The tissue microarray data exchange specification: A community-based,open source tool for sharing tissue microarray data

Background  

Tissue Microarrays (TMAs) allow researchers to examine hundreds of small tissue samples on a single glass slide. The information held in a single TMA slide may easily involve Gigabytes of data. To benefit from TMA technology, the scientific community needs an open source TMA data exchange specification that will convey all of the data in a TMA experiment in a format that is understandable to both humans and computers. A data exchange specification for TMAs allows researchers to submit their data to journals and to public data repositories and to share or merge data from different laboratories. In May 2001, the Association of Pathology Informatics (API) hosted the first in a series of four workshops, co-sponsored by the National Cancer Institute, to develop an open, community-supported TMA data exchange specification.     

Prevalence and burden of bipolar disorders in European countries.

A literature search, supplemented by an expert survey and selected reanalyses of existing data from epidemiological studies was performed to determine the prevalence and associated burden of bipolar I and II disorder in EU countries. Only studies using established diagnostic instruments based on DSM-III-R or DSM-IV, or ICD-10 criteria were considered. Fourteen studies from a total of 10 countries were identified. The majority of studies reported 12-month estimates of approximately 1% (range 0.5-1.1%), with little evidence of a gender difference. The cumulative lifetime incidence (two prospective-longitudinal studies) is slightly higher (1.5-2%); and when the wider range of bipolar spectrum disorders is considered estimates increased to approximately 6%. Few studies have reported separate estimates for bipolar I and II disorders. Age of first onset of bipolar disorder is most frequently reported in late adolescence and early adulthood. A high degree of concurrent and sequential comorbidity with other mental disorders and physical illnesses is common. Most studies suggest equally high or even higher levels of impairments and disabilities of bipolar disorders as compared to major depression and schizophrenia. Few data are available on treatment and health care utilization.     

Expression levels of TEL, AML1, and the fusion products TEL-AML1 and AML1-TEL versus drug sensitivity and clinical outcome in t(12;21)-positive pediatric acute lymphoblastic leukemia.

PURPOSE: t(12;21)(p13; q22), present in approximately 25% of pediatric precursor B-ALL, is highly sensitivity to L-asparaginase and the prognosis depends on the intensity of the treatment protocol. This study analyzes the relationship between the mRNA expression of the genes and fusion products involved in t(12;21), in vitro sensitivity to prednisolone, vincristine, and L-asparaginase, and long-term clinical outcome in t(12;21)+ acute lymphoblastic leukemia (ALL) patients. EXPERIMENTAL DESIGN: Long-term clinical outcome in 45 t(12;21)+ ALL patients was related to mRNA expression of TEL, AML1, TEL-AML1, and AML1-TEL, determined by real-time quantitative PCR, and the in vitro sensitivity to prednisolone, vincristine, and L-asparaginase, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. RESULTS: A significant approximately 3.5-fold lower TEL expression in t(12;21)+ compared with t(12;21)- ALL samples (P = 0.006) and normal controls (P = 0.004) was found. Expression of AML1 did not differ between t(12;21)+ and t(12;21)- ALL. However, AML1 expression in the leukemic cells was 2-fold higher compared with normal controls (P = 0.02). The TEL-AML1 fusion product was expressed in all t(12;21)+ cases, whereas the reciprocal fusion product AML1-TEL was expressed in only 76%. High expression levels of TEL-AML1 [hazard ratio (HR), 1.3; 95% confidence interval (95% CI), 1.10-1.57; P = 0.003], AML1-TEL (HR, 4.9; 95% CI, 1.99-12.40; P = 0.001) and AML1 (HR, 1.1; 95% CI, 1.03-1.22; P = 0.006) were associated with a poor long-term clinical outcome within t(12;21)+ ALL. Cellular drug resistance towards prednisolone, vincristine, and L-asparaginase could not explain this predictive value. Multivariate analysis including age and WBC showed that only high AML1-TEL expression is an independent poor prognostic factor in t(12;21)+ childhood ALL. CONCLUSION: High AML1-TEL expression is an independent poor prognostic factor in t(12;21)+ childhood ALL.     

ACCUMULATION OF ANTIBODIES IN THE CENTRAL NERVOUS SYSTEM

1. Antibodies can be extracted from the brain and spinal cord of rabbits actively or passively immunized with typhoid bacilli. 2. The titers of the antibodies in the extracts of brain and cord depend upon the titer of the blood serum. In actively immunized rabbits the following numerical relationships exist between the titers of the serum and of these organ extracts: The ratio of the titer of the serum is to the titers of extract of brain and of the spinal cord about as 100 is to 0.8; the titer of the serum is to the titer of the cerebrospinal fluid as 100 is to 0.3. In passively immunized rabbits the titer of the serum is to the titer of brain and spinal-cord extract as 100 is to 0.7. 3. The antibodies recovered from the brain are not due to the presence of blood in it for perfusion of the brain does not reduce its antibody content appreciably. 4. Antibodies penetrate into the spinal fluid from the blood even in the absence of inflammation of the meninges. When the penetration is completed the following numerical relationship exists between the titer of the serum and that of the cerebrospinal fluid: 100 to 0.25. 5. The penetration into the cerebrospinal fluid of antibodies injected intravenously proceeds at a slow rate, being completed only several hours after the immune serum has been injected. The penetration of antibodies into the tissue of the brain occurs at a very rapid rate. It is completed within 15 minutes. 6. It is very unlikely that when the immune serum is injected intravenously the antibodies reach the brain tissue by way of the cerebrospinal fluid, for (1) the antibody titer of the cerebrospinal fluid is lower than that of the brain extract, and (2) antibodies penetrate faster into the tissue of the brain than into the cerebrospinal fluid.     

Re-emergence of Posttraumatic Stress Disorder Nightmares With Nursing Home Admission: Treatment With Prazosin

Seniors with a history of emotional trauma decades earlier can experience a recurrence of posttraumatic stress disorder symptoms when transitioning to a nursing home. We present the case of an 86-year-old male Holocaust survivor admitted to a nursing home for physical therapy and rehabilitation 6 weeks after the death of his wife; the patient was expressing a persistent death wish. Despite the multiple risk factors for depression, his distress was specifically related to the reemergence of nightly posttraumatic nightmares. Over the course of 1 week of treatment with 1 mg prazosin at bedtime, his nightmares and his death wish completely resolved. He achieved his rehabilitation goals and was discharged to a community setting. This report highlights the importance of considering posttraumatic stress disorder in nursing home residents with a history of emotional trauma, and understanding how to address these symptoms pharmacologically and nonpharmacologically.     

Pain and the physician

Readers are invited to submit questions relating to problem cases. Inquiries will be answered by qualified consultants and replies forwarded by mail promptly. Selected problems and solutions are published every month in this section.     

Pedicle subtraction osteotomy in the thoracic spine and thoracolumbar junction: a retrospective series of 28 cases

Purpose

Pedicle subtraction osteotomy is a well-described surgical technique for treatment of kyphotic deformity in the spine. It is not widely used for treatment of thoracic kyphosis. We present the first documented series of 28 patients who underwent this procedure in 3 international centers. These patients presented with severe deformity with a wide range of aetiologies.

Indications

Kyphosis larger than 70 degrees, which is demonstrably rigid based on dynamic imaging.

Materials and methods

28 patients underwent surgery following pre-op neurological and radiographic assessment to fully assess the deformity. A triangular osteotomy was carried out using intraoperative navigation techniques. The patients were assessed post-operatively again with clinical and radiographic parameters at regular follow-up.

Results

The mean ODI score after surgery was 24.7 (16–42) while the pre-op was 53.4 (38–76). Mean thoracic kyphosis was improved from 64.2° (±20.1°) to 41.1° (±17.4°) resulting in a mean sagittal correction of 23.1°. Mean segmental correction at the PSO for all 28 cases was 17.8° (±8.1°). Stratified by region we found different values for the PSO correction: between T1 and T5 (6 cases) it was 17.5° (±5.4°) and between T6 and T9 (4 cases) 18.2° (±4.7°) and between T10 and L1 (18 cases) 26.2° (±5.2°). FBI index was 22.3° pre-op and improved to 7.8° post-op. Calculations were performed with Microsoft excel (2011 Microsoft, Redmond, WA).

Conclusions

Global sagittal balance was statistically improved in this series as demonstrated by FBI and C7 SVA correction.