Glial cell line-derived neurotrophic factor (GDNF) gene expression in the human brain: A post mortem in situ hybridization study with special reference to Parkinson's disease

Summary Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for dopaminergic neurons. Since dopaminergic neurons degenerate in Parkinson's disease, this factor is a potential therapeutical tool that may save dopaminergic neurons during the pathological process. Moreover, a reduced GDNF expression may be involved in the pathophysiology of the disease. In this study, we tested whether altered GDNF production may participate in the mechanism of cell death in this disease. GDNF gene expression was analyzed by in situ hybridization using riboprobes corresponding to a sequence of the exon 2 human GDNF gene. Experiments were performed on tissue sections of the mesencephalon and the striatum from 8 patients with Parkinson's disease and 6 control subjects matched for age at death and for post mortem delay. No labelling was observed in either group of patients. This absence of detectable expression could not be attributed to methodological problems as a positive staining was observed using the same probes for sections of astroglioma biopsies from human adults and for sections of a newborn infant brain obtained at post-mortem. These data suggest that GDNF is probably expressed at a very low level in the adult human brain and its involvement in the pathophysiology of Parkinson's disease remains to be demonstrated. GDNF may represent a powerful new therapeutic agent for Parkinson's disease, however.     

Gallbladder dyskinesia in chronic acalculous cholecystitis

To test the hypothesis that there is an early stage of cholesterol gallstone formation in man characterized by symptoms of chronic cholecystitis, poor gallbladder emptying, and biliary cholesterol crystals, we studied cholecystokinin-stimulated gallbladder emptying by DISIDA scintigraphy and examined bile for cholesterol crystals in symptomatic patients with normal oral cholecystography and gallbladder sonography. Of 36 patients studied, 16 had biliary cholesterol crystals; their mean 30-min gallbladder ejection fraction was 25.9±14.8%. Among the 20 patients without crystals, the mean ejection fraction was 60.3±23.3%. Fifteen patients, 11 with crystals and four without, had cholecystectomy because of persistent symptoms. All with crystals preoperatively and three without had chronic cholecystitis histologically. One patient without crystals had normal histology. We conclude that poor gallbladder contractility, well-established as an etiologic factor in animal models of cholesterol cholelithiasis, is now linked to acalculous cholecystitis, an early stage of human cholesterol cholelithiasis.     

Cardiac arrhythmia observed in 400 workers without obvious heart disease by Holter monitoring

To obtain information on the cardiac rhythm characteristics of subjects without heart disease during their daily work, we examined the continuous 24-hour electrocardiographic recordings of 400 workers from 4 factories in Eastern France presenting with criteria of cardiac normality. Sex, age and socio-professional category were taken into account. Supraventricular extrasystoles were extremely common, being observed in 52 p. 100 of men and 39 p. 100 of women. In men, the frequency of these extrasystoles increased with age (p less than 0.001), and their number was less than 20 per 24 hours in 90 p. 100 of the cases. Ventricular extrasystoles were detected in 40 p. 100 of men and 32 p. 100 of women. They too were age-related, though not significantly. Their number was less than 10 per 24 hours in 68 p. 100 of the cases and 10 to 50 per 24 hours in 28 p. 100. These ventricular extrasystoles usually were monomorphous, regularly coupled (92 p. 100) and isolated. However, 2 attacks of tachycardia were discovered. Episodes of bradyarrhythmia (RR superior or equal to 1500 ms) were present in 25 p. 100 of men and 19 p. 100 of women. They occurred more frequently before the age of 35 than later (p less than 0.001) and the recordings confirmed that they were predominantly nocturnal. Recordings without "disorders of rhythm" were relatively rare (20 p. 100 of men, 28.5 p. 100 of women). Finally, there was no clear-cut correlation between the prevalence or characteristics of these various "rhythmic abnormalities" and the type of professional activity.     

Medication Outcome in ECT-Resistant Depression

The outcome of antidepressant treatment in 12 cases of electroconvulsive therapy (ECT)-resistant depression is presented. Eight patients had been refractory to a clinically adequate course of ECT (Hamilton Depression Scale improvement <20%) and four were partial responders (improvement 20-49%). All remitted completely on antidepressant medication within 2.2 +/- 1.1 (mean +/- SD) months of the ECT course. Remission was associated with clomipramine treatment (139 +/- 49.7 mg/day) in seven cases and maprotiline (125 mg/day) in one case. Four patients who did not respond to a tricyclic antidepressant alone remitted following supplementation (of clomipramine in 2 cases, clomipramine + haloperidol in 1 case, and imipramine in 1 case) with lithium carbonate. Although a delayed therapeutic response to ECT cannot be excluded, the results suggest that ECT may alter the sensitivity of refractory patients to antidepressant medication.     

“Afterwork”: A clinical-phenomenological report

This paper explores a number of the dimensions of the process of afterwork: the psychological work that former patients engage in after treatment has terminated. Ten former patients, who had worked with 10 different therapists, were interviewed utilizing a semi-structured interview protocol, and their experiences form the basis for the findings and observations that are described. It was found that subjects remembered little by way of lessons or insights; rather, what remained with them were changes of perspective, the internalization of the process of the treatment, and the experience of their therapists' human qualities. In addition, it was found that most subjects had had some form of contact with their therapists post-termination. The implications of these findings are discussed.     

Human ventral mesencephalic xenografts to the catecholamine-depleted striata of athymic rats: ultrastructure and immunocytochemistry

On the basis of animal studies, grafts of fetal human dopaminergic cells have been suggested as a therapy for Parkinson's disease. The purpose of this study was to characterize the ultrastructure and immunocytochemistry of human ventral mesencephalic xenografts placed into the catecholamine-depleted striata of athymic "nude" rats. Human fetal tissue was obtained from tissue fragments derived from elective abortions during the first trimester of pregnancy. Small pieces of the basal mesencephalon were grafted into the catecholamine-depleted striata of four athymic nude rats. The rats were allowed to survive from 3 to 6 months after grafting; following fixation, the striatal tissue containing the grafts was labeled with antibodies against tyrosine hydroxylase and serotonin. Immunocytochemistry revealed tyrosine-hydroxylase-like-immunoreactive (THLI) and serotoninlike-immunoreactive (5HTLI) cell bodies within the human grafts. Both 5HTLI and THLI fibers crossed the graft-host interface and innervated the previously lesioned striatum. Both types of fibers also entered the host cortex from the adjacent human graft. At the ultrastructural level, THLI and 5HTLI fibers and synaptic terminals were observed in the host neuropil. THLI and 5HTLI dendrites and axon terminals were also observed in the neuropil of the grafts themselves. THLI axon terminals are not normally present in the substantia nigra. The results of our study indicate that human xenografts can survive in the neuropil of the host striatum and form morphologically appropriate synapses within the host brain.