial hyperresponsiveness and symptoms have responded poorly to inhaled corticosteroids and leukotriene antagonists. As discontinuing high-level exercise has proved effective in reducing eosinophilic airway inflammation, exercise or training should be restricted in athletes having troublesome symptoms and sputum eosinophilia. Switching training to less irritating environments should be considered whenever possible. It appears to be difficult to change the 'natural course' of asthma in athletes by anti-inflammatory treatment.     

A Prospective Analysis of the Effect of Blue-Dye Volume on Sentinel Lymph Node Mapping Success and Incidence of Allergic Reaction in Patients With Breast Cancer

Background This study examined whether the volume of isosulfan blue dye used in sentinel lymph node (SLN) mapping in breast cancer is related to the SLN identification rate or to the incidence of allergic reactions.Methods From January 2001 to November 2002, 1728 breast cancer patients underwent 1832 SLN mapping procedures with the combined technique of intraparenchymal blue dye and intradermal radioisotope. Details of each procedure and all allergic reactions were prospectively recorded. Bilateral synchronous SLN procedures were considered as one dye exposure but as two distinct procedures for determining mapping success. Dye-only success was defined as the proportion of cases in which the SLN was identified by blue dye alone. Overall dye success was defined as the proportion of cases in which the SLN was identified by blue dye with or without isotope.Results When stratified by volume of blue dye, there were no significant differences in dye-only successes, overall dye successes, or mapping failures. Allergic reactions were documented in 31 (1.8%) of 1728 patients. Hypotensive reactions occurred in 3 (.2%) of 1728 patients; 2 (.1%) required pressor support. There was a nonsignificant trend toward fewer allergic reactions with smaller volumes of blue dye.Conclusions In combined-technique SLN mapping protocols for breast cancer, using smaller volumes of blue dye may represent a means of optimizing the safety of the procedure without compromising its success.     

Asthma and atopy – the price of affluence?

Irrespective of improved knowledge of many aspects of atopic diseases, the unfavorable trends in their prevalence particularly among children could not have been reversed. A growing body of evidence suggests that something may lack from our societal affluence that has the capacity to provide protection against the development of atopic diseases. Much attention during the last years has been devoted to the hygiene hypothesis. This review outlines the impact of environment and lifestyle, particularly from the perspective of the East-West gradient, on the development of atopic diseases, with a special emphasis on the hygiene hypothesis in its broadest sense.