Scintigraphic head-to-head comparison between 99mTc-WBCs and 99mTc-LeukoScan in the evaluation of inflammatory bowel disease: a pilot study

Scintigraphy with technetium-99m labelled white blood cells (WBCs) is routinely used in our hospital for the assessment of inflammatory bowel disease (IBD). The main disadvantages of this diagnostic tool are its time-consuming nature and the handling of blood itself. 99mTc-LeukoScan is a relatively new, easily prepared agent that is used for the detection of osteomyelitis. To assess its value in IBD, a scintigraphic head-to-head comparison was performed between 99mTc-LeukoScan and 99mTc-WBCs. 99mTc-LeukoScan scintigraphy was performed in six patients with clinically active IBD and increased uptake on 99mTc-WBC images. The interval between the scintigraphic studies ranged from 2 to 7 days, and endoscopy was subsequently performed to confirm active IBD. In three out of six patients with increased uptake on the 99mTc-WBC scans, 99mTc-LeukoScan images showed very discreet activity in the bowel, but the sites did not correspond with the inflammation sites seen on 99mTc-WBC scintigraphy and found at endoscopy. In the other three patients, 99mTc-LeukoScan scintigraphy revealed a physiological distribution but no abnormalities. In conclusion, 99mTc-LeukoScan is not an alternative agent for the assessment of IBD. A prospective study is not justified owing to the false-negative results.     

Decreased S100-beta protein in schizophrenia: preliminary evidence

The S100 proteins are a family of calcium-binding proteins found in the central and peripheral nervous systems of vertebrates. S100beta, the most abundant member of this family in the CNS, mediates calcium signal transduction, and shows neurotrophic, gliotrophic and mitogenic actions that influence the development and maintenance of the nervous system. Another member of the S100 family (S100A10) was found to modulate phospholipid turnover by inhibiting the activity of enzyme phospholipase A2 (PLA2). We determined the concentration of S100beta protein in the plasma of 23 medicated schizophrenic patients and 23 healthy controls. S100beta protein accounts for 96% of the total S100 in the brain. Schizophrenic patients showed reduced S100beta concentrations (p=0.003), and this finding was not related to clinical variables or to intake of antipsychotic medication. Decreased S100beta could be related to the findings of increased PLA2 activity and to brain maldevelopment in schizophrenia. These results are discussed further with respect to the role of adenosine in S100beta release.     

Vulvar carcinoma presenting during pregnancy,associated with recurrent bone marrow hypoplasia: a case report and literature review

BACKGROUND: Carcinoma of the vulva has predominantly been a disease of the elderly. Although occasionally it occurs in women under the age of 40 years, carcinoma of the vulva has been rarely diagnosed in pregnancy. Bone marrow hypoplasia can occur as a transient, pregnancy-related event; however, the recurrence of this pathology in future pregnancies is quite rare in the literature. CASE: A 29-year-old woman in her second pregnancy that was complicated by bone marrow hypoplasia had developed a squamous vulvar carcinoma. Each of these two conditions are quite rare in pregnancy, they may have occurred by chance, but there is a hypothetical possibility that bone marrow hypoplasia is an autoimmune disorder, with vulvar carcinoma occurring as a further complication in this immunoimpaired individual. CONCLUSION: This case also emphasizes the need to consider malignancy as a differential diagnosis in vulvar ulcers occurring in young women.     

Associates of Neonatal,Infant and Child Mortality in the Islamic Republic of Pakistan: A Multilevel Analysis Using the 2012–2013 Demographic and Health Surveys

Objectives Pakistan is one of five nations contributing to half of the world’s child mortality and holds under-five mortality rates which are nearly double global targets. Reasons for this shortfall include civil conflicts, political uncertainty, low education, poverty, rural–urban disparities, and limited health care access. The aim of this study was to explore associations between individual characteristics, community factors, and child mortality in Pakistan. Methods Data were derived from the 2012 to 2013 Pakistan Demographic and Health Survey, and included 7399 live births and 380 child deaths. Multivariate, multilevel logistic regression was used to model risk of neonatal, infant and under-five child deaths. Results Seventy-one percent of child deaths occurred during the neonatal period. Significant factors (p < 0.05) associated with lower odds of child mortality included adhering to recommended minimum of 24 months interpregnancy interval and higher household wealth. These were significant for neonatal (OR 0.448; 0.871), infancy (OR 0.465; 0.881), and under-five deaths (OR 0.465; 0.879). Employed mothers had higher odds of neonatal (OR 1.479), infant (OR 1.506), and child mortality (OR 1.459). Likewise, women living in consanguineous marriages had higher odds of infant (OR 1.454) and under-five deaths (OR 1.381). Children in Balochistan, Punjab, and Sindh, regions disproportionately poor, rural with low levels of education, were at highest risk of dying. Conclusions for Practice Findings may assist in designing targeted interventions, developing appropriate public health messaging, and implementing policies designed to lower child mortality. Focusing on lowering rates of maternal poverty, increasing opportunities for education, and improving access to health care could assist in reducing child mortality in Pakistan.     

Thymidine kinase 2 mutations in autosomal recessive progressive external ophthalmoplegia with multiple mitochondrial DNA deletions

Autosomal-inherited progressive external ophthalmoplegia (PEO) is an adult-onset disease characterized by the accumulation of multiple mitochondrial DNA (mtDNA) deletions in post-mitotic tissues. Mutations in six different genes have been described to cause the autosomal dominant form of the disease, but only mutations in the DNA polymerase gamma gene are known to cause autosomal recessive PEO (arPEO), leaving the genetic background of arPEO mostly unknown. Here we used whole-exome sequencing and identified compound heterozygous mutations, leading to two amino acid alterations R225W and a novel T230A in thymidine kinase 2 (TK2) in arPEO patients. TK2 is an enzyme of the mitochondrial nucleotide salvage pathway and its loss-of-function mutations have previously been shown to underlie the early-infantile myopathic form of mtDNA depletion syndrome (MDS). Our TK2 activity measurements of patient fibroblasts and mutant recombinant proteins show that the combination of the identified arPEO variants, R225W and T230A, leads to a significant reduction in TK2 activity, consistent with the late-onset phenotype, whereas homozygosity for R225W, previously associated with MDS, leads to near-total loss of activity. Our finding identifies a new genetic cause of arPEO with multiple mtDNA deletions. Furthermore, MDS and multiple mtDNA deletion disorders are manifestations of the same pathogenic pathways affecting mtDNA replication and repair, indicating that MDS-associated genes should be studied when searching for genetic background of PEO disorders.     

中医院开展临床药学的实践与设想

本文从情报资料、科学的中药质量管理系统、治疗药物监测、发展方向与设想等五个方面,探讨了中医院的临床药学工作。拟在继承祖国医学的基础上,借鉴现代医学理论及实验方法,逐渐形成自己的体系,使之适应现代医学发展的需要。     

Mutant mitochondrial helicase Twinkle causes multiple mtDNA deletions and a late-onset mitochondrial disease in mice

Defects of mitochondrial DNA (mtDNA) maintenance have recently been associated with inherited neurodegenerative and muscle diseases and the aging process. Twinkle is a nuclear-encoded mtDNA helicase, dominant mutations of which cause adult-onset progressive external ophthalmoplegia (PEO) with multiple mtDNA deletions. We have generated transgenic mice expressing mouse Twinkle with PEO patient mutations. Multiple mtDNA deletions accumulate in the tissues of these mice, resulting in progressive respiratory dysfunction and chronic late-onset mitochondrial disease starting at 1 year of age. The muscles of the mice faithfully replicate all of the key histological, genetic, and biochemical features of PEO patients. Furthermore, the mice have progressive deficiency of cytochrome c oxidase in distinct neuronal populations. These "deletor" mice do not, however, show premature aging, indicating that subtle accumulation of mtDNA deletions and progressive respiratory chain dysfunction are not sufficient to accelerate aging. This model is a valuable tool for therapy development and testing for adult-onset mitochondrial disorders.