Do organic solvents induce changes in the dopaminergic system? Positron emission tomography studies of occupationally exposed subjects

Objectives: The objective of this study was to test the hypothesis that long-term occupational exposure to organic solvents may effect the levels and turnover of dopamine in man. Methods: A study was performed on 17 patients with neuropsychiatric symptoms due to occupational solvent exposure, and 11 healthy non-exposed male volunteers (controls). Positron emission tomography (PET) was used to assess striatal dopaminergic function, using l-[¹¹C]DOPA, [¹¹C]nomifensine and [¹¹C]raclopride as tracers. Results: The rate of dopamine synthesis was significantly increased among subjects with occupational exposure to organic solvents compared with non-exposed controls. After controlling for the difference in age between exposed and controls, the effect of solvent exposure became less apparent and was reduced from +32% (P = 0.009) to +25% (P = 0.07). There were no differences with regard to the binding of [¹¹C]nomifensine. Patients with and without the diagnosis of toxic encephalopathy did not differ with regard to their putaminal uptake of l-[¹¹C]DOPA, [¹¹C]nomifensine and [¹¹C]raclopride. Conclusion: The data support the hypothesis that long-term exposure to organic solvents may increase the rate of dopamine synthesis in the brain without affecting the number of presynaptic terminals or postsynaptic dopamine receptors. Received: 8 October 1996 / Accepted: 7 February 1997     

Chemokine-mediated distribution of dendritic cell subsets in renal cell carcinoma

Background  

Renal cell carcinoma (RCC) represents one of the most immunoresponsive cancers. Antigen-specific vaccination with dendritic cells (DCs) in patients with metastatic RCC has been shown to induce cytotoxic T-cell responses associated with objective clinical responses. Thus, clinical trials utilizing DCs for immunotherapy of advanced RCCs appear to be promising; however, detailed analyses concerning the distribution and function of DC subsets in RCCs are lacking.     

Clozapine: Dopamine D1 Receptor Agonism in the Prefrontal Cortex as the Code to Decipher a Rosetta Stone of Antipsychotic Drugs

Abstract: A large number of ligand binding studies have shown that clozapine has a number of receptor affinities, including those of the dopamine (DA) D₁ and D₂ receptor families. The study of intrinsic efficacy at these receptors is less straightforward. In the experiments summarised here, evidence is presented that clozapine behaves as an agonist at DA D₁ receptors. Thus, the hypothermia produced by clozapine (2.5 mg kg^–1) in the rat is fully antagonised by either of the selective DA D₁ receptor antagonists SCH-23390 (0.1 mg kg^–1) or NNC-687 (4 mg kg^–1). These results provide an intriguing explanation for the clinical profile of clozapine as an atypical antipsychotic drug. Thus, there are supporting clinical and laboratory observations implicating DA D₁ receptors in the prefrontal cortex in cognitive functions. Finally, clozapine displays features with regard to extrapyramidal motor mechanisms, and seizure thresholds, that could be explained by its properties as a DA D₁ receptor agonist.     

Impact of internal capsule lesions on outcome of motor hand function at one year post-stroke.

OBJECTIVE: To investigate the association between damage to different levels of the corticofugal tract and long-term hand motor recovery. DESIGN: Prospective cohort study. PATIENTS: Seventy-five first-ever middle cerebral artery stroke survivors. METHODS: Hand motor function was assessed with the Fugl-Meyer Motor Assessment Scale at one year post-stroke. Localization of the corticofugal tract was assessed on axial magnetic resonance imaging slices using a corticofugal mask defining involvement of the motor cortex, corona radiata or internal capsule and combinations of these structures, adjusted for lesion volume. RESULTS: Longitudinal involvement of all 3 levels of the corticofugal tract and partial involvement of the internal capsule were associated with a significant probability of poor motor hand function recovery. The probability of regaining hand function ranged from 54% if the corticofugal tract was only partly affected to 13% if both motor cortex and internal capsule were affected. CONCLUSION: At one year post-stroke, lesions of the internal capsule were associated with a significantly lower probability of return of isolated hand motor function than lesions of the cortex, subcortex and corona radiata. Since recovery of isolated hand and finger movements is important for regaining a functional upper limb in everyday living, these patients should be identified early post-stroke in order to evaluate specific hand function training.     

Treatment of withdrawal symptoms using clonidine during pregnancy

In order to prevent symptoms of drug withdrawal during pregnancy, we treated a woman with clonidine, an alpha-2 adrenergic agonist with central and peripheral actions. We saw a good response of the withdrawal symptoms without any period of severe hypotension or bradycardia. Two healthy babies were subsequently delivered by cesarean section.     

Mortality related to cardiac catheterization and angiography

During a 14-month period, 75 deaths occurring in relation to 53,581 cardiac catheterizations were consecutively and prospectively reported to the Registry Committee of the Society for Cardiac Angiography. Three of the patients died several days after their catheterization from an unrelated cause and are excluded from this analysis. There were 21 patients (group I) who arrived at the laboratory in extremis and whose deaths were expected irrespective of the catheterization. Most of these patients suffered from recent myocardial infarctions and cardiogenic shock, or had complex congenital malformations. In 35 patients (group II), a cardiovascular complication occurring during the catheterization resulted in death. In 16 patients (group III) catheterization seemed uneventful, but death occurred suddenly 10 min to 10 h after the procedure. Of these 16 patients, eight had left main coronary artery obstruction ≥ 90%, five had three-vessel disease all with 90% obstructions, one had 2-vessel disease both with 90% obstructions, and two had critical aortic stenosis. The 51 unexpected deaths (groups II and III) were considered to be causally related to the procedure, a mortality rate of 0.10%. Subsets with an increased mortality rate (M), were patients with: (a) left main disease > 50% (M = 0.94%); (b) ejection fraction < 30% (M = 0.54%); (c) NYHA class III or IV (m = 0.24%); (d) age over 60 years (M = 0.23%); or (e) three-vessel disease (M = 0.13%). In conclusion, catheterization related mortality occurs mostly in patients with far advanced cardiac disease. Nearly 1/3 of the unexpected deaths occurred suddenly after a seemingly uneventful procedure. Close monitoring after catheterization of patients with similar characteristics (left main disease ≥ 90%, or three-vessel disease all ≥ 90%) might disclose avenues for reducing mortality occurring after catheterization.     

Distribution and fate of C14-amitriptyline in mice and rats

Summary The physiological distribution of intramuscularly and intravenously injected C¹⁴-amitriptyline was studied in mice using an autoradiographic technique. The compound rapidly leaves the blood and concentrates in the brain, lung and heart. High concentrations are also seen in the gastric mucosa, intestines, salivary glands and lachrymal glands.The compound is rapidly metabolized in the body. The excretion studies indicate that amitriptyline is excreted to a large extent into the bile as a glucuronide conjugate.The significance of the tissue distribution in relation to the main pharmacological action and to some of the side effects are discussed.The authors are indebted to Professor J. Rieder, Fa. Hoffmann-La Roche & Co., Basel, Switzerland for his helpful suggestions. Thanks are due to Mrs. G. Mabo, Mr. A. Nilsson and Mrs. B. Hagtorn for their valuable technical assistance. The authors are also indebted to Knut and Alice Wallenbergs Stiftelse for general equipment for isotope research work.