SEM Age Research Articles

S133 Eosinophilic airway inflammation is associated with FEV1 decline in severe asthma

BackgroundSevere asthma is a multidimensional disease, with recent evidence supporting the notion that eosinophilic airway inflammation (EAI) is an important driver for exacerbations. In addition EAI has been shown to...

Sensitivity to 6-n-propylthiouracil is associated with gustin (carbonic anhydrase VI) gene polymorphism, salivary zinc, and body mass index in humans

The individual ability to taste 6-n-propylthiouracil (PROP) may be correlated with body mass index (BMI) and differences in the salivary proteins involved in taste function, such as the zinc-dependent enzyme gustin, which is a trophic factor of taste buds. We investigated the possible association of PROP taste responsiveness with gustin gene polymorphism rs2274333 (A/G), salivary ionic zinc concentrations, and BMI. We measured cognitive eating behaviors and BMI in 75 volunteers (28 men and 47 women; mean plusmn SEM age: 25 plusmn 3 y). The intensity of taste perception evoked by PROP and sodium chloride solutions was estimated to evaluate PROP taster status. Salivary ionic zinc concentrations were measured, and molecular analyses of the gustin gene polymorphism were performed in individuals classified by PROP status by using polymerase chain reaction techniques. We classified subjects as PROP supertasters (n = 27), medium tasters (n = 28), or nontasters (n = 20). Salivary ionic zinc concentrations and BMI were greater in nontasters than in supertasters (P = 0.003 and P = 0.042, respectively). Molecular analyses of gustin DNA showed that allele A and genotype AA were significantly more frequent in supertasters, whereas allele G and genotype GG were significantly more frequent in nontasters (P lt 0.001). These data showed that responsiveness to PROP is inversely related to BMI and salivary ionic zinc concentrations. The gustin gene dimorphism rs2274333 observed in supertaster and nontaster subjects may influence the protein conformation and, thereby, affect zinc ion binding. Our data showed a direct association between PROP sensitivity and a polymorphism in the gustin gene that is hypothesized to affect its function. This trial was registered at clinicaltrials.gov as UNICADBSITB-1.

Orally Disintegrating and Oral Standard Olanzapine Tablets Similarly Elevate the Homeostasis Model Assessment of Insulin Resistance Index and Plasma Triglyceride Levels in 12 Healthy Men

Treatment with olanzapine is associated with obesity, diabetes mellitus, and dyslipidemia. Reports have indicated that orally disintegrating tablets (ODT) cause less weight gain than oral standard tablets (OST). The aim of this study was to compare the effect of short-term treatment with these 2 distinct olanzapine formulations on glucose and lipid metabolism in healthy men. Twelve healthy men (mean ± SEM age: 25.1 ± 5.5 years) received olanzapine ODT (10 mg od, 8 days), olanzapine OST (10 mg od, 8 days), or no intervention in a randomized crossover design. At breakfast and dinner, glucose, insulin, free fatty acids (FFA), and triglyceride concentrations were measured at 10-minute intervals from 30 minutes prior to 2 hours after ingestion of standard meals. Leptin and adiponectin concentrations were measured at 20- and 30-minute intervals, respectively, between 0000h-1200h. Physical activity was assessed with an accelerometer. Fuel oxidation was measured in fasting condition by indirect calorimetry. The study was conducted from April 2006 through September 2006. Treatment with olanzapine ODT and OST equally elevated the homeostasis model assessment of insulin resistance (HOMA-IR) (P = .005). At breakfast, both formulations equally increased fasting and postprandial triglyceride concentrations (P = .013 and P = .005, respectively) while decreasing fasting and postprandial FFA concentrations (P = .004 and P = .009, respectively). Body weight, body composition, physical activity, or fuel oxidation did not differ between treatment modalities. Eight days of treatment with both olanzapine formulations similarly increased HOMA-IR and triglyceride concentrations and decreased FFA concentrations in response to standard meals without affecting anthropometrics or physical activity. These data suggest that olanzapine hampers insulin action via mechanistic routes other than body adiposity or physical inactivity. controlled-trials.com. Identifier: ISRCTN17632637.

Cinnamon extract lowers blood glucose in hyperglycemic subjects

Based on insulin potentiating activity of cinnamon, effects of a water extract of cinnamon were tested in a 2‐mo double‐blind placebo trial with 137 participants in China. Mean±SEM age was 61.3 ± 0.8 years, BMI was 25.3 ± 0.3 and M/F ratio was 65/72. A placebo capsule or a 250 mg dried water‐extract cinnamon (CinSulin) capsule was given twice per day. At baseline, homeostasis model assessment‐estimated insulin resistance (HOMA‐IR) was significantly correlated with diastolic blood pressure (r=0.23) postprandial glucose (r=0.45) and insulin (r=0.42), triglycerides (r=0.29), fructosamine (0.23), BMI (r=0.29) and negatively correlated with HDLC (r=0.37). After 2 mo, fasting glucose decreased (p<0.001) in the aqua‐cinnamon‐supplemented group (8.85 ± 0.36 to 8.19 ± 0.29 mmol/L) compared with 8.57 ± 0.32 to 8.44 ± 0.34 mmol/L in the placebo group (p=0.45). Glucose 2 h after a 75 g carbohydrate load also decreased (p<0.0001) with CinSulin (15.09 ± 0.57 to 13.30 ± 0.55 mmol/L) compared to 14.18 ± 0.60 to 13.74 ± 0.58 mmol/L with placebo. Insulin concentrations and HOMA‐IR tended to be improved by aqua‐cinnamon supplements but differences were not significant. In summary, supplementation of a water extract of cinnamon had beneficial effects in subjects with hyperglycemia. (Supported by USDA‐ARS, Tang‐An Medical & Oklahoma State Univ).

Pediatric ovarian malignancy presenting as ovarian torsion: incidence and relevance

Purpose With ovarian torsion, concern for underlying malignancy in the enlarged ovary has previously driven surgeons to resection. Detorsion alone has been recommended to allow for resolution of edema of the ovary with follow-up ultrasound surveillance to evaluate for a persistent mass, yet is not routine practice. However, the incidence of malignancies presenting as ovarian torsion is not documented. Does the risk of an underlying malignancy justify salpingoophorectomy and decreased fertility? Method After institutional review board exemption (IRB#-022008-095), a 15½-year retrospective review was conducted to identify cases of operative ovarian torsion in our medical center. Tumors with neoplastic pathology (malignant and benign) were analyzed and compared with all reported cases in the literature. Results A total of 114 patients (mean ± SEM age, 10 years, 2 days to 19 years ± 0.53) with operatively proven ovarian torsion were identified. Four malignancies (3.5%) and 26 benign neoplasms (23%) were present in this age group. Malignancies consisted of serous borderline tumors (2), juvenile granulosa cell tumor (1), and dysgerminoma (1). All were stage I: the former were stage IA and cured with resection alone, and 1 was a stage IB dysgerminoma, which required chemotherapy. The literature yielded a total of 593 cases of operative ovarian torsion with 9 (1.5%) malignancies and 193 (33%) benign neoplasms. The malignancies were juvenile granulosa cell tumor (n = 4), dysgerminoma (n = 2), serous borderline tumors (n = 2), and 1 undifferentiated adenocarcinoma. Conclusion By combining our series with 13 in the literature, a 1.8% malignancy rate occurred in 707 patients with ovarian torsion, markedly less than the reported malignancy rate of 10% in children with ovarian masses. Thus, neither a pathologic nor malignant lead point should be assumed in cases of torsion. In our series, which represents the largest series of torsion in the pediatric literature, all malignancies presented as stage I. These data further support the implementation of operative detorsion and close postoperative ovarian surveillance, with reoperation for persistent masses. Further study is needed to determine if delaying resection by weeks in those cases of persistent masses would result in tumor progression and thus change prognosis.

Use of Propofol–Xylazine and the Anderson Sling Suspension System for Recovery of Horses from Desflurane Anesthesia

To characterize the behavior of horses recovering in the Anderson Sling Suspension System after 4 hours of desflurane anesthesia and postdesflurane intravenous (IV) administration of propofol and xylazine. Experimental study. Healthy horses (n=6), mean+/-SEM age 12.3+/-1.8 years; mean weight 556+/-27 kg. Each horse was anesthetized with xylazine, diazepam, and ketamine IV and anesthesia was maintained with desflurane in O(2). At the end of 4 hours of desflurane, each horse was positioned in the sling suspension system and administered propofol-xylazine IV. Recovery events were quantitatively and qualitatively assessed. Venous blood was obtained before and after anesthesia for biochemical and propofol analyses. Anesthetic induction and maintenance were without incident. Apnea commonly accompanied propofol administration. All horses had consistent recovery behavior characterized by a smooth, careful, atraumatic return to a standing posture. Results of this study support careful, selective clinical use of desflurane, propofol-xylazine, and the Anderson Sling Suspension System to atraumatically transition horses with high anesthetic recovery risk to a wakeful standing posture. Technique choices to facilitate individualized, atraumatic recovery of horses from general anesthesia are desirable. Use of IV propofol and xylazine to transition horses from desflurane anesthesia during sling recovery to standing posture may facilitate improved recovery management of high-injury risk equine patients requiring general anesthesia.

Abdominal volume contribution to tidal volume as an early indicator of respiratory impairment in Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is characterised by progressive loss of muscular strength that leads to an increasingly restrictive pulmonary syndrome. However, it is still not clear whether this determines alterations in the breathing pattern. We studied: 66 DMD patients at different stages of the disease (mean+/- sem age 12.6+/-0.6 yrs, range 5-22 yrs of age), subdivided into four groups according to age; and 21 age-matched healthy male controls. Spirometry, lung volumes and nocturnal oxygen saturation were measured in all DMD patients. Ventilatory pattern and chest wall volume variations were assessed by optoelectronic plethysmography during spontaneous breathing both in seated and supine positions. Whilst in a seated position, no significant differences were found between patients and controls or between different age groups. In the supine position, the average contribution of abdominal volume change (DeltaV(AB)) to tidal volume progressively decreased with age (p<0.001). The patients who showed nocturnal hypoxaemia showed significantly lower Delta V(AB). In conclusion, chest wall motion during spontaneous breathing in awake conditions and in supine position is an important indicator of the degree of respiratory muscle impairment in DMD. DeltaV(AB) is not only an important marker of the progression of the disease but is also an early indicator of nocturnal hypoxaemia.

Time course for autoregulation recovery following severe traumatic brain injury

The aim of the present study was to evaluate the time course for cerebral autoregulation (AR) recovery following severe traumatic brain injury (TBI). Thirty-six patients (27 males and 9 females, mean +/- SEM age 33 +/- 15.1 years) with severe TBI underwent serial dynamic AR studies with leg cuff deflation as a stimulus, until recovery of the AR responses was measured. The AR was impaired (AR index < 2.8) in 30 (83%) of 36 patients on Days 3-5 after injury, and in 19 individuals (53%) impairments were found on Days 9-11 after the injury. Nine (25%) of 36 patients exhibited a poor AR response (AR index < 1) on postinjury Days 12-14, which eventually recovered on Days 15-23. Fifty-eight percent of the patients with a Glasgow Coma Scale score of 3-5, 50% of those with diffuse brain injury, 54% of those with elevated intracranial pressure, and 40% of those with poor outcome had no AR recovery in the first 11 days after injury. Autoregulation recovery after severe TBI can be delayed, and failure to recover during the 2nd week after injury occurs mainly in patients with a lower Glasgow Coma Scale score, diffuse brain injury, elevated ICP, or unfavorable outcome. The finding suggests that perfusion pressure management should be considered in some of the patients for a period of at least 2 weeks.

Effect of Insulin Catheter Wear-Time on Subcutaneous Adipose Tissue Blood Flow and Insulin Absorption in Humans

Insertion of an insulin catheter for continuous subcutaneous insulin infusion into the subcutaneous adipose tissue (SAT) causes a tissue trauma that may have consequences for insulin absorption. We evaluated the importance of insulin catheter wear-time on subcutaneous adipose tissue blood flow (ATBF) and absorption of the rapid-acting insulin analog insulin aspart over a period of 4 days. Teflon insulin catheters (Medtronic, Minneapolis, MN) were inserted into the abdominal SAT of 10 healthy men without diabetes (mean +/- SEM age, 23.0 +/- 1.1 years; body mass index, 22.1 +/- 0.7 kg/m(2)) and connected to an insulin pump delivering a constant rate of isotonic saline for 4 days. Subjects participated in four study days (days 0, 1, 2, and 4) during which ATBF around the catheter tip was measured by (133)Xe clearance and absorption of an insulin aspart bolus (0.1 U/kg) was measured for 4 h. ATBF increased from day 0 to day 2 after catheter insertion (2.6 +/- 0.6 to 4.5 +/- 0.8 mL/100 g/min; P = 0.030). By day 4, ATBF had returned to day 0 level. Time to peak plasma insulin aspart concentration after bolus administration decreased with catheter wear-time from 55 +/- 3 min on day 0 to 45 +/- 4 min on day 4 (P = 0.019). Neither peak plasma concentration nor area under the curve of insulin aspart changed significantly. Insertion of a Teflon insulin catheter into the SAT results in increased ATBF and faster absorption of insulin aspart in a period of 4 days without any change in the total amount of insulin aspart absorbed.

Comparative Efficacy of Water and Land Treadmill Training for Overweight or Obese Adults

No known previous research has been published to explore the efficacy of underwater treadmill (UTM) exercise training for the obese. Thus, the purpose of this study was to compare changes in physical fitness, body weight, and body composition in physically inactive, overweight, and obese adults after 12 wks of land treadmill (LTM) or UTM training. Fifty-seven physically inactive, overweight, and obese men (n = 25) and women (n = 32) participated in this investigation. The mean +/- SEM age, weight, body mass index (BMI), and V O2max upon entry were 44 +/- 2 yr, 90.5 +/- 2.4 kg, 30.5 +/- 0.7 kg.m, and 27.1 +/- 0.7 mL O2.kg.min, respectively. Subjects were randomly assigned to exercise three times per week for 12 wk on either LTM (n = 29) or UTM (n = 28) matched for intensity and volume. Session volume was progressively increased from 250 to 500 kcal per session by week 6 and remained at 500 kcal through week 12. Before and after training, V O2max was assessed by the Bruce treadmill protocol with open-circuit calorimetry, and body composition was assessed by dual-energy ray absorptiometry. Data were analyzed by a 2 (training) x 2 (exercise mode) x 2 (gender) ANOVA repeated across training (alpha = 0.05). Training responses were not different between genders. After either UTM or LTM training, V O2max was significantly increased (+3.6 +/- 0.4 mL O2.kg.min), whereas body weight (-1.2 +/- 0.3 kg), BMI (-0.56 +/- 0.11 kg.m), body fat percentage (-1.3% +/- 1.3%), and fat mass (-1.1 +/- 0.3 kg) were significantly reduced (pooled means for UTM and LTM). Regional leg lean body mass (LBM) was significantly increased with both CTM and UTM (0.4 +/- 0.3 and 0.8 +/- 0.2 kg, respectively). An increase in total LBM approached significance with UTM training only (+0.6 +/- 0.3 kg, P = 0.0599). UTM and LTM training are equally capable of improving aerobic fitness and body composition in physically inactive overweight individuals, but UTM training may induce increases in LBM.

Effect of administration of propofol and xylazine hydrochloride on recovery of horses after four hours of anesthesia with desflurane

To compare characteristics of horses recovering from 4 hours of desflurane anesthesia with and without immediate postanesthetic IV administration of propofol and xylazine. Animals-8 healthy horses (mean +/- SEM age, 6.6 +/- 1.0 years; mean body weight, 551 +/- 50 kg). Horses were anesthetized twice. Both times, anesthesia was induced with a combination of xylazine hydrochloride, diazepam, and ketamine hydrochloride and then maintained for 4 hours with desflurane in oxygen. Choice of postanesthetic treatment was randomly assigned via a crossover design such that each horse received an IV injection of propofol and xylazine or saline (0.9% NaCl) solution after the anesthetic episode. Recovery events were quantitatively and qualitatively assessed. Venous blood samples were obtained before and after anesthesia for determination of serum creatine kinase activity and plasma propofol concentration. Anesthetic induction and maintenance were unremarkable in all horses. Compared with administration of saline solution, postanesthetic administration of propofol and xylazine resulted in an increased interval to emergence from anesthesia but improved quality of recovery-related transition to standing. Compared with administration of saline solution, administration of propofol also delayed the rate of decrease of end-tidal concentrations of desflurane and carbon dioxide and added to conditions promoting hypoxemia and hypoventilation. Propofol and xylazine administered IV to horses after 4 hours of desflurane anesthesia improved the quality of transition from lateral recumbency to standing but added potential for harmful respiratory depression during the postanesthetic period.

Ingestion of a protein hydrolysate is accompanied by an accelerated in vivo digestion and absorption rate when compared with its intact protein

Background:It has been suggested that a protein hydrolysate, as opposed to its intact protein, is more easily digested and absorbed from the gut, which results in greater plasma amino acid availability and a greater muscle protein synthetic response. Objective:We aimed to compare dietary protein digestion and absorption kinetics and the subsequent muscle protein synthetic response to the ingestion of a single bolus of protein hydrolysate compared with its intact protein in vivo in humans. Design:Ten elderly men (mean ± SEM age: 64 ± 1 y) were randomly assigned to a crossover experiment that involved 2 treatments in which the subjects consumed a 35-g bolus of specifically producedl-[1-13C]phenylalanine-labeled intact casein (CAS) or hydrolyzed casein (CASH). Blood and muscle-tissue samples were collected to assess the appearance rate of dietary protein–derived phenylalanine in the circulation and subsequent muscle protein fractional synthetic rate over a 6-h postprandial period. Results:The mean (±SEM) exogenous phenylalanine appearance rate was 27 ± 6% higher after ingestion of CASH than after ingestion of CAS (P < 0.001). Splanchnic extraction was significantly lower in CASH compared with CAS treatment (P < 0.01). Plasma amino acid concentrations increased to a greater extent (25–50%) after the ingestion of CASH than after the ingestion of CAS (P < 0.01). Muscle protein synthesis rates averaged 0.054 ± 0.004% and 0.068 ± 0.006%/h in the CAS and CASH treatments, respectively (P = 0.10). Conclusions:Ingestion of a protein hydrolysate, as opposed to its intact protein, accelerates protein digestion and absorption from the gut, augments postprandial amino acid availability, and tends to increase the incorporation rate of dietary amino acids into skeletal muscle protein.

Plasma Ammonia Concentrations and the Slow Component of Oxygen Uptake Kinetics During Cycle Ergometry

The purposes of this study were to 1) compare the patterns of responses for plasma ammonia concentration ([NH3]) during moderate- vs. heavy-intensity cycle ergometry, and 2) examine the relationship between the V O2 slow component (V O 2SC) and plasma [NH3]. Thirteen healthy, untrained men (mean +/- SEM age = 24.8 +/- 0.6 years) performed a total of eight constant power output exercises (7 minutes in duration) at two different intensities (moderate, 60% gas exchange threshold [GET] = 60% of the gas exchange threshold; and heavy, Delta 50% = 50% of the difference between GET and V O2 max). Blood was collected from an antecubital vein before the exercise, during the last 3 minutes of the 6-minute warm-up, and during each minute of the 7-minute constant power output workbout. The time course of changes in plasma [NH3] and V O2 during the two constant power output exercise intensities were assessed separately using 2 (intensity) x 7 (time) repeated-measures analyses of variance. For 60% GET, there were no significant differences in the mean normalized plasma [NH3] during the 7-minute workbout. For Delta 50%, there was a significant increase in the mean normalized plasma [NH3] during the 7-minute workbout. These findings suggest a potential relationship between exercise-induced hyperammonemia and the V O 2SC during heavy-intensity exercise.

Neutrophil-Degranulation and Lymphocyte-Subset Response after 48 hr of Fluid and/or Energy Restriction

The aim was to investigate the effects of 48 hr of fluid, energy, or combined fluid and energy restriction on circulating leukocyte and lymphocyte subset counts (CD3+, CD4+, and CD8+) and bacterially stimulated neutrophil degranulation at rest and after exercise. Thirteen healthy men (M +/- SEM age 21 +/- 1 yr) participated in 4 randomized 48-hr trials. During control (CON) participants received their estimated energy (2,903 +/- 17 kcal/day) and fluid (3,912 +/- 140 ml/day) requirements. During fluid restriction (FR) they received their energy requirements and 193 +/- 19 ml/day water to drink. During energy restriction (ER) they received their fluid requirements and 290 +/- 6 kcal/day. Fluid and energy restriction (F+ER) was a combination of FR and ER. After 48 hr, participants performed a 30-min treadmill time trial (TT) followed by rehydration (0-2 hr) and refeeding (2-6 hr). Circulating leukocyte and lymphocyte counts remained unchanged for CON and FR. Circulating leukocyte, lymphocyte, CD3+, and CD4+ counts decreased by ~20% in ER and ~30% in F+ER by 48 hr (p < .01), returning to within 0-hr values by 6 hr post-TT. Circulating neutrophil count and degranulation were unaltered by dietary restriction at rest and after TT. In conclusion, a 48-hr period of ER and F+ER, but not FR, decreased circulating leukocyte, lymphocyte, CD3+, and CD4+ counts but not neutrophil count or degranulation. Circulating leukocyte and lymphocyte counts normalized on refeeding. Finally, dietary restriction did not alter circulating leukocyte, lymphocyte, and neutrophil responses to 30 min of maximal exercise.

Aerobic and Resistance Training in Coronary Disease

The purpose of this study was to compare resistance training (RT) (one set vs three sets) combined with aerobic training (AT) versus AT alone in persons with coronary artery disease. Subjects (n = 72) were randomized to AT (5 d x wk(-1)) or combined AT (3 d x wk(-1)) with either one set (AT/RT1) or three sets (AT/RT3) of RT performed 2 d x wk(-1). VO2peak, ventilatory anaerobic threshold (VAT), strength and endurance, body composition, and adherence were measured before and after 29 wk of training. Fifty-three subjects (mean +/- SEM age 61 +/- 2) completed the training. The increase from baseline in VO2peak (L x min(-1)) averaged 11% for AT (P < 0.05), 14% for AT/RT1 (P < 0.01), and 18% for AT/RT3 (P < 0.001), however, the difference between groups was not significant. VAT improved significantly in the AT/RT3 group only (P < 0.05). The AT/RT3 group gained more lean mass than the AT group (1.5 versus 0.4 kg, P < 0.01), yet gains between AT/RT1 and AT were similar (P = 0.2). Only AT + RT groups demonstrated a reduction in body fat (P < 0.05). Strength and endurance increased more in the AT + RT groups than AT alone (P < 0.05). Adherence to number of sets performed was lower in AT/RT3 than AT/RT1 (P < 0.02). Combined AT + RT yields more pronounced physiological adaptations than AT alone and appears to be superior in producing improvements in VO2peak, muscular strength and endurance, and body composition. The data support the use of multiple set RT for patients desiring an increased RT stimulus which may further augment parameters that affect VO2peak, VAT, lower body endurance, and muscle mass in a cardiac population.

P.2.e.019 Adult attention-deficit hyperactivity disorder in bipolar disorder

To assess the pulmonary and systemicdistribution and elimination of perflubron(C8F17Br1; Liqui Vent; Alliance Pharmaceutical; San Diego, CA) during and following the period ofpartial liquid ventilation.Prospective phase, I and II clinical trial.Adult surgical, ICU.Eighteen adult patients(mean ± SEM age, 37.9 ± 3.4 years) with severe respiratoryfailure, some of whom required extracorporeal life support (72%), andwho were managed with partial liquid ventilation with perflubron.Perflubron was administered into thetrachea, and gas ventilation of the perfluorocarbon-filled lung(partial liquid ventilation) was then performed. Additional doses wereadministered daily for from 1 to 7 days, with a median cumulative doseof 31 m, L/kg (range, 3 to 60 m, L/kg).Patient blood samples were evaluated by gaschromatography for serum perflubron levels. Sequential lateral andanteroposterior radiographs were assessed, using a 5-point ratingscale, for the degree of perflubron fill following the final dose. Samples of expired gas were collected, and the rate of loss ofperflubron in the expired gas was measured by gas chromatography. Meanserum perflubron levels increased to 0.16 ± 0.05 mg/dL at 24 hfollowing administration of the initial dose. A mean maximum level of0.26 ± 0.05 mg/dL of perflubron was present in the serum 24 hfollowing the administration of the last dose. This level slowlytrended downward to 0.18 ± 0.06 mg/dL over the ensuing 7 days(p = 0.281). Perflubron elimination via expired gas occurred at amean rate of 9.4 ± 3.0 m, L/h at 1 h, and 1.0 ± 0.4 m, L/h at48 h after the last dose (p = 0.012). By radiologic evaluation, perflubron was eliminated from the lungs progressively from4.2 ± 0.2 at the time of administration of the last dose, to2.8 ± 0.3 at 4 days later (p < 0.001). Perflubron tended todistribute and remain for longer periods in the dependent regions ofthe lung when compared to the nondependent regions (96-h perflubronfill score: posterior, 3.8 ± 0.5; anterior, 1.9 ± 0.4;p = 0.004).Perflubron is eliminated ata maximum rate of 9.4 ± 3.0 m, L/h by evaporative loss from theairways and is retained in greater amounts in the dependent lungregions when compared to the nondependent lung regions. There is a lowbut measurable maximum blood concentration of 0.26 ± 0.05 mg/dL inpatients after perflubron administration, which did not decreasesignificantly after cessation of partial liquidventilation.

Is the efficacy of psoralen plus ultraviolet A therapy for vitiligo enhanced by concurrent topical calcipotriol? A placebo-controlled double-blind study

Background Encouraging results of previous uncontrolled trials suggest that calcipotriol may potentiate the efficacy of psoralen plus ultraviolet (UV) A (PUVA) therapy in patients with vitiligo. Objectives We performed a placebo-controlled double-blind study to investigate whether the effectiveness of PUVA treatment could be enhanced by combination with topical calcipotriol in the treatment of vitiligo. Methods Thirty-five patients with generalized vitiligo enrolled in the study. Symmetrical lesions of similar dimensions and with no spontaneous repigmentation on arms, legs or trunk were selected as reference lesions. In this randomized left-right comparison study, calcipotriol 0·05 mg g−1 cream or placebo was applied to the reference lesions 1 h before PUVA treatment (oral 8-methoxypsoralen and conventional UVA units) twice weekly. Patients were examined at weekly intervals. The mean number of sessions and the cumulative UVA dosage for initial and complete repigmentation were calculated. Results Twenty-seven patients (nine women, 18 men; mean ± SEM age 29·8 ± 13·5 years) were evaluated. The mean ± SEM cumulative UVA dose and number of UVA exposures for initial repigmentation were 52·52 ± 6·10 J cm−2 and 9·33 ± 0·65 on the calcipotriol side, and 78·20 ± 7·88 J cm−2 and 12·00 ± 0·81 on the placebo side, respectively (P < 0·001). For complete repigmentation, respective values were 232·79 ± 14·97 J cm−2 and 27·40 ± 1·47 on the calcipotriol side and 259·93 ± 13·71 J cm−2and 30·07 ± 1·34 on the placebo side (P = 0·001). Treatment with calcipotriol and PUVA resulted in significantly higher percentages of repigmentation for both initial (81%) and complete pigmentation (63%), compared with placebo and PUVA (7% and 15%, respectively). Conclusions Our results have shown that concurrent topical calcipotriol potentiates the efficacy of PUVA in the treatment of vitiligo, and that this combination achieves earlier pigmentation with a lower total UVA dosage.

Fuel metabolism during exercise in euglycaemia and hyperglycaemia in patients with type 1 diabetes mellitus—a prospective single-blinded randomised crossover trial

We assessed systemic and local muscle fuel metabolism during aerobic exercise in patients with type 1 diabetes at euglycaemia and hyperglycaemia with identical insulin levels. This was a single-blinded randomised crossover study at a university diabetes unit in Switzerland. We studied seven physically active men with type 1 diabetes (mean +/- SEM age 33.5 +/- 2.4 years, diabetes duration 20.1 +/- 3.6 years, HbA1c 6.7 +/- 0.2% and peak oxygen uptake [VO2peak] 50.3 +/- 4.5 ml min(-1) kg(-1)). Men were studied twice while cycling for 120 min at 55 to 60% of VO2peak, with a blood glucose level randomly set either at 5 or 11 mmol/l and identical insulinaemia. The participants were blinded to the glycaemic level; allocation concealment was by opaque, sealed envelopes. Magnetic resonance spectroscopy was used to quantify intramyocellular glycogen and lipids before and after exercise. Indirect calorimetry and measurement of stable isotopes and counter-regulatory hormones complemented the assessment of local and systemic fuel metabolism. The contribution of lipid oxidation to overall energy metabolism was higher in euglycaemia than in hyperglycaemia (49.4 +/- 4.8 vs 30.6 +/- 4.2%; p < 0.05). Carbohydrate oxidation accounted for 48.2 +/- 4.7 and 66.6 +/- 4.2% of total energy expenditure in euglycaemia and hyperglycaemia, respectively (p < 0.05). The level of intramyocellular glycogen before exercise was higher in hyperglycaemia than in euglycaemia (3.4 +/- 0.3 vs 2.7 +/- 0.2 arbitrary units [AU]; p < 0.05). Absolute glycogen consumption tended to be higher in hyperglycaemia than in euglycaemia (1.3 +/- 0.3 vs 0.9 +/- 0.1 AU). Cortisol and growth hormone increased more strongly in euglycaemia than in hyperglycaemia (levels at the end of exercise 634 +/- 52 vs 501 +/- 32 nmol/l and 15.5 +/- 4.5 vs 7.4 +/- 2.0 ng/ml, respectively; p < 0.05). Substrate oxidation in type 1 diabetic patients performing aerobic exercise in euglycaemia is similar to that in healthy individuals revealing a shift towards lipid oxidation during exercise. In hyperglycaemia fuel metabolism in these patients is dominated by carbohydrate oxidation. Intramyocellular glycogen was not spared in hyperglycaemia.

Endothelial Function in Highly Endurance-Trained Men: Effects of Acute Exercise

Exercise training reverses endothelial dysfunction, but the effect in young, healthy subjects is less clear. We determined the influence of maximal oxygen uptake (VO2max) and a single bout of high-intensity exercise on flow-mediated dilatation (FMD), brachial artery diameter, peak blood flow, nitric oxide (NO) bioavailability, and antioxidant status in highly endurance-trained men and their sedentary counterparts. Ten men athletes (mean +/- SEM age 23.5 +/- 0.9 years, height 182.6 +/- 2.4 cm, weight 72.5 +/- 2.4 kg, VO2max 75.9 +/- 0.8 mL.kg.min) and seven healthy controls (age 25.4 +/- 1.2 years, height 183.9 +/- 3.74 cm, weight 92.8 +/- 3.9 kg, VO2max 47.7 +/- 1.7 mL.kg.min) took part in the study. FMD, brachial artery diameter, and peak blood flow were measured using echo-Doppler before, 1 hour, 24 hours, and 48 hours after a single bout of interval running for 5 x 5 minutes at 90% of maximal heart rate. NO bioavailability and antioxidant status in blood were measured at all time points. Maximal arterial diameter and peak flow were 10-15% (P < 0.02) and 28-35% (P < 0.02) larger, respectively, in athletes vs. controls at all time points, and similar FMD were observed, apart from a transient decay of FMD in athletes 1 hour post exercise. NO bioavailability increased significantly after exercise in both groups and decreased to baseline levels after 24 hours in controls but remained increased 80% and 93% above baseline 24 and 48 hours post exercise in athletes. Antioxidant status was equal in the two groups at baseline and increased by approximately 10% 1 hour post exercise, an effect that lasted for 24 hours. Athletes had larger arterial diameter but similar FMD as untrained subjects, i.e., athletes had larger capacity for blood transport compared with their untrained counterparts. The observed FMD, bioavailability of NO, and antioxidant status in blood were highly dependent on the time elapsed after the exercise session.

Serum inhibin B concentration as a prognostic factor for prediction of sperm retrieval in testis biopsy of patients with azoospermia.

This study was conducted to determine if serum inhibin B concentration can predict spermatogenesis in azoospermic infertile men. This cross-sectional study included 70 patients with male-factor infertility referred to Alvand and Vali-e-Asr Infertility Centers, Tehran, Iran. All patients had azoospermia. Standard evaluation consisted of history and physical examination with extreme attention to sexual history and testis examination including testis size, consistency, and presence of varicocele. Laboratory evaluation done for all cases consisted of FSH, testosterone, LH, prolactin, and inhibin B. Testis biopsy was performed in all cases with acceptable testis volume and FSH. The mean inhibin B level was compared in groups with positive and negative sperm retrieval. The mean+/-SEM age of 70 azoospermic patients was 32.1+/-6.2 (range: 20 - 50) years. All couples had primary infertility with a mean+/-SEM duration of infertility of 74.3+/-7.7 months. The mean+/-SEM testicular volume was 10.14+/-0.75 mL. The mean+/-SEM FSH and LH levels were 17.55+/-1.68, and 11.33+/-0.99 mIU/mL, respectively. The mean+/-SEM serum prolactin and testosterone levels were 308.77+/-17.35 and 5.45+/-0.91 ng/dL, respectively. The mean+/-SEM serum inhibin B concentration was 138.23+/-28.58 (range: 15 - 1500) pg/mL. Sperm was not retrieved in 82% of the patients; in 13% of the cases, biopsy revealed spermatogenesis. The mean+/-SEM serum FSH level of positive and negative groups was 9.78+/-2.13 and 22.56+/-2.46 mIU/mL, respectively (P<0.05). The mean serum LH, prolactin, and testosterone levels were not statistically different between the two groups. The mean+/-SEM serum inhibin B was 129+/-45.46, and 158.93+/-47.24 pg/mL in positive and negative groups, respectively (P>0.05). Inhibin B concentration is not an appropriate predicting factor for testicular spermatogenesis.