Hypertrophic cardiomyopathy-the clinical challenge of managing a hereditary heart condition.

See doi:10.1016/S1095-668X(00)00522-5for the article to whichthis editorial refers. Within this issue of the European Heart Journal van Lange andcoworkers investigated current genetic knowledge and practiceof Dutch cardiologists regarding counselling and DNA-testingof familial hypertrophic cardiomyopathy (HCM). The study revealedthat Dutch cardiologists regarded their genetic knowledge asinsufficient and demonstrated that a substantial proportionof HCM patients did not receive adequate information about thehereditary nature of their disease. In addition clinical investigationsof relatives at risk of having inherited the disease and geneticanalysis to identify disease-causing mutations in affected familieswere seldom initiated. The authors concluded that the currentgenetic care for HCM patients is poor and     

Congenital lobar emphysema

Congenital lobar emphysema, a life-threatening respiratory disorder presenting in infancy is best diagnosed by chest x-ray. Abnormality of bronchial cartilage is one of the suspected aetiological factors. Prompt lobectomy is the treatment of choice as conservative treatment carries an unacceptably high mortality and morbidity. One such patient, a 3-month-old child who underwent successful emergency left upper lobectomy is presented.     

Carnitine in the streptozotocin-diabetic rat

Rats made moderately diabetic by streptozotocin (decreased growth without decreased body mass, blood glucose, 588-840 mg/dl) and nondiabetic rats were either fed a purified diet with no measurable carnitine (diet 1), the same diet supplemented with carnitine (44.5 nmol/g food, diet 2), or a closed formula, nonpurified diet (3.3 nmol/g food, diet 3). Levels of total carnitine (free + acyl) were lower (P less than 0.05) in plasma, heart, soleus, extensor digitorum longus and kidney of rats fed diet 1 compared to those fed diet 2. Liver carnitine in diabetic animals was 2.6- to 4.4-fold higher than in nondiabetic animals with urinary carnitine of rats fed diet 1 being four times greater in diabetic than in nondiabetic rats. Other changes in tissue total carnitine were less pronounced. Compared to diabetic rats, insulin-treated diabetics had lower urinary excretion of carnitine and blood glucose levels (P less than 0.05), and tissue carnitine approximating nondiabetic levels. Significant catabolism of carnitine was not found. Apparent carnitine biosynthesis (diet 1) showed no difference between nondiabetic and diabetics (31.5 +/- 1.6 and 31.2 +/- 2.2 nmol/g of body weight per day, respectively) suggesting elevated liver levels resulted from redistribution.     

Comparison of the profiles of agonists as stimulants of the beta 3-adrenoceptor in vitro with their gastroprotective effects in the conscious rat.

1. This paper compares the activity of a range of agonists as stimulants of the beta 3-adrenoceptor in rat isolated oesophagus with their ability to afford protection against indomethacin-induced gastric damage in the conscious rat. 2. The beta 3-adrenoceptor agonists, CL 316243 and BRL 37344, the non-selective beta-adrenoceptor agonist, isoprenaline and the selective beta 2-adrenoceptor agonist, salmeterol, all evoked concentration-dependent relaxation of precontracted muscularis mucosa from rat oesophagus. The rank order of agonist potency was BRL 37344 > CL 316243 > isoprenaline >> salmeterol. The selective beta 1-adrenoceptor agonist, denopamine, did not relax the preparation. 3. The relaxant responses to all agonists were resistant to blockade by atenolol (10 microM), and ICI 118551 (1 microM) thus suggesting that they were not mediated by either beta 1- or beta 2-adrenoceptor stimulation. In contrast, cyanopindolol and propranolol did inhibit responses to BRL 37344, CL 316243 and isoprenaline, giving pA2 values or pKB estimates which were consistent with an interaction at beta 3-adrenoceptors (i.e. approximately 8.0 and 6.5 respectively). However, responses to salmeterol were resistant to blockade by all the antagonists tested, which suggests that the high (> 1 microM) concentrations of salmeterol used exerted non-specific relaxant effects. 4. The agonist effects of CL 316243 and BRL 37344 on beta 1- and beta 2-adrenoceptors were assessed on guinea-pig right atrium and precontracted trachea respectively. Both agonists had minimal activity as stimulants of heart rate, but did relax trachea, being 380 (CL 316243) and 21 (BRL 37344) fold less potent than isoprenaline. 5. CL 316243 and BRL 37344 were potent inhibitors of indomethacin-induced gastric antral ulceration in the conscious rat (ED50 values = 0.24 and 0.09 mumol kg-1, p.o.) Salmeterol was approximately 100 times less potent than BRL 37344 as a gastroprotective agent and denopamine was without effect. 6. The gastroprotective effects of CL 316243 and BRL 37344 were resistant to blockade by ICI 118551 (10 mg kg-1, p.o.) and propranolol (10 mg kg-1, p.o.). In contrast, both antagonists caused dose-related inhibition of the protective action of salmeterol (10 mg kg-1, p.o.). Cyanopindolol was not assessed as an antagonist in vivo because preliminary experiments revealed that it exacerbated indomethacin-induced gastric damage in its own right. 7. In conclusion, the beta 3-adrenoceptor agonists CL 316243 and BRL 37344 were potent inhibitors of indomethacin-induced gastric antral ulceration in the rat. These data suggest that an agonist which is potent and selective for the human beta 3-adrenoceptor may confer mucosal protection in man.     

Changes in muscle carnitine during regeneration

Carnitine in rat skeletal muscle was measured before, during, and after muscle regeneration. Early regenerating tibialis anterior muscle consequent to bupivacaine injection was found to have smaller amounts of total, free, and acyl carnitine per milligram wet weight, but returned toward normal values as muscle regeneration was completed. Accumulation of DL-[3H]carnitine per milligram wet weight in regenerating muscle was less than one-half that of control muscle at day 4 (P less than 0.005), but was not significantly different from the control value at day 7. Our results are consistent with the hypothesis that the reported decrease in muscle carnitine content in several different human neuromuscular diseases is in part a manifestation of muscle fiber regeneration.     

Preclinical diabetes mellitus in precocious myocardial infarction

A series of 45 patients who had a myocardial infarction before the age of 45 years has been studied and investigated for alterations of glucose tolerance, as shown by standard and prednisolone-primed glucose tolerance tests.Abnormal responses to standard glucose tolerance tests and prednisolone-primed glucose tolerance tests were obtained in 75.5 per cent of patients with myocardial infarction, compared with 8.8 per cent of controls.Sex, hypertension, obesity, and a positive family history did not affect the abnormalities of glucose tolerance.Various views concerning these abnormalities in glucose metabolism are discussed.     

A study of placenta in relation to birth weight and gestational age

Summary A study on 469 placentae was undertaken. The mean weight of the placenta was found to be higher for males as compared to females. The placental weight increased with the increase in birth weight and gestational age. The macroscopic placental abnormalities were detected only in 21 (4.4%) cases and included infarction, retroplacental haematomas, calcification, yellow stained placentae, friable and degenerated placentae and battle-dore placentae. No correlation between the birth weight and macroscopic abnormalities of the placentae was detected in either of the gestational groups. From the Department of Pediatrics, Institute of Medical Sciences, Varanasi-5.