In-depth investigation of the molecular pathogenesis of bladder cancer in a unique 26-year old patient with extensive multifocal disease: a case report

Background

The objective of our work was to investigate both the contractile function and the release of ATP and NO from strips of bladder tissue after removal of the urothelium.

Methods

The method of removal was a gentle swabbing motion rather than a sharp surgical cutting to separate the urothelium from the smooth muscle. The contractile response and ATP and NO release were measured in intact as well as on swabbed preparations. The removal of the urothelial layer was affirmed microscopically.

Results

After the swabbing, the smaller contractions were evoked by electrical as well as by chemical stimulation (50 μM carbachol or 50 μM α, β meATP). Electrical stimulation, carbachol and substance P (5 μM) evoked lower release of ATP in the swabbed strips than in intact strips. Although release of NO evoked by electrical stimulation or substance P was not changed, release of NO evoked by carbachol was significantly less in the swabbed preparations.

Conclusion

Since swabbing removes only the urothelium, the presence of the suburothelial layer may explain the difference between our findings and those of others who found an increase in contractility. Evoked release of ATP is reduced in swabbed strips, indicating that ATP derives solely from the urothelium. On the other hand, electrical stimulation and substance P evoke identical degrees of NO release in both intact and swabbed preparations, suggesting that NO can be released from the suburothelium. Conversely, carbachol-induced release of NO is lower in swabbed strips, implying that the cholinergic receptors (muscarinic or nicotinic) are located in the upper layer of the urothelium.     

Pharmacological inhibition of Akt and downstream pathways modulates the expression of COX-2 and mPGES-1 in activated microglia

Background  

Microglia are considered a major target for modulating neuroinflammatory and neurodegenerative disease processes. Upon activation, microglia secrete inflammatory mediators that contribute to the resolution or to further enhancement of damage in the central nervous system (CNS). Therefore, it is important to study the intracellular pathways that are involved in the expression of the inflammatory mediators. Particularly, the role of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and glycogen synthase kinase-3 (GSK-3) pathways in activated microglia is unclear. Thus, in the present study we investigated the role of Akt and its downstream pathways, GSK-3 and mTOR, in lipopolysaccharide (LPS)-activated primary rat microglia by pharmacological inhibition of these pathways in regard to the expression of cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase-1 (mPGES-1) and to the production of prostaglandin (PG) E₂ and PGD₂.     

A study on the immunological basis of the dissociation between type I-hypersensitivity skin reactions to <Emphasis Type="Italic">Blomia tropicalis</Emphasis> antigens and serum anti-<Emphasis Type="Italic">B. tropicalis</Emphasis> IgE antibodies

Background

Two conditions are used as markers of atopy: the presence of circulating anti-allergen IgE antibodies and the presence of positive skin prick test (SPT) reactions to allergenic extracts. The correlation between these conditions is not absolute. This study aimed at investigating immunological parameters that may mediate this lack of correlation. Individuals whose sera contained anti-B. tropicalis extract IgE antibodies (α-Bt E IgE) were divided into two groups, according to the presence or absence of skin reactivity to B. tropicalis extract (Bt E). The following parameters were investigated: total IgE levels; α-Bt E IgE levels; an arbitrary α-Bt E IgE/total IgE ratio; the proportion of carbohydrate-reactive α-Bt E IgE; the proportion of α-Bt E IgE that reacted with Ascaris lumbricoides extract (Al E); the production of IL-10 by Bt E- and Al E-stimulated peripheral blood cells (PBMC).

Results

Total IgE levels were similar in the two groups, but α-Bt E IgE was significantly higher in the SPT-positive group (SPT+). A large overlap of α-Bt E IgE levels was found in individuals of both groups, indicating that these levels alone cannot account for the differences in SPT outcome. Individuals of the two groups did not differ, statistically, in the proportion of α-Bt E IgE that reacted with carbohydrate and in the production of IL-10 by Bt E- and Al E-stimulated PBMC. Both groups had part of α-Bt E IgE activity absorbed out by Al E, indicating the existence of cross-reactive IgE antibodies. However, the α-Bt E IgE from the SPT-negative individuals (SPT-) was more absorbed with AlE than the α-Bt E IgE from the SPT+ individuals. This finding may be ascribed to avidity differences of the α-Bt E IgE that is present in the two groups of individuals, and could occur if at least part of the α-Bt E IgE from the SPT- individuals were elicited by A. lumbricoides infection.

Conclusion

The present results suggest that a low ratio of specific IgE to total IgE levels (in a minority of individuals), and differences in α-Bt E IgE avidities (which would have high affinities for A. lumbricoides antigens in SPT- than in SPT+ individuals) may play a role in the down-modulation of type-I hypersensitivity reaction against aeroallergens described in helminth-infected individuals.

     

Efficient integrated education for older patients with chronic obstructive pulmonary disease using the Lung Information Needs Questionnaire

Aim: Education is a key issue for the long‐term management of chronic obstructive pulmonary disease in older patients. We tested the hypothesis that integrated care focusing on patient information needs for self‐management can improve patient information needs and health outcomes. Methods: Patients with chronic obstructive pulmonary disease (n = 102) were randomized into integrated care (group I) and usual care (group U) groups. Group I underwent a program of educational sessions for 6 months (integrated education period), and then repeatedly received an individually tailored education according to the Lung Information Needs Questionnaire score. Both groups were followed up monthly for 6 months. Results: A total of 85 patients (mean age: 71.7 years) were followed up for 12 months. The total Lung Information Needs Questionnaire score was significantly better in group I than in group U at 12 months (P < 0.03). Activities of daily living scores were significantly improved in group I at 6 months (P < 0.03). The dyspnea score and the BODE index (body mass index, dyspnea, airflow obstruction and exercise capacity) were significantly improved in group I at 12 months (P < 0.01 and P < 0.02, respectively). During the integrated education period, the frequency of hospitalization was significantly lower in group I than in group U (P = 0.033). Conclusion: Integrated education for older patients with chronic obstructive pulmonary disease effectively improved patients' information needs, activities of daily living, dyspnea score, BODE index and reduced hospitalizations during the observed period. Geriatr Gerontol Int 2011; 11: 422–430.     

Blood transfusion during cardiac surgery is associated with inflammation and coagulation in the lung: a case control study

Introduction  

Blood transfusion is associated with increased morbidity and mortality in cardiac surgery patients, but cause-and-effect relations remain unknown. We hypothesized that blood transfusion is associated with changes in pulmonary and systemic inflammation and coagulation occurring in patients who do not meet the clinical diagnosis of transfusion-related acute lung injury (TRALI).     

Management of mitochondrial disease on an intensive care unit

Patients with mitochondrial disease may present to the IntensiveCare Unit (ICU) with a variety of neurological and general medicaldisorders. Eleven patients were admitted to a neurological ICUbetween 1970 and 1992 because of respiratory insufficiency,status epilepticus and/or metabolic encephalopathy associatedwith mitochondrial disease. Respiratory impairment occurredin eight patients and was associated with nocturnal hypoventilationdue to respiratory muscle weakness, aspiration due to bulbarweakness and abnormalities of central control leading to a reducedCO₂ drive, irregular respiratory patterns and sleep apnoea.Seven patients received continuous respiratory support duringthe acute illness; three were subsequently weaned to domiciliaryventilation, and four died. Five patients had stroke-like episodes,which in two were recurrent. Four patients developed tonic-clonicgrand mal epilepsy associated with myoclonic fits (2 patients),absences (2), focal fits (1) and status epilepticus (2). Encephalopathywas associated with recurrent lactic acidosis (2 patients),cardiac failure (2), hyponatraemia (2), renal abnormalities(3) and complete heart block (1). Although rare, mitochondrialdisease should be considered in any patient with unexplainedrespiratory failure, intractable epilepsy, lactic acidosis orrecurrent stroke.     

Paving the way: Stepping stones to evidence-based nursing

Wallace MC, Shorten A, Russell KG. International Journal of Nursing Practice 1997; 3: 147–152
Paving the way: Stepping stones to evidence-based nursing
Evidence-based practice is an emerging paradigm in health care. This paper outlines the main features of this paradigm and its potential value to nursing. Evidence-based practice is based on a conceptual framework that examines the extent of evidence available in support of particular clinical practices. The Quality of Evidence Ratings adapted by the National Health and Medical Research Council (NHMRC) from the United States Preventive Services Task Force are discussed, and the strengths and weaknesses of different categories of evidence are highlighted. Potential barriers to implementation of research into practice are identified. The authors suggest that legal, ethical, economic and humane imperatives oblige nursing to develop evidence-based practice as one of several viable contributions to nursing knowledge. Suggestions for analysing current research and for the planning of the direction of future nursing research are made.