Quin 2 and manganese define multiple alterations in cellular calcium homeostasis in diabetic rat pancreas.

The effects of streptozocin-induced diabetes on Ca2+ fluxes and intracellular free-Ca2+ [( Ca2+]i) levels were studied in isolated rat pancreatic acini. The basal rates of 45Ca influx in acini and of 45Ca efflux from acini that were preloaded with 45Ca were similar in normal and diabetic rats. The gastrointestinal hormone cholecystokinin octapeptide (CCK-8, 0.1 nM) and the Ca2+ ionophore A23187 (2 microM) increased 45Ca influx to the same extent in both groups of acini. CCK-8 and the divalent cation manganese exerted marked stimulatory effects on 45Ca efflux. In contrast to the rapid effect of CCK-8 on 45Ca efflux, the effect of manganese was slow in onset and was greater in diabetic rat acini. The diabetic state was also associated with a significant decrease in resting [Ca2+]i levels, as determined with the Ca2+ indicator quin 2. Furthermore, the ability of CCK-8 to raise [Ca2+]i levels was significantly attenuated in these cells. Insulin did not alter either basal or CCK-8-mediated increases in [Ca2+]i levels. Our findings suggest that insulin deficiency is associated with multiple alterations in Ca2+ homeostasis in the pancreatic acinar cell. These include a decrease in basal [Ca2+]i levels, perturbations in the signal transduction system that mediates the rapid mobilization of [Ca2+]i after CCK-8-receptor binding, and enhanced sensitivity to the actions of manganese on intracellular Ca2+ pools.

The calcium hypothesis of cystic fibrosis.

Data have been presented which suggests that various CF cell types show evidence of alterations in calcium homeostasis. The significance of these observations and the exact nature of the putative calcium defect in CF remains to be elucidated. It must also be determined whether this possible defect is primary, or is secondary or tertiary to some more basic lesion. The data reviewed suggests that altered calcium homeostasis may play some focal role in the aetiology or the pathogenesis of CF.

Intracellular free calcium levels in mononuclear cells of patients with cystic fibrosis and normal controls.

The time course of resting free intracellular calcium concentrations in isolated mononuclear blood cells following a one hour incubation period with the fluorescent dye quin2 was evaluated. Under equal experimental conditions, a slow time-dependent increase of intracellular free calcium in patients with cystic fibrosis and normal healthy controls was noted. Using regression analysis, cystic fibrosis patients were seen to exhibit significantly higher free intracellular calcium concentrations than the controls over the time span covered. At an arbitrarily selected time (60 minutes) the free calcium level was 143.7 +/- 4.3 nM (SEM) in the patients, and 125.5 +/- 2.6 nM in controls. From these data it is concluded that neglecting the time-dependent (Ca2+)i changes following quin2 incubation leads to over- and/or underestimation of the unstimulated resting, basic free calcium levels and prevents the detection of differences between normals and cystic fibrosis patients.

Nutrition and lung function in cystic fibrosis patients: review.

Complex interactions between nutrition, skeletal and respiratory muscle function and energy expenditure in cystic fibrosis patients exist. Malnutrition significantly contributes to muscle weakness in patients with chronic obstructive pulmonary disease of the adult or in cystic fibrosis in childhood. Together with a measurable increase in resting energy expenditure the malnutrition, as a consequence of pancreatic insufficiency, leads to pulmonary deterioration. Whether pulmonary disease, pancreatic insufficiency, increased energy expenditure or insufficient intake of nutrition are the starters for the destructive circle or whether the basic defect is responsible for some of the components interacting with each other remains to be determined.

High altitude climate therapy reduces peripheral blood T lymphocyte activation, eosinophilia, and bronchial obstruction in children with house-dust mite allergic asthma.

Asthma is a multifactorial disease of unknown etiology but often associated with atopy and inflammation. Previous studies in adult asthma have demonstrated the presence of activated T cells in blood, bronchoalveolar lavage (BAL) fluid, and bronchial tissue, and the relevance of their soluble products for eosinophil function. In view of these observations, it was hypothesized that similar pathogenetic mechanisms also occur in childhood asthma. In fact, peripheral blood T lymphocytes in 14 children with house-dust mite allergic asthma showed clear evidence of T cell activation as measured by the expression of CD25 and HLA-DR antigen. Without changing medication, significant reduction of the IL-2 receptor alpha-chain expression within the CD4+ lymphocyte population was observed after only 3 weeks of allergen avoidance. Within this time period, absolute and relative eosinophil numbers decreased to normal levels. After 5 weeks in an area of low house-dust mite exposure, lung function also presented evidence for clinical improvement of the asthmatic disease. These results indicate similar pathogenetic mechanisms in childhood and adult asthma. Furthermore, they suggest that allergen avoidance may contribute to the efficient therapy of asthma in patients with house-dust mite IgE-meditated allergy.

The anaerobic threshold in cystic fibrosis: comparison of V-slope method, lactate turn points, and Conconi test.

Physical exercise can improve sputum clearance in patients with cystic fibrosis (CF). To set up individual training protocols it is desirable to know the anaerobic threshold (AT). Established methods such as blood lactate measurements and ergometry can only be performed in specialized centers. Conconi showed that the heart rate threshold (HRT), i.e., the deflection point from the linear relationship between work load and heart rate, correlated significantly with the AT in healthy adults. To assess the reliability of the HRT in CF, we performed ergometry in 32 CF patients (mean age, 21.0 +/- 5.5 years; mean Shwachman score, 77.8 +/- 12.0) according to the Conconi protocol. The HRT was compared with the aerobic threshold (AeT) as determined by the V-slope method and with two turn points in the lactate performance curve (LTP1, LTP2). An HRT could be obtained in only 17 of the 32 patients (53%). In these 17 patients there was a significant correlation between HRT and the other thresholds, but the absolute values for the AT differed considerably: The mean HRT was 132% higher than the AeT according to Beaver, 107% higher than LTP1, and 19% higher than LTP2. Exercise protocols that rely solely on the HRT in CF will lead to excessive exertion during exercise training programs in these patients. According to these results the HRT of Conconi is not a suitable method to determine appropriate exercise levels in CF training programs and might even be harmful in CF patients. These results also indicate the need to test the reliability of a diagnostic procedure that has been developed only for healthy people.

Occupational exposure to inhalative irritants and methacholine responsiveness.

OBJECTIVES: Occupational exposures to inhalative irritants have been associated with an increased reporting of respiratory symptoms in previous studies. Methacholine responsiveness represents a continuous measure of airway responsiveness. As such, it may be less subject to recall bias and more sensitive to detecting effects of occupational exposure on airways. Such effects may be stronger among atopic persons. The objective of the study was to examine the relationship between self-reports of occupational exposure to dusts, gases, vapors, aerosols, and fumes and methacholine responsiveness. METHODS: A sample was studied of never smokers (N=3044) chosen randomly from 8 areas in Switzerland. Atopy was defined as any positive skin test to 8 inhalative allergens. Nonspecific bronchial reactivity was tested using methacholine chloride and quantified by calculating the slope of the dose-response. RESULTS: The methacholine slopes were 19% [95% confidence interval (95% CI) 6-32] higher for never smokers with exposure to dusts, fumes, vapors, gases, or aerosols than for the unexposed group. When only atopic never smokers were examined. the increase was larger (37%, 95% CI 7-75), and for persons with >2 positive skin prick tests the effect was still higher (42%, 95% CI -1.5-104). Exposure to vapors and aerosols was strongly associated with increased methacholine slopes among the atopic subjects. CONCLUSIONS: Occupational exposure, particularly to dusts and fumes, was associated with increased bronchial reactivity in never smokers in this study. The magnitude of the effect was larger among atopic subjects.

Cystic fibrosis associated with neuronal intestinal dysplasia type B: a case report.

The authors present the case of a newborn girl who had cystic fibrosis associated with neuronal intestinal dysplasia type B (NID-B). The association is rare but must be considered in the differential diagnosis of gastrointestinal problems in patients with cystic fibrosis. The present case elucidates the intestinal problems that can arise with this combination of diseases. Although the unusual association found in this patient could have been a random occurrence, the possibility of an NID-B determining gene localized on chromosome 7q should be considered.

[Inhibition of renal carbonic anhydrase as a respiratory stimulant-- an obsolete indication?]. / Hemmung der renalen Carboanhydrase als Atemstimulans--eine obsolete Indikation?

Inhibition of carbonic anhydrase in general or specific inhibition of one the different isoenzymes results in a significant metabolic acidosis due to renal bicarbonate loss. The increase of arterial pCO2 stimulates central and peripheral chemoreceptors and enhances ventilation. The inhibition of carbonic anhydrase as a respiratory stimulant is an accepted measure for the prevention of acute mountain sickness, has been used for a restricted number of subjects with sleep-disordered breathing or chronic hypoxaemic lung disease. The few indications and the narrow therapeutic index restrict the use of carbonic anhydrase blockers as stimulants for ventilation.

[Tuberculosis]. / Tuberkulose.

Tuberculosis is a continuous threat for health in all parts of the world. In industrialized centers an emerging increase of tuberculosis is observed due to low health standards, poor health education and control, increasing migration and the HIV epidemic. This should alert the pediatrician, since most tuberculosis infections in childhood start with contacts of infected adults with children. There is still a good response to most drugs against tuberculosis, but in some parts of the world the resistance to conventional treatment is an emerging problem. In general incidence, morbidity and mortality of tbc in children of the western world is low and has good prognosis. However, the diagnostic principles and the education of pediatricians for recognizing tbc is still of utmost importance.

[Compliance with inhalation therapy in children with respiratory diseases]. / Compliance der Inhalationstherapie bei Kindern mit respiratorischen Erkrankungen.

Air compressors for inhalation devices were equipped with counters which were activated whenever the inhalation was started. They recorded the time of the activated inhaler. The counters were invisible for the parent and the doctor. 40 outpatients, all children, were randomly given such a device for treatment at home under surveillance of their parents. The duration, dose and frequency of inhalation was explained, and the parents were instructed that if the child should not be well, the inhalation frequency could be doubled. 21 children (age: 3.8 +/- 3.7 years from two months to 14 years), five girls, 16 boys, were on the inhalation devices equipped with the counter; ten had asthma, four acute bronchitis, four mild bronchiolitis, one had pertussis, one cystic fibrosis and one pneumonia. The prescribed inhalation treatment extended over 21 +/- 14 days (3 to 50), the inhalation frequency per day was one to three times. The measured inhalation unit (recorded inhalation time times frequency) amounted to 4.87 +/- 5.01 vs. 4.31 +/- 3.58 (n.s.) for the expected unit (expected inhalation units according to the prescription). The maximum and the minimum differences for the measured vs. the expected unit were significantly different (p < 0.001). Ten children inhaled 80 to 120% of the prescribed inhalation units, six children inhaled more than 140%, and five children less than 70% of the prescribed units. This resulted in an overall inhalation compliance of 47.6%. This is the first double-blind study carried out so far studying inhalation compliance in children with respiratory diseases.

[Case report from the Department of Pediatrics, University of Berne, Switzerland]. / Purpura Henoch-Schönlein. Falldemonstration aus der kindermedizinischen Poliklinik der Med. Universitäts-kinderklinik Bern.

Classic purpura of Henoch-Schönlein is described in a seven years old girl. Prominent clinical markers of this disease entity are: cutaneous, non thrombozytopenic, purple skin lesions, swollen and painful joints, micro- or macrohematuria and abdominal pain. No causal therapy exists; for ambulatory control of painful symptoms non steoidal anti-inflammatory agents and steroids should not be prescribed (danger for intestinal hemorrage). Prognosis in childhood is good, development of chronic glomerulopathy can occur.

[Introduction and critical comparison of clinical scores for characterizing the degree of morbidity of patients with cystic fibrosis]. / Vorstellung und kritischer Vergleich klinischer Scores zur Charakterisierung des Krankheitsgrades von Patienten mit Cystischer Fibrose.

Scoring systems for evaluation of the degree of severity in patients with cystic fibrosis are critically evaluated. Cross-sectional comparison of Shwachman's score, Cooperman's score, Taussig-NIH score, Bernese score and Huang score reveals that advantages and disadvantages of each score exist. In early days used as a marker of disease progression, later on integrated in research studies for patients survival, the scoring systems loose their power due to the possibility of computerized data storage of unlimited variables. Computerized networking allows immediate access to all measured data of an individual or of groups of patients with detailed criteria. Analysis of such data are less vulnerable for mistakes than individually scored patients data; scoring systems in cystic fibrosis will probably become an historical measure.

[Air pollution and the juvenile lungs]. / Luftverschmutzung und Kinderlunge.

The present overview summarizes data from the literature dealing with effects of air pollution on lung health in children. Special care was taken to critically review manuscripts which were published in peer reviewed international journals. In doing so, one realizes that the degree of air pollution is closely related to pulmonary problems of children. However, since single peak loads of polluted air might not be a sufficient indicator for long-term effects of contaminated air on human health, special care has to be taken to search for connections between air toxicity and data of epidemiology, physiology, and pathophysiology.