Cutaneous plasmacytosis associated with lung and anal carcinomas

Cutaneous plasmacytosis is a rare disorder characterized by a benign proliferation of mature plasma cells that appears as multiple dark-brown to purplish skin lesions, often associated with polyclonal hypergammaglobulinaemia. We present the case of a 55-year-old Caucasian man who suffered from a cutaneous plasmacytosis associated with two different carcinomas. Cutaneous plasmacytosis seems to be a reactive process because most cases reported are not associated with any apparent underlying disease. Nevertheless, because few reported cases were associated with malignancies, screening of additional neoplasms would be justified.     

Outcomes of low-vision services using optometric and multidisciplinary approaches: a non-randomized comparison

Consecutive patients (n = 215) who were referred to optometric (55%) or multidisciplinary (45%) low-vision services and above 50 years of age were recruited from four hospitals in the Netherlands. They completed two vision-related quality of life questionnaires, the Vision Quality of Life Core Measure (VCM1) and the Low Vision Quality of Life Questionnaire (LVQOL), before their first visit with low-vision services and 1 year later. At follow-up, patients referred to multidisciplinary low-vision services had lower scores on the mobility subscale of the LVQOL than patients referred to optometric low-vision services [5.3 points; 95% confidence interval (CI): 0.2-10.5]. Paired sample t-tests for the two groups of patients taken together show improvement for the VCM1 (3.1 points; 95% CI: 0.6-5.6) and deterioration for the basic aspects of vision (3.5 points; 95% CI: 1.1-5.9) and the mobility (6.6 points; 95% CI: 3.7-9.5) subscales of the LVQOL. In conclusion, people referred to optometric services showed less deterioration in mobility than those referred to multidisciplinary services. No differences were observed for any of the other subscales of the LVQOL and the VCM1. Future research in this field should include randomized controlled designs comparing low-vision services with no treatment or placebo.     

Update on the management of neuromuscular block: focus on sugammadex

Steroidal neuromuscular blocking agents (NMBAs), such as rocuronium, are widely used in clinical anesthesia and emergency medicine to facilitate endotracheal intubation and artificial ventilation and to allow surgical access to body cavities. Reversal of neuromuscular blockade is important for the acceleration of patient recovery and prevention of postoperative residual neuromuscular blockade and reduces the incidence of severe morbidity and mortality associated with anesthesia management. Sugammadex is the first selective relaxant binding agent (SRBA) and has been designed to reverse the steroidal neuromuscular blocking drug rocuronium. Encapsulation of the rocuronium molecule by sugammadex results in a rapid decrease in free rocuronium in the plasma and subsequently at the nicotinic receptor at the motor endplate. After encapsulation, rocuronium is not available to bind to the nicotinic receptor in the neuromuscular junction. This promotes the liberation of acetylcholine receptors, and muscle activity reappears. This new concept of reversal of neuromuscular block induced by rocuronium (or vecuronium) led to impressive results in animal and phase 1 and 2 studies. Sugammadex is currently in phase 3 clinical studies and may be commercially available by 2008.     

Affinity profiles of BTM-1086 and BTM-1041 at muscarinic receptor subtypes and at H1- and alpha 1-receptors

The affinities of the (+) and (-) enantiomers of the antimuscarinic benzothiazepinone derivative, cis-2,3-dihydro-3-(4-methyl-1-piperazinylmethyl)-2-phenyl-1,5-benzoth iazepin-4 (5H)-one (BTM-1041 and BTM-1086), for muscarinic receptor subtypes, histamine H1-receptors and alpha 1-adrenoceptors were determined in vitro using isolated organs: field-stimulated rabbit vas deferens (M1-receptors), guinea-pig left atrium (M2-receptors), guinea-pig ileum (M3- and histamine H1-receptors) and rat vas deferens (alpha 1-adrenoceptors). We also assessed the binding profile of BTM-1041 and BTM-1086 at muscarinic receptor subtypes in guinea-pig cortex (M1), heart (M2) and salivary glands (M3) as well as at alpha 1-adrenoceptors in rat cerebral cortex. Functional and binding experiments showed that the (-) enantiomer (BTM-1086) had a high affinity (pA2 = 7.98-8.81; pKi = 8.31-9.15) for the three muscarinic receptor subtypes, whereas the (+) enantiomer (BTM-1041) showed a low antimuscarinic potency (pA2 = 4.87-5.31; pKi = 4.85-5.55). This results in an extremely high stereoselectivity for these optical isomers [-)/(+) ratios = 1023 to 6918). The affinity of the (-) enantiomer BTM-1086 was lower for both histamine H1- and alpha 1-receptors than for muscarinic receptors, whereas the reverse was true for the (+) enantiomer, BTM-1041. Thus, the stereochemical demands for the two optical isomers were most stringent at muscarinic receptors but were inverse and less pronounced at histamine H1- and alpha 1-receptors (stereoselectivity ratios = 0.16-0.22).     

Deficiency of nitric oxide in allergen-induced airway hyperreactivity to contractile agonists after the early asthmatic reaction: an ex vivo study.

1. Using a guinea-pig model of allergic asthma, we investigated the role of nitric oxide (NO) in allergen-induced airway hyperreactivity after the early asthmatic reaction, by examining the effects of the NO-synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) on the responsiveness to methacholine and histamine of isolated perfused tracheae from unchallenged (control) animals and from animals 6 h after ovalbumin challenge. 2. All animals developed airway hyperreactivity to inhaled histamine at 6 h after ovalbumin challenge, with a mean 3.11 +/- 0.45 fold increase in sensitivity to the agonist (P < 0.001). 3. In perfused tracheal preparations from the ovalbumin-challenged guinea-pigs, the maximal responses (Emax) to methacholine and histamine were significantly enhanced compared to controls, both after intraluminal (IL) and extraluminal (EL) administration of the contractile agonists. In addition, a small but significant increase in the pD2 (-log10 EC50) for IL and EL methacholine and for IL histamine was observed. As a consequence, the delta pD2 (EL-IL) for histamine was slightly decreased from 1.67 +/- 0.13 to 1.23 +/- 0.14 (P < 0.05). However, the delta pD2 for methacholine was unchanged (1.85 +/- 0.11 and 1.77 +/- 0.12, respectively; NS). 4. Incubation of control tracheae with 100 microM L-NAME (IL) significantly enhanced the Emax for both IL and EL methacholine and histamine to approximately the same degree as observed after ovalbumin challenge, with no effect on the pD2 and delta pD2 for both agonists. On the contrary, L-NAME had no effect on Emax and pD2 values of tracheal preparations from ovalbumin-challenged guinea-pigs. 5. L-NAME (10 microM-1 mM) had no effect on methacholine-induced contraction of isolated tracheal strip preparations obtained from control animals, indicating that L-NAME has no antimuscarinic effect on tracheal smooth muscle. 6. Histological examination of the intact tracheal preparations indicated epithelial and subepithelial infiltration of eosinophils after ovalbumin challenge. However, no apparent damage of the airway epithelium was observed in these preparations. 7. The results indicate that a deficiency of NO contributes to allergen-induced airway hyperreactivity after the early asthmatic reaction and that this deficiency appears not to be due to epithelial shedding.     

Arachidonic acid metabolites in CSF in hypoxic-ischaemic encephalopathy of newborn infants

The aim of this study was to evaluate the cerebral synthesis of eicosanoids in the asphyctic newborn and to investigate the relation between the prostanoid profiles in cerebrospinal fluid (CSF) and the appearance and severity of hypoxic-ischaemic encephalopathy (HIE). Levels of 6-keto-PGF _1-α, TXB₂, PGE₂ and PGF_2-α in CSF were measured in 40 full term newborns during the first day of life. Thirty of these newborns had birth asphyxia and were divided into three groups: 10 without HIE, 12 with mild HIE and 8 with moderate-severe HIE. They were compared to a control group of 10 non-hypoxic newborns. Determinations of the metabolites in CSF were performed by RIA and expressed as pg/ml (mean ± SD). The CSF TXB₂ (thromboxane A₂ metabolite) in asphyxiated newborns was always higher than in the control group (28.12 ± 10.6), and related to the severity of HIE ( p = 0:005): without HIE (50.84 ± 16.4; p = 0:02), mild HIE (80.65 ± 12.64; p ± 0:01) and moderate-severe HIE (178.14 ± 20.5; p < 0:01). The CSF 6-keto-PGF _1-α (prostacyclin metabolite) in asphyxiated newborns was always higher than in the control group (80.55 ± 12.56), but indirectly related to the severity of HIE: without HIE (240.95 ± 28.12; p < 0:01), mild HIE (183.65 ± 30.1; p < 0:01) and moderate-severe HIE (140.55 ± 25.12; p < 0:01). In the moderate-severe HIE group, the increase in TXB₂ was higher than the rise in 6-keto-PGF _1-α.