Low Dose Disopyramide Often Fails to Prevent Neurogenic Syncope During Head-Up Tilt Testing

Low dose disopyramide has been used to prevent neurally-mediated syncope during head-up tilt testing but a correlation between blood levels and efficacy has not been described. We measured disopyramide levels in 15 patients with recurrent syncope and positive 70° head-up tilt tests who underwent one or more repeat tests on the drug. There were 9 males and 6 females, age range 15–78 years. Fourteen of the 15 patients had structurally normal hearts. The daily disopyramide dose was 645 ± 165 mg (mean ± SD). Patients developed syncope during 9 tests and had no syncope during 12 tests. The mean disopyramide level in patients with positive tests was significantly lower than the level in patients with negative tests (2.4 ± 0.15 μ/mL vs 3.2 ± 0.22 μ/mL, P = 0.018). Six patients were tested twice on different disopyramide doses. Five of these six patients had syncope during head-up tilt testing on the lower dose and negative tests on the higher dose (disopyramide levels 2.2 μ 0.17 μ/mL vs 3.2 μ0.17 fi/mL, P = 0.004). Thus, disopyramide is effective in preventing neurogenic syncope during head-up tilt testing, but higher blood levels are often necessary for efficacy. In a given patient, failure to respond to low dose disopyramide does not preclude success on higher doses.     

Morphological evidence for calcium-dependent association of calgranulin with the epidermal cytoskeleton in inflammatory dermatoses

The association of calgranulins, intracellular calcium-binding proteins, with the keratinocyte cytoskeleton has been studied. These molecules are expressed in various inflammatory dermatoses and in organ-culture explants. Triton X-100 extraction in the presence of calcium or EDTA suggested that calgranulins are detergent insoluble in the presence of calcium. The molecules were localized in a plaque-like structure at the cell periphery in lesional skin and in organ-culture explants. Following induction of calgranulins in vitro there was a redistribution of the intermediate filament cytoskeleton into a perinuclear halo, although desmosomes remained intact. These various features suggest that these members of the S-100 protein family have a role in cytoskeletal changes seen in various skin diseases.     

Conformational free energy of armadillo metmyoglobin

The conformational free energy of armadillo metmyoglobin was examined over a pH range of 4.4–8.0 and a guanidinium chloride concentration of 0–2.3 M. For isothermal unfolding at 25′ essentially the same value was obtained for the conformational free energy from all the data: 27 ± 2 kJ/mol. These data suggest that the armadillo has the least stable metmyoglobin of any mammal thus far examined. The cooperativity of the unfolding with respect to denaturant is considerably less than for other mammalian myoglobins. On unfolding only three to four side chains with a pK_A of 6 in the unfolded protein are protonated instead of the six found for horse and sperm whale myoglobins.     

EFFECT OF MORPHINE ON CORTISOL AND PROLACTIN SECRETION IN ANOREXIA NERVOSA AND DEPRESSION

Endogenous opioid peptides are involved in feeding regulation, and alterations in opioidergic regulation have been implicated in the pathophysiology of eating disorders. To investigate further this hypothesis, we conducted a placebo-controlled study of the effect of the opiate alkaloid morphine on cortisol and prolactin secretion in six patients with anorexia nervosa and six age-matched healthy volunteers, and compared the results with those obtained in nine depressed patients. Basal cortisol but not basal prolactin levels were elevated in patients with anorexia nervosa and patients with depression. Following the administration of morphine plasma concentrations of cortisol levels declined progressively and at a similar rate in all three groups. The prolactin response to morphine was attenuated significantly in patients with depression. Neither the cortisol and prolactin response to morphine in the anorectic patients nor the cortisol response in the depressed patients we observed in this study suggests altered opiate receptor sensitivity. However, the decreased prolactin response to morphine in depressed patients remains compatible with this hypothesis.     

The Role of Contrast Angiography in Gastrointestinal Bleeding with the Advent of Technetium Labelled Red Blood Cell Scans

This study suggests that in cases of GI bleeding emergency angiography is likely to be more rewarding when it follows a Tc-99m RBC scintigram which demonstrates active GI bleeding. The added advantages of angiography include more accurate anatomical localization and the possibility of therapeutic radiological intervention. These advantages should be considered in the individual patient before deciding to proceed directly to surgical intervention based on positive scintigraphy alone. Where the scintigram does not demonstrate active bleeding there is no need to perform emergency angiography, however, elective angiography may demonstrate a possible cause for bleeding. Chronic GI bleeding remains a diagnostic dilemma, however, elective angiography has a small but definite role in the diagnostic workup of these cases because of its ability to demonstrate a possible causative lesion.     

A randomized controlled trial of non-stress antepartum cardiotocography

Summary. In a prospective randomized controlled study of non-stress antepartum cardiotocography (CTG), involving 569 tracings in 300 patients, 'non-reactive' traces showed a significant association with stillbirths and neonatal deaths, intrauterine growth retardation, admission to special care baby unit for conditions associated with intrauterine hypoxia, and low Apgar scores at 1 and 5 min. The report of the CTG was made available to the clinician in 144 patients and withheld in 156 patients. With the report available, significantly more patients were allowed to continue their antenatal care as out-patients, and significantly more antenatal inpatients were allowed home. There were no other significant differences in management, or outcome in the two groups.