Relative contributions of cardiopulmonary and sinoaortic baroreflexes in causing sympathetic activation in the human skeletal muscle circulation during orthostatic stress

The aim of this study was to reexamine the hypothesis that cardiopulmonary baroreflexes are more important than sinoaortic baroreflexes in causing vasoconstriction in the skeletal muscle circulation during orthostatic stress. We recorded muscle sympathetic nerve activity (MSNA) with microelectrodes in the peroneal nerve (and forearm blood flow with venous occlusion plethysmography) in normal subjects (innervated ventricles) and in heart transplant recipients (denervated ventricles) during graded lower body negative pressure (LBNP) performed alone and in combination with intravenous infusion of phenylephrine, which was titrated to eliminate the orthostatically induced fall in blood pressure and thus the unloading of both carotid and aortic baroreceptors. The principal new findings are as follows: (1) The increases in both MSNA and forearm vascular resistance during multiple levels of LBNP were not attenuated by heart transplantation, which causes ventricular but not sinoaortic deafferentation. (2) In heart transplant recipients, a small increase in MSNA during mild LBNP was dependent on a decrease in arterial pressure, but in normal subjects, a similar increase in MSNA occurred in the absence of any detectable decrease in the aortic pressure stimulus to the sinoaortic baroreceptors. (3) In normal subjects, the large increase in MSNA during a high level of LBNP was dependent on a decrease in arterial pressure and could be dissociated from the decrease in central venous pressure. Taken together, the findings strongly suggest that sinoaortic baroreflexes are much more important and ventricular baroreflexes are much less important than previously thought in causing reflex sympathetic activation and vasoconstriction in the human skeletal muscle circulation during orthostatic stress.     

Activation of mu opioid receptors inhibits microglial cell chemotaxis

Opiates modulate many macrophage functions. Microglia, the resident macrophages of the brain, migrate to sites of inflammation within the CNS. Using primer sets designed to span the entire open reading frame of the human brain mu opioid receptor (MOR), we found that microglial cells constitutively expressed MOR mRNA. The cDNA sequences of the MOR open reading frame in microglia were identical to those of human brain tissue. Using enriched human fetal microglial cell cultures, we found that morphine potently inhibited the directed migration (chemotaxis) of microglial cells toward C5a in a dose-dependent manner with an IC50 value of 1 fM morphine. We also found that DAMGO, a selective MOR ligand, dose-dependently suppressed microglial cell chemotaxis with an IC50 value of 1 nM, which was significantly attenuated by 10 nM beta-funaltrexamine. Taken together, these findings suggest that activation of constitutively expressed MOR inhibits microglial cell chemotaxis and support the notion of an anti-inflammatory role of MOR within the brain.     

Drosophila ecdysone receptor mutations reveal functional differences among receptor isoforms

The steroid hormone ecdysone directs Drosophila metamorphosis via three heterodimeric receptors that differ according to which of three ecdysone receptor isoforms encoded by the EcR gene (EcR-A, EcR-B1, or EcR-B2) is activated by the orphan nuclear receptor USP. We have identified and molecularly mapped two classes of EcR mutations: those specific to EcR-B1 that uncouple metamorphosis, and embryonic-lethal mutations that map to common sequences encoding the DNA- and ligand-binding domains. In the larval salivary gland, loss of EcR-B1 results in loss of activation of ecdysone-induced genes. Comparable transgenic expression of EcR-B1, EcR-B2, and EcR-A in these mutant glands results, respectively, in full, partial, and no repair of that loss.     

Infectious ocular complications in orthotopic liver transplant patients

We report the frequency and type of infectious ocular complications following orthotopic liver transplantation (OLT) and review diagnostic and therapeutic strategies. During the period September 1988 through November 1994, 684 patients underwent OLT at Mount Sinai Hospital (New York). Nine orthotopic liver transplant patients (1.3%) developed ocular infections: Candida albicans endophthalmitis (2), Aspergillus fumigatus endophthalmitis (1), cytomegalovirus retinitis (4), herpes simplex virus keratitis (1), and varicella-zoster virus panophthalmitis (1). The mean time from OLT to ocular symptoms was 42 days for patients with fungal infections and 128 days for patients with viral infections. Blurred vision was the commonest symptom (five of nine cases). The mean duration of follow-up was 2 years (range, 33 days to 5 years). Permanent loss of vision occurred in three patients, five had improvement in visual acuity, and one died of disseminated aspergillosis 33 days after OLT. Infectious ocular complications following OLT may occur as isolated events or with disseminated disease. Fungal infections occur earlier (mean, 42 days after OLT) than viral infections (mean, 4 months after OLT). The clinical presentation may be atypical; aggressive vitreoretinal procedures and serial examinations may be required to establish the diagnosis. Cytomegalovirus retinitis in orthotopic liver transplant patients may not require life-long maintenance therapy with antiviral agents.     

Review: the Michigan cleft twin study

The combined effects of clefting of the lip and/or palate and of their surgical repair have been examined for a cross-sectional sample of 20 MZ and 25 DZ like-sexed twins discordant for clefting, in the age range of 4 to 17 years. The findings of four studies published since 1975 on that sample are explored for the primary, contiguous and pleiotropic effects of clefting. The primary effects on facial structures of repaired cleft lip appear to be minimal. However, for twins with repaired cleft of the palate (with or without cleft of the lip), the maxilla was both deficient antero-posteriorly and was positioned more posteriorly than in their non-cleft co-twins. The maxillary first molars were usually slightly less erupted in the cleft twins than in the non-cleft twins. The cleft palate only twins had larger cranial base angles than their non-cleft co-twins. A contiguous effect of the posteriorly positioned maxilla was a mandibular rotation downward and backward in the cleft palate and bilateral cleft lip and palate groups but not in the unilateral cleft lip and palate group. The slightly larger cranial base angles found for cleft palate only, although contiguous in location, are more likely pleiotropic effect. The pleiotropic effects include a deficit in height and weight for cleft subjects which appears only after puberty. Although the teeth of the cleft twins tended to be smaller than those of the non-cleft twins, the amount was not clinically significant.     

Kikuchi-Fujimoto disease: benign cause of fever and lymphadenopathy

The purpose of this study was to determine the advantages and disadvantages of several techniques for performing the pneumoperitoneum. We studied 75 patients divided into three groups of 25 each. In the first group, we used the Veress needle technique in the umbilicus. In the second group, the insertion was in the upper left quadrant, and in the third group the insertion was direct with a disposable trocar in the umbilicus without pneumoperitoneum. In the first group, we made 32 attempts, and the time varied from 8 to 35 min. In the second group we made 28 attempts and the time was from 3 to 6 min. In both we had complications. In the third group, we made 25 direct insertions without complications, and the time was from 45 s to 3 min.     

Melatonin protects 6-OHDA-induced neuronal death of nigrostriatal dopaminergic system

In vivo neuroprotective effects of melatonin on the nigrostriatal dopaminergic system in rats unilateral 6-hydroxydopamine (6-OHDA) lesions were tested. Two weeks after lesioning the dopamine receptor agonist, apomorphine produced rotational asymmetry. In contrast, melatonin treatment significantly reduced the motor deficit following apomorphine challenge. Analysis by tyrosine hydroxylase (TH) immunocytochemistry revealed the loss of cell bodies in the substantia nigra (SN) and absence of terminals in the dorsolateral striatum ipsilaterally. Melatonin treatment also resulted in the survival of dopaminergic neurons in SN and TH-immuoreactive terminals in the dorsolateral striatum. These behavioral and histochemical results may indicate a neuroprotective action of melatonin and suggest a potential pharmacological role in the treatment of Parkinson's disease.     

The force-frequency relationship is altered in regenerating and senescent rat skeletal muscle

Maximal tetanic tension was elicited at 200, 150, and 150 Hz in control tibialis anterior muscles and at 150, 100, and 100 Hz in 14-day regenerating muscles of young (3 months), adult (18 months), and old (31 months) Fischer 344/Brown Norway F1 rats, respectively. In contrast to young rats, increasing stimulation frequency from 50 to 150 Hz did not elicit significantly greater tetanic tension in control or regenerating muscles of old rats. At higher stimulation frequencies, tetanic fade was prevalent in control and regenerating muscles of adult (250-300 Hz) and old rats (200-300 Hz), but was only present at 14 days of recovery in regenerating muscles of young rats (300 Hz). The decreased efficacy of rehabilitative and physical medicine procedures in adult and elderly patients who have suffered skeletal muscle injury could be explained, in part, by the postulate that tetanic fade is indicative of inadequate synaptic transmission.     

Liver abscess secondary to intrahepatic perforation of the gallbladder, presenting as a liver mass

We present an unusual case of a large pyogenic liver abscess containing multiple stones caused by perforation of a necrotic gallbladder and spread of the infection into the liver. It manifested by weakness, weight loss, and a palpable liver mass, pointing toward a neoplastic process. Workup for metastatic disease was negative, and tumor markers also were negative. Ultrasound and computerized tomography were inconclusive, and the diagnosis was established by laparoscopy. Open drainage and cholecystectomy were performed, with good outcome. In the literature, there have been very few reports of intrahepatic perforation of the gallbladder resulting in formation of hepatic abscess. The presentation, diagnosis, and management of liver abscesses, as well as the complications of acute cholecystitis, are discussed.