Intermittent hypoxia as a means to improve aerobic capacity in type 2 diabetes.

Physical inactivity and a low maximal aerobic capacity (VO2max) strongly predict morbidity and mortality in patients with type 2 diabetes (T2D). Patients with T2D have a reduced VO2max when compared with healthy individuals of similar age, weight, and physical activity levels, and this lower aerobic capacity is usually attributed to a reduced oxygen delivery to the working muscles. The oxygen carrying capacity of the blood, as well as increases in cardiac output and blood flow, contribute to the delivery of oxygen to the active muscles during exercise. Hemoglobin mass (Hb mass), a key determinant of oxygen carrying capacity, is suggested to be reduced in patients with T2D following the observation of a lower blood volume (BV) in combination with normal hematocrit levels in this population. Therefore, a lower Hb mass, in addition to a reported lower BV and impaired cardiovascular response to exercise, likely contributes to the reduced oxygen delivery and VO2max in patients with T2D. While exercise training increases Hb mass, BV, and consequently VO2max, the majority of patients with T2D are not physically active, highlighting the need for alternative methods to improve VO2max in this population. Exposure to hypoxia triggers the release of erythropoietin, the hormone regulating red blood cell production, which increases Hb mass and consequently BV. Exposure to mild intermittent hypoxia (IH), characterized by few and short episodes of hypoxia at a fraction of inspired oxygen ranging between 10 and 14% interspersed with cycles of normoxia, increased red blood cell volume, Hb mass, and plasma volume in patients with coronary artery disease or chronic obstructive pulmonary disease, which resulted in an improved VO2max in both populations. We hypothesize that 12 exposures to mild IH over a period of 4weeks will increase Hb mass, BV, cardiac function, and VO2max in patients with T2D. Therefore, exposures to mild IH may increase oxygen delivery and VO2max without the need to perform exercise in patients with T2D.

Determination of blood volume by pulse CO-oximetry.

The objective of this study was to determine whether changes in carboxyhaemoglobin (COHb) saturation following carbon monoxide (CO) rebreathing can be accurately detected by pulse CO-oximetry in order to determine blood volume. Noninvasive measurements of carboxyhaemoglobin saturation (SpCO) were continuously monitored by pulse CO-oximetry before, during and following 2 min of CO rebreathing. Reproducibility and accuracy of noninvasive blood volume measurements were determined in 16 healthy non-smoking individuals (15 males, age: 28 ± 2 years, body mass index: 25.4 ± 0.6 kg m(-2)) through comparison with blood volume measurements calculated from invasive measurements of COHb saturation. The coefficient of variation for noninvasive blood volume measurements performed on separate days was 15.1% which decreases to 9.1% when measurements were performed on the same day. Changes in COHb saturation and SpCO following CO rebreathing were strongly correlated (r = 0.90, p < 0.01), resulting in a significant correlation between invasive and noninvasive blood volume measurements (r = 0.83, p = 0.02). Changes in SpCO following CO rebreathing can be accurately detected by pulse CO-oximetry, which could potentially provide a simplified, convenient and reproducible method to rapidly determine blood volume in healthy individuals.

Variability in pulmonary function following rapid altitude ascent to the Amundsen-Scott South Pole station.

The impact of acute altitude exposure on pulmonary function is variable. A large inter-individual variability in the changes in forced expiratory flows (FEFs) is reported with acute exposure to altitude, which is suggested to represent an interaction between several factors influencing bronchial tone such as changes in gas density, catecholamine stimulation, and mild interstitial edema. This study examined the association between FEF variability, acute mountain sickness (AMS) and various blood markers affecting bronchial tone (endothelin-1, vascular endothelial growth factor (VEGF), catecholamines, angiotensin II) in 102 individuals rapidly transported to the South Pole (2835 m). The mean FEF between 25 and 75% (FEF(25-75)) and blood markers were recorded at sea level and after the second night at altitude. AMS was assessed using Lake Louise questionnaires. FEF(25-75) increased by an average of 12% with changes ranging from -26 to +59% from sea level to altitude. On the second day, AMS incidence was 36% and was higher in individuals with increases in FEF(25-75) (41 vs. 22%, P = 0.05). Ascent to altitude induced an increase in endothelin-1 levels, with greater levels observed in individuals with decreased FEF(25-75). Epinephrine levels increased with ascent to altitude and the response was six times larger in individuals with decreased FEF(25-75). Greater levels of endothelin-1 in individuals with decreased FEF(25-75) suggest a response consistent with pulmonary hypertension and/or mild interstitial edema, while epinephrine may be upregulated in these individuals to clear lung fluid through stimulation of ß(2)-adrenergic receptors.

Effect of reduced total blood volume on left ventricular volumes and kinetics in type 2 diabetes.

AIM: Although impaired left ventricular (LV) diastolic function is commonly observed in patients with type 2 diabetes, it remains unclear whether the impairment is caused by altered LV relaxation or changes in LV preload. The purpose of this study was to examine the influence of LV function and LV loading conditions on stroke volume in men with type 2 diabetes. METHODS: Cardiac magnetic resonance imaging scans were performed in eight men with type 2 diabetes and 11 non-diabetic men matched for age, weight and physical activity level. Total blood volume was determined with the Evans blue dye dilution technique. RESULTS: End-diastolic volume (EDV), the ratio of peak early to late mitral inflow velocity (E/A) and stroke volume were lower in men with type 2 diabetes than in non-diabetic individuals. Peak filling rate and peak ejection rate were not different between diabetic and non-diabetic individuals; however, men with type 2 diabetes had proportionally longer systolic duration than non-diabetic individuals. Heart rate was higher and total blood volume was lower in men with type 2 diabetes. The lower total blood volume was correlated with a lower EDV in men with type 2 diabetes. CONCLUSIONS: Men with type 2 diabetes have an altered cardiac cycle and lower end-diastolic and stroke volume. A lower total blood volume and higher heart rate in men with type 2 diabetes suggest that changes in LV preload, independent of changes in LV relaxation or contractility, influence LV diastolic filling and stroke volume in this population.

Breathing strategy to preserve exercising cardiac function in patients with heart failure.

The heart and lungs are closely linked as they lie in series, share a common surface area and compete for space within the thoracic cavity. The heart and lungs are exposed to the similar changes in intrathoracic pressure, and reflexes within one organ can influence the other (i.e. vagal influence of lung inflation on heart rate). In patients with heart failure, these cardiopulmonary interactions may be altered due to decreased lung and left ventricular compliance, increased cardiac size, high cardiac filling pressure and altered receptor sensitivity to neural activation. Exercise further affects the cardiopulmonary interactions by stimulating an increase in the depth and frequency of breathing which accentuates the fluctuations in intrathoracic pressure, and by requiring large increases in stroke volume and heart rate in order to respond to the increased metabolic demand. Previous work from our laboratory suggested that patients with heart failure avoid high lung volumes during exercise, often at the expense of unnecessary large positive expiratory intrathoracic pressures resulting in significant wasted effort. Moreover, we also observed that voluntarily increases in lung volume in patients with heart failure induced a mild relative bradycardia, a response not observed in similar aged healthy individuals. Thus, we hypothesized that the rapid shallow low lung volume breathing, in combination with positive expiratory intrathoracic pressure, often adopted by patients with heart failure during exercise is an attempt to preserve, or even enhance, the cardiac response to exercise.

Impaired stroke volume and aerobic capacity in female adolescents with type 1 and type 2 diabetes mellitus.

AIM/HYPOTHESIS: This study was designed to determine whether type 2 diabetic adolescents have reduced aerobic capacity and to investigate the role of cardiac output and arteriovenous oxygen difference (a-vO(2)) in their exercise response. METHODS: Female adolescents (age 12-18 years) with type 2 diabetes mellitus (n = 8) and type 1 diabetes mellitus (n = 12) and obese (n = 10) and non-obese (n = 10) non-diabetic controls were recruited for this study. Baseline data included maximal aerobic capacity (cycle ergometer) and body composition. Cardiac output and a-vO(2) were determined at rest and during submaximal exercise. RESULTS: Diabetic groups had lower aerobic capacity than non-diabetic groups (p < 0.05). Adolescents with type 2 diabetes had lower aerobic capacity than the type 1 diabetic group. Maximal heart rate was lower in the type 2 diabetic group (p < 0.05). Exercise stroke volume was 30-40% lower at 100 and 120 beats per min in the diabetic than in the non-diabetic groups (p < 0.05). The a-vO(2) value was not different in any condition. CONCLUSIONS AND INTERPRETATION: Type 2 diabetic adolescents have reduced aerobic capacity and reduced heart rate response to maximal exercise. Furthermore, type 2 and type 1 diabetic adolescent girls have a blunted exercise stroke volume response compared with non-diabetic controls. Central rather than peripheral mechanisms contribute to the reduced aerobic capacity in diabetic adolescents. Although of short duration, type 2 diabetes in adolescence is already affecting cardiovascular function in adolescents.

Follow-up of bone mineral density in 27 cases of anorexia nervosa.

Cortical and trabecular bone loss can lead to osteoporosis in chronic forms of anorexia nervosa (AN). As there is some debate about the reversibility of this condition, we performed a longitudinal follow-up study of 27 cases in which clinical, biological, X-ray and lumbar and femoral neck dual photon absorptiometry examinations were conducted every 6 months for up to 30 months. Three groups were distinguished: G1, untreated amenorrheic AN (N = 14, total follow-up 126 months); G2, effectively treated AN (N = 11, total follow-up 192 months), with two subgroups: fluoride (N = 5) and estrogen (N = 6); and G3, remitting AN with normalization of the gonadic function (N = 2, total follow-up 36 months). Results were adjusted for each patient to a 6-month variation. Semestrial variations in lumbar bone mineral density (BMD) were -2.1 +/- 1.3%, +2.8 +/- 1.5%, and -0.3 +/- 1.3% (mean +/- SEM), respectively for G1, G2 and G3; those for femoral neck BMD semestrial variations were -5.9 +/- 2.1%, -3.8 +/- 1.2% and -1.0 +/- 0.6%. Femoral neck and lumbar BMD variations for G1 were mainly correlated positively with bone-forming markers (serum osteocalcin, alkaline phosphatase) and negatively with initial lumbar BMD. Estrogen alone increased lumbar BMD by +1.4 +/- 2.3% every 6 months but did not stabilize femoral neck BMD (-3.5 +/- 1.4%). Fluoride increased lumbar BMD by 4.8 +/- 1.8%. Both lumbar and femoral neck BMD were stabilized in the remission group (-0.3 +/- 1.3% and -1.0 +/- 0.6%), despite half of the follow-up time with amenorrhea. In conclusion, untreated AN is associated with a marked trabecular and cortical bone loss (4-10% per year), which can lead to osteoporotic fractures. In prevention of bone loss, the efficacy of estrogen is difficult to investigate in AN, even with a well-controlled trial. Our study could provide argument that, when the observance of this preventive treatment is assessed, lumbar BMD can be stabilized in chronic forms of AN.

Osteoporotic fractures revealing anorexia nervosa in five females.

Anorexia nervosa affects 0.5% to 1% of female adolescents. The course is chronic in 50% of cases, causing substantial bone loss with osteoporotic fractures after a few years of amenorrhea. This is probably an underestimated problem. The diagnosis of anorexia nervosa is readily missed, as illustrated by five cases reported herein. The five patients were females aged 17 to 44 years who were only slightly underweight (mean weight, 43.6 kg; body mass index < 20 kg/m2). The first fracture occurred seven to 24 years after the onset of anorexia nervosa. Three patients had vertebral crush fractures, and two had peripheral insufficiency fractures. Bone mineral density measured by absorptiometry was very low (mean lumbar z-score, -3.7 SD). Three patients, who were all members of health care professions, knew that they had anorexia nervosa but failed to report this condition. In the other two patients, the amenorrhea had been mistakenly ascribed to other causes (Stein-Leventhal syndrome and psychogenic anovulation). None of the patients was receiving medical follow-up. Anorexia nervosa should be considered routinely in women who are slightly underweight. The patients often deny abnormal menstruation or eating behaviors. The diagnosis rests on determination of the body mass index, a thorough history emphasizing current and past gonadal dysfunction, and evaluation of the diagnostic criteria for anorexia nervosa. Osteoporosis is probably a common but underestimated complication of anorexia nervosa, particularly before the menopause. Enhanced awareness of this condition should allow earlier detection of a greater number of cases.

[Sports, bones and hormones. Multiple interactions]. / Sport, os, hormones. De multiples interactions.

Classically, sports activities are thought to have a beneficial effect on bone tissues. Actually, there are many interactions between sports activities and bone tissue and in certain cases complex hormone disorders may develop. Recent progress in the evaluation of bone structure (absorptiometry) and better understanding of the neuroendocrine functions have improved our knowledge of these interactions and helped provide answers as to the true effect of sports, and particular high-level training, on bone tissue. Mechanical stimulation of bone increases the level of both cortical and cancellous bone formation. The mechanical effect is localized in areas under particular constraint such as the lower limbs in runners and the upper predominant limb in tennis players. Inversely, hypoestrogenism, similar to anorexia nervosa, has been observed to be the cause of general bone loss and increased risk of osteoporosis in certain high level athletes. When these two opposing phenomena occur simultaneously, there is generally an overall loss of cancellous bone mass while bones submitted to major mechanical stress may be relatively protected. Amenorrhoea, particularly in long distance runners, generally occurs when training exceeds 30 km per week. Menarche may be delayed by 1 or 2 years when training begins early and dismenorrhoea is seen in 50% or more of the athletes. Amenorrhoea results from a central disorder due to insufficient pulsatile secretion of luteo-releasing hormone and subsequent hypogonadism. The role of beta-endorphins or catelestrogens on hypothalamic receptors has been suggested as the underlying mechanism. These different observations help provide answers to the different problems raised when providing counselling and care for high level athletes.

Dorsal scalloping by calcified disc herniation.

SUMMARY OF BACKGROUND DATA: Disc herniation responsible for scalloping of vertebral body had been reported only at the lumbar level. RESULTS: The authors report on an unusual etiology of dorsal scalloping. A voluminous and calcified dorsal disc herniation was responsible for this, and within the center of the mass there was an unexpected hypersignal on nuclear magnetic resonance imaging. CONCLUSION: Scalloping does not preclude disc herniation, even at the dorsal level. Hyperintensity in T1-weighted images can reveal calcifications, as indicated in previous studies.

Effects of right and left hemisphere cerebrovascular lesions on discrimination of prosodic and semantic aspects of affect in sentences.

Ten nonaphasic left cerebrovascular accident (CVA) patients, 12 right CVA patients, and 16 normals were matched for age, education, lesion sizes, and postonset intervals; all were right handed. One task consisted of 36 sentences connoting one of six primary emotions (joy, sadness, fear, surprise, disgust, anger) presented binaurally with a neutral emotional tone. Subjects were required to point to the appropriate emotion name on a vertically arranged list. A second task consisted of the same 36 sentences voiced emotionally by humming with a closed mouth, presented binaurally, and requiring the same response as for the preceding task. A third task consisted of 18 of the sentences spoken with concordant emotional tone and the remaining 18 sentences spoken with discordant emotional tone, presented binaurally and requiring pointing to the word "SAME" or "DIFFERENT" arrayed vertically. The right hemisphere (RH) patients were significantly impaired, relative to the left hemisphere (LH) patients and normals, on the pure prosody task (2) and on the emotional concordance task (3), the latter effect being significant only for mismatch categorization. The LH patients performed (nonsignificantly) less well than the RH patients and normals on the verbal contextual task (1). Performances on the three tasks were not significantly correlated in the patient groups. It was concluded that the RH probably dominates for phonetic discrimination of vowel trains (fundamental frequency and/or single vowel or multivowel contour) and that the RH probably dominates for certain forms of selective attention in the verbal domain perhaps involving simultaneous mismatch treatment of ongoing sentence-level, distracting, complementary, verbal processes. Comparison of similar right and left, cortical (frontoparietal), and subcortical (capsule and basal ganglia) lesions suggested, but did not prove, that the RH pure prosody impairment is cortical whereas the RH tonal-semantic mismatch categorization impairment involves subcortical as well as cortical contributions.