H3 Propranolol serum levels following lidocaine administration in rats with CCL4 induced liver damage.

Liver disease alters the pharmacokinetic and pharmacodynamic properties of hepatically eliminated drugs. The main factors influenced are plasma albumin levels, enzyme balance (induction & inhibition) and drug binding to tissue proteins. The influence of lidocaine on serum, heart and liver propranolol levels in Wistar rats after liver injury induced by carbon tetrachloride CCl4 0.4 ml/kg x 2/wkl, was investigated. 40 male Wistar rats were divided into four groups (I, II, III, IV; n=10), Group I animals received only propranolol (labelled + cold substance) 40 mg/kg/12 h p.o., group II propranolol plus lidocaine in a single dose of 4mg/kg s.c., group III was treated with CCl4 for 6 weeks and received propranolol x2 at the same dosage as group I, while group VI was treated with CCl4 and the same drug dosage as group II. The simultaneous administration of H3-propranolol and lidocaine increased propranolol levels in the serum and tissues. The liver in damaged animals showed an increase of propranolol level under lidocaine co-administration, probably due to CCl4 induced liver enzyme activity, resulting in a rapid propranolol metabolism or to competition between both drug protein binding sites. The increased propranolol levels in the heart after lidocaine administration were probably due to attributed to its high affinity for heart tissue. Consequently, as regards the therapeutic approach for patients with liver disease receiving propranolol their propranolol dosage should be reduced when lidocaine is co-administered.     

Coronary Magnetic Resonance Angiography

Coronary magnetic resonance angiography (CMRA) is a technique in clinical evolution. Current clinical applications include assessment for coronary anomalies, aneurysms, bypass graft patency, and, in experienced centers, the exclusion of proximal and multivessel coronary artery disease (CAD). As local expertise increases and more extensive multicenter data become available, additional applications will be established. CMRA promises to supplement and in some cases obviate the need for X-ray contrast angiography, and to expand our understanding of the pathophysiology of CAD. Zusammenfassung Die Magnetresonanzangiographie der Koronargefäße (CMRA) ist eine sich ständig weiterentwickelnde Technik. Etablierte Anwendungen sind zurzeit die Beurteilung von koronaren Anomalien, Aneurysmen und der Durchgängigkeit von Bypasses. Auch der Ausschluss proximaler Koronarstenosen und einer koronaren Mehrgefäßerkrankung ist in einigen spezialisierten Zentren möglich. Mit zunehmender Erfahrung der jeweiligen Anwender und der Verfügbarkeit von Ergebnissen großer multizentrischer Studien können zukünftig weitere klinische Anwendungen etabliert werden. In der Zukunft könnte die CMRA ergänzende Informationen zur Indikationsstellung einer konventionellen Röntgenangiographie bringen und in einigen Fällen diese Untersuchung sogar ersetzen. Die CMRA wird unseren Einblick in die Pathophysiologie der koronaren Herzerkrankung sicher erweitern.     

An update on the overnight dexamethasone suppression test for the diagnosis of Cushing's syndrome: limitations in patients with mild and/or episodic hypercortisolism.

The overnight one-mg dexamethasone suppression test has been used for many years to screen for Cushing's syndrome. This test has usually been evaluated in controls versus patients with severe hypercortisolism. Under these conditions, the overnight dexamethasone suppression test has been reported to have high sensitivity and specificity. The objective of this study was to determine the sensitivity of the one mg overnight dexamethasone suppression test in patients with mild and/or periodic Cushing's syndrome. Therefore, an overnight dexamethasone suppression test was performed in 17 consecutive patients presenting to an endocrinology clinic with signs and symptoms of hypercortisolemia who were later proven to have Cushing's syndrome. The majority of patients were found to have both mild and periodic hypercortisolism. One mg of dexamethasone was given at midnight and a plasma cortisol was measured by radioimmunoassay at 08:00 the following morning. Using a cut-off for a morning cortisol following overnight dexamethasone of > 5 microg/dL, only three of 17 patients failed to suppress to a value less than this cut-off (sensitivity 18 %). A cut-off of > 2 microg/dL gave similar sensitivity. Even with a stringent cut-off point of > 1.8 microg/dL, only seven of 17 patients failed to suppress to a value less than this cut-off point (sensitivity of 41 %). These results demonstrate that the great majority of patients with mild and/or periodic Cushing's syndrome suppress to overnight dexamethasone. Since patients with mild and/or periodic Cushing's syndrome are the patients in whom the identification of hypercortisolism is difficult, our results from this relatively small study suggest that this test should no longer be used to exclude these patients from further workup for Cushing's syndrome.     

Energy cost of activity and exercise in children and adolescents with cystic fibrosis.

In cystic fibrosis (CF), perturbations of total daily energy expenditure (TDEE) may be a major determinant of altered nutrition and growth. Measurement of TDEE is problematic, though the flex-heart rate method (FHRM) provides a close estimation of TDEE, as compared to the cost-prohibitive, gold standard, the double-labeled water method, and permits estimates of the energy cost of daily activities (ECA) above resting energy expenditure (REE). We hypothesize that alterations in ECA affects TDEE in CF. PURPOSE: To measure components of TDEE in adolescents with CF and normal lung function compared with controls, and to determine whether ECA can be improved by diet and exercise. METHODS: Clinically stable CF subjects (aged 9-13, n=12) and age- and gender-matched controls (n=13) had repeated measurements of TDEE by FHRM, REE, and maximal cardiopulmonary exercise testing (CPET) during a 6-week exercise and diet program. RESULTS: While the mean REE was similar in both groups, ECA was significantly lower in CF adolescents as compared to controls (p=0.02). During CPET, maximal exercise in CF was characterized by hyperventilation, which was unrelated to ventilation-perfusion mismatching. There were no changes in REE after dietary intervention. CONCLUSION: ECA in CF adolescents with normal lung function is lower when compared to healthy controls. These findings support the hypothesis that clinically stable patients with CF have inefficient energy metabolism or alternatively conserve energy during activities of daily living.     

Oral beta2-agonist use by preschool children with asthma in East and Central Harlem, New York.

Although studies have documented underuse of controller medications and overuse of short-acting inhaled ss(2)-agonist among children with persistent asthma in disadvantaged communities, the persistence of oral ss(2)-agonist use in pediatric practice has not been studied since inhaled short-acting ss(2)-agonists became widespread. We describe medications used to treat asthma among children 3 to 5 years of age at 10 Head Start and other subsidized preschool centers in East and Central Harlem, New York City. We interviewed 149 parents/guardians of children who were identified as having probable asthma based on physician's diagnosis, persistent symptoms, hospitalization, and medication use. We classified 86 of the 149 children (58%) as having current persistent asthma. Only 15 of them (17%) were reported to have used controller medications at least 5 days/week in the last 4 weeks-only 2 of whom used inhaled corticosteroids. By contrast, 53 children (62%) used oral ss(2)-agonist in the last 4 weeks, often (72%) in conjunction with nebulized or inhaled short-acting ss(2)-agonist. Use of oral ss(2)-agonist was associated with more severe symptoms. This study documents the continued widespread use of oral ss(2)-agonist for treatment of children in a low-income community with high prevalence of asthma.     

Psoriasis confined strictly to vitiligo areas – a Koebner‐like phenomenon?

Vitiligo and psoriasis are both common skin disorders. However, psoriasis strictly confined to pre-existing vitiligo areas is rare and suggests a causal relationship. We report here on two patients with a strict anatomical colocalization of vitiligo and psoriasis. The histopathological examinations showed typical changes for both diseases together with a dense infiltrate of CD4+ and CD8+ T cells. By immunohistochemistry, intracytoplasmatic granzyme B and tumour necrosis factor alpha (TNF-alpha) were detected within the T-cell population, suggesting the functional activity of these cells and the creation of a local T helper 1 (Th1)-cytokine milieu. Additionally, in one patient we could identify anti-melanocytic T cells by tetramer staining and enzyme-linked immunospot (ELISPOT) analysis. These skin-infiltrating lymphocytes might trigger, by the local production of Th-1 cytokines such as TNF-alpha and interferon-gamma (IFN-gamma), the eruption of psoriatic plaques in patients with a genetic predisposition for psoriasis.