GWA study data mining and independent replication identify cardiomyopathy-associated 5 (CMYA5) as a risk gene for schizophrenia.

We conducted data-mining analyses using the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and molecular genetics of schizophrenia genome-wide association study supported by the genetic association information network (MGS-GAIN) schizophrenia data sets and performed bioinformatic prioritization for all the markers with P-values ≤0.05 in both data sets. In this process, we found that in the CMYA5 gene, there were two non-synonymous markers, rs3828611 and rs10043986, showing nominal significance in both the CATIE and MGS-GAIN samples. In a combined analysis of both the CATIE and MGS-GAIN samples, rs4704591 was identified as the most significant marker in the gene. Linkage disequilibrium analyses indicated that these markers were in low LD (3 828 611-rs10043986, r(2)=0.008; rs10043986-rs4704591, r(2)=0.204). In addition, CMYA5 was reported to be physically interacting with the DTNBP1 gene, a promising candidate for schizophrenia, suggesting that CMYA5 may be involved in the same biological pathway and process. On the basis of this information, we performed replication studies for these three single-nucleotide polymorphisms. The rs3828611 was found to have conflicting results in our Irish samples and was dropped out without further investigation. The other two markers were verified in 23 other independent data sets. In a meta-analysis of all 23 replication samples (family samples, 912 families with 4160 subjects; case-control samples, 11 380 cases and 15 021 controls), we found that both markers are significantly associated with schizophrenia (rs10043986, odds ratio (OR)=1.11, 95% confidence interval (CI)=1.04-1.18, P=8.2 × 10(-4) and rs4704591, OR=1.07, 95% CI=1.03-1.11, P=3.0 × 10(-4)). The results were also significant for the 22 Caucasian replication samples (rs10043986, OR=1.11, 95% CI=1.03-1.17, P=0.0026 and rs4704591, OR=1.07, 95% CI=1.02-1.11, P=0.0015). Furthermore, haplotype conditioned analyses indicated that the association signals observed at these two markers are independent. On the basis of these results, we concluded that CMYA5 is associated with schizophrenia and further investigation of the gene is warranted.

Observations on switching patients with schizophrenia to risperidone treatment. Risperidone Switching Study Group.

This study examined one possible strategy for switching patients to treatment with risperidone involving immediate cessation of current neuroleptics and gradual withdrawal of anticholinergic treatments. All patients received risperidone monotherapy for at least 4 weeks. Side-effects and symptoms were rated and successful switching was defined as completion of the study with no consistent worsening in any rating scales. Of the 41 patients entered, five withdrew for reasons unconnected with the study. Of the remaining 36 patients, 64% (23 patients) were switched successfully. Overall, the rating scales showed significant improvements (mean score on Krawiecka scale, 11.0 to 6.6, P < 0.001), and side-effects decreased (mean score on Simpson & Angus scale, 5.1 to 2.9, P = 0.004). The strategy appeared to be successful for most patients, especially those who had previously received depot medication. However, more gradual withdrawal of previous treatments, including anticholinergics, may be advisable in some cases.

Abdominoperineal resection and perineal colostomy for low rectal cancer. The Lazaro da Silva technique.

PURPOSE: We sought to evaluate a new technique for creation of a continent perineal colostomy following abdominoperineal resection (APR) of the rectum for low rectal cancer. METHODS: Nine selected patients with low rectal cancer (two males; median age, 55.6 years; classified as Dukes A, 6 patients and as Dukes B, 3 patients) underwent APR. Following this, the original Lazaro da Silva technique was used as follows: 1) for performance of three circular myotomies in the distal sigmoid with a distance between each couple of no more than 8 cm; 2) repair of the myotomies, thus creating three circular colonic valves, the most distal of which remained extraperitoneally; 3) for construction of a perineal colostomy lying flush with the perineal skin; 4) after the patient starts consuming a regular diet, enemas through the perineal stoma are done, usually twice per week, to achieve defecation. Functional outcome was assessed by evaluation of bowel movements and neoanal continence. RESULTS: There were no deaths. From January 1994 until October 1995, no tumor recurrence has occurred, and fecal continence has been good. Four of the patients were able to defecate without enemas (2-4 times per week), and in five patients the self-administration of enemas (2-4 times a week) were necessary to accomplish defecation. CONCLUSION: Initial results with the Lazaro da Silva technique have been encouraging.

The Lichtenstein open tension-free inguinal hernia repair using a new prosthetic mesh-Bulgarian irresorbable ampoxen.

The routine use of mesh for repair of inguinal hernia has been popularized by Lichtenstein and coworkers. We adopted this technique and performed it widely using a mesh unknown in the Western world. Ampoxen [multifilamented polycaproamide, impregnated with 5-Nitro-8-Hydroxyquinolinum (Nitroxolinum, DCI), MEDICA, SA, Sandanski, Bulgaria] was discovered in 1975 and proved to be an excellent prosthetic material for replacement of attenuated or destroyed abdominal wall; furthermore, this mesh is very cheap and became widely applicable in our country. This report describes our experience with the first 846 adult inguinal hernia repairs under local anesthesia using Ampoxen. All 846 patients had excellent results, without recurrence. There were nine wound infections (1.1%), 16 testicular oedemas (1.9%), no seromata and no deaths. In no patient was the prosthetic mesh removed. There were no complications related to the use of Ampoxen; this mesh is permanent, has a great degree of fibrous tissue reaction, and wide spectrum antimicrobic activity. We advocate the Lichtenstein technique using irresorbable mesh (particularly Ampoxen) for all adult groin hernias except Types 1 and 2 (according to Nyhus' classification), and for all adult recurrent groin hernias.

Plasma magnesium levels in a population of psychiatric patients: correlations with symptoms.

Plasma magnesium levels were tested in a group of 155 psychiatric in-patients with a variety of diagnoses and were correlated with the severity of their symptoms. We hypothesized that lower Mg levels would correlate with a higher degree of anxiety, tiredness and other symptoms characteristic of Mg deficiency. No such correlations were observed. However, Mg levels varied widely, with 22.4% below, and 10.4% above the normal range. There was a strong association for more disturbed and excitable patients to have abnormal (either high or low) levels. We speculate that more disturbed patients might have some abnormality of Mg metabolism with possible therapeutic implications.

Magnesium, schizophrenia and manic-depressive disease.

Plasma magnesium (Mg) levels were estimated in 15 schizophrenic, 10 depressed, 6 manic and 6 presenile Alzheimer's disease patients and compared with those in 303 healthy controls. The schizophrenic and depressed patients showed lower levels, but the levels were normal in the other two groups. Mg levels increased on achieving clinical remission in the schizophrenic patients. A hypothesis is proposed according to which the high level of stress found in severely ill psychiatric patients can lead to marginal Mg deficiency in susceptible individuals. This could exacerbate symptoms such as anxiety, fear, hallucinations, weakness and somatic complaints.