Influence of inhaled corticosteroids on growth: a pediatric endocrinologist''s perspective

Given the increasing advocacy for the use of inhaled corticosteroids as a treatment of choice for persistent asthma, growing numbers of children are being exposed to the possible growth-suppressing effects of glucocorticoids. Recent evidence strongly suggests that, when consistently administered at moderate doses, inhaled corticosteroids (IC) are capable of slowing growth in children. Whether such growth suppression would persist and ultimately affect final adult height remains unknown. Therapeutic goals which aim for uninterrupted inflammatory disease control rather than periodic symptom control may increase the occurrence of growth failure in children treated with IC. In this article, current information about the mechanisms of growth suppression by glucocorticoids and the effects of IC on growth is reviewed, and recommendations for designing studies to investigate the effects of drugs on growth are presented.     

Effects of dietary fat and a vegetable-fruit mixture on the development of intestinal neoplasia in the ApcMin mouse

The variation in colorectal cancer (CRC) incidence worldwide strongly suggests a role for dietary influences. Based on epidemiological data, protective effects of vegetables and fruit intake on CRC are widely claimed, while other data indicate a possible increased CRC risk from (higher) dietary fat intake. Therefore, we have investigated single and interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in the ApcMin mouse, a mouse model for multiple intestinal neoplasia. In this study, four different diets (A-D) were compared, which were either low in fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced by a freeze-dried VFM. The diets were balanced so that they only differed among each other in fat/carbohydrate content and the presence of specific plant-constituents. Because the initiation of intestinal tumors in ApcMin mice occurs relatively early in life, exposure to the diets was started in utero. Without the addition of VFM, mice maintained at a high-fat diet did not develop significantly higher numbers of small or large intestinal adenomas than mice maintained at a low-fat diet. VFM added to a low-fat diet significantly lowered multiplicity of small intestinal polyps (from 16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in male ApcMin mice only. Strikingly, addition of VFM to female mice maintained on a low-fat diet and to both sexes maintained on a high-fat diet significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7 polyps/mouse). In conclusion, our results indicate that neither a lower fat intake nor consumption of VFM included in a high-fat diet decreases the development of polyps in mice genetically predisposed to intestinal tumor development.      

Effects of aerobic exercise training and irbesartan on blood pressure and heart rate variability in patients with chronic obstructive pulmonary disease

BACKGROUND AND OBJECTIVES:

The present pilot study was undertaken to evaluate the efficacy of an aerobic exercise training (AET) program alone or combined with an antihypertensive agent (irbesartan) to reduce blood pressure (BP) and enhance heart rate variability (HRV) in chronic obstructive pulmonary disease patients.

METHODS:

Twenty-one patients were randomly assigned to a double-blind treatment with exercise and placebo (n=11) or exercise and irbesartan (n=10). Subjects underwent 24 h BP monitoring and 24 h electrocardiographic recording before and after the 12-week AET. HRV was investigated using three indexes from the power spectral analysis and three indexes calculated from the time domain. The AET program consisted of exercising on a calibrated ergocycle for 30 min three times per week. Five patients in the placebo group were excluded during follow-up because they were not compliant.

RESULTS:

There was no change in 24 h systolic and diastolic BP before (130±14 mmHg and 70±3 mmHg, respectively) and after (128±8 mmHg and 70±8 mmHg, respectively) exercise training in the placebo group, whereas in the irbesartan group systolic and diastolic BP decreased from 135±9 mmHg and 76±9 mmHg to 126±12 mmHg and 72±8 mmHg, respectively (P<0.02). There were no changes in HRV parameters in either group.

CONCLUSIONS:

The present study suggests that a 12-week AET program is not associated with a significant reduction in BP or enhancement in HRV, whereas an AET program combined with irbe-sartan is associated with a reduction in 24 h BP.     

Platelet kinetics in patients with idiopathic thrombocytopenic purpura and moderate thrombocytopenia

We studied ten normal subjects and 20 patients with stable, untreated idiopathic thrombocytopenic purpura (ITP) and platelet counts in the range of 35,000 to 110,000/microL. The diagnosis was made by clinical criteria. Platelet-associated IgG was increased in all nine of the nine patients studied. Autologous platelets were labeled with chromium 51 and reinfused for measurement of mean cell life and platelet production rate. Mean cell life was calculated by two methods, weighted mean and multiple hit, with excellent agreement between the two. As expected, mean cell life was significantly reduced in ITP patients as compared to the normal subjects (2.9 days v. 8.0 days, P less than .001). However, mean platelet production rates in ITP patients and normal subjects, 3.5 and 3.8 X 10(9) platelets/k/d respectively, were not significantly different. Platelet production rate was above and below the normal range (2 to 5.6 X 10(9) platelets/k/d) in two and four patients, respectively. We conclude that the rate of platelet production is not increased in most patients with ITP who have platelet counts greater than 35,000/microL. We did find that platelet size was increased in eight of the 12 patients in whom it was measured, including two of the patients with low platelet production.     

Cardiovascular manifestations in patients with COPD

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is characterized mainly by airway obstruction due to chronic bronchitis and/or emphysema. In addition, COPD is frequently associated with other health problems with serious systemic manifestations. In particular, COPD patients are at increased risk of cardiovascular disease. BACKGROUND: Current knowledge about cardiovascular disease in patients with COPD mainly concerns the high prevalence of cardiac arrhythmias in this population. Systemic hypertension, cardiovascular disease, heart failure and cerebro-vascular disease are also frequently encountered. This review discusses the cardiovascular manifestations associated with COPD, excluding right heart failure due to pulmonary hypertension. VIEWPOINTS AND CONCLUSION: Non pulmonary health problems in patients with COPD, such as cardiovascular disease, are arousing increasing interest in the medical community. More studies are needed to increase our knowledge of cardiovascular disease in COPD and allow better medical management of patients.     

Contractile fatigue, muscle morphometry, and blood lactate in chronic obstructive pulmonary disease

We hypothesized that patients with chronic obstructive pulmonary disease developing contractile fatigue of the quadriceps during cycle exercise may have characteristic metabolic and muscle features that could increase their susceptibility to fatigue, thus differentiating them from those who do not develop fatigue. We examined, in 32 patients, the fiber-type proportion, enzymatic activities, and capillary density in the vastus lateralis and the arterial blood lactate level during constant work-rate cycling exercise. Contractile fatigue was defined as a postexercise fall in quadriceps twitch force greater than 15% of resting values. Twenty-two patients developed contractile fatigue after exercise. No significant differences were found between fatiguers and non-fatiguers for the endurance time, fiber-type proportion, and oxidative enzyme activities. The lactate dehydrogenase activity was significantly higher (p < 0.05) and muscle capillarization significantly reduced in fatiguers (p < 0.05). Compared with non-fatiguers, the arterial lactate level during exercise was significantly higher in fatiguers (p < 0.001). A significant relationship was found between the fall in quadriceps twitch force and lactate dehydrogenase activity, capillary/fiber ratio, and blood lactate level. We conclude that changes in muscle enzymatic profile and capillarization with a greater reliance on glycolytic metabolism during exercise are associated with contractile fatigue in patients with chronic obstructive pulmonary disease.