Clozapine-associated neutropenia following augmentation with sodium valproate.

Clozapine is gold standard for the management of treatment-resistant schizophrenia. It can offer life-changing symptom reduction where other antipsychotics have failed, and for these patients, treatment with clozapine should be maintained, if in any possible way. However, treatment with clozapine comes with a risk of developing potentially fatal adverse reactions, for example, severe neutropenia or agranulocytosis, in which case, treatment must be discontinued. Here, we present a case of clozapine-related neutropenia that commenced after the addition of sodium valproate. A subsequent re-challenge to clozapine resulted in severe neutropenia and led to the permanent cessation of clozapine treatment. The patient had been tolerating clozapine for more than a year before the addition of sodium valproate. The awareness of an interaction between clozapine and sodium valproate could help reduce the risk of clozapine-induced neutropenia and subsequent clozapine discontinuation.

Properties and outcomes of spinal rehabilitation units in four countries.

OBJECTIVE: Compare rehabilitation after spinal cord lesions (SCL) in different countries. DESIGN: Multicenter comparative study. SETTING: Four spinal rehabilitation units, in Denmark, Russia, Lithuania and Israel. SUBJECTS: 199 SCL patients. INTERVENTIONS: Information was collected about unit properties, rehabilitation objectives, American Spinal Injury Association (ASIA) scale and spinal cord independence measure (SCIM) assessments, and patient data. chi (2)-test, t-test, ANOVA and ANCOVA were used for statistical analysis. MAIN OUTCOME MEASURES: Time from lesion onset to admission for rehabilitation (TAR), length of stay in rehabilitation (LOS), SCIM and spinal cord ability realization measurement index (SCI-ARMI) scores, SCIM gain, SCI-ARMI gain and rehabilitation efficiency (RE). RESULTS: Differences were found between the units in rehabilitation objectives, facilities and special equipment for rehabilitation. Staff/bed ratio was 1.7 in Lithuania and Denmark, 1.1 in Israel and 0.9 in Russia. Russian patients were the youngest and had the most severe lesions among participating units. Admission SCIM and SCI-ARMI were the lowest in Israel: 25.1+/-17.2 and 34.3+/-17.3. TAR was highest in Russia (12.4 month) and lowest in Israel (2 weeks; P<0.01). LOS was longest in Denmark (176.9 days; P<0.001). SCIM score at the end of rehabilitation was highest in Denmark (67.3+/-23). SCIM gain and SCI ARMI gain were highest in Israel (36.9+/-18.3 and 38.5+/-19.4, respectively) and lowest in Russia (P<0.001). RE was highest in Lithuania and lowest in Denmark (P<0.001). CONCLUSIONS: In the participating units, SCL rehabilitation outcomes depend on SCL severity and unit-specific properties. A moderately delayed rehabilitation with long LOS achieved high functioning, and early or slightly delayed rehabilitation combined with shorter LOS achieved high functional gain or efficiency.

The internalising and externalising dimensions of affective symptoms in depressed (unipolar) and bipolar patients.

OBJECTIVE: To analyse the internalising and externalising dimensions of affective states in depressed (unipolar) and bipolar patients approximately 2 years after discharge from psychiatric hospitals in Denmark. METHOD: The 42-item symptom scale based on the Beck Depression Inventory was used for the measurement of both the internalising dimension of affective symptoms (depression including suicidal ideas, anxiety and asthenia) and the externalising dimension (mania). To supplement the latter dimension, the WHO-5 questionnaire was included. These questionnaires were mailed to a large population of patients with depressive (unipolar) or bipolar disorders, representative of patients treated in hospital settings in Denmark, approximately 2 years after discharge from hospital. RESULTS: In total, 244 unipolars and 214 bipolars were included in the study. Mokken analysis showed that depressive (unipolar) patients could be measured more validly than bipolar patients on the internalising subscales of depression, anxiety and asthenia. On the externalising dimension of psychological well-being (WHO-5), both groups of patients could be validly measured. Approximately 2 years after discharge from hospital, around 36% of the unipolars and 19% of the bipolars had a moderate to severe depression. In a control group of healthy subjects, 4% had a moderate to severe depression. Less than 5% even in the bipolar group of patients were hypomanic. CONCLUSION: Approximately 2 years after discharge from psychiatric hospitals in Denmark, depressive (unipolar) patients scored significantly higher than bipolar patients on the internalising dimension and suicidal ideas, and significantly lower on the externalising dimension of psychological well-being.

Enforced mobilization, early oral feeding, and balanced analgesia improve convalescence after colorectal surgery.

OBJECTIVE: A postoperative regimen using a multimodal approach with enforced mobilization and early oral nutrition has been reported to improve convalescence but has not been compared with other postoperative regimens. METHODS: Forty patients undergoing elective colorectal surgery were randomly allocated to an intervention group receiving comprehensive information on the importance of mobilization, balanced anesthesia, and postoperative analgesia including epidural local anesthetics and enforced postoperative mobilization or a control group receiving anesthesia without epidural local anesthetics, postoperative analgesia with epidural morphine, and mobilization without fixed goals. All patients were offered early oral nutrition. The regimens were compared by means of ambulation time and physical activity, voluntary muscle strength, pulmonary function, and body composition. RESULTS: The ambulation time improved substantially within 22 h in the intervention group versus 3 h in the control group on day 1 (P = 0.0004) and within 8 h versus 2 h on day 4 (P = 0.0003). The voluntary strength of the quadriceps muscle decreased by 3% in the intervention group versus 15% in the control group on day 7 (P = 0.04). Two months postoperatively, the difference between groups was the same (P = 0.02). CONCLUSION: This active per- and postoperative regimen based on a multimodal approach improved ambulation time and muscle function during admission and late convalescence.

Psychosis and pregnancy: five cases of severely ill women.

An increasing number of patients with chronic mental disease are now integrated in society. As a consequence, women with severe psychiatric illness may become pregnant and wish to complete the pregnancy and to give birth to a child. The lack of sensation of reality in these patients and their social situation may result in particular problems in their treatment, and it may be necessary to admit them to a psychiatric ward before delivery. In this paper five cases of pregnant women with severe and chronic psychosis are described. These patients had many problems in common. Thus, they were all schizophrenics with very severe psychopathology, had poor understanding of their own situation, and lacked social networks. All the fathers were non-Danish. Coercion was used in all cases. To help women with severe mental illness to go through pregnancy and childbirth requires close collaboration between psychiatric and obstetric staff and social workers, and this should be organized in an institution with experience in the treatment of this type of patient.

Urethral epithelial cells on the surface on hydrophilic catheters after intermittent catheterization: cross-over study with two catheters.

AIM: To count the number of cells on the surface of the two commercial hydrophilic catheters, Lofric and EasiCath used for intermittent catheterization (IC) after 30-60 s in water without the necessity of catheter jelly. PARTICIPANTS: Twenty spinal cord lesioned (SCL) individuals. Six were women, and 14 men. METHODS: IC was performed on average five times a day (range: 4-10). In a randomised cross-over design all catheterizations were performed either with Lofric or EasiCath in two consecutive 24 h periods. The catheter used for the last catheterization in each 24 h period was fixed, and divided into pieces of 5 cm. From each of these a piece with the length of 5 mm was taken for surface microscopy after staining. The total number of cells was counted without knowledge of the type of catheter. According to the fractionator principle an unbiased estimate of the total number of cells on the surface of the cateter was calculated. RESULTS: There was no difference in the number of urethral epithelia cells on the catheters. No granulocytes were identified. The number of cells identified on the catheters were from 30 to > 10 000. No differences related to age, level of SCL, ASIA impairment scale, months since SCL or type of IC were found. There was a trend that women had higher cell counts than men. CONCLUSION: No difference was found regarding number of urethral epithelial cells on the surface of the catheters after catheterization. This indicates no difference in urethral trauma between the two catheters.

Long-term cyclosporin A nephrotoxicity in the rat. Evaluation of a morphological scoring system and of co-treatment with isradipine.

Cyclosporin A (CyA) nephrotoxicity was examined in Spraque-Dawley rats given CyA (12.5 (n = 45) or 25 (n = 45) mg/kg/day perorally for 16 weeks. Control rats (n = 45) received CyA vehicle. All rats were given either isradipine (ISRA) 1 or 5 mg/kg/day orally, or isradipine vehicle. Fifteen rats died from interstitial pneumonia caused by Staphylococcus xylosus. A predefined morphological CyA nephrotoxicity scoring system, based on semiquantitative scores for basophilic tubules and for interstitial fibrosis, performed on hematoxylin-eosin-stained tissue, yielded mean scores for basophilic tubules of 0.2 (range 0-1) in controls, 1.4 (range 0-3) in rats given CyA 12.5 mg/kg/day (p < 0.001), and 1.7 (range 0-3) in CyA 25 mg/kg/day rats (p < 0.001 as compared to controls). Rats given CyA were grouped according to their score for interstitial fibrosis: 0.2 (range 0-1) in CyA 12.5 mg/kg/day and 1.7 (range 0-3) in CyA 25 mg/kg/day rats (p < 0.001). When scores for basophilic tubules and interstitial fibrosis were pooled, none of the control rats had a score above 1, while 47% of the low-dose and 95% of the high-dose rats scored above 1. Thus, this CyA nephrotoxicity scoring system provided an easy, efficacious, and reproducible identification of rats with morphological CyA nephrotoxicity, and may be of clinical interest in the assessment of CyA nephrotoxicity. Kidney tissue from rats not treated with isradipine was further investigated with periodic acid-Schiff (PAS) with and without diastase treatment, and with Sirius Red. The latter confirmed the increase in connective tissue following tubular atrophy in CyA-treated rats. PAS reaction disclosed diastase-resistant positivity in the glomerular arterioles (score in controls: mean 0.4, range 0-1, in CyA 12.5 mg/kg/day mean 2.2, range 1-3, p < 0.001 as compared to controls; in CyA 25 mg/kg/day mean 1.1, range 0-2, p < 0.005 as compared to controls, p < 0.05 as compared to CyA 12.5 mg/kg/day). Furthermore, the straight part of the distal tubules of rats given the highest CyA dose contained considerable amounts of glycogen. The significance of this finding is unknown. Renal functional studies confirmed previous results since CyA decreased inulin clearance (Cin) from 1.2 +/- 0.5 to 0.8 +/- 0.3 ml/min/g kidney weight (kW) (p < 0.05), and lithium clearance (CLi) was reduced from 263 +/- 113 to 119 +/- 61 microliters/min/gKW (p < 0.001). Isradipine had no significant effect.

Antagonist capacity of felodipine on cyclosporin A nephrotoxicity in the rat.

Functional and morphological cyclosporin A (CsA) nephropathy has been attributed to a CsA-induced constriction of the afferent glomerular arteriole. Calcium-channel blockade with nifedipine prevented the development of short-term functional nephrotoxicity in CsA-treated rats. This study investigated whether the calcium antagonist felodopine, a structural analogue of nifedipine, which reduces renal tubular fractional sodium reabsorption, could prevent both short- and long-term functional and long-term morphological CsA nephropathy. In short-term experiments, four groups of Spraque-Dawley rats (n = 39) were given CsA (either 0 or 12.5 mg/kg per day by daily gastric intubation for 2 weeks), and felodipine (0 or 30 mg/kg per day) in the diet. In long-term experiments, rats (n = 39) were given CsA (12.5 mg/kg per day for 16 weeks), and felodipine (0 or 30 mg/kg per day in the diet). Renal function was investigated with clearance methods (inulin, lithium, and sodium), and kidney morphology was studied by light-microscopy. In short-term experiments, CsA treatment reduced GFR (730 versus 1181 microliters/min per g kidney weight (KW), P < 0.05) and CLi (130 versus 271 microliters/min per gKW, P < 0.02). Felodipine decreased proximal fractional reabsorption (PFR) (67.5% versus 71.4%, P < 0.05) and increased CNa (15.9 versus 8.4 microliters/min per gKW, P < 0.02) as compared to controls. In CsA-treated rats felodipine increased C in (1260 versus 730 microliters/min per gKW, P < 0.05) and CLi (319 versus 130 microliters/min per gKW, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Complement C3d,g/Epstein-Barr virus receptor density on human B-lymphocytes estimated by immunoenzymatic assay and immunocytochemistry.

The density of the C3d,g/Epstein-Barr virus receptor (CR2) on human mononuclear cells (MNC) isolated from CPD stabilized blood, was determined by comparing the concentration of CR2 antigen in extracts from Raji cells, with a known receptor density, with extracts of MNC. The concentration of CR2 was determined by a sandwich ELISA using two mutually non-inhibiting monoclonal anti CR2 antibodies (HB5 and OKB7). The percentage of CR2+ MNC was determined by an immunocytochemical staining method. Analysis of MNC from 20 healthy donors, revealed that the density of CR2 molecules varied from 3,600-7,700 on CR2+ cells, and that the percentage of CR2+ MNC had a mean of 13%.