Chromogranin A assay in clinical practice

Chromogranins belong to the family of secretory chromogranin and secretogranin proteins. They are found in secretory vesicles throughout the neuroendocrine system. Chromogranin A (CgA) is the main component. CgA acts as a prohormone submitted to processes of degradation through which active peptides are generated. CgA has auto, para and endocrine functions. It is widely used as an immunohistochemical marker. Despite the lack of international standardization, and the lack of an accurate definition of the diagnostic cut-off levels, some CgA assays are reliable. Numerous studies have suggested that CgA determination may be of interest for the diagnosis and the follow-up of various endocrine tumors. Plasma levels of this general marker are proportional to tumor mass. The localization of the primitive tumor, the presence of associated hormonal secretions and possible renal failure and/or hypergastrinemia must be taken into consideration for proper interpretation of CgA levels. New clinical indications are emerging for the evaluation of stress in intensive care units and the assessment of cardiovascular risk. New assays estimating the concentration of active peptides are under development.     

Biology of endoplasmic reticulum stress in the heart

The endoplasmic reticulum (ER) is a multifunctional intracellular organelle supporting many processes required by virtually every mammalian cell, including cardiomyocytes. It performs diverse functions, including protein synthesis, translocation across the membrane, integration into the membrane, folding, posttranslational modification including N-linked glycosylation, and synthesis of phospholipids and steroids on the cytoplasmic side of the ER membrane, and regulation of Ca(2+) homeostasis. Perturbation of ER-associated functions results in ER stress via the activation of complex cytoplasmic and nuclear signaling pathways, collectively termed the unfolded protein response (UPR) (also known as misfolded protein response), leading to upregulation of expression of ER resident chaperones, inhibition of protein synthesis and activation of protein degradation. The UPR has been associated with numerous human pathologies, and it may play an important role in the pathophysiology of the heart. ER stress responses, ER Ca(2+) buffering, and protein and lipid turnover impact many cardiac functions, including energy metabolism, cardiogenesis, ischemic/reperfusion, cardiomyopathies, and heart failure. ER proteins and ER stress-associated pathways may play a role in the development of novel UPR-targeted therapies for cardiovascular diseases.     

A canine Arylsulfatase G (ARSG) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis

Neuronal ceroid lipofuscinoses (NCLs) represent the most common group of inherited progressive encephalopathies in children. They are characterized by progressive loss of vision, mental and motor deterioration, epileptic seizures, and premature death. Rare adult forms of NCL with late onset are known as Kufs’ disease. Loci underlying these adult forms remain unknown due to the small number of patients and genetic heterogeneity. Here we confirm that a late-onset form of NCL recessively segregates in US and French pedigrees of American Staffordshire Terrier (AST) dogs. Through combined association, linkage, and haplotype analyses, we mapped the disease locus to a single region of canine chromosome 9. We eventually identified a worldwide breed-specific variant in exon 2 of the Arylsulfatase G (ARSG) gene, which causes a p.R99H substitution in the vicinity of the catalytic domain of the enzyme. In transfected cells or leukocytes from affected dogs, the missense change leads to a 75% decrease in sulfatase activity, providing a functional confirmation that the variant might be the NCL-causing mutation. Our results uncover a protein involved in neuronal homeostasis, identify a family of candidate genes to be screened in patients with Kufs'' disease, and suggest that a deficiency in sulfatase is part of the NCL pathogenesis.     

DNA polymerase θ up-regulation is associated with poor survival in breast cancer,perturbs DNA replication,and promotes genetic instability

“Replicative stress” is one of the main factors underlying neoplasia from its early stages. Genes involved in DNA synthesis may therefore represent an underexplored source of potential prognostic markers for cancer. To this aim, we generated gene expression profiles from two independent cohorts (France, n = 206; United Kingdom, n = 117) of patients with previously untreated primary breast cancers. We report here that among the 13 human nuclear DNA polymerase genes, DNA Polymerase θ (POLQ) is the only one significantly up-regulated in breast cancer compared with normal breast tissues. Importantly, POLQ up-regulation significantly correlates with poor clinical outcome (4.3-fold increased risk of death in patients with high POLQ expression), and this correlation is independent of Cyclin E expression or the number of positive nodes, which are currently considered as markers for poor outcome. POLQ expression provides thus an additional indicator for the survival outcome of patients with high Cyclin E tumor expression or high number of positive lymph nodes. Furthermore, to decipher the molecular consequences of POLQ up-regulation in breast cancer, we generated human MRC5-SV cell lines that stably overexpress POLQ. Strong POLQ expression was directly associated with defective DNA replication fork progression and chromosomal damage. Therefore, POLQ overexpression may be a promising genetic instability and prognostic marker for breast cancer.     

Local governments’ dependence on tobacco tax revenue: a?deterrent to tobacco control in the Republic of Korea

Objective

To investigate, in the Republic of Korea, whether local governments’ participation in an anti-smoking programme supported by the National Health Promotion Fund in 2002–2003 was related to the percentage of local tax revenue comprised by the tobacco consumption tax (TCT).

Methods

Using financial and administrative data on 163 municipalities, the authors estimated logit models of local governments’ participation in the anti-smoking programme as a function of the proportion of local tax revenue that came from the TCT and a set of control variables, namely local socioeconomic characteristics and the size of the staff in the local public health centre (PHC).

Findings

Local governments that derived a greater percentage of their local tax revenue from the TCT, particularly those that ranked in the upper fourth in terms of this percentage, were less likely to participate in the anti-smoking programme. Insufficient staff in the PHC was also found to be associated with lower participation in the anti-smoking programme.

Conclusion

Local governments’ dependence on revenue from the TCT may be a deterrent to tobacco control in the Republic of Korea.     

Laparoscopic surgery for submucosal tumors located at the esophagogastric junction and the prepylorus

Background  Laparoscopic partial gastric resection is widely accepted as a treatment for gastric submucosal tumors (SMTs). However, SMTs of either end of the stomach are generally managed by subtotal gastrectomies or total gastrectomies. This study was conducted to evaluate surgical techniques for management of SMTs located at the ends of the stomach. Methods  Among 63 patients who were diagnosed and underwent laparoscopic surgery for gastric SMTs at Seoul National University Bundang Hospital from May 2003 to May 2007, 11 SMTs located at the ends of the stomach were identified. The clinicopathologic results of these 11 SMTs were analyzed. Results  Laparoscopic partial wedge resections or tumor excisions were successfully performed on all patients except for those who had prepyloric tumors. Six men and five women had SMTs at the ends of the stomach. The patients ranged in age from 21–63 years (mean 43.4 ± 13.5 years). Of six esophagogastric junctional tumors that showed low, homogeneous contrast enhancement on computed tomography (CT) scans, five were treated by laparoscopic transgastric enucleation and one by tumor-everting resection. One esophagogastric junctional tumor that leaned toward the fundus and showed a 6-cm-diameter endophytic mass with heterogeneous enhancement on CT scan was resected by laparoscopic wedge resection. The mean operation time was 100 min (range 60–210 min). Three laparoscopy-assisted distal gastrectomies and one laparoscopic wedge resection were performed on SMTs located near the prepyloric antrum. There were no intra- or postoperative complications. Duration of postoperative hospital stay ranged from 4–7 days. Conclusion  Laparoscopic local resection is an effective treatment for SMTs located at the esophagogastric junction and can be used instead of a total or proximal gastrectomy. However, gastrectomies should be considered for SMTs located near the pylorus because of the small volume of the lower third of the stomach.     

Escherichia coli extensive cellulitis after laparoscopic radical prostatectomy

A 59-year-old patient underwent laparoscopic radical prostatectomy (LRP) in our department. After surgery, he had an extensive cellulitis of the right flank develop. Urine, drainage effluent, and blood cultures were all positive for Escherichia coli. Prolonged broad spectrum antibiotherapy allowed progressive resolution of the cellulitis. This case shows that severe cellulitis can occur after LRP. Urinary tract infection and vesicourethral anastomotic leakage may contribute to this complication.     

Insufficiency fractures of both femoral necks in a young adult caused by osteoporosis: a case report

Insufficiency fractures of femoral necks due to osteoporosis of unknown aetiology occurring coincidentally on both sides in young adults, have not been described in English literature so far. A 18-year-old young girl presented with a 3-month history of gradual onset of bilateral thigh pain and progressive inability to walk. At the first look, plain radiographs of both hips showed no gross abnormal findings other than some tips on reduced bone mineral density of the femoral necks. MRI was ordered upon a high suspicion of fracture and T1-weighed MRI showed a linear low signal on both femoral necks. Dual-energy X-ray absorptiometry of the lumbar spine and femoral neck showed low mineral density. She was treated surgically with in-situ internal fixation using cannulated screws. The bilateral thigh pain was resolved and walking started immediately after the treatment. Insufficiency fracture of the femoral neck due to osteoporosis should be kept in mind even in young adults complaining of atypical pain without evidence of unusual activities. We used both the terms of stress fracture and insufficiency (osteoporotic) fracture interchangeably as the mechanism of fractures resemble each other.     

Removal of a bent inflatable femoral nail: a case report

Intramedullary nailing is the gold standard for the treatment of diaphyseal femoral fractures. Bending of the nail secondary to trauma is a rare complication encountered in unhealed and comminuted fractures. A 23-year-old man was admitted with refracture of the right femoral shaft and a 32-degree bending of an inflatable intramedullary nail due to a fall, two months after the initial surgical treatment. The nail was first straightened by exerting an external force, which decreased the angulation to 10 degrees. Then, the fracture site was opened, the lateral wall of the nail was drilled, and one of the four metal bars of the nail was cut. This allowed complete straightening of the nail by the same maneuver and its removal. A new inflatable intramedullary nail was placed and union was achieved after four months. Tools that may be necessary to cut the nail partially or totally should be made available for removal of bent nails.