Abnormal spinal interactions from hand afferents to forearm muscles in writer's cramp.

OBJECTIVE: Spinal reflexes from hand to wrist muscles were investigated in writer's cramp. METHODS: Stimulus-triggered rectified EMG averages after ulnar nerve and cutaneous stimulation, in wrist flexors and extensors during tonic contraction, were compared in 18 controls and 19 patients. RESULTS: On the patient dystonic side, ulnar-induced EMG suppression was decreased in wrist extensors, and facilitation in wrist flexors modified dependent on the dystonic wrist posture during writing. No change was found on the patient non-dystonic side. Cutaneous stimulation increased wrist flexor EMG on both sides of the patients with normal wrist posture during writing, but had no effect in controls and patients with abnormal wrist posture. CONCLUSIONS: Comparison between cutaneous and mixed nerve stimuli suggests that spindle afferents from intrinsic hand muscles may mediate patients' ulnar-induced EMG modulations. Abnormal proprioceptive control was only observed on dystonic side, while bilateral unusual cutaneous control was found in patients. Changes in spinal transmission were partly related to the dystonic wrist posture, suggesting that systems involved in sensory processing can be differentially altered in writer's cramp. SIGNIFICANCE: Changes in spinal transmission, probably related to peripheral and/or cortical inputs, might either take part in primary or adaptive mechanisms underlying writer's cramp.     

Repetitive transcranial magnetic stimulation (rTMS): a new therapeutic approach in subjective tinnitus?

Subjective (non-recordable) tinnitus is the conscious perception of a phantom sound, and a very frequent, sometimes disabling, condition. Even if subjective tinnitus is often related to peripheral hearing loss, neurophysiological and functional imaging studies provide increasing evidence for an involvement both auditory and non-auditory central nervous pathways in the generation of tinnitus and related distress. Repetitive transcranial magnetic stimulation (rTMS) has been proposed to relieve tinnitus by reducing auditory cortex hyperexcitability associated with this condition. This paper will review the first clinical results reported in auditory cortex rTMS studies, with special reference to the pathophysiology of tinnitus processing and the mechanisms of action of rTMS. Although rTMS appears to be a very promising tool for the diagnosis and the treatment of tinnitus patients, available knowledge is still very limited at the moment. Further basic research and clinical studies are needed in order to optimize the parameters of stimulation (stimulus frequency, cortical target definition) and to validate the application of this technique in the management of patients with disabling tinnitus.     

In vivo Intracellular Recording of Neurons in the Supraoptic Nucleus of the Rat Hypothalamus

Intracellular recordings were made from cells in the hypothalamic supraoptic nucleus in the urethane-anaesthetized male rat using the ventral surgical approach. Impalements lasted from 5 min to 1 h and recorded cells had an input resistance of 55 to 170 megohms. Spikes of over 50 mV were recorded from 14 cells which could be antidromically activated by stimulation of the neural stalk. The spikes showed a hyperpolarizing afterpotential and the broadening characteristic of rapidly firing magnocellular neurons, which recovered rapidly (<200 ms). When depolarized, the cells showed evidence of a transient potassium current. Recurrent synaptic coupling between the recorded cell and adjacent cells would be expected to alter the hyperpolarizing afterpotential of an antidromic spike as compared with a spontaneous spike; no perceptible difference in the waveforms of the different types of spike could be detected in 11 spontaneously active cells. Application of just subthreshold stimuli to the neural stalk did not evoke depolarizing or hyperpolarizing potentials. Suprathreshold shocks to the neural stalk, when the antidromic spike was prevented by collision, also had no discernible effect on membrane potential. Thus intracellular recordings from magnocellular neurons in vivo revealed electrophysiological properties similar to those seen in vitro. No evidence for synaptic interconnection between magnocellular neurons was found in male rats.     

Acute myocardial infarction and cardiac perforation on non-gated CT

A 79-year-old man was referred to emergency department for vagueabdominal pain. In the past, the patient had cardiac arrhythmiasnecessitating a pacemaker placement. On admission, the patienthad a normal ausculation and the abdomen examination was unremarkable.Postero-anterior chest radiograph revealed normal cardiac sizeand a small left pleural effusion.     

The use of a new hydrophilic polymer, Kollicoat IR, in the formulation of solid dispersions of Itraconazole.

Kollicoat IR, a new pharmaceutical excipient developed as a coating polymer for instant release tablets, was evaluated as a carrier in solid dispersions of Itraconazole. The solid dispersions were prepared by hot stage extrusion. Modulated temperature differential scanning calorimetry and X-ray powder diffraction were used to evaluate the miscibility of the drug and the carrier. The pharmaceutical performance was evaluated by dissolution experiments, performed in simulated gastric fluid without pepsin (SGF(sp)). In the X-ray diffractograms no Itraconazole peaks were visible; the polymer on the other hand appeared to be semi-crystalline. Moreover, its crystallinity increased during the extrusion process due to exposure to heat and shear forces. Modulated temperature differential scanning calorimetry analysis showed that the drug and the polymer formed a two phase system. Separate clusters of glassy Itraconazole were present for drug loads of 40% or higher, indicating further phase separation. Dissolution measurements demonstrated a significantly increased dissolution rate for the solid dispersions compared to physical mixtures. Interestingly the physical mixture made up of glassy Itraconazole and Kollicoat IR (20/80, w/w) showed a dissolution rate and maximum that was much higher than that of the physical mixture made up of crystalline Itraconazole and that of pure glassy Itraconazole. The results of this study show that Kollicoat IR is a promising excipient for the formulation of solid dispersions of Itraconazole prepared by hot stage extrusion.     

Antiemetic neurokinin-1 antagonist aprepitant and ifosfamide-induced encephalopathy.

We report the occurrence of an acute encephalopathy followingifosfamide infusion, that we believe directly triggered by aprepitant(Emend^TM, Merck & Co., Inc.). Aprepitant, the first neurokinin-1receptor antagonist, is a new antiemetic indicated for highlyand moderately emetogenic chemotherapy, in association with     

rt-PA Lyse bei Patienten mit schwerer Lungenembolie und rechtskardialen Transitthromben Diagnostik und Verlaufskontrolle mit Hilfe der transösophagealen Echokardiographie

Zusammenfassung Bei Nachweis von rechtskardialen Thromben handelt es sich in den meisten F?llen um sogenannte ,,Transit-Thromben`` aus dem peripheren Venensystem, die nur kurz im rechten Herzen verweilen. Die Inzidenz von transthorakal echokardiographisch nachgewiesenen ,,Transit-Thromben`` bei Patienten mit Lungenembolie liegt bei etwa 3 – 4%. Unbehandelt ist die Letalit?tsrate dieser Patienten jedoch auf Grund der hohen Rate konsekutiver fulminanter Lungenembolien sehr hoch (30 – 40%). Bis vor einigen Jahren galt die operative Embolektomie als das Therapieverfahren der Wahl, das jedoch heute zunehmend durch die systemische, intraven?se Lysetherapie als Alternative ersetzt wird. Im Zeitraum von 1/94 bis 12/95 wurden in unserer Klinik 66 Patienten mit nachgewiesener Lungenembolie behandelt. Bei sieben dieser Patienten mit schwerer oder fulminanter Lungenembolie (10,6%; 5 M?nner, 55 – 74 Jahre alt) fanden sich rechtskardiale Thromben, die in allen F?llen mittels transthorakaler/ trans?sophagealer Echokardiographie (TEE) diagnostiziert wurden. In sechs F?llen sahen wir extrem mobile, wurmf?rmige Thromben im rechten Atrium, die zum Teil diastolisch tief in den rechten Ventrikel prolabierten. Bei einem Patienten waren die Thromben im rechten Ventrikel lokalisiert und fielen ventrikel-systolisch in den rechtsventrikul?ren Ausflu?trakt. In drei F?llen lie?en sich mittels TEE auch Thromben in der rechten Pulmonalarterie darstellen. Fünf Patienten wurden unmittelbar im Anschlu? an die TEE-Untersuchung ohne weitere angiographische Diagnostik mit einer systemischen, intraven?sen Lysetherapie mit 100 mg front-loaded rt-PA über 90 Minuten behandelt. Ein prim?r reanimationspflichtiger Patient erhielt als ,,Ultima Ratio`` 100 mg rt-PA als Bolus, eine weitere Patientin 50 mg rt-PA als Bolus gefolgt von 50 mg über 2 Stunden. Bei allen Patienten stabilisierte sich der h?modynamische Zustand innerhalb kürzester Zeit. In sechs F?llen konnte mittels TEE und einmal mittels transthorakaler Echokardiographie innerhalb von 15 Stunden die komplette Aufl?sung der rechtskardialen Thromben dokumentiert werden. Bei einem Patienten kam es zu einer intracerebralen Blutung und ein Patient verstarb nach 10 Tagen an den Folgen der protrahierten Reanimation mit hypoxischem Hirnschaden. Mittels TTE/TEE lassen sich rechtskardiale Transitthromben als koinzidenter Befund bei Patienten mit klinischen Hinweisen für eine fulminante Lungenembolie gut diagnostizieren sowie der Therapieerfolg verfolgen. In diesen F?llen ist die sofortige systemische Lysetherapie ohne weitere bildgebende Diagnostik durchzuführen, um einer weiteren Verschlechterung der klinischen Situation in Folge Transports und Umlagerung des Patienten mit der Gefahr des Abschwemmens des Transitthrombus vorzubeugen. Eingegangen: 15. Mai 1996 Akzeptiert: 23. Oktober 1996     

CHANGES IN PREJUNCTIONAL POTENCY OF B-HT 933 DURING AGING IN THE RAT VAS DEFERENS

1. Age-related changes in prejunctional alpha 2-adrenoceptors were examined in the rat vas deferens using pharmacological techniques. 2. B-HT 933 (1 x 10(-8) - 1 x 10(-6) mol/L) caused a concentration-dependent inhibition of isometric contractions (tetrodotoxin-sensitive) induced by stimulation with single field-stimulus pulses, in both the epididymal and prostatic regions of rat vas deferens. The concentration-response curve to B-HT 933 was shifted to the right with age in the prostatic regions of the vas deferens. 3. In high concentrations (10(-6) - 3 x 10(-4) mol/L), B-HT 933 caused concentration-dependent enhancement of the contractile response to stimulation and evoked spontaneous contractile activity. No significant difference in this postjunctional activity occurred with age in either the prostatic or epididymal regions of the vas deferens. 4. Schild analysis revealed no significant differences in pA2 values for the antagonisms of the prejunctional inhibitory effect of B-HT 933 by rauwolscine in either the prostatic or epididymal regions of vas deferens between young and old rats. 5. These results could be interpreted as a decrease in alpha 2-adrenoceptor number with age. The more marked decrease in the prejunctional inhibitor potency of B-HT 933 in prostatic regions of vas deferens with aging may be due to a smaller receptor reserve in this region of the vas deferens.     

What is the place of electroneuromyographic studies in the diagnosis and management of pudendal neuralgia related to entrapment syndrome?

Entrapment of the pudendal nerve may be at the origin of chronic perineal pain. This syndrome must be diagnosed because this can result in the indication of surgical decompression of the entrapped nerve for pain relief. Electroneuromyographic (ENMG) investigation is often performed in this context, based on needle electromyography and the study of sacral reflex and pudendal nerve motor latencies. The limits of ENMG investigation, owing to various pathophysiological and technical considerations, should be known. The employed techniques do not assess directly the pathophysiological mechanisms of pain but rather correlate to structural alterations of the pudendal nerve (demyelination or axonal loss). In addition, only direct or reflex motor innervation is investigated, whereas sensory nerve conduction studies should be more sensitive to detect nerve compression. Finally, ENMG cannot differentiate entrapment from other causes of pudendal nerve lesion (stretch induced by surgical procedures, obstetrical damage, chronic constipation...). Thus, perineal ENMG has a limited sensitivity and specificity in the diagnosis of pudendal nerve entrapment syndrome and does not give direct information about pain mechanisms. Pudendal neuralgia related to nerve entrapment is mainly suspected on specific clinical features and perineal ENMG examination provides additional, but no definitive clues, for the diagnosis or the localization of the site of compression. In fact, the main value of ENMG is to assess objectively pudendal motor innervation when a surgical decompression is considered. Perineal ENMG might predict the outcome of surgery but is of no value for intraoperative monitoring.