[Clozapine-induced toxic hepatitis]. / Clozapin-udløst toksisk hepatitis.

A case of clozapine-induced toxic hepatitis in a 49-year old woman with schizophrenia is described. The daily clozapine dose was clinically titrated to 300 mg. Subsequently, the patient experienced lethargy and anorexia, and fever, eosinophilia, leucocytosis and abnormal liver parameters were found. The serum concentration of clozapine was 8595 nmol/l, and treatment was discontinued. After eight days, the condition stabilised, and low-dose clozapine treatment was successfully reinstituted with serum monitoring (TDM).

Codeine in post-operative pain. Study of the influence of sparteine phenotype and serum concentrations of morphine and morphine-6-glucuronide.

OBJECTIVE: Within the past decade, human experimental pain studies have supported the 50-year-old hypothesis that codeine is a prodrug, which has to be converted to morphine to exert an analgesic effect. This study aimed at evaluating the impact of sparteine phenotype and serum concentrations of morphine on the efficacy of codeine in post-operative pain. METHODS: Eighty-one patients with a pain rating of 3 or more on a 0-10 numerical rating scale 0.5 h after surgery were included in the study. The patients were given an oral dose of 100 mg codeine and rated pain with the numerical rating scale 0.5 h and 1 h after medication. Blood for determination of serum concentration of codeine and its metabolites was collected 1 h after medication, and a 12-h urine sample after administration of 100 mg sparteine was used to determine the sparteine phenotype. RESULTS: Eight patients were poor metabolizers and 66 were extensive metabolizers of sparteine, while the urine samples for the remaining seven patients were lost. In 22 patients, including the eight poor metabolizers, the serum concentrations of both morphine and morphine-6-glucuronide (M6G) were below the limit of determination of the assay, i.e. 1.5 nmol x l(-1) and 2 nmol x l(-1), respectively. A sum of the concentration of these two substances below 10 nmol x l(-1) was found in an additional eight patients. The sum of differences between pre- and post-operative pain ratings did not differ between the two phenotypes (P = 0.60), whereas the 30 patients with serum concentrations of morphine plus M6G below 10 nmol x l(-1) had a marginally significant lower sum than the 51 patients with higher levels of these substances (median 1.5 vs 2.5, P = 0.058). CONCLUSION: A low serum concentration of morphine and M6G seems to be common in patients treated with codeine for post-operative pain, and low concentrations of these active substances may be related to decreased efficacy of codeine.

[Incapacitating angina pectoris treated with electric stimulation of the spinal cord]. / Invaliderende angina pectoris behandlet med elektrisk rygmarvsstimulation (ERS).

Thirty patients who had severe incapacitating angina pectoris which had not reacted to the conventional therapeutic measures and which required massive daily opioid consumption were treated with electrical spinal cord stimulation (SCS) by means of a completely implantable stimulation system. The therapeutic effect was good in 87% of the patients who experienced considerably reduced frequency of attacks and markedly reduced opioid consumption (p less than 0.00005). Nine of the patients could reduce opioid consumption and 14 out of 27 could cease their otherwise daily opioid consumption. In four patients, the therapeutic effect was unsatisfactory. In the first 22 patients in whom a unipolar electrode was introduced, displacement of the electrode and subsequent reoperation was a frequent problem. This problem disappeared after change to multipolar electrodes as slight changes in placing of the electrode could easily be compensated for via the external programming equipment. This investigation reveals that SCS is a good therapeutic alternative for this selected patient category.

[Continuous subcutaneous morphine--treatment of pain in patients with terminal cancer]. / Kontinuerlig subkutan morfin--smertebehandling af terminale cancerpatienter.

Nine patients with terminal cancer were treated for pain with continuous subcutaneous injection of morphine via a portable battery-driven injection pump. Treatment was instituted on account of failure of other forms of treatment with oral or epidural morphine derivatives or on account of severe nausea and vomiting which necessitated parenteral administration. Treatment proved reasonably effective and no side effects of significance occurred. Two of the patients could be treated in their homes. The method is thus considered as suitable for treatment of pain in patients with terminal cancer.

[Local reactions following intravenous injection of Valium mixed micelles and Diazemuls]. / Lokale reaktioner efter intravenøs injektion af Valium mixed micelles og Diazemuls.

The frequency of local venous reactions after intravenous injection of Diazemuls and Valium Mixed Micelles was studied. A material of 224 patients undergoing surgery for prolapsed lumbar disc was allocated into two groups, receiving either 10 mg of Diazemuls or Valium Mixed Micelles. The incidences of thrombophlebitis in the two groups were 1 and 2%, respectively.

Five years experience with treatment of lung cancer. The role of mediastinoscopy.

Over a five-year period, 304 patients with non small cell carcinoma of the lung were evaluated for pulmonary resection. The patients were divided into three groups: 1) 180 patients operated without preoperative mediastinoscopy based on a normal appearing mediastinum on plain chest x-ray; 2) 107 patients with resection of both lung tissue and mediastinal tissue due to localised positive mediastinoscopic findings; 3) 17 patients who were found inoperable either due to poor lung function or diffuse mediastinal seeding. In group 1, 24% were peroperatively found to be inoperable due to mediastinal involvement. The rest were resected and received no further therapy. In group 2, 84 patients were resected and postoperatively irradiated on the mediastinal area. The incidence of bronchopleural fistulae in group 1 was 0.7% and in group 2 16%, and the survival at any period was significantly poorer for group 2 than for group 1. We conclude that every patient with pulmonary infiltrates must be subjected to mediastinoscopy before thoracotomy and should be excluded from operative intervention in the presence of positive mediastinoscopic findings.

Epidural morphine for outpatients with severe anginal pain.

Seven patients who had chronic coronary artery disease and had undergone coronary artery bypass surgery still suffered from anginal attacks several times daily despite optimal medical treatment. An epidural system of analgesia was implanted subcutaneously and treatment with epidural morphine started. The morphine was administered by the patients themselves or members of their family. During a median observation time of four months (range three to 11) all patients were free of pain while receiving this treatment.

Neutrophil lysosomal enzyme release and complement activation during cardiopulmonary bypass.

Complement activation and neutrophil degranulation were concomitantly studied during uncomplicated cardiopulmonary bypass (CPB). Plasma concentrations of complement factor C4, complement split product C3d, the neutrophil lysosomal enzyme elastase complexed with alpha 1-proteinase inhibitor (PI) and fibronectin were measured in 12 patients, C3d and elastase/PI increased significantly during CPB (volume-corrected results). The C3d rise was almost linear, whereas elastase/PI showed exponential increase. Mean elastase/PI and mean C3d concentrations at different times during CPB covaried closely. The study showed that during CPB neutrophil lysosomal enzyme release is intimately related to complement activation, although activation of the two systems may be caused by a common third activator within the extracorporeal circuit.