Inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD) is a progressive, fatal genetic disorder with variable penetrance, predominantly affecting three main tissue types: muscle (IBM), bone (PDB), and brain (FTD). IBMPFD is caused by mutations in the ubiquitously expressed valosin-containing protein (VCP) gene, a member of the AAA-ATPase superfamily. The majority of individuals who develop IBM have progressive proximal muscle weakness. Muscle biopsies reveal rimmed vacuoles and inclusions that are ubiquitin- and TAR DNA binding protein-43 (TDP-43)-positive using immunohistochemistry. PDB, seen in half the individuals, is caused by overactive osteoclasts and is associated clinically with pain, elevated serum alkaline phosphatase, and X-ray findings of coarse trabeculation and sclerotic lesions. FTD diagnosed at a mean age of 55 years in a third of individuals is characterized clinically by comprehension deficits, dysnomia, dyscalculia, and social unawareness. Ubiquitin- and TDP-43-positive neuronal inclusions are also found in the brain. Genotype-phenotype correlations are difficult with marked intra-familial and inter-familial variations being seen. Varied phenotypes within families include frontotemporal dementia, amyotrophic lateral sclerosis, Parkinsonism, myotonia, cataracts, and anal incompetence, among others. Cellular and animal models indicate pathogenetic disturbances in IBMPFD tissues including altered protein degradation, autophagy pathway alterations, apoptosis, and mitochondrial dysfunction. Currently, mouse and drosophila models carrying VCP mutations provide insights into the human IBMPFD pathology and are useful as tools for preclinical studies and testing of therapeutic strategies. In this review, we will explore the pathogenesis and clinical phenotype of IBMPFD caused by VCP mutations.
The objective of this study was to investigate the incidence of oesophageal adenocarcinoma and its contribution to mortality in patients with Barrett's oesophagus, and to identify a subgroup of patients who may benefit from endoscopic surveillance. This was a retrospective study of a cohort of 70 patients diagnosed in the endoscopy unit of a Scottish teaching hospital as having Barrett's oesophagus between 1976 and 1986. Information was obtained from case notes, endoscopy records, histology reports and death certificates. Patients were included if they had: (a) columnar-lined oesophagus of at least 3 cm; (b) histological confirmation; and (c) absence of cancer when endoscopically diagnosed as having Barrett's oesophagus. The main outcome for the patients was development of adenocarcinoma or death. Information was available for 59 of 70 patients (84%). Forty-four patients were confirmed to have Barrett's oesophagus and were followed up for 418 patient-years. Only two patients developed oesophageal adenocarcinoma, resulting in an incidence of one case in 209 patient-years, a 55-fold risk compared with age- and sex-matched population in Scotland. Both these patients had intestinal metaplasia and Barrett's ulcer. The majority (90%) of patients died as a result of causes unrelated to adenocarcinoma of oesophagus. In patients under 70 years with intestinal metaplasia, 189 annual endoscopies would have been required to detect one cancer. Adenocarcinoma is an uncommon cause of mortality in patients with Barrett's oesophagus. Endoscopic surveillance is unlikely to alter overall mortality in patients with Barrett's oesophagus. However, by limiting endoscopic surveillance to patients under 70 years with intestinal metaplasia, the estimated cost per cancer detected can be reduced to ł23000.
Tumor-induced hypoglycemia (TIH) associated with hepatocellular carcinoma (HCC) results from tumor production of insulin-like growth factor 2 (IGF-2), resulting in recurrent hypoglycemia. Serum levels of insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2), or pro-insulin-like growth factor 2 (pro-IGF-2) are required for the diagnosis. However, due to the limited availability of testing in many laboratories, this condition is often overlooked. As this condition is often overlooked, prompt recognition and implementation of tumor directed therapies and/or systemic therapies can help mitigate the consequences of hypoglycemia. We present a 38-year-old man with advanced multifocal HCC who presented with abdominal pain and was found to have recurrent symptomatic hypoglycemia. Evaluation revealed elevated levels of IGF-2, suggesting a diagnosis of HCC with production of IGF-2.
Objective-To assess whether patients with deep vein thrombosis (DVT) could be satisfactorily treated on an outpatient basis with low molecular weight (LMW) heparin and warfarin. Design-A 22 month prospective study of adults attending St Peter's Hospital accident and emergency department with DVT. Results-1093 patients were referred and assessed; 160 were venogram positive, of which 159 patients between the ages of 22 and 89 years of age have now been treated with LMW heparin as outpatients. Direct liaison with community nurses has minimised the impact on general practitioner workload. Conclusions-1272 bed days were saved during this period (an estimated £320 000). The outpatient treatment of thromboembolism has been shown to be effective and safe. (7Accid Emerg Med 1998;15:292-293)
Summary A case of tuberculosis of the colon is described. Attention is drawn to the similarity between this and other inflammatory diseases of the bowel. Colonic tuberculosis is now a rarity even where mycobacterial infection is endemic, and may mimic other inflammatory diseases of the bowel with important consequences for treatment and prognosis. Such a case is now described.
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