A randomised comparison of two intranasal dexmedetomidine doses for premedication in children

We compared sedation levels in children following administration of intranasal dexmedetomidine. One hundred and sixteen children aged between 1 and 8 years were enrolled in this prospective, randomised trial. Children were assigned to receive either intranasal dexmedetomidine 1 μg.kg^?1 (Group 1) or 2 μg.kg^?1 (Group 2). Thirty‐one (53%) patients from Group 1 and 38 (66%) patients from Group 2 were satisfactorily sedated at the time of anaesthetic induction. Logistic regression showed a significant interaction effect (p = 0.049), with the odds ratio between Group 2 over Group 1 estimated as 1.1 (95% CI 0.5–2.7) for the 1–4 year age group, and 10.5 (95% CI 1.4–80.2) for the 5–8 year age group. Both doses produced a similar level of satisfactory sedation in children aged 1–4 years, whereas 2 μg.kg^?1 resulted in a higher proportion of satisfactory sedation in children aged 5–8 years. There were no adverse haemodynamic effects. We conclude that intranasal dexmedetomidine in a premedication dose of 2 μg.kg^?1 resulted in excellent sedation in children.     

Role of inducible nitric oxide synthase in induction of RhoA expression in hearts from diabetic rats

AIMS: Recent studies from our laboratory demonstrated that increased expression of the small GTP-binding protein RhoA and activation of the RhoA/rho kinase (ROCK) pathway play an important role in the contractile dysfunction associated with diabetic cardiomyopathy in hearts from streptozotocin (STZ)-induced diabetic rats. Nitric oxide (NO) has been reported to be a positive regulator of RhoA expression in vascular smooth muscle, and we have previously found that the expression of inducible NO synthase (iNOS) is increased in hearts from STZ-diabetic rats. Therefore, in this study, we investigated the hypothesis that induction of iNOS positively regulates RhoA expression in diabetic rat hearts. METHODS AND RESULTS: To determine whether NO and iNOS could increase RhoA expression in the heart, cardiomyocytes from non-diabetic rats were cultured in the presence of the NO donor sodium nitroprusside (SNP) or lipopolysaccharide (LPS) in the absence and presence of the selective iNOS inhibitor, N(6)-(1-iminoethyl)-l-lysine dihydrochloride (L-NIL). In a second study, 1 week after induction of diabetes with STZ, rats were treated with L-NIL (3 mg/kg/day) for 8 more weeks to determine the effect of iNOS inhibition in vivo on RhoA expression and cardiac contractile function. Expression of iNOS was elevated in cardiomyocytes isolated from diabetic rat hearts. Both SNP and LPS increased RhoA expression in non-diabetic cardiomyocytes. The LPS-induced elevation in RhoA expression was accompanied by an increase in iNOS expression and prevented by L-NIL. Treatment of diabetic rats with L-NIL led to a significant improvement in left ventricular developed pressure and rates of contraction and relaxation concomitant with normalization of total cardiac nitrite levels, RhoA expression, and phosphorylation of the ROCK targets LIM (Lin-11, Isl-1, Mec-3) kinase and ezrin/radixin/moesin. CONCLUSION: These data suggest that iNOS is involved in the increased expression of RhoA in diabetic hearts and that one of the mechanisms by which iNOS inhibition improves cardiac function is by preventing the upregulation of RhoA and its availability for activation.     

Serum osteocalcin and total body calcium in normal pre- and postmenopausal women and postmenopausal osteoporotic patients

Serum osteocalcin was measured in 51 normal pre- and 114 postmenopausal women and in 41 postmenopausal osteoporotic patients. Total body calcium (TBCa) was determined in the same individuals by neutron activation analysis. Many of the perimenopausal nonosteoporotic women had increased serum osteocalcin values, but 15 yr or more after the menopause most of the women had serum osteocalcin levels in the normal range. Comparing normal women before and after menopause, the mean serum osteocalcin levels [7.8 +/- 4.7 (+/- SE) and 10.1 +/- 9.4 ng/mL] were not significantly different; however, the TBCa values (898 +/- 99 and 806 +/- 111 g) were significantly different (P less than 0.001). When the normal postmenopausal women were regrouped according to high vs. low osteocalcin values, TBCa and phosphorus content as well as forearm linear bone density were significantly lower in the high osteocalcin group, even though most of the other variables, including urinary hydroxyproline excretion, serum alkaline phosphatase, age, height, and weight, were not different. Osteoporotic women had a mean serum osteocalcin concentration of 17.4 +/- 8.6 ng/ml and a TBCa of 657 +/- 83 g, both significantly different from the respective values in normal and pre- and postmenopausal women (P less than 0.001 for both variables in comparison to each group). These data suggest that high serum osteocalcin levels, at least on a group basis, are an index of low skeletal mass.     

The different types of alpha-thalassemia: practical and genetic aspects

From May 1985 to October 1987, 1,564 Southeast Asians living in Hawaii were screened for hereditary anemias. Microcytosis was determined by electronic red cell indices and morphology; iron deficiency was ruled out by normal red cell distribution width and normal protoporphyrin levels; Hb E was determined by electrophoresis; beta-thalassemia (thal) heterozygotes were identified by raised Hb A2 on column chromatography. alpha-Thalassemia heterozygotes were diagnosed by exclusion. Family studies helped identify or confirm diagnoses, especially for the alpha-thal-2 heterozygotes (-alpha/alpha alpha) and homozygotes (-alpha/-alpha). Provisional diagnoses are being checked by DNA analyses. Iron deficiency prevented detection of possibly coexisting alpha-thalassemias in 97 individuals. Technical problems included the obscuring of standard criteria for recognizing the alpha-thal variants by the presence of Hb E or beta-thal. In such cases, alpha-thal could only be detected by family studies or DNA analyses. Problems with hemoglobin (Hb) electrophoresis included Hb H migrating beyond the edge of the strip if incubation was not closely monitored, and difficulty in detecting the small amounts of unstable Hb Constant Spring. DNA analyses also had limitations, since the nondeletion alpha-thalassemias would not be detected by routine Southern blotting. DNA analyses suggested that about 50% of presumed alpha-thalassemias were alpha-thal-2 (-alpha/alpha alpha) variants, and a corresponding number of alpha-thal-2 variants were among the apparent normals. Gene frequencies in the unselected Lao subjects were approximately 0.2 for Hb E, at least 0.1 for (-alpha), usually a rightward (alpha -3.7) type, 0.04 for (-), and 0.01 for a beta-thal. Multistep screening for the alpha- and beta-thalassemias was an effective and efficient strategy.