Malignant astrocytomas treated with iodine-125 labeled monoclonal antibody 425 against epidermal growth factor receptor: a phase II trial.

Twenty-five patients with primary presentation of malignant astrocytoma, astrocytoma with anaplastic foci, and glioblastoma multiforme were treated with surgical resection and definitive radiation therapy followed by intravenous or intra-arterial administration of Iodine-125 labeled monoclonal antibody-425, which binds specifically to human epidermal growth factor receptor. The patients presented with primary untreated disease, positive contrast enhanced computed tomography scans of the brain, and compatible clinical symptoms. In this Phase II clinical trial, the patients had surgical debulking or biopsy followed by definitively administered external beam radiation therapy and one or multiple doses (35 to 90 mCi per infusion) of radiolabeled antibody. The total cumulative doses ranged from 40 to 224 mCi. The administrations of the radiolabeled antibody were performed in most cases 4-6 weeks following completion of the primary surgery and radiation therapy. Ten patients had astrocytoma with anaplastic foci and 15 had glioblastoma multiforme. No significant life-threatening toxicities were observed during this trial. At 1 year 60% of the patients with astrocytoma with anaplastic foci or glioblastoma multiforme are alive. The median survival for both groups was 15.6 months.     

Tumor thickness and prognosis in clinical stage I malignant melanoma

The current grouping of patients with malignant melanoma into thin, intermediate, and thick melanomas provides a convenient but arbitrary classification which, although providing "average" survival values for each group, offers crude prognostication for the individual patient. A review of 371 patients with clinical Stage I malignant melanoma, treated during the period 1970 to 1985, was conducted. The estimated 5-year survival rate for female patients with melanomas 1.0 mm thick was 94%; for each 1-mm increment in thickness the survival rate declined by about 3%, up to the 6 mm mark, the survival rate declining thereafter by about 8% for each additional millimeter in the range of 7 to 15 mm of thickness. The estimated 5-year survival rate for male patients with melanomas 1.0 mm thick was 80%; for each 1-mm increment the survival rate declined by about 9%, up to the 10 mm mark. The proposed method of estimating the expected survival according to the patient's sex and the thickness of the primary lesion hopefully provides a more accurate and convenient method of prognostication for the clinician dealing with specific patients with intermediate or thick melanomas.     

Serotonin transporter binding in Tourette Syndrome

Recent studies provided evidence for an involvement of the dopaminergic system in the pathophysiology of Tourette Syndrome (TS). However, little is known about possible impairment of other neurotransmitter systems. In obsessive-compulsive disorder (OCD), a common comorbidity in TS, it is suggested that the serotonergic system plays a major role in the pathogenesis. We, therefore, used [I-123]2[beta]-carbomethoxy-3[beta]-(4-iodophenyl)tropane ([123I]beta-CIT) and single photon emission computed tomography (SPECT) to investigate serotonin transporter (SERT) binding capacity in 12 patients with TS with various degrees of associated obsessive compulsive behaviour (OCB) and 16 age-matched healthy controls. Binding ratios in TS patients not receiving serotonin reuptake inhibitors (SSRI) (n=8) were significantly reduced compared to age-adjusted ratios from normal controls (2.8 versus 3.2, p=0.003). Treatment with SSRI resulted in a significant reduction of SERT availability. Performing linear regression analysis for this small group, SSRI-free patients indicated trends for a negative correlation between [123I]beta-CIT binding on SERT and OCB (r=-0.78, p=0.023) as well as complex motor tics (r=-0.68, p=0.064). In healthy controls, but not in the TS group, we found an age-related decline in SERT binding capacity (0.28% decrease per year, p=0.038). Our data are in agreement with previous results suggesting an impairment of the serotonergic system in TS. It can be speculated that the reduction in SERT binding capacity is associated with the degree of comorbid OCB.     

The effect of neuroleptic treatment and of high dosage diazepam therapy onβ-endorphin immunoreactivity in plasma of schizophrenic patients

Summary Synapsin I (Protein I), a neuron-specific phosphoprotein enriched in presynaptic nerve terminals, has been used as a quantitative marker for the density of nerve terminals in five brain regions (caudate nucleus, cingulate gyrus, hippocampus, mesencephalon and putamen) from patients who had suffered from Alzheimer disease/senile dementia of Alzheimer type (AD/ SDAT), from patients with multi-infarct dementia (MID), and from agematched controls. Samples were obtained at autopsy. Lower levels of Synapsin I were observed in the hippocampus of patients with AD/SDAT but not with MID. There were no significant differences in Synapsin I levels between patients and controls in any of the other four brain regions examined.     

In vivo effects of carbamazepine and haloperidol on GABA neurotransmission and LH secretion

The in vivo effects of carbamazepine (CBZ) and haloperidol (HAL) on the neuroendocrine pre-optico-pituitary feedback system were studied by local application of the drugs, in single and in combination mode, through a push-pull cannula into the pre-optic area and measurement of their local effects on γ-aminobutyric acid (GABA) and their distant effects on a subsequent biological response: the pituitary luteinizing hormone (LH) secretion. The perfusion flow rate was 20 μl cerebrospinal fluid (CSF)/min; the fraction period was 15 min. Perfusion with 8 μg CBZ/ml CSF caused a reduction in pre-optic pre-synaptic GABA release and, concomitantly, a suppression of plasma LH levels. Application of 100 ng HAL/ml CSF also caused a reduction in GABA release, but no significant change in plasma LH levels. During the combined perfusion, the effects of CBZ and HAL did not add up with regard to the pre-optic GABA release. These results suggest that both drugs interact with the GABA system, but they may involve two different mechanisms of action. Due to the known inhibitory role of pre-optic GABA in pituitary LH secretion, it can be inferred that, in contrast to HAL, CBZ increases post-synaptic GABAergic transmission.     

Effects of acamprosate on memory in healthy young subjects

OBJECTIVE: Several studies have shown acamprosate (calciumacetylhomotaurinate) to increase abstinence rates in weaned alcoholics. Chronic alcoholics often suffer from cognitive deficits. Since acamprosate appears to interact with N-methyl-D-aspartate (NMDA) receptors, a subclass of glutamate receptors playing an important role in learning and memory processes, this study was performed in order to investigate different cognitive functions during administration of acamprosate. METHOD: A randomized, double-blind, cross-over, placebo-controlled design, involving 12 healthy male volunteers was used. Acamprosate 2 g daily per os or placebo were administered for 7 days respectively, with a wash-out interval of 21 days between phases. Mood and different memory functions (i.e., working memory, delayed recall, recognition tasks) were assessed. RESULTS: It was shown that a dose of acamprosate 2 g/day for 7 days may produce an impairment in delayed free recall. Recognition tasks, short term working memory and mood were not altered. CONCLUSIONS: The present study supports the hypothesis that acamprosate impairs memory functions. This is in keeping with the concept of acamprosate acting as NMDA receptor antagonist. The limitations of the study are discussed.     

Hemodialysis in schizophrenia

Summary Therapeutic trials with hemodialysis have been performed in three cases of chronic schizophrenia. The severely ill patients had been hospitalized for more than ten years and had not responded to different types of conventional somatic treatment. Psychopathology was evaluated by use of the IMPS, BPRS, and NOSIE scales. No improvement could be observed as a consequence of 12 (11 in one case) hemodialysis treatments. Rather, some deterioration occurred in two of the patients. This result is not in accord with the markedly positive findings of Wagemaker and Cade (1977). However, further studies appear necessary to render final conclusions.Supported by a Stipendium of the Fritz-Thyssen-Foundation, Cologne