Randomized trial of a dual-hormone artificial pancreas with dosing adjustment during exercise compared with no adjustment and sensor-augmented pump therapy.

AIMS: To test whether adjusting insulin and glucagon in response to exercise within a dual-hormone artificial pancreas (AP) reduces exercise-related hypoglycaemia. MATERIALS AND METHODS: In random order, 21 adults with type 1 diabetes (T1D) underwent three 22-hour experimental sessions: AP with exercise dosing adjustment (APX); AP with no exercise dosing adjustment (APN); and sensor-augmented pump (SAP) therapy. After an overnight stay and 2 hours after breakfast, participants exercised for 45 minutes at 60% of their maximum heart rate, with no snack given before exercise. During APX, insulin was decreased and glucagon was increased at exercise onset, while during SAP therapy, subjects could adjust dosing before exercise. The two primary outcomes were percentage of time spent in hypoglycaemia (<3.9 mmol/L) and percentage of time spent in euglycaemia (3.9-10 mmol/L) from the start of exercise to the end of the study. RESULTS: The mean (95% confidence interval) times spent in hypoglycaemia (<3.9 mmol/L) after the start of exercise were 0.3% (-0.1, 0.7) for APX, 3.1% (0.8, 5.3) for APN, and 0.8% (0.1, 1.4) for SAP therapy. There was an absolute difference of 2.8% less time spent in hypoglycaemia for APX versus APN (p = .001) and 0.5% less time spent in hypoglycaemia for APX versus SAP therapy (p = .16). Mean time spent in euglycaemia was similar across the different sessions. CONCLUSIONS: Adjusting insulin and glucagon delivery at exercise onset within a dual-hormone AP significantly reduces hypoglycaemia compared with no adjustment and performs similarly to SAP therapy when insulin is adjusted before exercise.

Economic benefit of the PHLAME wellness programme on firefighter injury.

BACKGROUND: Work-related injuries and illness are prevalent and costly. Firefighting is especially hazardous and many firefighters sustain work-related injuries. Workplace health promotion programmes have shown positive return on investment (ROI). Little is known about how similar programmes would impact injury and cost among firefighters. AIMS: To evaluate the impact of a workplace health promotion intervention on workers' compensation (WC) claims and medical costs among Oregon fire departments participating in the PHLAME (Promoting Healthy Lifestyles: Alternative Models' Effects) health promotion programme compared with Oregon fire departments not participating in PHLAME. METHODS: Data from firefighters from four large urban fire departments in Oregon were evaluated using a retrospective quasi-experimental study design. Outcomes were (i) total annual firefighter WC claims, (ii) total annual incurred medical costs prior to and after implementation of the PHLAME firefighter worksite health promotion programme (iii) and an ROI analysis. RESULTS: Data were obtained from 1369 firefighters (mean age of 42 years, 91% white, 93% male). WC claims (P < 0.001) and medical costs (P < 0.01) were significantly lower among PHLAME fire departments compared with Oregon fire departments not participating in the programme. Fire departments participating in the PHLAME TEAM programme demonstrated a positive ROI of 4.61-1.00 (TEAM is used to indicate the 12-session peer-led health promotion programme). CONCLUSIONS: Fire department WC claims and medical costs were reduced after implementation of the PHLAME workplace health promotion programme. This is a low cost, team-based, peer-led, wellness programme that may provide a feasible, cost-effective means to reduce firefighter injury and illness rates.

Analgesic efficacy and safety of the diclofenac epolamine topical patch 1.3% (DETP) in minor soft tissue injury.

The diclofenac epolamine topical patch 1.3% was designed to deliver analgesic concentrations of diclofenac to an underlying soft tissue injury site, while limiting systemic exposure to diclofenac. This randomized, double-blind, placebo-controlled study evaluated the safety and efficacy of the diclofenac epolamine topical patch for the treatment of acute pain due to minor soft tissue injury. Patients (18-65 years, inclusive) with clinically significant minor soft tissue injuries (mild or moderate sprain, strain, or contusion) incurred within 7 days of study entry and having pain scores ≥ 5 on a Visual Analog Scale of 0-10 were enrolled. Patients were randomized to receive the diclofenac epolamine topical patch (n=207) or placebo patch (n=211) application twice daily for 14 days or until pain resolution. Patients recorded pain scores every 12 h at the time of patch removal using the Visual Analog Scale. Investigator-assessed global response to therapy was also evaluated. Safety data were collected throughout the study. Twice-daily treatment with diclofenac epolamine topical patch produced a statistically significant reduction in mean pain score relative to baseline by an additional 18.2% in the diclofenac epolamine topical patch group (0.435 ± 0.268) compared with the placebo group (0.532 ± 0.293) (p=0.002; overall) beginning after application of the second patch. Consistent with this treatment effect, median time to pain resolution was shortened by 2 days in the diclofenac epolamine topical patch group relative to the placebo group (p=0.007). These results were reinforced independently by investigators who reported treatment as good or excellent for 58% of diclofenac epolamine topical patch-treated patients compared with 49% in the placebo patch group (p=0.008). The most common adverse events were treatment site related (n=16, 7.9% diclofenac epolamine topical patch; n=12, 5.8% placebo patch). Most (80%) patients reported tolerability as excellent or good. In conclusion, the diclofenac epolamine topical patch provides effective, rapid pain relief for the treatment of acute pain from minor soft tissue injury and appears generally safe and well tolerated.

Modulation of membrane composition of swine vascular smooth muscle cells by homologous lipoproteins in culture.

Swine vascular smooth muscle cells were exposed to homologous low-density or high-density lipoprotein fractions for 24 h. Total cell membranes were isolated from the post-nuclear supernatant of the cell homogenates, fractionated by sucrose denisty gradient centrifugation and characterized by enzyme assays. The membrane fraction with the lowest density was enriched in plasma membrane marker enzymes. Cholesterol analysis showed that cells exposed to low-density lipoprotein had higher cholesterol-to-protein ratios in total cells, total cell membranes and individual membrane fractions than had the cells exposed to high-density lipoproteins. Cholesterol-to-phospholipid ratios of the plasma membrane-enriched fraction from cells exposed to low-density lipoprotein were higher than the same membrane fraction of cells exposed to high-density lipoprotein. Studies with iodinated lipoproteins showed that these compositional changes could not be due to lipoprotein contamination. Membrane microviscosity was determined by fluorescence depolarization with diphenylhextriene and the microviscosity of the plasma membrane-enriched fraction was different in the cells exposed to the two different lipoprotein fractions. This difference in membrane microviscosity was significant only when the medium cholesterol content was 40 micrograms per ml or greater; cells exposed to low-density lipoprotein gave membranes with higher microviscosity. These results demonstrate that the properties of vascular smooth muscle cell membranes are influcenced by exposure of the cells to homologous lipoprotein fractions.

Repair of anomalous origin of the left coronary artery in the infant and small child.

Anomalous origin of the left coronary artery from the pulmonary artery is associated with myocardial infarction, left ventricular dysfunction, mitral valve dysfunction and, occasionally, intracardiac congenital abnormalities. A technique that utilizes a flap of the anterior wall of the pulmonary artery to serve as a neocoronary artery to direct aortic flow from a created aortopulmonary window to the pulmonary artery orifice of the anomalous left coronary artery was used in five patients aged 2.5 months to 4.75 years. Two patients were less than 4 months of age at operation. There was one death 2 days after operation and one late death. The two youngest patients required mitral valve replacement. Two of the three surviving patients are well at follow-up at 7 to 44 months. One patient has been lost to follow-up study. One patient had postoperative catheterization which showed an intact repair. The pulmonary artery neocoronary procedure is applicable to infants and small patients with anomalous origin of the left coronary artery from the pulmonary artery.

Metabolic myopathies: evaluation by graded exercise testing.

Exertional muscle pain and fatigue are common complaints; some patients with these symptoms have a metabolic myopathy. We have performed graded exercise testing with analysis of expired ventilation on 13 individuals with various kinds of metabolic myopathies. Their results differed from normal and reflected the underlying biochemical abnormality. Patients with disorders of the mitochondrial electron transport chain demonstrated marked limitations in aerobic metabolism and a greatly reduced maximum oxygen consumption. During intense exertion, normal individuals increase carbon dioxide generation due to buffering of lactic acid. This did not occur in patients with McArdle disease, in whom the respiratory exchange ratio (carbon dioxide production/oxygen consumption) did not rise above 1.0 at maximum exercise. These results indicated a deficit in anaerobic metabolism. Pyruvate dehydrogenase complex allows pyruvate produced from carbohydrate metabolism to enter the citric acid cycle. Patients with this enzyme deficiency showed an initially normal pattern followed by an abrupt cessation in carbohydrate dependent aerobic metabolism at higher work loads. During high-intensity exercise, progressive anaerobic metabolism was not accompanied by additional oxygen consumption. Finally, results from a patient with carnitine palmitoyl transferase deficiency revealed an early dependence on carbohydrate metabolism. The ventilatory threshold occurred at a low percentage of maximal oxygen consumption, reflecting the limited availability of lipid substrates for aerobic metabolism. Detection of some muscle metabolic abnormalities can be made on small biopsy specimens. However, definitive diagnosis of the defect nearly always requires studies on fresh or frozen muscle tissue obtained by an open biopsy. The decision on how the tissue should be processed and which metabolic studies should be performed frequently needs to be made before the biopsy is obtained. Thus, a noninvasive method to initially characterize patients with potential metabolic disorders is useful. Exercise testing with expired gas analysis can indicate the presence of a metabolic myopathy and results can then be used to direct the appropriate biochemical evaluations.

Sustained depression of the resting metabolic rate after massive weight loss.

To assess potential long-term effects of weight loss on resting metabolic rate (RMR), the RMRs of seven obese women were measured by indirect calorimetry before weight loss, during a protein-sparing modified fast, and for 2 mo while at a stable reduced weight. Body composition was also determined at each interval. RMR significantly decreased 22% (p less than 0.01) with initiation of the modified fast. RMR values during the modified fast and during the maintenance diet at stable reduced weight were not different and all were significantly lower than the prediet RMR. Loss of lean tissue could not account for the decrease because changes in RMR per fat-free mass paralleled the total RMR reduction. A sustained decrement in RMR accompanied weight loss and persisted for greater than or equal to 8 wk despite increased caloric consumption and body weight stabilization.

Failure to diagnose congenital heart disease in infancy.

OBJECTIVE: To identify factors that predict failure to diagnose congenital heart disease in newborns. DESIGN: All fatal cases in the Baltimore-Washington Infant Study were compiled. The Baltimore-Washington Infant Study includes 4390 cases of infants with congenital cardiovascular malformations identified in a population-based study between 1981 and 1989 in the Baltimore-Washington metropolitan area. Death occurred in 800 such infants in the first year of life. In 76 of these infants, death occurred before diagnosis of heart disease. These cases were identified by community search of autopsy records. Their characteristics are compared with those of infants who died after a cardiac diagnosis was made. RESULTS: Infant characteristics (birth weight, gestational age, intrauterine growth retardation, and chromosomal anomaly) are associated with death of infants with congenital cardiovascular malformations and with death of such infants before diagnosis. Diagnoses of coarctation of the aorta, Ebstein's anomaly, atrial septal defect, and truncus arteriosus are overrepresented in infants found by community search, particularly in those infants without associated malformations. Paternal education is associated with failure to diagnose congenital heart disease in life but other sociodemographic characteristics of the infant's family are not. CONCLUSIONS: Diagnosis of congenital cardiovascular malformations requires close observation in the neonatal period. Analysis of age at death of infants with undiagnosed congenital cardiovascular malformation suggests that such infants may be at risk if discharged within the first 2 days of life.

Nucleocapsid- and virus-like particles assemble in cells infected with recombinant baculoviruses or vaccinia viruses expressing the M and the S segments of Hantaan virus.

The formation of Hantaan (HTN) virus nucleocapsid-like structures (NLS) or virus-like particles (VLP) from expressed gene products was investigated in two eukaryotic systems. Baculovirus expression of the HTN virus small segment (S), which encodes the viral nucleocapsid protein, resulted in assembly of NLS inside infected insect cells. The NLS and authentic ribonucleocapsids, prepared by detergent disruption of HTN virions, had similar sedimentation characteristics and morphologies, and were recognized by HTN virus N-specific antibodies. Co-expression of S and the medium segment (M), which encodes the two viral envelope glycoproteins (G1 and G2), did not efficiently generate VLP in the baculovirus-insect cell system, but VLP were observed in lysates and supernatants of cells infected with a recombinant vaccinia virus co-expressing HTN virus M and S. The VLP sedimented in sucrose to densities consistent with HTN virions, and some of them bore a striking resemblance to Hantaan virions when examined by immunoelectron microscopy.

Left ventricular false tendons in children: prevalence as detected by 2-dimensional echocardiography and clinical significance.

During a 28-month period, consecutive 2-dimensional echocardiograms were reviewed to determine the prevalence of left ventricular (LV) false tendons, their associated anomalies and clinical significance. LV false tendons were found in 31 (0.8%) of 3,847 consecutive 2-dimensional echocardiograms. Of 31 LV false tendons, 30 passed longitudinally from papillary muscle to septum and 1 went from free wall to free wall. The 31 patients were aged 1 day to 15 years. Associated heart disease, most often ventricular septal defect, bicuspid aortic valve and coarctation of the aorta, was present in 48%, of whom 73% were girls. Of those without heart disease, 69% were boys. In patients with heart disease, precordial murmurs were due to the underlying cardiac anomaly. Of those without heart disease, 15 of 16 (94%) had a precordial murmur, usually of the Still's type over the lower left sternal border. Four of 31 (13%), 1 with and 3 without heart disease, had unifocal premature ventricular contractions that were rate-dependent in the 2 patients undergoing stress testing. LV false tendons appear to occur in 0.8% of pediatric patients and usually are accompanied by a Still's type innocent murmur if unassociated with heart disease. Some LV false tendons are associated with rate-dependent premature ventricular contractions.

Assessment of exercise intensity formulas by use of ventilatory threshold.

Guidelines for training heart rate (HR) during aerobic exercise are often determined by predictive formulas. Measurement of the heart rate at ventilatory threshold (VT) by expired gas analysis provides a direct index of the upper limits of conditioning intensity. We evaluated 115 nonsmoking, healthy adults with measurement of peak oxygen uptake to classify groups as low- (n = 45), average-(n = 45), and high (n = 25) -fitness. Heart rate at VT was compared with the approximate midpoint (77 percent) of recommended training intensity as estimated by the Karvonen equation, predicted maximal (220-age), and measured maximal HR formulas. No significant difference among the various HR formulas at 77 percent and HR at VT were found for high-fitness individuals. Among the low- and average-fitness groups, the Karvonen formula at 77 percent was significantly higher (p less than 0.001) than HR at ventilatory threshold. Predicted and measured maximal HR at 77 percent were not above the VT among the low- and average-fitness individuals and are appropriate for training intensity. However, the Karvonen formula appears to overestimate heart rate intensity among those of low and average fitness and may be excessive for these groups.

Rapid postmortem invasion of cecal mucosa of macaques by nonpathogenic Entamoeba chattoni.

Although Entamoeba histolytica is the third leading parasitic cause of death in the world, most infections in humans are asymptomatic and restricted to the intestinal lumen. Entamoeba histolytica infections have also been reported in most species of captive nonhuman primates, with New World monkeys being particularly susceptible to fatal invasive amebiasis. In contrast, Old World monkeys appear to be resistant to the disease, although tissue invasion in asymptomatic monkeys has been reported. Our initial objectives were to determine the incidence, the predisposing factors, and the light microscopic and ultrastructural features of invasive amebiasis in Macaca mulatta (rhesus) and and M. fasicularis (cynomolgus) macaques. Our findings indicate that nonpathogenic E. chattoni in macaques can invade cecal mucosa rapidly (within 1 hr) after death. Therefore, the presence of invasive Entamoeba trophozoites in routinely collected necropsy materials should be interpreted with caution, particularly in cases where tissue fixation is delayed.

Does aerobic conditioning cause a sustained increase in the metabolic rate?

We measured the metabolic rate by indirect calorimetry for 90 minutes following exercise in six healthy individuals. Ten and 30 minutes of cycling at 80% of maximal intensity produced comparable increases in the resting metabolic rate, (37% and 32%, respectively) immediately after exercise. However, by 30 minutes following exertion, the metabolic rate was not different from control values. The total additional caloric use during the 90 minutes of recovery was similar for the two exercise durations, and the mean increment in recovery energy expenditure was 11.4 +/- 7.1 kcals. The majority of caloric use with exercise is during the activity. Recovery energy expenditure following usual aerobic training results in only a minor contribution to total energy use.

Should a school honor a student's DNR order?

Physicians first present the case of a sixteen-year-old cardiac patient who has refused a heart transplant and cardiac resuscitation. Her family and physicians accept the decision. The family has asked the school system to honor her do not resuscitate order if she goes into cardiac arrest in school The school system has refused to do so. Following the case presentation, a lawyer, a physician/ethicist, and an educator consider the important issues raised by this ongoing case.

Insurance and education determine survival in infantile coarctation of the aorta.

Health outcomes are determined by case severity, physician decisions, and patient variables. In a population-based study between 1981 and 1989, 103 cases of infant coarctation of the aorta were diagnosed before one year of age. The goal of this study was to determine whether patient race, gender, income, and insurance status had effects on outcome of coarctation of the aorta that were distinct from the effect of case severity. Survival of infants with coarctation of the aorta, a common congenital cardiovascular malformation, is associated with greater maternal education and with having any health insurance but not with measures of severity. Infants without health insurance are 12.8 times more likely to die than infants with any health insurance. Fifty-five percent of all deaths in infant coarctation occur prior to surgical treatment. One-third of deaths occur without diagnosis. Outcome measures require knowledge of the entire population and of insurance status to inform policy.

Characteristics of Anabolic-Androgenic Steroid-Free Competitive Male and Female Bodybuilders.

In brief: Anabolic-androgenic steroids are widely used in the community of bodybuilders. We defined a group of steroid-free bodybuilders by analyzing urine for the presence of these steroids, and compared the bodybuilders with both sedentary controls and runners. Male and female competitive bodybuilders had low percentages of body fat. One third of the female bodybuilders reported menstrual abnormalities (more than three missed menses during the past 12 months). Lipid values of bodybuilders were comparable to a group of lean, aerobically trained athletes. Despite their high volume of training, the bodybuilders' oxygen uptake during cycle ergometry was augmented only in proportion to the increase in lean body mass.