Skeletal muscle contractility is preserved in COPD patients with normal fat‐free mass

Aim: Peripheral muscle dysfunction often occurs in patients with chronic obstructive pulmonary disease (COPD). The muscle dysfunction may be caused by a loss of force‐generating capacity, resulting from a loss of muscle mass, as well as by other alterations in contractile properties of skeletal muscle. Methods: The maximal isometric voluntary strength and fatigability were determined in hand‐grip and quadriceps muscles from nine male COPD patients (FEV₁ 30–50% predicted) and control subjects matched for fat‐free mass (FFM), physical activity level and age. Contractile properties and fatigability of the quadriceps muscle were also studied with electrically evoked isometric contractions. Results: The maximal voluntary force (MVC) and fatigability of the handgrip muscle did not differ between the COPD patients and control subjects. Also the MVC of the quadriceps muscle and the rate of force rise, contraction time, force–frequency relationship and fatigability, as determined with electrically evoked contractions, were similar in patients with COPD and control subjects. Conclusion: Skeletal muscle strength, contractile properties and fatigability are preserved in patients with moderate COPD and a normal FFM and activity level. This suggests that skeletal muscle dysfunction does not take place during moderate COPD until cachexia and/or a decline in physical activity occur.     

Stem cell factor and interleukin-4 induce murine bone marrow cells to develop into mast cells with connective tissue type characteristics in vitro

In this study, we have developed a method to obtain mast cells with connective tissue type mast cell (CTMC) characteristics directly from mouse bone marrow (BM) cells. BM cells were grown for 3 weeks in presence of interleukin-4 (IL-4) plus stem cell factor (SCF). SCF alone poorly supported growth and development of mast cells. IL-4 dose-dependently enhanced the expression of c-kit and high-affinity receptor for IgE (Fc(epsilon)RI) on the cell surface of SCF-cultured BM cells. Furthermore, cytoplasmic granulation and histamine synthesis of BM-derived mast cells were increased in presence of IL-4 and SCF. Histochemical staining demonstrated that granules were safranin positive. BM-derived mast cells could be activated for granule exocytosis (beta-hexosaminidase release) and lipid mediator generation (LTC4 production) via Fc(epsilon)RI after sensitization with IgE and subsequent crosslinking with multivalent antigen. In addition, mast cells derived from BM cells cultured with SCF plus IL-4 could be activated by substance P, a nonimmunologic stimulus, to release beta-hexosaminidase. The results presented indicate that IL-4 and SCF both have a prominent role in the development of mast cells from murine BM cells in vitro. Mast cells can directly be derived from BM cells in presence of SCF and IL-4 and the cultured cells show typical hallmarks of CTMC, indicating that precursor cells for CTMC may be present in BM. The described culture procedure may be useful to investigate the molecular aspects of the development of committed mast cell lineages.     

Bupropion: an effective new aid for smoking cessation

Smoking is responsible for a substantial percentage of the total morbidity and mortality in western society. In the Netherlands 34% of the population smoke. A considerable part of the smokers tried to stop smoking, but did not succeed. Since December 1999 a new type of anti-smoke therapy is available; bupropion chloride (Zyban). With this treatment an improvement in success ratio in comparison with placebo is described of 11-15% after a year in a healthy population. Combined with nicotine patches this percentage was 20%. These percentages are higher than those of nicotine replacement therapy alone (3-13%). It is very important that effects of bupropion are tested in high-risk patients with asthma, chronic obstructive pulmonary disease (COPD) and cardiovascular diseases as these groups may benefit most from cessation of smoking. Especially in the COPD group cessation of smoking makes a more substantial contribution to improvement of the disease process than the medication now available. Therefore, it might be considered to prescribe bupropion under strict control in this group even now, before definitive research results are obtained.     

Therapeutic dilemmas in patients with a centrally-located pulmonary embolism confirmed by spiral CT-scan but with no cardiogenic shock

3 patients, 2 women aged 64 and 44 and 1 man aged 67, had severe dyspnoea and a large centrally-located pulmonary embolism (PE) without any accompanying arterial hypotension. They were all given conventional anticoagulation therapy, although thrombolytic therapy was also considered. The women recovered but the man eventually died of a second massive embolism. PE is a disease with a potentially high mortality. Patients with cardiogenic shock due to PE are candidates for thrombolytic therapy. A subset of patients with right-ventricular dysfunction (submassive PE) also have a poorer prognosis despite the absence ofarterial hypotension or shock. Spiral CT-scan is becoming the first-line imaging test of preference in patients with suspected PE. Spiral CT enables the accurate visualization ofthrombi. The value of risk management using cardial biomarkers, spiral CT and echocardiography is not yet clear. There is no evidence that thrombolytic therapy is beneficial in patients with acute PE and right-ventricular dysfunction without overt shock.     

Volumetric measurements of peripheral oedema in clinical conditions.

Water-displacement volumetry can be used for quantifying the volume of the leg. However, not much is known about its application in patients with peripheral oedema of cardiopulmonary origin. We measured the reproducibility of a water-displacement apparatus with a solid object and in ten non-oedematous clinical patients (group A). The day-to-day variability of the leg volume was assessed in the same group. The diurnal variability was assessed in ten patients with persisting peripheral oedema (group B). The effect of treatment on the severity of peripheral oedema was evaluated in another nine patients with peripheral oedema, who were in need of diuretic treatment (group C). Volumetric results were compared to the ankle circumference method and the body weight method. The coefficient of variation was 0.16% in the fixed object and 0.47% in group A. The day-to-day variability was 1.52% after 1 day and 1.76% after a mean interval of 4.8 days. In group B, leg volume and circumference increased during the day (5.9%, P<0.001, and 2.4%, P<0.01, respectively), while body weight remained unchanged. In group C, leg volume, circumference and body weight decreased significantly after treatment (13.1%, P<0.01, 7.1%, P<0.05, and 5.9%, P<0.05). The correlation between the changes in volume and body weight was poor (r=0.37, P=0.33). In conclusion, (1) water-displacement volumetry is highly reproducible, (2) a diurnal variability of peripheral oedema was found, and (3) volumetry is a suitable tool for monitoring peripheral oedema, while the body weight method appears to be less accurate.     

Determinants of alcohol use among young males in two Indian states: A population-based study

Objectives

There is insufficient evidence about the determinants of alcohol use amongst young people in India and other low-and middle-income countries, despite alcohol's high contribution to disease burden and increasing consumption in this population. We aimed to identify and estimate the determinants of alcohol use in a representative sample of 2716 young men from Bihar and Uttar Pradesh who participated in the ‘Understanding the Lives of Adolescents and Young Adults’ (UDAYA) study.

Methods

First, we developed an exploratory conceptual framework of potential alcohol use determinants in the study settings based on available literature. We then estimated the effects of 35 potential alcohol use determinants identified in the conceptual framework (including 14 latent factors identified through exploratory factor analysis) on any alcohol use in the past 3 years and regular alcohol use amongst past three-year drinkers, using mixed-effects logistic models. The determinants explored were operationalised using longitudinal data from the UDAYA study.

Results

Our adjusted models identified 18 determinants for past 3-year alcohol use and 12 determinants for regular use. Distal determinants (e.g., socioeconomic status), intermediate determinants (e.g., parental alcohol use, media use), and proximal determinants (e.g., emotional regulation, early tobacco use) were identified. Geographical variations in both outcomes indicate potential differences in unmeasured community-level determinants (e.g., alcohol availability and acceptability).

Conclusions

Our findings extend the generalizability of several known determinants across settings, yet highlight the importance of addressing alcohol use in young people as a complex and context-dependent issue. Many identified determinants (e.g., education, media use, poor parental support, early tobacco use) are amenable to intervention through multi-sectoral prevention programs/policies. Such determinants should be the focus of ongoing policy/intervention development efforts in the region, and our revised conceptual framework may inform further research in India or similar South Asian settings.