Dexamethasone as an adjuvant for peripheral nerve blockade: a randomised,triple-blinded crossover study in volunteers

Background

The efficacy of dexamethasone in extending the duration of local anaesthetic block is uncertain. In a randomised controlled triple blind crossover study in volunteers, we tested the hypothesis that neither i.v. nor perineurally administered dexamethasone prolongs the sensory block achieved with ropivacaine.

The Well-being Model: A New Drug Interaction Model for Positive and Negative Effects

Background: Drugs are routinely combined in anesthesia and pain management to obtain an enhancement of the desired effects. However, a parallel enhancement of the undesired effects might take place as well, resulting in a limited therapeutic usefulness. Therefore, when addressing the question of optimal drug combinations, side effects must be taken into account.

Methods: By extension of a previously published interaction model, the authors propose a method to study drug interactions considering also their side effects. A general outcome parameter identified as patient's well-being is defined by superposition of positive and negative effects. Well-being response surfaces are computed and analyzed for varying drugs pharmacodynamics and interaction types. In particular, the existence of multiple maxima and of optimal drug combinations is investigated for the combination of two drugs.

Results: Both drug pharmacodynamics and interaction type affect the well-being surface and the deriving optimal combinations. The effect of the interaction parameters can be explained in terms of synergy and antagonism and remains unchanged for varying pharmacodynamics. For all simulations performed for the combination of two drugs, the presence of more than one maximum was never observed.     

Low level of response to alcohol as associated with serotonin transporter genotype and high alcohol intake in adolescents.

BACKGROUND: A low level of response to alcohol has been associated with both the genetic constitution of the regulatory region (SLC6A4) of the human serotonin (5-hydroxytryptamine, 5-HT) transporter (5-HTT) and with future alcohol intake and an increased risk for alcoholism. To date, all studies of relevant polymorphisms have been carried out in populations in the United States. METHODS: Data were extracted from a subset (n = 243) of a cohort of children who have been observed since birth through evaluation of the family history of alcoholism and psychosocial risk influences. At age 16 years, the response to alcohol was assessed with the Self-Rating of the Effects of Alcohol (SRE) questionnaire, and the average amount of alcohol intake per month was assessed during the prior 6 months. Additional variables that were measured included the 5-HTT genotype, externalizing behavior, and sociodemographic variables, such as gender and age. RESULTS: The level of response to alcohol was significantly lower among carriers of two long alleles of the 5-HTT regulatory region compared with carriers of one or two short alleles (Mann-Whitney U = 5225.0, p = .005). In a multiple regression analysis, the level of response to alcohol and externalizing behavior but not psychosocial factors significantly predicted the average amount of alcohol intake per month. CONCLUSIONS: This study demonstrates that, independent of the assessed psychosocial variables, the 5-HTT genotype correlated with the level of response to alcohol and predicted alcohol intake among 16-year-old adolescents.     

A QUANTITATIVE THEORY OF THE PRECIPITIN REACTION : VII. THE EGG ALBUMIN-ANTIBODY REACTION IN ANTISERA FROM THE RABBIT AND HORSE

1. In two rabbits subjected to prolonged injections with crystalline egg albumin the antibodies in one showed progressive changes such as noted in an earlier paper; the antibodies in the other did not. 2. The significance of this behavior in the production of sera for therapeutic use is pointed out. 3. Quantitative studies are reported on the low grade or incomplete antibody present in the early stages of immunization of a horse with egg albumin. 4. Quantitative studies on the flocculating antibody from later bleedings from the horse are given, and the dissociation of the soluble pre-zone compounds by rabbit anti-egg albumin is studied. Rough velocity estimations are reported. 5. The bearing of the findings on the mechanism of precipitin and flocculation reactions and of the Danysz effect is discussed in terms of the union of multivalent antigen with multivalent antibody.     

Cutaneous leishmaniasis: Clinical report of two cases and review of the recent literature

With 1–1.5 million cases reported every year cutaneous leishmaniasis represents an increasing health problem. The course of cutaneous leishmaniasis varies from a single self‐healing ulcer to a persistent ulcer or progressive mucosal disease with nasopharyngeal destruction. An enormous array of topical and systemic treatment modalities has been endorsed. The response to treatment depends on the species of parasite as well as the host's immunological and genetic status. Species‐specific treatment guidelines based on evidence from controlled studies are highly desirable. We present two cases of cutaneous leishmaniasis, one in a child and one during pregnancy, reviewing various diagnostic and therapeutic measures with special attention to problems in young and pregnant patients.     

Long-term Effects of Botulinum Toxin on Neuromuscular Function

Background: Recent reports indicate increased incidence of Clostridium botulinum infections, particularly among drug abusers and tissue allograft recipients. Botulinum toxin also has potential application in biochemical warfare. The neurotoxin-induced paralysis often requires mechanical ventilation with and without muscle relaxants. The authors investigated the long-term effects of botulinum toxin on muscle function, expression of nicotinic acetylcholine receptors (nAChRs), and their interaction with muscle relaxant, atracurium.

Methods: Rats (n = 30) were injected with varying doses (0.625, 2.5, and 10 U) of botulinum toxin into the tibialis muscle. Control animals (n = 9) received an equivalent volume of saline. At 128 days after injection, neuromuscular function, pharmacodynamics of atracurium, and nAChRs were evaluated.

Results: Nerve-evoked tensions, including tetanic tension and muscle mass, were decreased on the toxin-injected side in a dose-dependent manner relative to saline-injected controls as well as the contralateral side. Specific muscle tension and specific tetanic muscle tension (tensions/muscle mass) were not reduced. The ED10 of atracurium was reduced, the ED50 was unchanged, and the ED90 was increased in the highest (10-U) dose of toxin group. The atracurium plasma concentration to maintain a steady state 50% paralysis was significantly reduced in the 10-U toxin group. The nAChR concentrations in the tibialis muscle were significantly increased in a dose-dependent manner in all experimental groups.     

Fingerprinting of Salmonella enterica subsp. enterica serovar Enteritidis by ribotyping

Objective: To carry out an epidemiologic evaluation of Salmonella enterica subsp. enterica serovar Enteritidis outbreaks in households and small communities by means of rRNA gene restriction pattern analysis (ribotyping).
Method: One hundred Enteritidis isolates dating from 1989 to 1994 which could be allocated epidemiologically to different sources or to small community outbreaks were investigated with ribotyping, a fingerprinting method in which bacterial DNA is hybridized with the biotin-labeled plasmid pKK 3535 containing a ribosomal RNA operon of Escherichia coli to determine the ribosomal RNA gene restriction patterns.
Results: Four different ribotyping patterns were found with the restriction endonuclease Sma I and nine with Sph I. Ribotypes of isolates which could be allocated epidemiologically to a common source usually corresponded. Almost 60% of the Enteritidis infections had the ribotyping pattern Sph I-A. In contrast, this pattern was not found in any of the five Enteritidis strains isolated in 1989. The suspicion that Enteritidis phage type 4 infections are caused by consumption of insufficiently heated eggs is supported by the fact that the ribotyping pattern Sph 1-A was found in isolates from eggs and from human specimens.
Conclusions: As patterns Sph I-A and Sma I-J appeared in 58% and 75% of the isolates, respectively, ribotyping cannot be used for the differentiation between various outbreaks with these two patterns. In cases where the Enteritidis strains showed less frequent patterns, ribotyping seems to be a practical tool for the identification of infection chains. In addition newly appearing ribotyping patterns can give information about the epidemiologic development of Enteritidis infection.     

Urodilatin, not nitroprusside, combined with dopamine reverses ischemic acute renal failure.

The present study was undertaken to: (a) clarify the comparative renal potency of bolus injection of the natriuretic peptides urodilatin and ANF99-126 in the rat; (b) establish whether or not intravenous (i.v.) infusion of urodilatin (200 ng/min) combined with dopamine (UD) to maintain mean arterial pressure could improve GFR or renal histology in established experimental ischemic acute renal failure (ARF) induced by 30 minutes of bilateral renal artery clamping; (c) assess comparative efficacies of nitroprusside, an activator of soluble guanylate cyclase, combined with dopamine (ND) or control infusions of dopamine alone (DA), under equivalent conditions; and (d) determine effects of intra-renal arterial infusions of the stable cGMP analogue dibutyryl-cGMP immediately after renal artery clamping (RAC). After initial dose finding studies, i.v. infusion of UD 24 hours after 30 minutes of RAC improved GFR over five hours from 0.24 +/- 0.04 to 1.0 +/- 0.16 ml/min in association with a threefold rise in plasma cGMP and a 13-fold increase in urinary cGMP excretion. Plasma creatinine dropped by 41% from 230 +/- 16 to 135 +/- 18 microM/liter and was still reduced 24 hours later with values averaging 106 +/- 14 compared to 274 +/- 53 microM/liter in non-treated animals. During infusion, UV and FENa+ increased from 1.4 +/- 0.2 to 8.3 ml/min, and from 2.9 +/- 0.5 to maximum values of 15.8 +/- 2.4%. ND or DA alone were less effective, increasing GFR only to 14 and 20%, respectively, of normal values, but improvements were not sustained; in contrast to UD, ND did not alter plasma or urinary cGMP. In addition, DBcGMP was ineffective in improving GFR during early ARF. Histologically UD, but not ND, markedly reduced the incidence of granular casts, tubular desquamation and tubular necrosis in cortical areas and increased the incidence of medullary mitoses.