Effect of almitrine bismesylate on breathing pattern during hypoxia/hypercapnia in rats and ferrets

1. Ventilatory measurements and functional residual capacity (FRC) were recorded from anaesthetized rats and ferrets using a whole body plethysmograph. Simulation of aspects of human chronic obstructive airways disease (COAD) was attempted by making animals acutely hypoxic or hypoxic and hypercapnic by causing them to breath appropriate gas mixtures or by increasing the tracheal resistance or dead-space. Some chronically hypoxic rats, which have muscularized pulmonary arterioles similar to COAD patients, were also studied. 2. In 18 chronically hypoxic (CH) rats and 17 littermate control rats (C), breathing air, doses of almitrine bismesylate caused greater increases in ventilation (VE) in C than in CH rats. FRC, which was initially greater in CH rats, increased significantly in both groups after almitrine. 3. In C rats, breathing hypoxic or hypoxic/hypercapnic gas mixtures caused large increases in VE. Slow infusions of almitrine caused a further increase in VE usually via an increase in tidal volume (VT) but not frequency (f). 4. In two series of rats (n = 9; n = 6) severe and moderate degrees of tracheal obstruction caused a fall in PaO2 and a rise in PaCO2, a fall in VE due to both VT and f and large changes in oesophageal pressure (Poes), which often became positive on expiration. Almitrine infusions usually caused a rise in PaO2, a rise in VT and no change in f; with moderate obstruction, Poes also rose. The results were thought to depend on the balance between improved ventilation and increased O2 demand of the respiratory muscles. 5. Eleven ferrets were made hypoxic and hypercapnic by adding a large dead-space to the trachea. A slow infusion of almitrine caused a significant rise in PaO2 before any significant change in VE was detected; PaCO2 fell at some time during the infusion, but not significantly. The initial significant rise in PaO2, at 2.5 min, was not associated with significant changes in T1 (time of inspiration) and VT/TI. At 5 min VT/TI and PaO2 were all significantly altered. 6. Infusions of almitrine into hypoxic and hypercapnic animals caused improvements in the arterial oxygen tension which were associated with subtle changes in the breathing pattern; inspiratory time and inspiratory flow rate changed in the absence of an increase in total VE. Possible conclusions with respect to the action of almitrine in patients with COAD are discussed.     

Quality of life in smokers: focus on functional limitations rather than on lung function?

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification of severity of chronic obstructive pulmonary disease (COPD) is based solely on obstruction and does not capture physical functioning. The hypothesis that the Medical Research Council (MRC) dyspnoea scale would correlate better with quality of life than the level of airflow limitation was examined. AIM: To study the associations between quality of life in smokers and limitations in physical functioning (MRC dyspnoea scale) and, quality of life and airflow limitation (GOLD COPD stages). DESIGN: Cross-sectional study. SETTING: The city of IJsselstein, a small town in the centre of The Netherlands. METHOD: Male smokers aged 40-65 years without a prior diagnosis of COPD and enlisted with a general practice, participated in this study. Quality of life was assessed by means of a generic (SF-36) and a disease-specific, questionnaire (QOLRIQ). RESULTS: A total of 395 subjects (mean age 55.4 years, pack years 27.1) performed adequate spirometry and completed the questionnaires. Limitations of physical functioning according to the MRC dyspnoea scale were found in 25.1% (99/395) of the participants and airflow limitation in 40.2% (159/395). The correlations of limitations of physical functioning with all quality-of-life components were stronger than the correlations of all quality-of-life subscales with the severity of airflow limitation. CONCLUSION: In middle-aged smokers the correlation of limitations of physical functioning (MRC dyspnoea scale) with quality of life was stronger than the correlation of the severity of airflow limitation with quality of life. Future staging systems of severity of COPD should capture this and not rely on forced expiratory volume in one second (FEV1) alone.     

Immune Responses to Differentiated Forms of Helicobacter pylori in Children with Epigastric Pain

Helicobacter pylori infection affects human populations of all ages. This gastric bacterium exists in spiral form and the reported viable but nonculturable coccoid form. The present study aims to examine the probable role of the coccoid form in H. pylori infection by comparing the seroprevalences of the spiral and the coccoid forms in children with epigastric pain. Four hundred eighty-nine children (mean age, 8.5 years) with epigastric pain formed the basis of this study. Five hundred ninety-nine schoolchildren of comparable ages and with no record of dyspepsia served as controls. The seroprevalence of antigens prepared from both morphological forms was examined by enzyme-linked immunosorbent assay. The results showed that 65 (13.3%) and 273 (55.8%) of 489 symptomatic children were seropositive for antigens of the H. pylori spiral and coccoid forms, respectively. In contrast, only 7.0% of the control group had elevated levels of immunoglobulin G antibodies against the spiral form, while 26.5% were positive for antibodies against the coccoid form. There were no significant differences between genders or among ethnic groups. The study showed a rise in seroprevalence corresponding with age: 7.1% for those ≤5 years to 21.4% for those ≥11 years. The seroprevalence of antigens of the H. pylori spiral and coccoid forms in children with epigastric pain was twofold higher than that in the control subjects. Interestingly, there was a fourfold increase in seropositivity for coccoid-form antigen compared to that for the spiral-form antigen among the symptomatic pediatric patients as well as the control group, indicating a possible infective role of the coccoid form of H. pylori in the pediatric patients with epigastric pain.     

Timed unilateral ovarian follicular aspiration prior to administration of human chorionic gonadotrophin for the prevention of severe ovarian hyperstimulation syndrome in in-vitro fertilization: a prospective randomized study

Unilateral ovarian follicular aspiration 6-8 h prior to trigger administration of human chorionic gonadotrophin (HCG) was performed or not in 31 women at serious risk of ovarian hyperstimulation syndrome (OHSS) after ovarian stimulation for in-vitro fertilization (IVF)- embryo transfer or intracytoplasmic sperm injection (ICSI) in this prospective randomized study. Unilateral follicular aspiration was performed in 16 women (group 1) matched for age, indication for fertility treatment, and the amount and duration of gonadotrophin exposure with 15 women not receiving aspiration treatment (group 2). There was a statistically significantly (P < 0.001) lower mean number of oocytes obtained from group 1 women (14.9 +/- 1.8 vs 22.6 +/- 2.4). The fertilization (53.2 +/- 2.6 vs 65.5 +/- 1.35%) and embryonic cleavage (91.3 +/- 2.1 vs 90.2 +/- 1.75%) rates were similar in both groups. OHSS occurred in women from both groups (group 1: 25% vs group 2: 33.3%) being severe OHSS in two women from group 1 and one from group 2. We conclude that unilateral ovarian early follicular aspiration prior to HCG trigger administration does not reduce the occurrence of severe OHSS in women at risk.      

Quality of life of parents and siblings of children with cochlear implants

Objectives

This study examined the quality of life (QoL) of the parents and siblings of hearing-impaired children with cochlear implants (CIs).

Proteasome inhibition alleviates prolonged moderate compression-induced muscle pathology

Background  

The molecular mechanism initiating deep pressure ulcer remains to be elucidated. The present study tested the hypothesis that the ubiquitin proteasome system is involved in the signalling mechanism in pressure-induced deep tissue injury.     

Agreement between pQCT‐ and DXA‐derived indices of bone geometry,density, and theoretical strength in females of varying age,maturity, and physical activity

Measurement of bone mass, geometry, density, and strength are critical in bone research and clinical studies. For peripheral quantitative computed tomography (pQCT), single and repeated measurements are particularly adversely affected by movement and positional variation. Dual‐energy X‐ray absorptiometry (DXA)–derived indices may alleviate these problems and provide useful alternative assessments. To evaluate this hypothesis, distal radius DXA and pQCT indices were compared in 101 healthy females aged 8.0 to 22.8 years (prepuberty to adulthood), reflecting a broad range of body sizes, physical maturity, and activity exposures. At the diaphysis, correlations were ρ = +0.74 to +0.98, with strong intermethod agreement for most indices. At the metaphysis, correlations were ρ = +0.64 to +0.97; intermethod agreement improved with modifications to the simplified geometric formulas more closely reflecting metaphyseal bone geometry. Further improvements may be possible because skeletal size and maturity‐related biases in agreement were detected. Overall, DXA‐derived indices may provide a useful assessment of bone geometry, density, and theoretical strength contingent on appropriate consideration of their limitations. © 2011 American Society for Bone and Mineral Research.     

Interleukin-3, GM-CSF, and G-CSF receptor expression on cell lines and primary leukemia cells: receptor heterogeneity and relationship to growth factor responsiveness

Recombinant human granulocyte-macrophage (GM) colony-stimulating factor (GM-CSF), G-CSF, and interleukin-3 (IL-3) labeled with 125I were used to study the characteristics and distribution of receptors for these factors on in vitro cell lines and on cells from patients with acute nonlymphocytic leukemia (ANL) and acute lymphocytic leukemia (ALL). Receptors for GM-CSF and G-CSF were restricted to a subset of myelomonocytic cell lines whereas IL-3 receptors were also found on pre- B- or early B-cell lines. Receptors for all three CSFs were broadly distributed on ANL cells, with considerable variability in levels of expression. Measurement of the colony-forming ability of ANL cells in response to the CSFs showed that there was no direct correlation between the ability of the cells to respond to a growth factor and the absolute number of receptors expressed for that growth factor. Binding of radiolabeled IL-3 and GM-CSF to ANL cells produced complex biphasic curves. Further analysis showed that both IL-3 and GM-CSF were able to partially compete for specific binding of the heterologous radiolabeled ligand to cells from several ANL patients, suggesting that heterogeneity may exist in human CSF receptors. These results provide new insights into the complex role that CSFs may play in ANL.