Early effects of acetazolamide on hemoglobin mass and plasma volume in chronic mountain sickness at 5100 m.

INTRODUCTION AND OBJECTIVES: Chronic Mountain Sickness (CMS) syndrome, combining excessive erythrocytosis and clinical symptoms in highlanders, remains a public health concern in high-altitude areas, especially in the Andes, with limited therapeutic approaches. The objectives of this study were to assess in CMS-highlanders permanently living in La Rinconada (5100-5300 m, Peru, the highest city in the world), the early efficacy of acetazolamide (ACZ) and atorvastatin to reduce hematocrit (Hct), as well as the underlying mechanisms focusing on intravascular volumes. MATERIALS AND METHODS: Forty-one males (46±8 years of age) permanently living in La Rinconada for 15 [10-20] years and suffering from CMS were randomized between ACZ (250 mg once-daily; N = 13), atorvastatin (20 mg once-daily; N = 14) or placebo (N = 14) uptake in a double-blinded parallel study. Hematocrit (primary endpoint) as well as arterial blood gasses, total hemoglobin mass (Hbmass) and intravascular volumes were assessed at baseline and after a mean (±SD) treatment duration of 19±2 days. RESULTS: ACZ increased PaO2 by +13.4% (95% CI: 4.3 to 22.5%) and decreased Hct by -5.2% (95% CI: -8.3 to -2.2%), whereas Hct remained unchanged with placebo or atorvastatin. ACZ tended to decrease Hbmass (-2.6%, 95% CI: -5.7 to 0.5%), decreased total red blood cell volume (RBCV, -5.3%, 95% CI: -10.3 to -0.3%) and increased plasma volume (PV, +17.6%, 95% CI: 4.9 to 30.3%). Atorvastatin had no effect on intravascular volumes, while Hbmass and RBCV increased in the placebo group (+6.1%, 95% CI: 4.2 to 7.9% and +7.0%, 95%CI: 2.7 to 11.4%, respectively). CONCLUSIONS: Short-term ACZ uptake was effective to reduce Hct in CMS-highlanders living at extreme altitude >5,000 m and was associated with both an increase in PV and a reduction in RBCV.

Global REACH 2018: The influence of acute and chronic hypoxia on cerebral haemodynamics and related functional outcomes during cold and heat stress.

KEY POINTS: Thermal and hypoxic stress commonly coexist in environmental, occupational and clinical settings, yet how the brain tolerates these multi-stressor environments is unknown Core cooling by 1.0°C reduced cerebral blood flow (CBF) by 20-30% and cerebral oxygen delivery (CDO2 ) by 12-19% at sea level and high altitude, whereas core heating by 1.5°C did not reliably reduce CBF or CDO2 Oxygen content in arterial blood was fully restored with acclimatisation to 4330 m, but concurrent cold stress reduced CBF and CDO2 Gross indices of cognition were not impaired by any combination of thermal and hypoxic stress despite large reductions in CDO2 Chronic hypoxia renders the brain susceptible to large reductions in oxygen delivery with concurrent cold stress, which might make monitoring core temperature more important in this context ABSTRACT: Real-world settings are composed of multiple environmental stressors, yet the majority of research in environmental physiology investigates these stressors in isolation. The brain is central in both behavioural and physiological responses to threatening stimuli and, given its tight metabolic and haemodynamic requirements, is particularly susceptible to environmental stress. We measured cerebral blood flow (CBF, duplex ultrasound), cerebral oxygen delivery (CDO2 ), oesophageal temperature, and arterial blood gases during exposure to three commonly experienced environmental stressors - heat, cold and hypoxia - in isolation, and in combination. Twelve healthy male subjects (27 ± 11 years) underwent core cooling by 1.0°C and core heating by 1.5°C in randomised order at sea level; acute hypoxia ( PET,O2  = 50 mm Hg) was imposed at baseline and at each thermal extreme. Core cooling and heating protocols were repeated after 16 ± 4 days residing at 4330 m to investigate any interactions with high altitude acclimatisation. Cold stress decreased CBF by 20-30% and CDO2 by 12-19% (both P < 0.01) irrespective of altitude, whereas heating did not reliably change either CBF or CDO2 (both P > 0.08). The increases in CBF with acute hypoxia during thermal stress were appropriate to maintain CDO2 at normothermic, normoxic values. Reaction time was faster and slower by 6-9% with heating and cooling, respectively (both P < 0.01), but central (brain) processes were not impaired by any combination of environmental stressors. These findings highlight the powerful influence of core cooling in reducing CDO2 . Despite these large reductions in CDO2 with cold stress, gross indices of cognition remained stable.

A recess intervention to promote moderate-to-vigorous physical activity.

BACKGROUND: Schools provide a prime environment for interventions that attempt to increase physical activity and prevent obesity. OBJECTIVE: This study examined the effect of a 30-min, structured recess using 22 games of known energy expenditure on moderate-to-vigorous physical activity when compared to free play implemented with third graders from two elementary schools over 9 weeks. METHODS: Moderate-to-vigorous physical activity and other cardiovascular risk factors were assessed pre- and post-intervention in 27 children. RESULTS: Moderate-to-vigorous physical activity during recess increased significantly in intervention school children from 6.9 ± 0.8 to 14.9 ± 0.9 min pre- and post-intervention, respectively (adjusted mean change 8.0 ± 1.1; P < 0.0001), with no differences by gender or body mass index (BMI). In-school, moderate-to-vigorous physical activity also increased significantly more for intervention compared to control children (adjusted mean change 14 ± 4 min vs. 3 ± 3 min; P = 0.014, respectively). CONCLUSION: There was no significant difference in BMI and cardiovascular risk factors. A structured recess is feasible to implement and can significantly increase moderate-to-vigorous physical activity.

Calibrating a novel multi-sensor physical activity measurement system.

Advancing the field of physical activity (PA) monitoring requires the development of innovative multi-sensor measurement systems that are feasible in the free-living environment. The use of novel analytical techniques to combine and process these multiple sensor signals is equally important. This paper describes a novel multi-sensor 'integrated PA measurement system' (IMS), the lab-based methodology used to calibrate the IMS, techniques used to predict multiple variables from the sensor signals, and proposes design changes to improve the feasibility of deploying the IMS in the free-living environment. The IMS consists of hip and wrist acceleration sensors, two piezoelectric respiration sensors on the torso, and an ultraviolet radiation sensor to obtain contextual information (indoors versus outdoors) of PA. During lab-based calibration of the IMS, data were collected on participants performing a PA routine consisting of seven different ambulatory and free-living activities while wearing a portable metabolic unit (criterion measure) and the IMS. Data analyses on the first 50 adult participants are presented. These analyses were used to determine if the IMS can be used to predict the variables of interest. Finally, physical modifications for the IMS that could enhance the feasibility of free-living use are proposed and refinement of the prediction techniques is discussed.

Immunogenic properties of an anti-DNA antibody-derived peptide, 88H.64-80: location of a dominant idiotope defined by T and B cells.

Immunization of normal (BALB/cxNZW)F1 H-2(dxu) mice with peptide 88H. 64-80 derived from the framework (FR) 3 VH region sequence of anti-DNA mAb, V-88, induces the production of IgG anti-peptide antibodies which cross-react specifically with the parent mAb. However, immunization of these normal mice with peptide 88H.64-80 sometimes provokes increased production of anti-dsDNA antibodies. A set of alanine substitute homologues of peptide 88H.64-80 were made to identify the amino acid residues that contribute to the antigenic status of the peptide. Peptide 88H.64-80 contained an antibody epitope at the carboxyl terminus of the peptide, while substitution of particular residues throughout the peptide had a significant inhibitory effect on T cell stimulation. Finally, subclass analysis of IgG anti-88H.64-80 peptide antibodies revealed a close correlation between the production of IgG2a anti-peptide antibodies (associated with a TH1 T cell response) and the production of IgG anti-dsDNA antibodies, but there was no correlation with any other antibody subclass. Despite the ability of peptide 88H.64-80 to provoke both the production of anti-dsDNA antibodies as well as anti-V region antibodies, the sequence of this peptide differs by only one amino acid residue from a number of murine germline gene-encoded homologues. Peptide 88H.64-80 probably represents an epitope whose appearance correlates with the level of expression of the VH genes that carry its sequence, and as such is characteristic of cross-reactive idiotypes associated with pathology.

Current provision of care for older persons in A & E units in the UK.

This study investigates the state of care for older persons within Accident and Emergency (A & E) units in the UK. As the proportion of older persons in the population continues to inexorably increase, A & E units will be expected to cope with a greater number of older people than ever before. Are they prepared for this increase, and do they possess the skills, knowledge and environment to care adequately for older people and the many special problems they present? One hundred A & E units were surveyed by a postal questionnaire consisting of a benchmark of best practice deemed by literature search and expert opinion to be important in caring for older persons in A & E. The data produced gives an overall picture of the current provision of care for older persons in A & E units, and indicates to fellow A & E nursing professionals where current performance may be improved.

Blood lactate and perceived exertion relative to ventilatory threshold: boys versus men.

The purpose of this study was to examine blood lactate (BLa) levels and ratings of perceived exertion (RPE) in nine boys (10.5 +/- 0.7 yr) and nine men (25.3 +/- 2.0 yr) during exercise relative to ventilatory threshold (VT). VT and VO2max were determined during a graded exercise test on a cycle ergometer. On three additional days each subject exercised for 10 min at either 80, 100, or 120% of the VO2 at VT. Capillary BLa levels and RPE were assessed at minutes 5 and 10 of each trial. VO2max averaged 47.7 +/- 5.4 and 50.2 +/- 6.2 mL x g(-1) x min(-1) in the boys and men, respectively (P > 0.05). VT expressed as %VO2max was 67.2 +/- 3.5% in the boys and 67.3 +/- 4.9% in the men (P > 0.05). BLa levels ranged from 2.0 +/- 0.7 to 4.7 +/- 0.9 mmol x L(-1) in the boys and from 2.6 +/- 0.5 to 8.2 +/- 2.1 mmol x L(-1) in the men across the three intensities. Corresponding RPE values ranged from 11.2 +/- 1.8 to 16.2 +/- 2.2 in the boys and from 10.2 +/- 1.2 to 15.8 +/- 1.7 in the men. A group x time x intensity interaction (P < 0.05) indicated that BLa in the men increased more so across time and intensity. There were no significant group difference or interactions involving RPE during exercise. Setting exercise intensity relative to VT did not abolish child-adult differences with respect to submaximal BLa levels. Despite maintaining lower BLa levels, RPE values were similar between boys and men.

Physiological correlates of 3-kilometer running performance in male children.

The purpose of this study was to examine the influence of body fatness, aerobic and anaerobic ability on 3-km running performance in 19 physically active boys (mean +/- SD, age = 10.4 +/- 0.9 yrs). The sum of six skinfolds, VO2 at 8.04 and 9.65 km.hr-1, and VO2max were measured in the laboratory. Run time for 3 km was assessed twice on separate days on a 200-meter indoor track. Prior to each run, every child performed two 55-meter sprints and two vertical jumps. Mean +/- SD values for the sum of skinfolds, %VO2max at each running speed, VO2max and 3-km run time were: 33.9 +/- 14.9 mm; 70.6 +/- 6.6% and 81.0 +/- 7.9%; 54.6 +/- 5.0 ml.kg-1.min-1; 16.41 +/- 2.58 min, respectively. Significant (p < 0.05) correlations were observed between the following variables and run time: sum of skinfolds (r = 0.72); vertical jump (r = 0.67); sprint time (r = 0.59); VO2max (r = 0.61); and, %VO2max at each treadmill speed (r = 0.79 and r = 0.75, respectively). Stepwise multiple regression analysis indicated that the combination of the %VO2max at 8.04 km.hr-1 and vertical jump accounted for 83% (adjusted R2) of the variance in running time (SEE = 1.06 min, p < 0.05). This study suggests that 3-km run time in physically active boys is influenced by aerobic and anaerobic indices as well as body fatness, supporting the notion that children, compared to adults, are not metabolic specialists.

The effect of exercise on serum and salivary cortisol in male children.

The purpose of this study was to examine serum and salivary cortisol responses to cycling exercise in male children, 10.6 +/- 0.2 yr (mean +/- SE). Each child performed a graded exercise test on a cycle ergometer to determine VO2max. On a separate day, a 30-min bout of exercise at 70% of VO2max was performed. Blood, obtained from a venous catheter, and saliva samples were collected at rest, at 15 and 30 min of exercise, and 15 min post-exercise. The mean serum cortisol level at 15 min (7.94 +/- 1.43 micrograms.dl-1) and 30 min (8.72 +/- 1.77 micrograms.dl-1) of exercise and at 15 min post-exercise (8.21 +/- 1.59 micrograms.dl-1) were significantly greater than rest (5.54 +/- 0.86 micrograms.dl-1). The increase in salivary cortisol levels over time approached (P = 0.08), but did not reach significance. However, effect size analyses indicated that the increase in salivary cortisol at 30 min of exercise (0.64) and 15 min post-exercise (0.62) was similar to the change in serum cortisol at these same two time points (0.72 and 0.66, respectively). Serum and salivary cortisol were correlated (P < 0.05) at 15 min of exercise (r = 0.77), 30 min of exercise (r = 0.90), and 15 min post-exercise (r = 0.84), but not at rest (r = 0.46). In conclusion, 30 min of submaximal exercise at 70% of VO2max significantly increased serum cortisol level; and salivary and serum cortisol are correlated during and after exercise.

Evaluation of eyes with advanced stages of retinopathy of prematurity using standardized echography.

The authors evaluated 36 patients (72 eyes) who had either Stage 4 or Stage 5 retinopathy of prematurity (ROP) with standardized A-scan and B-scan echography. The eyes were evaluated for vitreous opacities, retrolental membranes, and retinal detachments. Stage 5 retinal detachments were present in 94% (68 of 72) of the eyes with 65% (47 of 72) having a wide anterior and narrow posterior configuration. Anterior retinal loops were noted in 36% of the eyes. Subretinal opacities were present in 47% of the eyes. Choroidal thickening and intraocular calcium were noted in 22% and 14% of eyes, respectively. The axial eye length was measured and adjusted for the differences in chronological and gestational age and compared with data from normal eyes. This showed that eyes with ROP were much smaller. The standardized A-scan was helpful in confirming the diagnosis of retinal detachment, evaluating the peripheral retina, and examining the subretinal space. The combination of A-scan and B-scan echography is helpful in predicting anatomic findings in patients with ROP undergoing surgery.

Effect of endodontic access preparation on resistance to crown-root fracture.

This investigation involved the creation of coronal-radicular fractures in vitro and compared the fracture resistance of intact human mandibular molars, with molars after varied tooth preparation. Forty freshly extracted, non-carious, nonrestored human mandibular molars were randomly divided into four treatment groups. The molars were subjected to constantly increasing occlusal load until coronal-radicular fracture occurred. Tooth preparations significantly diminished resistance to coronal-radicular fracture.

Barbiturates protect retinal cells from hypoxia in cell culture.

A culture system was used to screen for drugs that can protect mammalian retinal cells from damage induced by hypoxia. Using a special incubator, cultures could be made hypoxic for defined periods. Phase contrast photomicroscopy facilitated comparison of retinal cells before hypoxia and 1 to 2 days after hypoxia. Using 2- to 3-week-old cultures, certain glutamate antagonists, anesthetics, calcium blockers, and thiopental sodium were screened for their effect in protecting cells from hypoxia. The most remarkable effect was noted with thiopental. Quantitative measurements showed a significant increase in the percent of cells surviving after exposure to hypoxia in the presence of 100 mumol/L of thiopental sodium compared with control hypoxic cultures--82% vs 59% at 48 hours. A dose-response curve demonstrated maximal effect at 50 mumol/L of thiopental sodium, with toxic effects noted at 200 mumol/L of thiopental sodium. Our results show that thiopental reduces hypoxia-induced damage to retinal cells in culture.

Changes in brain alpha-adrenoceptors with increasing age in rabbits.

The effects of aging on rabbit brain alpha-adrenoceptor number was studied using radioligand binding techniques. The ligands [3H]prazosin and [3H]clonidine were used to examine binding to alpha 1 and alpha 2-adrenoceptors, respectively, in forebrain and hindbrain membranes from rabbits aged from 1 month to 3 years. Changes in specific [3H]clonidine binding were compared to changes in central alpha 2-adrenoceptor function as measured by the fall in blood pressure after intracisternal administration of clonidine. Both alpha 1- and alpha 2-adrenoceptor number decreased with age in the rabbit brain. The maximum fall in specific [3H]prazosin binding occurred in animals aged between 3 and 6 months. [3H]clonidine binding in forebrain was also reduced in 6-month-old animals but [3H]clonidine binding in hindbrain was only reduced in animals over 2 years old. Despite the reduction in [3H]clonidine binding no decrease in the in vivo response to centrally administered clonidine was observed in 2-year-old animals when compared to 3-month-old rabbits.