Diastolic dysfunction and altered energetics in the alphaMHC403/+ mouse model of familial hypertrophic cardiomyopathy

An arginine to glutamine missense mutation at position 403 of the beta-cardiac myosin heavy chain causes familial hypertrophic cardiomyopathy. Here we study mice which have this same missense mutation (alphaMHC403/+) using an isolated, isovolumic heart preparation where cardiac performance is measured simultaneously with cardiac energetics using 31P nuclear magnetic resonance spectroscopy. We observed three major alterations in the physiology and bioenergetics of the alphaMHC403/+ mouse hearts. First, while there was no evidence of systolic dysfunction, diastolic function was impaired during inotropic stimulation. Diastolic dysfunction was manifest as both a decreased rate of left ventricular relaxation and an increase in end-diastolic pressure. Second, under baseline conditions alphaMHC403/+ hearts had lower phosphocreatine and increased inorganic phosphate contents resulting in a decrease in the calculated value for the free energy released from ATP hydrolysis. Third, hearts from alphaMHC403/+ hearts that were studied unpaced responded to increased perfusate calcium by decreasing heart rate approximately twice as much as wild types. We conclude that hearts from alphaMHC403/+ mice demonstrate work load-dependent diastolic dysfunction resembling the human form of familial hypertrophic cardiomyopathy. Changes in high-energy phosphate content suggest that an energy-requiring process may contribute to the observed diastolic dysfunction.     

Pediatric head injuries and deaths from bicycling in the United States

OBJECTIVE: To estimate the potential benefit of increasing bicycle helmet use among children and adolescents in the United States. DESIGN: All bicycle-related deaths (Multiple Cause-of-Death Public Use Data Tapes, 1989 through 1992) and bicycle-related injuries treated in sampled emergency departments (National Electronic Injury Surveillance System, 1989 through 1993) were used to calculate traumatic brain injury-associated death and head injury rates per 1,000,000 US residents. Preventable injuries and deaths were estimated by calculating the population-attributable risk of head injury due to nonuse of bicycle helmets. PATIENTS: US residents aged 0 through 19 years who were injured or who died as a result of a bicycle crash. RESULTS: An average of 247 traumatic brain injury deaths and 140,000 head injuries among children and adolescents younger than 20 years were related to bicycle crashes each year in the United States. As many as 184 deaths and 116,000 head injuries might have been prevented annually if these riders had worn helmets. An additional 19,000 mouth and chin injuries were treated each year. The youngest age groups had the highest proportions of both head and mouth injuries. CONCLUSION: There continues to be a need to advocate for greater use of bicycle helmets, particularly among young children. Helmet design changes should be considered to prevent mouth injuries.     

Lipopolysaccharide induces sickness behaviour in rats by a vagal mediated mechanism

A 52-year-old man was hospitalized for a right adrenal tumor which had been incidentally found by abdominal CT scan for examination of colon cancer. Laboratory and endocrine findings were within the normal limits except for increased urinary concentrations of noradrenaline and dopamine. Adrenal angiography revealed that the feeding artery of the tumor was the inferior suprarenal artery. Adrenal venous blood sampling studies detected no abnormalities in the concentrations of catecholamine, cortisol or aldosterone. Right adrenalectomy was performed and the tumor was histologically diagnosed as ganglioneuroma. Ganglioneuroma is a benign tumor originating from the sympathetic nerve ganglion. The adrenal origin of the tumor is relatively rare and 60 cases of adrenal ganglioneuroma including our case have been reported in Japan.     

Hepatolithiasis, a clinical study

To examine the value of transient regional asynergy on dobutamine stress echocardiography as a noninvasive predictor of future cardiac events, 51 symptomatic patients (aged 54 +/- 9 years) with suspected coronary artery disease (CAD) were studied using an incremental regimen of 5, 10, 15 and 20 micrograms/kg/min. Pretest likelihood of CAD was (mean +/- standard error of the percentage) 79.7 +/- 5.6% before and 83.4 +/- 5.2% after exercise electrocardiography using probability analysis based on age, sex and symptoms. Two-dimensional images were analyzed with reference to an 11-segment model and gave good interrater agreement. During 24 +/- 4 months (range 19 to 32) of follow-up, 23 patients had events (1 myocardial infarction, 9 unstable angina, 10 coronary bypass surgery, 3 coronary angioplasty) and 28 were event free. Age, proportion with baseline asynergy and both pretest echocardiographic ejection fraction and its response to dobutamine were similar in these 2 groups (all p = not significant). Transient asynergy was seen in 17 of 23 patients (74%) with and 8 of 28 patients (29%) without events (p < 0.01); 5 of 6 patients (83%) with involvement of 3 segments had events. Myocardial infarction or unstable angina occurred in 8 of 25 (32%) with a positive and 2 of 26 (8%) with a negative stress echocardiogram (p < 0.05). Both exercise duration (389 +/- 195 vs 517 +/- 237 seconds, p < 0.05) and time to diagnostic ST-segment shift (291 +/- 192 vs 447 +/- 212 seconds, p = 0.05) were shorter in those with inducible asynergy.(ABSTRACT TRUNCATED AT 250 WORDS)