A case control study on psychopharmacotherapy before suicide committed by 61 psychiatric inpatients.

OBJECTIVE AND METHOD: The pharmacotherapy of 61 suicide victims (0.24 % of 27,078 admissions from January 1, 1980 to December 31, 1999) was compared to that of a control group matched for age, gender and diagnosis at the time of discharge. RESULTS: Both groups were also comparable regarding stay in hospital, history of psychiatric disease, and frequency of hospitalisations during the year preceding the index evaluation. Multiple but not single suicide attempts were significantly more frequent in patients who were later to complete the suicide than in controls. Schizophrenia (ICD-9, ICD-10) was the most frequent diagnosis among suicide victims (44.3 %). Affective psychosis (ICD-9, ICD-10) bore the highest relative risk (0.8 %). 50 % of the schizophrenic patients in the suicide group had been continuously treated with full-dose tricyclic antidepressants. The CPZ-equivalents in the patients treated with antipsychotics were not of discriminating value. Four of 27 schizophrenic patients in the suicide group had been off neuroleptics for ten days or more; this was never observed among the controls. Lorazepam applied in 40% of the schizophrenic and in 25 % of the affective psychosis suicide victims had more often been withdrawn or reduced during the ten days preceding suicide than among controls. No schizophrenic suicide victims but five controls had been on mood stabilisers. The use of antipsychotics (classical and atypical) and a recent change in tricyclic drug or drug dose were more frequent in suicide victims with affective psychosis. Lithium had been given to one patient, but it had also been administered to six controls; this difference is significant. CONCLUSION: Mood stabilisers, especially lithium, should be considered more often in patients with previous suicide attempt(s). When changing antidepressants in affective psychosis, benzodiazepines might be given more deliberate consideration. Patients in all diagnostic categories should be closely guided by means of intensified psychotherapeutic interventions while undergoing a benzodiazepine reduction. The treatment of patients suffering from schizophrenia with full-dose tricyclic regimens should be considered as possibly enhancing the acute suicide risk in some individuals.

Durable complete remission of metastatic sarcomatoid carcinoma of the bladder with cisplatin and gemcitabine in an 80-year-old man.

A patient with a durable, complete, local and pulmonary remission of a metastatic sarcomatoid carcinoma of the bladder treated with gemcitabine and cisplatin is presented. Sarcomatoid carcinoma arising in the bladder is a rare and notoriously aggressive variant of urothelial carcinoma for which an effective systemic treatment has not been reported up to now.

Therapeutic drug monitoring of clozapine in relapse prevention: a five-year prospective study.

Twenty-three outpatients with schizophrenia (ICD-10 F20.xx) treated with clozapine (CZ) as monotherapy entered a prospective study on relapse prevention. Every 4 weeks, psychopathology was assessed by the Brief Psychiatric Rating Scale (BPRS), and plasma CZ and norclozapine levels were measured. Patients were enrolled after complete remission of positive symptoms for at least 4 months according to the psychosis cluster of the BPRS and at a mean of 3.3 years after their last hospitalization. At the time of enrollment, the median BPRS total score was 29 points (range, 19-48). Within 4 months, the baseline CZ plasma level was established as the mean of CZ levels from at least four subsequent measurements. These baseline plasma levels were considered as the optimal relapse-preventing plasma CZ levels in the individual patients. When the patients were enrolled, they were considered to be prone to relapse. Relapse was defined as clinical deterioration, hospitalization, or both. Plasma levels were considered a prognostic factor, and patients were defined as at increased risk if plasma levels decreased by more than 40% from baseline CZ plasma level. The effect of plasma CZ levels on clinical outcome was evaluated by a Cox regression with plasma level as a time-dependent covariate. Within 46 months of enrollment, 32 episodes of relapse events in 10 patients were available for evaluation. Seventeen patients had a plasma level decrease of more than 40% at some point. In 12 of these, the decrease was present for more than 12% of the observation period. Eight patients of this group relapsed, and three of these had to be rehospitalized. Two patients relapsed, although their plasma levels decreased by more than 40% for less than 12% of the observation period. Within the first 2 years, relapse-free survival curves illustrate that both groups (episodes under elevated risk and episodes not under elevated risk) had identical relapse patterns, but from then on the relapse risk increased rapidly in the group with longer exposure to elevated risk. In a Cox model with a 40% decrease of plasma CZ levels as a dichotomous time-varying explanatory covariate, the risk ratio is 6 (95% confidence interval = 2-19, p = 0.003). The 10 patients who relapsed exhibited safe plasma levels (less than a 40% decrease from their baseline levels) for only 210 months, and 13 nonrelapsing patients had plasma levels defined as safe for 426 months.

Malignant fibrous histiocytoma of the ileum at a site of previous surgery: report of a case.

Sarcomas rarely arise in the intestinum, and leiomyosarcoma represents the majority of cases. With only seven cases reported in the available English literature up to now, malignant fibrous histiocytoma of the small intestine is exceedingly rare. Moreover, follow-up data are almost completely unavailable. We present herein the unique case of a malignant fibrous histiocytoma arising in a postoperatively adherent intestinal loop. To the best of our knowledge, this is the first such case ever to be described. The clinical history and the intraoperative findings suggested that chronic postoperative repair processes might have been a promoting factor in the tumorigenesis of this neoplasm, on the analogy of malignant fibrous histiocytoma arising at different sites. The patient recovered well but 9.5 years after surgical removal, a solitary recurrent tumor developed in the urinary bladder and progressed rapidly, highlighting the need for long-term, possibly life-long, surveillance of patients with this rare type of intestinal cancer.

Relevance of liver enzyme elevations with four different neuroleptics: a retrospective review of 7,263 treatment courses.

Data on liver enzyme elevations were collected in a retrospective study of 7,263 treatment courses with haloperidol, clozapine, perphenazine, and perazine. Charts of 233 patients hospitalized between 1980 and 1992 at Tübingen University Psychiatric Clinic were selected because clinically relevant increases of liver enzymes had been detected during monotherapy with one of the four examined neuroleptics. At least one hepatic enzyme (mostly alanine aminotransferase [ALAT]) exceeded the established reference range of 3-fold elevations of ALAT, aspartate aminotransferase, gamma-glutamyl transpeptidase, and glutamate dehydrogenase and 2-fold elevations of alkaline phosphatase (AP) during monotherapy with clozapine in 15%, perazine in 7.6%, perphenazine in 4%, and haloperidol in 2.4% of the cases. If all liver enzyme abnormalities with any elevation greater than the conventional upper limits are considered, incidences were as follows: clozapine, 78%; perphenazine, 62%; perazine, 59%; and haloperidol, 50%. Testing for overall differences within the four neuroleptics resulted in significantly different incidences of liver enzyme elevations (chi2 test,p < 0.0001). Threefold increases of AP (>540 U/L) were seen in three patients receiving haloperidol (0.3%) only. Twofold increases of AP (>360 U/L) were distributed as follows: clozapine, 1%; haloperidol, 0.8%; perazine, 0.3%; and perphenazine, 0.1%. Only in the group with 1-fold elevations of AP (>180 U/L) were the differences within the drug regimens significant (clozapine, 40.3%; haloperidol, 33.2%; perphenazine, 23.4%; and perazine, 23.1%; chi2 test, p < 0.0001). In the period under study, no instance of icterus occurred.

[Secondary high-grade MALT lymphoma of the stomach in a 69-year-old patient with gastrocolic fistula]. / Sekundär hoch malignes MALT-Lymphom des Magens bei einem 69-jährigen Patienten mit gastrokolischer Fistel.

A 69-year-old man was referred to our department with an exorbitant foetor ex ore, dysphagia and dyspepsia. Upper endoscopy had been performed prior by an outpatient gastroenterologist and the patient had received an eradication therapy for a Helicobacter pylori-induced gastritis. At admission upper endoscopy showed a gastric ulcer which drained a stinking fluid. Endosonography, computed tomography and an upper gastrointestinal series with water soluble media revealed a gastrocolic fistula. Multiple biopsies showed a low-grade gastric MALT lymphoma. Therefore, a surgical reconstruction with Roux-en-Y esophagojejunostomy and transverso-descendostomy was performed. The histology of the completely removed stomach revealed a high-grade Non Hodgkin Lymphoma (NHL) with parts of a low-grade NHL. 3 weeks after surgery chemotherapy was started with the CHOP-regime which was well-tolerated by the patient.

Ectopic submandibular thyroid tissue with a coexisting active and normally located thyroid gland: case report and review of literature.

Ectopic thyroid tissue in the submandibular space with the thyroid gland in its normal location is an extremely rare phenomenon. We present a case of a 75-year-old woman who had painless swelling in the left submandibular space and was referred to our hospital with the suspicion of having a malignant tumor originating from the submandibular gland. Histologic examination showed normal follicular thyroid tissue without any sign of malignancy. In general there are 3 explanations for the presence of ectopic thyroid tissue found in the submandibular region: (1) displacement during the course of embryonal development, (2) spread of tissue during surgery on a normally located thyroid gland, and (3) metastasis of a highly differentiated papillary thyroid carcinoma. We reviewed the literature with respect to the embryological background and the clinical management of such cases.

Retroperitoneal Leiomyosarcoma Associated with an Elevated beta-HCG Serum Level Mimicking Extragonadal Germ Cell Tumor.

Patient. A 65-year-old man was admitted with a large primary retroperitoneal tumor and an increased beta-human chorionic gonadotropin (beta-HCG) serum level. A germ cell tumor was suspected; however, a computed tomography-guided biopsy failed to enable tumor classification. After two courses of chemotherapy, the beta-HCG serum level had returned to the normal level and a diagnostic laparotomy with incisional biopsy was performed. The immunohistochemical examination of the specimen identified the tumor as a retroperitoneal pleomorphic leiomyosarcoma.Discussion. Tumor markers play only a marginal role in the work-up of patients with soft tissue sarcomas. In men with suspected retroperitoneal sarcomas, however, the determination of germ cell tumor markers occasionally enables a preoperative distinguishing of primary retroperitoneal germ cell tumors with considerable consequences for management. In this setting, a retroperitoneal tumor associated with a moderately elevated beta-HCG is a diagnostic dilemma, and surgeons should be aware of the pitfall of a beta-HCG-producing leiomyosarcoma in the differential diagnosis.

[An unusual picture of insulinoma in type-2 diabetes mellitus and morbid obesity]. / Ungewöhnliches Bild eines Insulinoms bei Diabetes mellitus Typ 2 und morbider Adipositas.

HISTORY AND CLINICAL FINDINGS: Marked hyperinsulinism was demonstrated in the course of an oral glucose tolerance test (oGTT) in a 63-year-old woman with severe obesity (height 1.59 m, body weight 123 kg, body-mass index 46.4 kg/m2). The diabetic metabolic state, first diagnosed 12 years ago, had been replaced by a low plasma glucose level: she often had attacks of ravenous hunger. A reducing diet of 800 kcal had not been tolerated. She had not had any syncopes. She had continually gained weight since puberty, but her weight had remained relatively constant for the past 5 years during which she had been treated with L-thyroxine for a diffuse goitre (stage II). INVESTIGATIONS: In the course of an oGTT (75 g glucose) the basal insulin concentration (146 pmol/l) had risen to 1663 pmol/l at 30 min. The basal proinsulin level was 50 times normal (66 pmol/l vs. 1.418 pmol/l), while the initial plasma glucose level had fallen from 4.3 mmol/l to 3.8 mmol/l. Spiral computed tomography of the pancreas showed a 3 x 2.5 cm mass in the region of the tail of the pancreas. TREATMENT AND COURSE: At laparoscopy a 4 cm tumor was palpated in the region of the pancreatic tail. Left resection of the pancreas was performed. Histopathological examination of the surgical specimen confirmed an insulinoma. A repeat of oGTT 6 months postoperatively demonstrated a markedly diminished insulin level compared with the preoperative results, as well as a diabetic metabolic state. CONCLUSION: In case of dramatic improvement of diabetes mellitus in an obese patient without drug treatment or weight reduction an insulin-producing tumour should be considered in the differential diagnosis. There may be no typical hypoglycaemic symptoms because of insulin resistance associated with the obesity.

Pharmacokinetics of clozapine and its metabolites in psychiatric patients: plasma protein binding and renal clearance.

AIMS: N-Desmethylclozapine and clozapine N-oxide are major metabolites of the atypical neuroleptic clozapine in humans and undergo renal excretion. The aim of this study was to investigate to what extent the elimination of these metabolites in urine contributes to the total fate of clozapine in patients and how they are handled by the kidney. METHODS: From 15 psychiatric patients on continuous clozapine monotherapy, blood and urine samples were obtained during four 2 h intervals, and clozapine and its metabolites were assayed in serum and urine by solid-phase extraction and h.p.l.c. Unbound fractions of the compounds were measured by equilibrium dialysis. RESULTS: The following unbound fractions in serum were found (geometric means): clozapine 5.5%, N-desmethylclozapine 9.7%, and clozapine N-oxide 24.6%. Renal clearance values calculated from unbound concentrations in serum and quantities excreted in urine were for clozapine on average 11% of the creatinine clearance, whereas those of N-desmethylclozapine and clozapine N-oxide amounted to 300 and 640%, respectively. The clearances of unbound clozapine and N-desmethylclozapine increased with increasing urine volume and decreasing pH. All renal clearance values exhibited large interindividual variations. The sum of clozapine and its metabolites in urine represented on average 14% of the dose. CONCLUSIONS: Clozapine, N-desmethylclozapine and clozapine N-oxide are highly protein-bound in serum. Clozapine is, after glomerular filtration, largely reabsorbed in the tubule, whereas the metabolites undergo net tubular secretion. Metabolic pathways alternative or subsequent to N-demethylation and N-oxidation must make major contributions to the total fate of clozapine in patients.

Spontaneous regression of hepatocellular carcinoma confirmed by surgical specimen: report of two cases and review of the literature.

Two cases with spontaneous regression of a histologically confirmed hepatocellular carcinoma (HCC) are presented. This rarely seen phenomenon of a spontaneous tumor involution is discussed and compared with the current literature. The clinical symptoms were very similar to that of a liver abscess. A 56-year-old male suffered from a multicentric, highly differentiated, trabecular HCC. First symptoms were epigastric pain, septic fever and arthritis. The tumor marker AFP was constantly normal and no hepatitis could be verified. A resection of the tumor was performed. In patient 2, a 74-year-old male, a multicentric, clear cell HCC was found. The patient had completely recovered from hepatitis type B and within the liver tissue no viruses could be identified. Clinical symptoms were mainly characterized by upper abdominal pain and septic fever. AFP was excessively elevated (3850 ng/ml) but returned to normal preoperatively. In both cases, the specimen showed a subtotal necrotic HCC with insignificant amounts of vital tumor cells. Neither patient had a liver cirrhosis macroscopically, however patient 2 had local periportal fibrosis histologically. After 24 and 41 months of follow-up, respectively, both patients are in good health

Elevated norharman plasma levels in alcoholic patients and controls resulting from tobacco smoking.

Plasma norharman and harman levels were measured by solvent extraction and HPLC with fluorescence detection in alcohol-dependent patients undergoing in-patient abstinence treatment and in control subjects. In both groups, randomly collected samples from smokers contained higher mean norharman levels than those from non-smokers. In three volunteers norharman concentrations rose sharply after smoking of one or two cigarettes and declined to near-basal levels within one hour after one cigarette. When 12 patients kept a smoking-free interval of at least 6 h, they had similarly low plasma norharman concentrations (20 +/- 8 pg/ml) as 18 non-smoking control subjects (17 +/- 8 pg/ml) or as 13 smoking controls who had abstained from smoking (20 +/- 6 pg/ml). Ten of the patients smoked one cigarette and within 5-10 min attained norharman levels of 177 +/- 147 pg/ml plasma. The high prevalence of smokers among chronic alcoholics probably explains the previous finding of elevated norharman plasma levels in these patients.

Colloid cyst of the third ventricle with XYY-syndrome.

Case presentation of an intra-uterine diagnosed third ventricle colloid cyst in a male with XYY-Syndrom. The inner cellular cover of cyst was composed by flat or cuboidal to columnar epithelium, which beared cilia in some areas. Other cells of the inner cover showed protrusions of cytoplasm, which extended into the cyst cavity. The cyst wall showed loosely arranged fibrous connective tissue, some Plasmocytes, and a few cells with granulated plasma. The histogenesis of this cyst was suggested immunohistologically from primitive neuroepithelial structures. According to sonographic findings an intra-uterine diagnosed intracerebral cyst should be a cause to search other malformations.

Haloperidol and lorazepam combined: clinical effects and drug plasma levels in the treatment of acute schizophrenic psychosis.

In 61 acute schizophrenic patients the effects of haloperidol (HPL) and lorazepam combined vs. HPL alone and the interaction between these drugs were evaluated. Patients were assigned to groups randomly. The study design was open. Study duration was 28 days. Psychopathology was evaluated on the basis of BPRS scores. Extrapyramidal side-effects were rated according to Simpson and Angus (1970). Pharmacological parameters included serum levels of lorazepam, HPL, and reduced HPL. Mean daily lorazepam dosage was 0.05 mg/kg, mean HPL dosage 0.5 mg/kg. None of the patients treated with lorazepam and HPL achieved better BPRS total or subscores, nor did their condition improve faster than in patients treated with HPL alone. A significant linear relationship between lorazepam serum levels and oral dosage was found, but none between lorazepam serum levels and BPRS total score, subscore reduction, or extrapyramidal side-effects. The authors conclude that beneficial effects of lorazepam in the treatment of acute psychosis are scant and may not justify the risks incurred with routine comedication of lorazepam.

Haloperidol and reduced haloperidol serum levels: correlation with psychopathology in acute schizophrenia.

Serum levels of haloperidol (HPL) and reduced haloperidol (RHPL) as well as the RHPL/HPL ratio were determined in 55 acute schizophrenics on oral haloperidol medication and correlated over 28 days with psychopathology and extrapyramidal symptom scores. Linear and nonlinear models of serum concentration and psychopathology were tested at several time points. No single consistent model could be established for either HPL or RPHL. However, when non-parametrical methods are used HPL levels between 10 and 25 ng/ml can be shown to be significantly associated with better outcome during the first three weeks of treatment. RHPL is unsuitable for therapy monitoring, since equilibrium is not reached in the first four weeks of treatment. The RHPL/HPL ratio was found to rise continuously during the study, and it neither separated responders from nonresponders nor did it correlate with clinical outcome.

[Contribution to hypochondrogenesis]. / Beitrag zur Hypochondrogenese.

Hypochondrogenesis is one of non-viable skeleton dysplasiae which recently has been delimited as an entity of its own and with its classification between spondylo-epiphysary dysplasia and achondrogenesis. An accurate differential diagnosis requires specialised histo-pathological investigations of the patient's cartilage tissue. Five new observations compared to a classical case of dysplasia spondylo-epiphysaria congenita are added to the references made in literature.

Urinary dolichol--a doubtful marker of alcoholism.

The purpose of this study was to replicate the results of Pullarkat and Raguthu and Roine et al. who found elevated levels of urinary dolichol (long-chain 2,3-dihydropolyprenols) in chronic alcoholic patients. We investigated a sample of 21 alcohol-dependent inpatients voluntarily entering detoxification treatment. Urinary dolichol was only slightly increased as compared to 21 healthy controls. When dolichol was related to urinary creatinine no differences between alcoholic patients and controls could be found. Under conditions of confirmed abstinence the slightly elevated levels of dolichol returned to normal within 2 weeks. Compared with the sensitivity of gamma-glutamyltransferase which ranges from 72-85%, the value of urinary dolichol (sensitivity 9-19%) as a biochemical marker of alcoholism must be doubted.