Beneficial antipsychotic effects of celecoxib add-on therapy compared to risperidone alone in schizophrenia

OBJECTIVE: Abnormalities in the immune system in schizophrenia have been described. However, important findings such as high levels of activating cytokines in the CSF and signs of CNS inflammation have been controversial. The authors conducted a trial of the new selective cyclooxygenase-2 inhibitor celecoxib, an immunomodulatory drug, in schizophrenic patients to evaluate its therapeutic effects. METHOD: In a prospective, double-blind evaluation, 50 patients with an acute exacerbation of schizophrenia were randomly assigned to either risperidone plus celecoxib or risperidone plus placebo. After a washout period, 25 patients received 2-6 mg/day of risperidone plus placebo and 25 received risperidone plus 400 mg/day of celecoxib for 5 weeks. The treatment effect was calculated by analysis of covariance. There were no significant differences between groups in age, sex, duration or severity of disease or psychopathology, or risperidone dose or plasma level. RESULTS: Over 5 weeks, both groups of patients showed significant improvement in scores on the Positive and Negative Syndrome Scale and on all subscales. However, the celecoxib group showed significantly greater improvement in the total score. CONCLUSIONS: Additional treatment with celecoxib has significant positive effects on the therapeutic action of risperidone with regard to total schizophrenia psychopathology. Moreover, the fact that treatment with an immunomodulatory drug showed beneficial effects on schizophrenia symptoms indicates that immune dysfunction in schizophrenia is not just an epiphenomenon but is related to the pathomechanism of the disorder. However, a nonimmunological therapeutic effect of celecoxib mediated by the N-methyl-D-aspartic acid receptor has to be taken into account.     

Mediators of antigen-induced gastrin release: role of antigen-antibody complexes and the complement system

That orally administered antigen was shown to induce gastrin release in immunized animals was a new aspect of gastrointestinal physiology. The mediators responsible for this immunological effect are still unclear. In an attempt to discover more about the mechanisms regarding antigen-induced gastrin release, we developed an in vitro system where fragments of rat antral mucosa were challenged. This makes it possible to determine the role of antigen-antibody complexes and the complement system in the mechanism of antigen-induced gastrin release. Wistar rats were immunized in vivo with NIP-OVA and mucosal fragments were challenged in vitro with NIP-HGG. Gastrin was determined after a preincubation and a challenged incubation period without supernatants. After antigenic challenge, supernatants were used for in vitro challenge in order to rule out the presence of a soluble mediator and activation of complement. In a second group of experiments Wistar rats were used to study in vitro the release of specific antibodies after antigenic challenge. With this experimental design we were able to show increased gastrin secretion after antigenic challenge in vitro in the presence of intact tissue. It is shown that the increased gastrin release is most probably mediated by activation of the complement system in the presence of antigen-antibody complexes. These are built up by specific anti-NIP antibodies and NIP-HGG used for the challenge. The complement system might be the final pathway of the observed in-creased gastrin release.     

Screening for drugs of abuse in oral fluid--correlation of analysis results with serum in forensic cases

The testing of saliva or oral fluid at the roadside could be a powerful tool to detect drivers under the influence of drugs and has several advantages over urine screening. In 177 cases of individuals suspected of driving under the influence of drugs, oral fluid was collected at the roadside and analyzed in parallel to serum samples. The study was performed to investigate the variability of oral fluid analysis results in relation to blood/serum. In 45% of the cases single-drug use was found, and in 50% poly-drug use was found. Cannabis was most prevalent (78%), and 70% of these individuals were also positive for tetrahydrocannabinol in serum. Overall, 97% of oral fluid samples positive for any substance were also positive in serum. Comparing data of oral fluid and serum for amphetamine, MDMA, morphine, benzoylecgonine, and tetrahydrocannabinol, the sensitivities were 100%, 97%, 87%, 87%, and 92%, respectively. Overall specificity and accuracy were in the range of 91-98%. Discrepancies between a negative oral fluid sample and a positive serum sample could be explained by analytical insensitivity in the lower volume of oral fluid analyzed (estimated for 0.1 mL confirmation vs. 1 mL of serum) or a shorter detection window in oral fluid. The low prevalence of discrepancies with positive oral fluid and negative serum results (2-9% of the cases) may be explained by persistent oral contamination especially for orally consumed drugs, like MDMA and cannabis. It is concluded that the detection of a psychoactive substance in oral fluid taken at the roadside is highly predictive for the detection of the corresponding drug or its metabolite in serum. Oral fluid testing is therefore suitable for the efficient confirmation of drug use of drivers suspected of being under the influence of drugs.     

Relationships of psychiatric disorders with overweight and obesity in an adult general population

OBJECTIVE: To explore relationships of smoking and risk drinking status, nicotine and alcohol dependence, and anxiety, depressive, and somatoform disorders with overweight and obesity. RESEARCH METHODS AND PROCEDURES: A probability sample was drawn that was representative for the adult general population, 18 to 64 years of age, in one region of Germany; the participation rate was 70.2%. After excluding those who were pregnant or had a current eating disorder according to the DSM-IV, 4063 individuals remained. Overweight and obesity were defined according to the BMI that was assessed in the face-to-face in-home standardized interview (Composite International Diagnostic Interview) on psychiatric disorders. RESULTS: Men with a former nicotine dependence had higher odds of being overweight than men who never had a nicotine dependence (adjusted odds ratio, 1.5; confidence interval, 1.1 to 2.1). Men at current risk for drinking and current alcohol-dependent or abusing men had lower odds of being overweight compared with men who never were alcohol dependent, abusing, or at risk for drinking (adjusted odds ratio, 0.3; confidence interval, 0.8 to 0.9). Effect sizes were small. No relationship of overweight with depressive, anxiety, or somatoform disorders was found in the multivariate analysis. DISCUSSION: There is a relationship between being overweight and nicotine and alcohol dependence or abuse among men but not among women. Even though one reason for women to refrain from quitting smoking is the fear of weight gain, these results do not support this. This information could help convince women to try to quit smoking.     

Diagnostic ultrasound of the shoulder--a method for experts only? Results from an orthopedic surgeon with relative inexpensive compared to operative findings

Background Diagnostic ultrasound examination of the shoulder is generally considered to require long experience. We examined the results of an orthopedic surgeon with little experience of ultrasound.

Patients and methods A relatively inexperienced examiner performed preoperative ultrasound scanning of 79 patients with symptoms from the rotator cuff and/or the long head of the biceps muscle. Tears of the rotator cuff and rupture or dislocation of the long head of the biceps muscle were the positive findings of interest. Results were compared to operative findings.

Results In 66 of 79 shoulders, ultrasonographic rotator cuff findings were confirmed at surgery (accuracy 84%). 20 of 26 full-thickness tears were diagnosed correctly. 6 of 7 partial-thickness tears were overlooked. Ultrasound was false positive in 1 case. For the long head of the biceps muscle, all 8 cases of dislocation or rupture of the tendon were diagnosed but differentiation between the two conditions was not possible in 2 cases.

Interpretation Our results may encourage orthopedic surgeons to start using ultrasound as a diagnostic technique for full-thickness tears of the rotator cuff and for pathology in the long head of the biceps muscle.     

Absence of muscle capillary basement membrane thickening and retinopathy in patients with myocardial infarction and impaired I.V. glucose tolerance

Summary We have investigated the possible contribution of an early capillaropathy to the increased incidence of myocardial infarction (MI) in patients who had impaired glucose tolerence (IGT) during an i.v. glucose tolerance test (IVGTT). In lieu of the myocardium, biopsies from the quadriceps femoris muscle were studied for muscle capillary basement membrane (MCBM) thickening. Fluorescence angiography was performed to detect capillary retinopathy. Plasma growth hormone (GH) concentrations were determined during IGT. Data were obtained from 14 male patients with MI and IGT on IVGTT. Nine healthy subjects served as controls. MCBM thickness was similar in patients and controls (1,107±55vs 1,067±88 ?). None of the patients had signs of capillary retinopathy, and plasma GH concentrations were not higher in the patients as compared to control subjects. It is concluded that, in patients with IGT on IVGTT, MCBM thickening is probably not a factor for the development of MI.     

Mosaics of ancient mitochondrial DNA: positive indicators of nonauthenticity

Research into ancient mitochondrial DNA is plagued by contamination, post mortem damage, and other artefacts. The stringent set of controls suggested by Cooper and Poinar a few years ago are, however, rarely followed in practice, and even when applied carefully, these criteria need not be sufficient to guarantee authenticity. The fairly relaxed prerequisites now common for ancient population studies have opened the door for all kinds of contamination and sequencing errors to enter ancient mtDNA data. To reject or question authenticity of particular sequencing results a posteriori, one can follow similar strategies of focused database comparisons that have proven to be effective and successful in the case of flawed modern mtDNA data.