Predictors of language restitution following stroke: a multivariate analysis

A consecutive sample of 50 language-impaired patients was evaluated prospectively during the first 3 to 4 months following unilateral left- or right-hemisphere stroke. A multiple logistic linear regression model was used to assess the relative importance of eight predictor variables on the likelihood of language recovery. Those found to be significantly associated with language recovery included age (favoring younger patients) and length of hospital stay (favoring shorter stays). Gender (favoring males), type of stroke (favoring hemorrhages), and side of lesion (favoring right) were only moderate correlates of recovery. Neither race nor history of previous stroke was a significant predictor of language recovery. Multivariate statistical analysis was useful in illuminating the joint relationship between clinical and demographic predictor variables and language recovery.     

Effect of Zonisamide (CI-912) on a Synaptic System Model

The effect of the experimental antiepileptic drug zonisamide (1,2-benzisoxazole-3-methanesulfonamide, ZNS) on the trigeminal complex of cats was compared with the effect of established antiepileptic drugs. Intravenous administration of 10-40 mg/kg ZNS significantly depresses descending excitatory mechanisms, as well as segmental and descending inhibitory mechanisms, but has only a minor effect on segmental excitatory mechanisms. This spectrum of activity is similar to that of valproate, and suggests that ZNS should also be a broad-spectrum antiepileptic drug. In agreement with our experimental observations, it has been found that ZNS is effective against complex partial, generalized tonic clonic, and myoclonic seizures. The antiepileptic profile of ZNS in conventional screening tests resembles that of carbamazepine (CBZ) and phenytoin. However, CBZ exacerbates rather than prevents myoclonic seizures. Our experimental model thus provides a more accurate prediction of ZNS's clinical spectrum of activity. The relationship of these findings to the mechanism of action of antiepileptic drugs is discussed.     

Reconstruction of the anterior cruciate ligament with a cyropreserved ACL allograft

Summary. The ACL in the rabbit is innervated by three types of nerve fibres. These subserve vasoconstriction, nociceptive and proprioceptive purposes. The aim of this paper was to investigate the revascularisation and reinnervation of cyropreserved ACL allografts in 22 New Zealand white rabbits. Cyropreserved grafts were used as they may excite less host immune response. Both microangiographic and immunohistochemical methods were used. We found that cryopreserved allografts exhibited little immune response, revascularisation was considerable by the 24th postoperative week and reinnervation was essentially complete by then. No mechanoreceptors were found in ACL allografts. In rabbits, the anatomical basis for the participation of ACL allografts in sensorimotor reflexes is not given before the twelfth week after transplantation.

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Résumé. Nous avons examiné par méthodes micro-angiographiques et immuno-histo-chimiques la revascularisation et l’innervation d’un allogreffon cryopréservé (os – ligament croisé antérieur – os), chez 22 lapins de Nouvelle Zélande. Au sein de la greffe, existe une hypervascularisation maximale à 6 semaines, persistante à 12 semaines et se normalisant 24 semaines après la transplantation. Le panicule adipeux du genou était une source importante pour la revascularisation du greffon. L’immuno-histo-chimie a montré la présence de 3 types de fibres nerveuses au sein du ligament croisé: des afférents sensoriels mécano-réceptifs, des afférents sensoriels nociceptifs et des efférents sympathiques vaso-moteurs. Les contr?les ont montré l’existence de plusieurs fibres des 3 types de nerf; les terminaisons sensitives étaient toutes des corpuscules de Ruffini. Il n’y avait pas de fibre nerveuse au sein de l’allogreffe du ligament croiséà 3 et 6 semaines après la transplantation. Des fibres d’aspect cicatriciel étaient détectées à 12 semaines, tandis que des contr?les plus tardifs montraient un nombre et une distribution presque normale des filets nerveux. Aucun récepteur mécanique ne fut trouvé dans l’allogreffe. Chez le lapin, les bases anatomiques de la participation sensitivo-motrice de l’allogreffe du ligament croisé antérieur n’existent pas avant la 12ème semaine après la transplantation.

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Accepted: 11 May 1995     

The mode of action and the structure of a herbicide in complex with its target: binding of activated hydantocidin to the feedback regulation site of adenylosuccinate synthetase.

(+)-Hydantocidin, a recently discovered natural spironucleoside with potent herbicidal activity, is shown to be a proherbicide that, after phosphorylation at the 5' position, inhibits adenylosuccinate synthetase, an enzyme involved in de novo purine synthesis. The mode of binding of hydantocidin 5'-monophosphate to the target enzyme was analyzed by determining the crystal structure of the enzyme-inhibitor complex at 2.6-A resolution. It was found that adenylosuccinate synthetase binds the phosphorylated compound in the same fashion as it does adenosine 5'-monophosphate, the natural feedback regulator of this enzyme. This work provides the first crystal structure of a herbicide-target complex reported to date.     

Phase I trial of the polyelectrolyte carbetimer administered i.v. once every four weeks

Summary Carbetimer, a new synthetic low molecular weight polyelectrolyte with a novel structure displayed antitumor activiy in a number of animal tumor model systems and in vitro investigations. Based on these findings it was brought to a phase I clinical trial in patients with advanced malignant disease after failure of conventional treatment or with no conventional treatment available. Forty-eight patients received 98 courses. The schedule was a one hour i.v. infusion every four weeks. The starting dose was 180 mg/m² and dose escalation was performed according to a modified Fibonacci formula up to 16,690 mg/m². At least three patients were treated at each dose level and each patient was eligible to receive repeat courses at the same dose, until progressive disease or dose-limiting toxicity intervened. No hematological toxicity was encountered. Some adverse effects such as reversible proteinuria, hypercalcaemia, pain at infusion site, nausea and vomiting and fatigue were seen partly in a dose-related manner but did not represent the maximum tolerated dose (MTD). The limiting toxicity at the highest dose level of 16,690 mg/m² consisted of ocular symptoms (light flashes) accompanied by a modest decrease of blood pressure and nausea or vomiting during a one hour infusion. 16,690 mg/m²/1 hour was considered the MTD. There were four deaths on study, all considered diseaserelated. Fourteen patients had stable disease for more than two courses, which, however, could also be explained by the natural course of disease. No clear-cut antitumor responses were noted in our study center.The recommended dose for phase II trials derived from our results is 12,550 mg/m²/2 hours. However, with regard to experiences in other phase I studies, the subsequent phase II studies will be performed with a dose of 6,500 mg/m².     

Trans/paracellular, surface/crypt, and epithelial/subepithelial resistances of mammalian colonic epithelia

The epithelial barrier function of the large intestine resides in the trans- and paracellular pathways of the surface epithelium and crypts. Conventional transmural resistance and permeability measurements, however, yield only the resistance of the whole tissue and not that of its individual components. Combining conductance scanning techniques and impedance analysis, we determined the resistance of epithelial and subepithelial tissues, crypts and surface epithelium, and trans- and paracellular pathways of the mouse distal colon. The subepithelial tissue contributed 15% to the transmural resistance of 118+/-9 omega x cm2. In the epithelium proper the resistance of crypts (429+/-86 omega x cm2) exceeded that of the surface epithelium (132+/-15 omega x cm2). The paracellular resistance (3.2+/-0.4 k omega x cm2) of the surface epithelium was 23-fold higher than the transcellular resistance (137+/-16 omega x cm2), and thus the epithelium was classified as "medium tight". In order to investigate the trans- and paracellular resistances of the crypt epithelium as well, flat monolayers of HT-29/B6 cultured colon crypt cells were studied, which had a transepithelial resistance of 349+/-32 omega x cm2. With transcellular resistance (377+/-41 omega x cm2) tenfold lower than the paracellular resistance (3.9+/-1.3 k omega x cm2), this cryptal monolayer was also classified as "medium tight". Hence, considering the 1.2 times larger area of the crypt epithelium, the surface epithelium has a 4 times larger ion permeability than the crypt epithelium. However, the paracellular resistances are not different. Thus the lower transcellular resistance of the surface compared to the crypt epithelium suggests a higher density of ion channels in the apical membrane of surface cells.