Precentral cortex stimulation for the treatment of central neuropathic pain: results of a prospective study in a 20-patient series

The authors report a series of 23 patients with central neuropathic pain who were treated with the recently developed technique of precentral cortex stimulation (PCS). Of the 20 patients with a follow-up of more than 1 year (mean of 23 months) 25% had an excellent, 35% a good and 15% a fair relief of pain. In 25% the method failed. On the basis of these findings and the literature data (127 reported cases), the authors advocate PCS in patients with severe and medically refractory poststroke pain.     

Vasopressin V2 (SR121463A) and V1a (SR49059) receptor antagonists both inhibit desmopressin vasorelaxing activity

Although [Arg(8)]vasopressin is a potent vasoconstrictor, it possesses vasorelaxant properties manifested either after vasopressin V1 receptor blockade or directly in some vascular beds. The nature of the receptor involved in the vasorelaxant effect of [deamino-Cys(1) D-Arg(8)]vasopressin (desmopressin), a vasopressin V2 receptor agonist, was studied on rat precontracted aortic rings by the use of highly selective new non-peptide vasopressin receptor antagonists. The present study demonstrates for the first time that desmopressin relaxant effect is antagonized by the vasopressin V2 receptor antagonist SR121463A, but also by the vasopressin V1A receptor antagonist SR49059, suggesting that desmopressin-induced relaxation is mediated by a receptor subtype sharing both V1A and V2 pharmacological profiles.     

Profil psychopharmacologique d'un nouvel agoniste Dopaminergique,le RU 24213

The psychopharmacological properties of RU 24213 were compared to those of other dopaminergic agonists (apomorphine, dexamphetamine, bromocriptine and l-dopa) in various behavioural tests. In naive mice the drug reduced the locomotor hyperactivity in the primary exploratory phase and produced stimulation in the subsequent stabilized activity period. In rats it provoked dose-related stereotypies, specially gnawing and sniffing. It delayed the cataleptic state induced by prochlorperazine without affecting its intensity. In animals unilaterally lesioned with 6-OHDA in the nigro-striatal pathway, RU 24213 caused contralateral turning. It exhibited relatively weak emetic and anorexic effects in dogs. Core temperature recordings in rats revealed a biphasic hypo- and hyperthermic activity. In drug interaction studies it was observed that stereotypies and rotations induced by RU 24213 were blocked by haloperidol and decreased by MT. Reserpine respectively decreased stereotypies and increased ipsilateral rotations in rats with unilateral electrolytical striatal lesion.The results obtained suggest that RU 24213 stimulates dopamine receptors both directly and indirectly. In this respect it could be compared to bromocriptine but unlike this latter compound it has an immediate effect which is of shorter duration.

     

Acute changes in forearm haemodynamics produced by cigarette smoking in healthy normotensive non-smokers are not influenced by propranolol or pindolol

Summary The aim of the present study was to examine the effect of cigarette smoking in healthy non-smokers on blood pressure and forearm haemodynamics after acute oral administration of non-selective -adrenoceptor blockers with and without intrinsic sympathomimetic activity, viz. pindolol 15 mg and propranolol 80 mg. A preliminary study was done to compare cigarette smoking and sham smoking to evaluate the time-course of the haemodynamic effects of cigarette smoking. The second experiment was then carried out in the same six volunteers, according to a double-blind randomized placebo-controlled crossover design, to evaluate the possible effect of pre-treatment with -adrenoceptor blockers on blood pressure, heart rate and forearm haemodynamics (forearm blood flow, brachial artery diameter and brachio-radial pulse-wave velocity) measured at baseline, during smoking and every five minutes up to 1 h afterwards.No major difference from placebo in blood pressure or forearm haemodynamics was found and pre-treatment with beta-blockers did not prevent the acute vascular effects of cigarette smoking.     

Evidence for voltage-activated outward currents in the neuropilar membrane of locust nonspiking local interneurons

Outward currents activated by depolarization were studied in the neuropilar membrane of locust nonspiking local interneurons, using the single-electrode voltage-clamp technique in situ. Preliminary observation of these currents in 272 neurons revealed two families. The first and most commonly observed (85% of recordings) showed a large transient current followed by a slowly decaying/late current. The second (15% of recordings) showed an additional outward current with a slow rate of activation, a peak within 100-150 msec, and a slow rate of inactivation. Only neurons of the first type were studied further. The transient current was activated by depolarization around -60 mV, with a time to peak of approximately 11 msec at -50 mV and less than 3 msec at -20 mV. This current decayed exponentially, with a time constant of 8.1 +/- 1.6 msec (n = 8 interneurons) at -30 mV. This time constant of inactivation did not appear to depend strongly on membrane voltage, in the range in which it was studied. A second and longer time constant of inactivation of 50-400 msec could not be assigned to either of the transient and late components of the outward current. The ratio of transient-to-late current varied between 1.6 and 5.4, with a mean of about 2.5. The reversal potential for the transient current could, on average, be shifted by 14 mV by a threefold increase in the bath K+ concentration, indicating that K+ is a charge carrier for the current. The transient current became inactivated with maintained depolarization and appeared half-inactivated at about -60 mV (slope factor k1/2 = 8 mV). This current was thus not fully inactivated at "resting" potential (average, -58 mV). Recovery from inactivation followed a single exponential time course, with a time constant of approximately 100 msec at -80 mV. The time course of recovery from inactivation of the transient current was well correlated with that of the recovery of transient outward rectification, as measured in current-clamp recording. Tetraethylammonium, at a bath concentration of 10 mM reduced the transient current by 70% and the delayed current by 60%. 4-Aminopyridine, at a bath concentration of 5 mM, had a significant effect in only two of five interneurons, reducing the transient current by approximately 85% and the late current by approximately 15%. Quinidine at a bath concentration of 100 microM was ineffective. Although these blockers did not allow a clear pharmacological separation of the currents, they were effective in reducing the outward rectification observed in current clamp during step depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)     

Marked increase of plasma hyaluronan after major thermal injury and infusion therapy

Hyaluronan (HYA) is an important structural element in skin and is presumably participating in regulation of the interstitial fluid volume. HYA is transported via the lymphatics from the tissues to the blood, where its concentration is normally very low. Fluid flux through the interstitium is markedly increased after thermal injury. The present study was performed to determine whether major thermal injury would affect plasma levels of HYA. In halothane-anesthetized sheep subjected to 40% BSA full-thickness scald burns, plasma HYA concentration increased from 116 +/- 19 (mean +/- SEM) to 172 +/- 18 ng/ml within 1 hr after injury (P less than 0.05). After 3 hr of fluid therapy plasma HYA concentration was further elevated to 10 times baseline (1417 +/- 322 ng/ml) (P less than 0.01). To clarify whether this rise represented an increased "washout" of interstitial HYA, attributable either to the burn injury or the subsequent fluid therapy, awake sheep were subjected to overhydration. Following a 3-hr infusion of lactated Ringer's 2.5 liter/hr, plasma HYA concentration increased to 2-3 times baseline. Lung lymph flow and its concentration of HYA increased, leading to an increase in the lymphatic flux of HYA to 10-20 times baseline. In peripheral lymph HYA flux increased 2-3 times baseline. Infusion of lactated Ringer's markedly increased lymphatic removal of HYA. However, plasma concentrations of HYA were 3 times higher after thermal injury than following fluid challenge alone, suggesting that thermal injury per se may also increase input of HYA into the systemic circulation.     

Distribution of epidermal growth factor in the kidneys of rats exposed to amikacin.

The distribution of epidermal growth factor (EGF) was examined by immunocytochemistry in the kidneys of rats exposed to amikacin, an aminoglycoside antibiotic causing tubular necrosis at high dose. Five-animal groups were treated for 4 or 10 days with amikacin at daily doses of 15, 40, 80 or 200 mg/kg. The drug was delivered i.p. twice a day. One hour before termination, each rat received an i.p. injection of [3H] thymidine to evaluate DNA synthesis in renal tissue. After sacrifice, the kidneys were processed for morphological (semithin and paraffin sections) and biochemical analysis (measurement of DNA synthesis by [3H] thymidine incorporation in vivo). Amikacin induced in proximal tubules a dose-related lysosomal phospholipidosis, which was assessed by the morphometric evaluation of altered lysosomes ("myeloid bodies") on semithin section. However, frank evidence of acute tubular necrosis was only observed in rats receiving amikacin at a daily dose of 200 mg/kg. Concomitantly with the development of tubular necrosis, there was a rise in the rate of cell turnover, reflected by an increase of DNA synthesis in renal tissue. This sign of tubular regeneration was accompanied by a redistribution of EGF immunoreactivity, as revealed by immunocytochemical staining. Within renal cortex of control rats, EGF immunoreactivity predominantly appeared in distal tubules and collecting ducts (97% of examined tubular sections). In contrast, in treated animals where the renal cortex displayed evidence of tubular necrosis/regeneration, EGF immunoreactivity was frequently associated with proximal tubules (more than 30% of examined tubular sections, as compared to 3% in controls).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of data from exercise tests and continuous electrocardiographic recording in patients with ventricular extrasystole. Apropos of 131 cases

A series of 131 patients aged from 4 to 70 years old with significant ventricular arrhythmias corresponding to at least Grade 2 of Lown's classification underwent exercise stress testing and continuous 24 hour electrocardiography. There were two objectives: to compare exercise electrocardiography and Holter monitoring in the detection and assessment of the seriousness of the arrhythmia, and to assess the arrhythmia's modifications on exercise. The patients were divided into 4 types: "chronic coronary insufficiency", "mitral valve prolapse", "other cardiac disease" and "idiopathic" arrhythmias. The maximum grade of arrhythmia corresponded to salvos of ventricular extrasystoles in 44 cases (33,5 p. 100), doublets in 44 cases (33,5 p. 100), polymorphic extrasystoles in 10 cases (7,6 p. 100) and monomorphic extrasystoles in 33 cases (25,2 p. 100). A significant arrhythmia was found in 90,8 p. 100 of cases by Holter and in 82,4 p. 100 of cases on exercise stress testing. The maximum grade of arrhythmia was also better appreciated on Holter monitoring (84,7 p. 100) compared to exercise stress testing (46,5 p. 100). The difference being more clear cut for repetitive forms. The superiority of Holter monitoring for assessing the grade of arrhythmia was obvious in the "idiopathic", "other cardiac disease" and "coronary" groups (79,4 p. 100 compared to 41,2 p. 100) but was not significant in the mitral valve prolapse group (73,9 p. 100 compared to 65,2 p. 100). Aggravation of the arrhythmia on exercise defined as a large increase, even transient of the number of extrasystoles (7 cases) or changing to a higher grade (59 cases) was significantly less common (p less than 0,01) in the idiopathic group (30 p. 100) than in the other groups (64,1 p. 100 in the coronary, 65,2 p. 100 in the mitral valve prolapse group). Aggravation of the arrhythmia in the coronary group was not observed more often in positive than in negative exercise electrocardiography. Complete regression of extrasystoles in the last two minutes was observed in 50 cases and significantly more often in idiopathic arrhythmias (p less than 0,01). There was no correlation between the behavior of the arrhythmia on exercise and the presence of salvos of extrasystoles, previous syncope or electrical cardioversion. Important individual differences were observed in all groups of patients. These observations suggest that the statistical superiority of Holter monitoring is debatable and imply that it is often necessary to request both investigations for the exact diagnosis of the arrhythmia and for the eventual therapeutic management of the patient and his mode of life.     

Differential mechanisms of impairment of remote memory in Alzheimer's and frontotemporal dementia

This paper describes retrograde memory performances of 12 Alzheimer's disease (AD) patients and 12 frontotemporal dementia (FTD) patients. First of all, we observed that FTD and AD patients did not differ for language tests (verbal fluency tests and oral denomination 80), for semantic memory tests, for logical memory test and Benton visual memory test and differed for anterograde verbal memory and frontal tests. Concerning retrograde memory, there was no difference between AD and FTD patients in retrograde memory scores (autobiographical memory interview, Crovitz's task, French public events interview battery) and both FTD and AD patients exhibited a retrieval deficit in their remote memory. We observed that the mechanisms of remote memory deficit was different in FTD and in AD patients. We observed no classical paradigm of Ribot for FTD patient's remote informations, and they appeared to have lost of access to memories and executive difficulties. In AD, the results indicated these patients' ability to learn new information and to search semantic memory failed.     

Adult familial cryptogenic fibrosing alveolitis in the United Kingdom

BACKGROUND: Familial cases of cryptogenic fibrosing alveolitis (CFA) have previously been reported; however, the prevalence and genetic background of this disorder are not known. The clinical and epidemiological findings of 25 families identified within the UK are reported. METHODS: Adult pulmonary physicians in the UK were asked to identify all families under their care in which two or more individuals had been diagnosed with fibrosing alveolitis of unknown cause. A detailed structured questionnaire was sent to each proband to delineate possible environmental/occupational exposures and to obtain complete pedigree data. Physicians were also asked to provide clinical and diagnostic information. RESULTS: Twenty five families were identified comprising 67 cases. Suitable data for analysis were available for 21 families (57 cases). The male:female ratio was 1. 75:1 (p<0.05). A high resolution computed tomographic (HRCT) scan was performed in 93% and a diagnosis of CFA confirmed on biopsy specimens in 32%. The mean age at diagnosis was 55.5 (2.5) years. Fifty percent of cases were ever smokers and 18% had been diagnosed as asthmatic. Exposure to known fibrogenic agents was recorded by 36% of patients. Clinical signs/symptoms and histological findings were indistinguishable from non-familial cases. CONCLUSIONS: This study represents the largest cohort of familial CFA cases reported to date and confirms a prevalence of 1.34 cases per 10(6) in the UK population. Although rare, such cases represent an important subgroup in which a genetic susceptibility to pulmonary fibrosis is particularly evident. Familial patients are younger at diagnosis but otherwise indistinguishable from non-familial cases. The mode of inheritance is as yet unclear but a number of genetic loci are likely to be involved and are the subject of ongoing studies.