Spatial learning impairments in rats with selective immunolesion of the forebrain cholinergic system.

A monoclonal antibody to the low-affinity NGF receptor, 192 IgG, coupled to a cytotoxin, saporin, was recently introduced as an efficient selective neurotoxin for the NGFr-bearing cholinergic neurones in the rat basal forebrain. In the present study we report that an intracerebroventricular injection of this 192 IgG-saporin conjugate induces a severe, long-lasting spatial learning impairment, as assessed in the Morris water-maze task. This behavioural impairment was associated with 65-90% depletion of choline acetyltransferase activity (ChAT) in the hippocampus and cortex. ChAT activity associated with other cholinergic neurone systems in the brain (striatum, mesencephalon, spinal cord), was left virtually unaffected. This new immunotoxin holds great promise as a tool for selective and efficient lesions of the forebrain cholinergic system in functional and behavioural studies.     

Gemfibrozil reduces plasma prothrombin fragment F1 + 2 concentration, a marker of coagulability, in patients with coronary heart disease.

The effects of gemfibrozil on several indices of haemostatic activity were explored in male patients with coronary heart disease (CHD). Sixty-three of 71 patients completed a crossover study in which gemfibrozil 1,200 mg/day and matching placebo were each taken in randomised order for 2 months in a double-blind manner, separated by a 2-month washout period. Serum cholesterol decreased by an average (95% confidence interval) of 12 (9 to 15)% and non-fasting triglyceride concentration by 43 (34 to 51)% during active treatment. Plasma prothrombin fragment F1 + 2 concentration, a marker of the in vivo rate of generation of thrombin, was 25 (12 to 37)% lower on average while on gemfibrozil than during the placebo phase. Factor VII coagulant activity (VIIc) and antigen concentration, and fibrinopeptide A concentration were not influenced by gemfibrozil in the group overall. However, the VIIc response appeared to be dependent upon the untreated cholesterol level. Hypercholesterolaemic men (cholesterol greater than 6.5 mmol/l) experienced a significant reduction in VIIc averaging 6% of standard during active therapy. Other effects of gemfibrozil were a 5 (2 to 9)% increase in plasma fibrinogen by a gravimetric method, an 11 (8 to 13)% increase in platelet count, and a 6 (2 to 10)% reduction in white cell count. The reduced incidence of CHD following gemfibrozil therapy in hyperlipidaemic patients may arise in part through a reduction in procoagulant activity and thus the risk of an occlusive coronary thrombosis.     

Binswanger's disease in the absence of chronic arterial hypertension

Summary The cerebral changes are described in a woman of 54 who suffered from Binswanger's encephalopathy: there were no signs or symptoms of chronic arterial hypertension. The disease presented as dementia of about 3 years duration. Computed tomography of the brain 2. 5 years before her death showed bilateral widespread hypodense lesions in the cerebral white matter. She died of an asthmatic attack. Autopsy disclosed extensive bilateral degeneration of the central white matter, lacunes and gliosis. Severe obliterative arteriolosclerosis occurred in the meningeal vessels and those supplying the affected parts of the brain. Light microscopy showed that the most severe lesions occurred in the arterioles. Immunohistochemistry demonstrated profound extravasation of plasma proteins chiefly albumin, indicating dysfunction of the blood-brain barrier. Thus, the lesions characteristic of Binswanger's encephalopathy may develop in the absence of chronic arterial hypertension. Additional pathogenic factors, possibly genetic predisposition to vascular injury may play a role in the development of this condition.Supported by grants from the Swedish Medical Research Council, Project No 12X-03020 and 1987 Års Stiftelse för Strokeforskning     

Peptides for calling? An immunohistochemical study of the avian n. intercollicularis.

We used two phylogenetically distant avian species (dark-eyed junco, hyemalis, Passeriformes; domestic pigeon, Columba livia, Columbiformes) to determine the immunocytochemical distribution of opioid (leucine-enkephalin, dynorphin B) and non-opioid (adrenocorticotropic hormone) peptides in the n. intercollicularis (ICo), a midbrain region which plays a central role in the control of vocalizations. We found that, in both species, the peptides under study are present as fibers and terminal-like structures, and are similarly distributed. The n. dorsomedialis intercollicularis division contains much less immunoreactivity than the rest of the ICo. Based on this and previous studies, we propose that opioid peptides, possibly transported from the preoptic and hypothalamic regions of the diencephalon to the ICo, regulate vocal behavior by altering respiratory function rather than syringeal mechanisms.     

T cells in the spinal cord in experimental autoimmune encephalomyelitis are matrix adherent and secrete tumor necrosis factor alpha.

We examined T cells isolated from an autoimmune tissue lesion and from lymphoid organs for their ability to secrete tumor necrosis factor-alpha (TNF-alpha) and to adhere to extracellular matrix (ECM) proteins. CD4+ T cells were obtained from spleens, popliteal lymph nodes, and spinal cords of Lewis rats that had been immunized with myelin basic protein (MBP) to induce experimental autoimmune encephalomyelitis (EAE). We now report that, irrespective of whether or not the T cells were activated with MBP or the T cell mitogen concanavalin A (ConA), the T cells isolated from the spinal cord lesions secreted greater amounts of TNF-alpha and adhered better to ECM than did T cells from the draining lymph node. Thus, the lesions of EAE concentrate a subpopulation of CD4+ T cells with enhanced ability to interact with blood vessel wall components and to secrete TNF-alpha.     

Treatment of stones in caliceal diverticula: extracorporeal shock wave lithotripsy versus percutaneous nephrolitholapaxy.

Stones in caliceal diverticula may cause symptoms for which treatment is indicated. Both extracorporeal shock wave lithotripsy (ESWL) and percutaneous nephrolitholapaxy (PNL) are recommended. We have evaluated the results of ESWL treatment of stone-containing caliceal diverticula and compared these with the results obtained by percutaneous surgery. In the ESWL group, 15 patients were treated with an electromagnetic lithotriptor (Siemens Lithostar). After 3 months, plain abdominal X-rays revealed that only 2 patients were both stone-free and symptom-free. Of the 13 patients with residual fragments, 7 had no symptoms. The remaining 6 were treated by a lower pole resection (n = 3), a percutaneous procedure (n = 2) and long-term administration of antibiotics (n = 1). Sixteen patients were treated percutaneously. Puncture failed in 3 and they underwent a lumbotomy. In the remaining 13 patients the stones were reached by direct puncture (n = 12) or via an adjacent calix (n = 1). After 3 months, 10 patients were stone-free and had no symptoms. Morbidity consisted of post-operative bleeding (n = 3) and high fever (n = 1). It was concluded that caution should be exercised in the treatment of stone-containing caliceal diverticula. Only in symptomatic cases is treatment indicated and ESWL is the first choice. If ESWL fails (residual stones and persistent symptoms), PNL should be performed, although it is associated with a higher morbidity rate.     

Evaluation of anaerobic performance capacity by the isokinetic Ariel computerized exercise system-reliability and validity.

The present study examines the reproducibility and validity of computerized muscle strength and endurance evaluation protocols using the Ariel Computerized Exercise System (ACE). Since the ACE has only recently become commercially available, there are no published normative data for various exercises, nor are the measurements' accuracy and validity for the various exercise protocols documented. Twenty males (17 to 30 years old) performed a set of isokinetic maximal leg and arm exercises on the ACE Multi Function Unit twice on 2 separate days. Test-retest correlation coefficient ranged from 0.44 (bench press) to 0.91 (bench pull and leg extension flexion). Thirty additional male subjects (16 to 31 years old) performed, on 2 separate days, the Wingate Anaerobic Test (WAnT) (leg), and various force and endurance leg exercises (squat) on the ACE. Correlation coefficients of the various performance indices between the 2 test systems ranged from -0.02 to 0.23. The results obtained on the ACE indicate moderate to high reproducibility and low concurrent validity with WAnT.