Schizophrenia in Translation: Is Active Psychosis Neurotoxic?

Positive symptoms of psychosis disrupt mentation. Do they also engineer brain cell death and deterioration? This hypothesis is currently popular as an explanation of the duration of untreated psychosis effect in early schizophrenia. The clinical and neurobiological evidence for its validity is visited and found wanting. Synaptic plasticity, not neurotoxicity, appears to be the mediating process.     

Sensitization to thimerosal (Merthiolate) is still present today

The results on thimerosal (Merthiolate) hypersensitivity of a retrospective study, together with the relevant data on thimerosal hypersensitivity referred to in the literature up to 1993, are presented. Positive patch test reactions to thimerosal (0.1% pet.) were observed in 32 (1.3%) of 2461 adult patients with suspected contact allergy examined in the period 1987–1992. 20 (0.8%) patients had a solitary positive patch test to thimerosal. The observed incidence is low. Clinical symptoms related to thimerosal hypersensitivity were observed in only 3 patients. The collected results are discussed with emphasis on the clinical implications of sensitization to thimerosal. It appears that a positive patch test to thimerosal is frequently clinically irrelevant.     

Low-dose cyclosporin A in severe psoriasis. A double-blind study

Twenty patients with severe plaque psoriasis were selected to receive either low-dose cyclosporin A (CyA) or placebo (CyA vehicle) in a double-blind randomized trial at two centres. Within 4 weeks the mean reduction in the Psoriasis Area and Severity Index (PASI) in 10 patients receiving CyA (mean dose 5.5 mg/kg/day) differed significantly from the mean reduction in 10 patients receiving placebo. In eight patients given placebo a switch to CyA therapy resulted within 4 weeks in a mean reduction in PASI of 90%. In a total 15 out of 18 patients given CyA (83%) (mean dose 5.6 mg/kg/day) there was an improvement of greater than or equal to 75% in PASI within 4 weeks. In a 2-month tapering off phase a lower mean CyA dose (3 mg/kg/day) was effective in maintaining the reduced PASI scores in seven of nine patients. Four out of five CyA treated patients who entered a post-treatment observation phase had a relapse (PASI score greater than or equal to 50% of score at baseline) after a mean interval of 6.5 weeks. The most important side-effects were mild reversible hypertension in 5 of 18 patients (28%), and reversible elevated serum creatinine levels in 7 of 18 patients (39%). We consider that further studies are justified in severe chronic psoriasis to establish suitable regimens for maintenance of remission in psoriasis with low-doses of CyA or a combination of CyA with other anti-psoriatic agents.     

Test battery for metal allergy in dentistry

Some alloys used in restorative dentistry may evoke an allergic contact stomatitis in certain persons. In order to protect patients from materials with undesired reactions, and considering corrosion characteristics of different alloys used, it is useful to devise an adequate patch test battery to include the most relevant metals. Dental alloys are composed of a combination of various metals. 12 different ions of frequent occurrence (Au3+, Pd2+, Zn2+, Mo6+, Sn2+, Ga3+, In3+, Co2+, Cr3+(6+), Ni2+, Fe2+(3+) and Si4+) were epicutaneously tested as the aqueous solution of the respective salt. The concentrations are given in g/100 ml and also in m.mole/l. The 12 different metal ion solutions were patch tested on patients in 3 groups: one group with a positive history of contact stomatitis (30 patients, group 1), one group with a positive history of contact dermatitis (16 patients, group 2), and a control group (17 persons, group 3). In contrast to the control group, a remarkable high percentage (11%) of positive skin reactions to Pd was found in groups 1 and 2. No allergic or irritant skin reactions were detected to Ga, Sn and Zn. No irritant reaction was observed at pH values as low as 1.5. In the case of SiCl4 (pH = 0.5), 41% positive irritant reactions were evoked. In the group with a positive history of contact dermatitis (group 1), a positive reaction was found more often (69%) than in the group with a positive history of contact stomatitis (30%) (group 2). The difference between these groups was mainly caused by reactions to Ni and Pd.(ABSTRACT TRUNCATED AT 250 WORDS)     

Autoimmune skin and connective tissue diseases and risk of venous thromboembolism: a population‐based case‐control study

Summary. Background: Systemic inflammation is associated with vessel wall damage, upregulation of procoagulants, downregulation of anticoagulants, and suppression of fibrinolysis. Autoimmune diseases may therefore increase the risk of venous thromboembolism (VTE). Objectives: To examine whether autoimmune skin and connective tissue diseases are associated with increased VTE risk. Methods: We conducted this population‐based case–control study in northern Denmark, using administrative databases. From 1999 to 2009, we identified 14 721 VTE cases and 147 210 birth year‐matched, sex‐matched and county‐matched population controls. The date of diagnosis/matching was considered to be the index date for cases and controls. For all study subjects, we identified hospital diagnoses of autoimmune skin or connective tissue diseases between 1977 and the index date. We used conditional logistic regression with adjustment for VTE risk factors to calculate odds ratios and 95% confidence intervals (CIs) for patients with vs. without autoimmune disease. Given the risk‐set sampling design, odds ratios estimate incidence rate ratios (IRRs). Results: Autoimmune skin disease was not associated with VTE (IRR 1.0; 95% CI 0.9–1.2). Patients with connective tissue disease had an increased VTE risk within 90 days (IRR 2.3; 95% CI 1.5–3.7) and 91–365 days (IRR 2.0; 95% CI 1.5–2.8) after diagnosis, but not thereafter (IRR 1.1; 95% CI 1.0–1.2). Among connective tissue diseases, the greatest overall risk increases were found for juvenile rheumatoid arthritis (IRR 3.0; 95% CI 1.4–6.4) and systemic lupus erythematosus (IRR 2.8; 95% CI 1.7–4.7). Conclusions: Autoimmune connective tissue disease was associated with an increased risk of VTE within 1 year after diagnosis, whereas skin diseases were not.     

Shortened duration of untreated first episode of psychosis: changes in patient characteristics at treatment.

OBJECTIVE: This study examined whether duration of untreated psychosis can be shortened in patients with first episodes of DSM-IV schizophrenia spectrum disorders and whether shorted duration alters patient appearance at treatment. METHOD: Two study groups were ascertained in the same Norwegian health care sector: one from 1993-1994 with usual detection methods and one from 1997-1998 with early detection strategies that included education about psychosis. RESULTS: Patients with early detection had a shorter median duration of untreated psychosis by 21.5 weeks than patients with usual detection. The number with psychosis was greater in the early detection group; the number with schizophrenia was less. Early detection patients had more substance abuse and were younger, better adjusted premorbidly, and less ill. CONCLUSIONS: Early detection can shorten duration of untreated psychosis and help more patients when they are less severely ill. Given the devastation of psychosis, this is a significant treatment advance.     

Effects of development on olanzapine-associated adverse events

OBJECTIVE: Atypical antipsychotic medications are increasingly prescribed for child and adolescent patients. Relatively little information on adverse events (AEs), specifically in children or adolescents taking atypical antipsychotics, is available. METHOD: The Food and Drug Administration spontaneous AE reporting postmarketing surveillance database was queried for olanzapine until March 31, 2000. Patient exposure estimates as of the same date were provided by the manufacturer. AE complaints and exposure estimates were divided by age: children (birth-9 years), adolescents (10-19), and adults (20+). AE complaint risks per 10,000 patients exposed were calculated along with risk ratios across age groups and their 95% confidence intervals. RESULTS: Extrapyramidal syndrome complaint risks were similar across development, and tardive dyskinesia complaint risks were comparable in adolescents and adults. Overrepresented AE complaints in children included sedation, weight gain, liver function abnormalities, and tardive dyskinesia. Overrepresented AE complaints in adolescents included sedation, weight gain, liver function abnormalities, and prolactin increase. CONCLUSIONS: Extrapyramidal syndromes may be no more common in children and adolescents with olanzapine than in adults. The frequency of some other AEs may differ across development. Caution is warranted because of the likelihood of reporting bias. Similar analyses should be conducted with other atypical antipsychotics.