The effects of resistance exercise training on arterial stiffness in metabolic syndrome.

PURPOSE: Arterial stiffness is a strong independent risk factor for cardiovascular disease and is elevated in individuals with metabolic syndrome (MetS). Resistance training is a popular form of exercise that has beneficial effects on muscle mass, strength, balance and glucose control. However, it is unknown whether resistance exercise training (RT) can lower arterial stiffness in patients with MetS. Thus, the aim of this study was to examine whether a progressive RT program would improve arterial stiffness in MetS. METHODS: A total of 57 subjects (28 healthy sedentary subjects; 29 MetS) were evaluated for arterial structure and function, including pulse wave velocity (cfPWV: arterial stiffness), before and after an 8-week period of RT or continuation of sedentary lifestyle. RESULTS: We found that 8 weeks of progressive RT increased skeletal muscle strength in both Con and MetS, but did not change arterial stiffness in either MetS (cfPWV; Pre 7.9 ± 0.4 m/s vs. Post 7.7 ± 0.4 m/s) or healthy controls (cfPWV; Pre 6.9 ± 0.3 m/s vs. Post 7.0 ± 0.3 m/s). However, when cfPWV is considered as a continuous variable, high baseline measures of cfPWV tended to show a decrease in cfPWV following RT. CONCLUSION: Eight weeks of progressive RT did not decrease the group mean values of arterial stiffness in individuals with MetS or healthy controls.

Is obesity predictive of cardiovascular dysfunction independent of cardiovascular risk factors?

INTRODUCTION: Obesity is thought to exert detrimental effects on the cardiovascular (CV) system. However, this relationship is impacted by the co-occurrence of CV risk factors, type 2 diabetes (T2DM) and overt disease. We examined the relationships between obesity, assessed by body mass index (BMI) and waist circumference (WC), and CV function in 102 subjects without overt CV disease. We hypothesized that obesity would be independently predictive of CV remodeling and functional differences, especially at peak exercise. METHODS: Brachial (bSBP) and central (cSBP) systolic pressure, carotid-to-femoral pulse wave velocity (PWVcf) augmentation index (AGI; by SphygmoCor), and carotid remodeling (B-mode ultrasound) were examined at rest. Further, peak exercise cardiac imaging (Doppler ultrasound) was performed to measure the coupling between the heart and arterial system. RESULTS: In backward elimination regression models, accounting for CV risk factors, neither BMI nor WC were predictors of carotid thickness or PWVcf; rather age, triglycerides and hypertension were the main determinants. However, BMI and WC predicted carotid cross-sectional area and lumen diameter. When examining the relationship between body size and SBP, BMI (ß=0.32) and WC (ß=0.25) were predictors of bSBP (P<0.05), whereas, BMI was the only predictor of cSBP (ß=0.22, P<0.05) indicating a differential relationship between cSBP, bSBP and body size. Further, BMI (ß=-0.26) and WC (ß=-0.27) were independent predictors of AGI (P<0.05). As for resting cardiac diastolic function, WC seemed to be a better predictor than BMI. However, both BMI and WC were inversely and independently related to arterial-elastance (net arterial load) and end-systolic elastance (cardiac contractility) at rest and peak exercise. CONCLUSION: These findings illustrate that obesity, without T2DM and overt CV disease, and after accounting for CV risk factors, is susceptible to pathophysiological adaptations that may predispose individuals to an increased risk of CV events.

Effects of downhill treadmill running on uncoupling protein 3 mRNA expression.

Eccentric biased exercise has been reported to elicit more muscle injury than concentric or isometric exercise and potentially generate increased oxidative stress one to two days post exercise. Increased oxidative stress has been shown to up-regulate the expression of UCP3 mRNA. The aim of this study was to investigate the effects of downhill running on skeletal muscle UCP3 mRNA expression. Twenty-four male Sprague Dawley rats were randomly assigned to run continuously for 30 minutes (30-C, n = 6), or run six 5-minute bouts separated by rest periods of 2 minutes (2-R, n = 6), 4 minutes (4-R, n = 6), and 6 minutes (6-R, n = 6) on a 16 degree declined treadmill at a speed of 16 m. min (-1). Sham control animals (n = 8) were placed in a treadmill chamber during the 30-minute run session. Semi-quantitative RT-PCR was conducted to evaluate UCP3 mRNA levels in the plantaris, a muscle used eccentrically during downhill running and tibialis anterior, a muscle which undergoes very little eccentric muscle contraction during this exercise. The level of gene expression was normalized to 18 S ribosomal mRNA expression from the same PCR product. Results are reported as mean +/- standard error. UCP3 of the plantaris muscles from 2-R animals (2.36 +/- 0.13) was significantly greater than UCP3 of the plantaris from control animals (1.72 +/- 0.13), p < 0.05. UCP3 of the tibialis anterior from the continuous group (1.51 +/- 0.17) was significantly less than the UCP3 of the tibialis anterior of the control group (2.09 +/- 1.4), p < 0.05. These data suggest that downhill treadmill running is associated with an increase in UCP3 mRNA expression in the plantaris muscle. These results indicate that exercise which is biased toward eccentric exercise may up-regulate UCP3 mRNA during the period post exercise when muscle damage and repair is elevated.

Practice parameter: evaluation of the child with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and The Practice Committee of the Child Neurology Society.

OBJECTIVE: To make evidence-based recommendations concerning the evaluation of the child with a nonprogressive global developmental delay. METHODS: Relevant literature was reviewed, abstracted, and classified. Recommendations were based on a four-tiered scheme of evidence classification. RESULTS: Global developmental delay is common and affects 1% to 3% of children. Given yields of about 1%, routine metabolic screening is not indicated in the initial evaluation of a child with global developmental delay. Because of the higher yield (3.5% to 10%), even in the absence of dysmorphic features or features suggestive of a specific syndrome, routine cytogenetic studies and molecular testing for the fragile X mutation are recommended. The diagnosis of Rett syndrome should be considered in girls with unexplained moderate to severe developmental delay. Additional genetic studies (e.g., subtelomeric chromosomal rearrangements) may also be considered in selected children. Evaluation of serum lead levels should be restricted to those children with identifiable risk factors for excessive lead exposure. Thyroid studies need not be undertaken (unless clinically indicated) if the child underwent newborn screening. An EEG is not recommended as part of the initial evaluation unless there are historical features suggestive of epilepsy or a specific epileptic syndrome. Routine neuroimaging, with MRI preferred to CT, is recommended particularly if abnormalities are found on physical examination. Because of the increased incidence of visual and auditory impairments, children with global developmental delay may undergo appropriate visual and audiometric assessment at the time of diagnosis. CONCLUSIONS: A specific etiology can be determined in the majority of children with global developmental delay. Certain routine screening tests are indicated and depending on history and examination findings, additional specific testing may be performed.

Basal insulin therapy in type 2 diabetes: 28-week comparison of insulin glargine (HOE 901) and NPH insulin.

OBJECTIVE: To determine the safety and efficacy of the long-acting analog insulin glargine compared with NPH insulin in patients with type 2 diabetes who were previously treated with insulin alone. RESEARCH DESIGN AND METHODS: A total of 518 subjects with type 2 diabetes who were receiving NPH insulin with or without regular insulin for postprandial control were randomized to receive insulin glargine (HOE 901) once daily (n = 259) or NPH insulin once or twice daily in = 259) for 28 weeks in an open-label, multicenter trial. Doses were adjusted to obtain target fasting glucose <6.7 mmol/l. At study end point, the median total daily insulin dose in both treatment groups was 0.75 IU/kg. RESULTS: The treatment groups showed similar improvements in HbA1c from baseline to end point on intent-to-treat analysis. The mean change (means +/- SD) in HbA1c from baseline to end point was similar in the insulin glargine group (-0.41 +/- 0.1%) and the NPH group (-0.59 +/- 0.1%) after patients began with an average baseline HbA1c of approximately 8.5%. The treatments were associated with similar reductions in fasting glucose levels. Overall, mild symptomatic hypoglycemia was similar in insulin glargine subjects (61.4%) and NPH insulin subjects (66.%) However, nocturnal hypoglycemia in the insulin glargine group was reduced by 25% during the treatment period after the dose-titration phase(26.5 vs. 35.5%, P = 0.0136). Subjects in the insulin glargine group experienced less weight gain than those in the NPH group (0.4 vs. 1.4 kg, P < 0.0007). CONCLUSIONS: In patients with type 2 diabetes, once-daily bedtime insulin glargine is as effective as once- or twice-daily NPH in improving and maintaining glycemic control. In addition, insulin glargine deonstrates a lower risk of nocturnal hypoglycemia and less weight gain compared with NPH insulin.

A 16-week comparison of the novel insulin analog insulin glargine (HOE 901) and NPH human insulin used with insulin lispro in patients with type 1 diabetes.

OBJECTIVE: To determine the safety and efficacy of the long-acting insulin analog, insulin glargine, as a component of basal bolus therapy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Patients with type 1 diabetes receiving basal-bolus insulin treatment with NPH human insulin and insulin lispro were randomized to receive insulin glargine (HOE 901), a long-acting basal insulin analog, once a day (n = 310) or NPH human insulin (n = 309) as basal treatment with continued bolus insulin lispro for 16 weeks in an open-label study NPH insulin patients maintained their prior schedule of administration once or twice a day, whereas insulin glargine patients received basal insulin once a day at bedtime. RESULTS: Compared with all NPH insulin patients, insulin glargine patients had significant decreases in fasting blood glucose measured at home (means +/- SEM, -42.0 +/- 4.7 vs. -12.4 +/- 4.7 mg/dl [-2.33 +/- 0.26 vs. -0.69 +/- 0.26 mmol/l]; P = 0.0001). These differences were evident early and persisted throughout the study More patients in the insulin glargine group (29.6%) than in the NPH group (16.8%) reached a target fasting blood glucose of 119 mg/dl (< 6.6 mmol/l). However, there were no differences between the groups with respect to change in GHb. Insulin glargine treatment was also associated with a significant decrease in the variability of fasting blood glucose values (P = 0.0124). No differences in the occurrence of symptomatic hypoglycemia, including nocturnal hypoglycemia, were observed. Overall, adverse events were similar in the two treatment groups with the exception of injection site pain, which was more common in the insulin glargine group (6.1%) than in the NPH group (0.3%). Weight gain was 0.12 kg in insulin glargine patients and 0.54 kg in NPH insulin patients (P = 0.034). CONCLUSIONS: Basal insulin therapy with insulin glargine once a day appears to be as safe and at least as effective as using NPH insulin once or twice a day in maintaining glycemic control in patients with type 1 diabetes receiving basal-bolus insulin treatment with insulin lispro.

Effects of resistance vs. aerobic training combined with an 800 calorie liquid diet on lean body mass and resting metabolic rate.

OBJECTIVE: Utilization of very-low-calorie diets (VLCD) for weight loss results in loss of lean body weight (LBW) and a decrease in resting metabolic rate (RMR). The addition of aerobic exercise does not prevent this. The purpose of this study was to examine the effect of intensive, high volume resistance training combined with a VLCD on these parameters. METHODS: Twenty subjects (17 women, three men), mean age 38 years, were randomly assigned to either standard treatment control plus diet (C+D), n = 10, or resistance exercise plus diet (R+D), n = 10. Both groups consumed 800 kcal/day liquid formula diets for 12 weeks. The C+D group exercised 1 hour four times/week by walking, biking or stair climbing. The R+D group performed resistance training 3 days/week at 10 stations increasing from two sets of 8 to 15 repetitions to four sets of 8 to 15 repetitions by 12 weeks. Groups were similar at baseline with respect to weight, body composition, aerobic capacity, and resting metabolic rate. RESULTS: Maximum oxygen consumption (Max VO2) increased significantly (p<0.05) but equally in both groups. Body weight decreased significantly more (p<0.01) in C+D than R+D. The C+D group lost a significant (p<0.05) amount of LBW (51 to 47 kg). No decrease in LBW was observed in R+D. In addition, R+D had an increase (p<0.05) in RMR O2 ml/kg/min (2.6 to 3.1). The 24 hour RMR decreased (p<0.05) in the C+D group. CONCLUSION: The addition of an intensive, high volume resistance training program resulted in preservation of LBW and RMR during weight loss with a VLCD.

Outcome and cost at a children's hospital following resuscitation for out-of-hospital cardiopulmonary arrest.

OBJECTIVE: To determine the outcome and cost for children resuscitated following out-of-hospital cardiopulmonary arrest. DESIGN: Retrospective case series. SETTING: An organized prehospital emergency medical system within Birmingham, Ala, in a county with 150,493 children under the age of 15 years. PATIENTS: Sixty-three pediatric victims of out-of-hospital cardiopulmonary arrest of any cause presenting to the emergency department of a children's hospital. INTERVENTION: Standard resuscitative techniques were performed for all patients until resuscitative efforts were discontinued in the hospital emergency department or successful resuscitation was achieved. MAIN OUTCOME MEASURES: Successful resuscitation, survival to hospital discharge, neurological outcome, final disposition, and cost of hospital care. RESULTS: Of 63 children with out-of-hospital cardiopulmonary arrest treated in the emergency department of a children's hospital, 60 were pulseless and apneic on arrival, 18 (28.6%) were successfully resuscitated and admitted to the intensive care unit, and six (9.5%) were discharged from the hospital. Five of the survivors had severe neurological deficits and one appeared normal. On follow-up, two patients had died (1 month and 7 months after discharge), three were in a vegetative state, and one was normal. The normal patient had successful defibrillation prior to arrival at the emergency department. The average inpatient charge was $10,667 per patient for those who died and $100,000 for those discharged. CONCLUSIONS: Aggressive treatment does not lead to intact survival for victims of out-of-hospital cardiopulmonary arrest who present to the pediatric emergency department with a preterminal rhythm and absence of spontaneous circulation. Resuscitation efforts in the emergency department are commonly successful but lead to death or severe neurological sequelae at discharge with extremely high cost of care.

In vitro intracanal temperatures produced during warm lateral condensation of Gutta-percha.

In vitro intracanal temperatures produced during the war lateral condensation of gutta-percha were measured using a computerized recording system that allowed repeated obturations of a root canal model. The obturations were performed using a Touch 'n Heat unit. Temperatures were recorded to an accuracy of a hundredth degree centigrade by 16 intracanal themocouples connected to the computerized measurement system. The highest intracanal temperature recorded was 114.51 degrees C at a power setting of 6, while the mean intracanal temperature increase above the average room temperature ranged from 8.18 to 65.05 degrees C. In addition, the spreader was not uniformly heated to the same temperature throughout its entire length. The hottest point on the spreader was located 5 mm from the tip.

A new model system for measuring intracanal temperatures.

A new model system was developed which allows intracanal temperature measurements to be recorded during repeated obturations of a human tooth root canal. A human central incisor was embedded in clear orthodontic resin and sectioned longitudinally. Sixteen thermocouples were secured at 2-mm intervals along two surfaces of the root canal. The thermocouples were connected to a computerized temperature recording system to measure intracanal temperatures produced by high-temperature thermoplasticized injectable gutta-percha. The system was capable of recording 16 simultaneous temperatures every second with an accuracy of a hundredth degree centigrade. There was a linear increase in the recorded temperatures in the root canal. However, the actual temperatures were lower than expected.

In vitro intracanal temperatures produced by low- and high-temperature thermoplasticized injectable Gutta-percha.

An in vitro computerized temperature measurement system was developed to measure intracanal temperatures produced by different heated gutta-percha obturation techniques. The temperatures produced by low- and high-temperature thermoplasticized injectable gutta-percha systems were recorded and compared in this investigation. The mean intrachamber temperature of the Obtura syringe was 178.68 degrees C. The mean temperature of the Ultrafil heater was 93.06 degrees C. The mean temperature of the extruded gutta-percha was 137.81 degrees C from the Obtura syringe and 62.88 degrees C from the Ultrafil cannule. The intracanal temperature of the gutta-percha recorded for both systems showed that the gutta-percha cools rapidly after injection into the canal.

Asphyxiated neonates: prognosis and outcome.

The prognosis of perinatal asphyxia depends on the severity and duration of the insult, the gestational age and weight of the affected infant, and the association with other serious medical conditions. The mortality is high in the newborn period. Survivors may escape unscathed or face long-term handicaps including cerebral palsy, mental retardation, and epilepsy. It is often difficult in the nursery to make predictions about later quality of life for an individual infant. Counseling the family can be especially difficult. By looking at data from longitudinal studies linking newborn findings with later outcome, some patterns emerge that may make prognostication more accurate.

Phenobarbital and cerebral blood flow during hypertension in the newborn beagle.

Phenobarbital sodium has been used in anticonvulsant concentrations (15 to 40 micrograms/mL serum) in premature newborns in attempts to prevent periventricular and intraventricular hemorrhages. Although its clinical usefulness in this regard is controversial, phenobarbital treatment has been shown to reduce periventricular and intraventricular hemorrhages after hypertensive insult in newborn beagles. In this study cerebral blood flow values in steady state and during phenylephrine-induced hypertension with and without phenobarbital pretreatment were measured in newborn beagles. At anticonvulsant dosage, phenobarbital sodium decreased mean arterial blood pressure transiently during steady state and significantly reduced total cerebral blood flow during phenylephrine-induced hypertension without reducing mean arterial blood pressure. This phenobarbital sodium effect on cerebral blood flow was not as great in the presence of acidosis, and the initial hypotensive effect of phenobarbital sodium was sustained for a longer period of time during acidosis. Phenobarbital sodium may reduce the incidence of hemorrhages in the newborn brain by providing protection against isolated hemodynamic stresses characterized by acute increases in cerebral blood flow, with or without increased mean arterial blood pressure.

Reversible neuromuscular syndrome in malnourished children.

Six young children are reported who were malnourished, with hypotonia, weakness and absent stretch reflexes, both proximally and distally, but with normal sensory examinations. Motor and sensory nerve conduction velocities also were normal. Five had mildly abnormal electromyograms, with scattered fibrillations, positive sharp waves and increased insertional activity, both proximally and distally. After adequate nutrition in hospital, all the children's reflexes returned and strength improved. Weight for height was an important indicator: it was decreased when the muscle stretch reflexes were absent and increased when they returned. The neurological and electrodiagnostic findings imply that this is a reversible lower motor-neuron or muscle disorder.

Pseudohypoparathyroidism, parkinsonism syndrome, with no basal ganglia calcification.

A 20 year old woman with pseudohypoparathyroidism, Parkinsonism and no basal ganglia calcifications shown by computed tomography is reported. She has typical features of pseudohypoparathyroidism and biochemical evidence of end-organ resistance to parathyroid hormone. She is mentally retarded and has tremor, rigidity, bradykinesia, and stooped posture. The cause of Parkinsonism in pseudohypoparathyroidism is thought to be basal ganglia calcification. This patient must have another pathophysiology, perhaps directly related to a G protein defect, causing impaired neurotransmission.

Suppression of murine neuroblastoma growth in vivo by mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase.

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase catalyzes the formation of mevalonate, an essential precursor for isoprenoid compounds in mammalian cells. Recent studies have shown that mevinolin, a competitive inhibitor of the reductase, inhibits cell proliferation and induces differentiation in cultured C1300 (Neuro-2A) murine neuroblastoma cells. We now report that mevinolin can inhibit neuroblastoma growth in vivo. The specific activity of HMG-CoA reductase in subcutaneous neuroblastomas increased more than 20-fold between the fifth and eighth days after tumor inoculation, and remained elevated for the remainder of the tumor lifetime in mice. The increase in reductase activity was correlated with a marked increase in tumor DNA content and exponential increase in tumor weight. Using an in vitro assay to monitor the ability of mouse serum to suppress sterol synthesis, we determined that mevinolin was inactivated or cleared from the circulation within 3-6 h after a single subcutaneous injection. However, by using subcutaneous osmotic pumps to deliver a constant infusion of mevinolin, we were able to maintain adequate blood levels of the drug for 7 d. Mevinolin (5 mg/kg per h) suppressed tumor growth (wet weight) significantly when treatment was carried out between day 1 and day 8 or between day 5 and day 12 after tumor inoculation. Histopathological examination of tumors from mevinolin-treated mice revealed few or no mitotic figures and marked cellular degeneration. Measurements of incorporation of (3H)acetate into neuroblastoma sterols and ubiquinones 24 h after implantation of osmotic pumps showed that mevinolin produced a marked inhibition of isoprenoid synthesis in the tumors in vivo. The data suggest that, in addition to their demonstrated utility as cholesterol-lowering drugs, competitive inhibitors of HMG-CoA reductase may have considerable potential as novel antineoplastic agents.