Nonalcoholic fatty liver disease and mitochondrial dysfunction

Nonalcoholic fatty liver disease (NAFLD) includes hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. NAFLD is the most common liver disorder in the United States and worldwide. Due to the rapid rise of the metabolic syndrome, the prevalence of NAFLD has recently dramatically increased and will continue to increase. NAFLD has also the potential to progress to hepatocellular carcinoma (HCC) or liver failure. NAFLD is strongly linked to caloric overconsumption, physical inactivity, insulin resistance and genetic factors. Although significant progress in understanding the pathogenesis of NAFLD has been achieved in years, the primary metabolic abnormalities leading to lipid accumulation within hepatocytes has remained poorly understood. Mitochondria are critical metabolic organelles serving as "cellular power plants". Accumulating evidence indicate that hepatic mitochondrial dysfunction is crucial to the pathogenesis of NAFLD. This review is focused on the significant role of mitochondria in the development of NAFLD.

Pulmonary vein thrombosis in a patient with polycythemia vera

Pulmonary vein thrombosis(PVT) is a rarely encountered disease entity with varied clinical presentations. It is usually associated with lung carcinoma, lung surgeries and as a complication of the radiofrequency catheter ablation procedure for atrial fibrillation. Its clinical manifestations can vary from mild hemoptysis to lung infarction with hemodynamic compromise. A 76-year-old male presented with a 2-d history of pleuritic left sided chest pain. His past medical history included polycythemia vera, atrial fibrillation, coronary artery disease, pulmonary embolism and pulmonary hypertension. Chest radiograph was normal, troponins were normal and the 12-lead electrocardiogram did not show any ischemic changes. A computerized tomography pulmonary angiogram revealed a filling defect in the left lower lobe pulmonary vein. He was treated with subcutaneous enoxaparin and his symptoms improved. This case highlights a rare etiology of chest pain and the first reported case of the association of polycythemia vera and pulmonary vein thrombosis. A high index of suspicion is required for appropriate diagnostic work up. PVT can mimic pulmonary embolism. The diagnostic work up and treatment strategies depend on acuity of presentation.

Effects of oral premedication on cognitive status of elderly patients undergoing cardiac catheterization

Background Sedatives and analgesics are often administered to achieve conscious sedation for diagnostic and therapeutic procedures. Appropriate concerns have been raised regarding post procedure delirium related to peri-procedural medication in the elderly. The objective of this study was to investigate the effect of premedication on new onset delirium and procedural care in elderly patients. Methods Patients 〉 70 years old and scheduled for elective cardiac catheterization were randomly assigned to receive either oral diphenhydramine and diaze- pam （25 rag/5 mg） or no premedication. All patients underwent a mini mental state exam and delirium assessment using confusion assess- ment method prior to the procedure and repeated at 4 h after the procedure and prior to discharge. Patients＇ cooperation during the procedure and ease of post-procedure were measured using Visual Analog Scale （VAS）. The degree of alertness was assessed immediately on arrival to the floor, and twice hourly afterwards using Observer＇s Assessment of Alermess/Sedation Scale （OAA/S）. Results A total of 93 patients were enrolled. The mean age was 77 years, and 47 patients received premedication prior to the procedure. None of the patients in either group developed delirium. Patients＇ cooperation and the ease of procedure was greater and pain medication requirement less both during and after the procedure in the pre-medicated group （P 〈 0.05 for both）. Nurses reported an improvement with patient management in the pre-medicated group （P = 0.08）. Conclusions In conclusion, prcmedication did not cause delirium in elderly patients undergoing cardiac catheterization. The reduced pain medication requirement, perceived procedural ease and post procedure management favors premedication in elderly patients undergoing cardiac catheterization.

Atrophy and Fibrosis of Extra-Ocular Muscles in Anti-Acetylcholine Receptor Antibody Myasthenia Gravis

Myasthenia gravis (MG) is an autoimmune disorder involving the neuromuscular junction that frequently affects the extra-ocular muscles (EOMs). It has been described as a very rare cause of bilateral EOM atrophy, but histological analysis of such cases is lacking. A 66-year-old man presented with two months of right eyelid drooping and vertical diplopia. Examination showed bilateral ophthalmoparesis and complete right ptosis. The remainder of his exam was normal, and an MRI showed small EOMs. Acetylcholine receptor antibodies were elevated, establishing the diagnosis of MG. Oral corticosteroids and pyridostigmine followed by azathioprine improved his ptosis, but not his ophthalmoparesis. One year later he had surgical correction of his diplopia, and the resected superior rectus muscle showed complete replacement of EOM by connective tissue. MG can rarely cause bilateral EOM atrophy, which is characterized histologically by fibrosis in the muscle itself. Atrophy in the EOMs of a myasthenic patient may indicate a poor response to medical management alone.

C-reactive protein and erythrocyte sedimentation rate: Continuing role for erythrocyte sedimentation rate

Background: Erythrocyte Sedimentation Rate (ESR) and C-reactive protein (CRP) tests are often done to detect or monitor patients with suspected inflammatory disorders. The objective of the study was to ascertain if the manual ESR test added value to the information available from automated CRP results alone. Methods: In this retrospective, observational study at a safety-net hospital, the ESR and CRP values were compared in 4527 instances when both tests were done. In 150 instances, involving 97 patients;when ESR was >60 mm/hr and CRP was ≤1.0 mg/dL, the medical records were reviewed to discern the cause of disparity between the ESR and CRP results and to assess the utility of continued use of the ESR test. Results: Review of medical records did not reveal an explanation for elevated ESR in 20 patients with normal CRP results. In the remaining 77 (79%) patients, an inflammatory disorder was noted despite a normal CRP value;in 27 (28%) patients, the disorder was osteomyelitis. Presence of skin necrosis was also a prominent factor in the discrepant results. Conclusions: ESR has value in detecting inflammatory disorders that may not be obvious by clinical examination or CRP results. ESR has a particularly useful role in patients with suspected bone lesions and osteomyelitis.

Nicotinamide Phosphoribosyl Transferase and Cancer: A Molecular Nutrition Link

Nicotinamide phosphoribosyl transferase (NAMPT, EC 2.4.2.12), a pleiotropic protein, is a key enzyme for cellular NAD synthesis and may function as a growth factor or cytokine. Dysregulation of NAMPT gene expression has been implicated in several human diseases. In recent years, an increasing attention has been drawn to NAMPT’s role in the pathogenesis of cancer and its value as a therapeutic target in cancer therapy. A molecular nutrition link between NAMPT and cancer looms large among the scientific findings. This review article will be centered on this theme. We will summarize the genomic discoveries of NAMPT in cancer and the current understanding of molecular mechanisms underlying NAMPT in the pathogenesis of cancer, especially on a molecular nutrition link. We will also synopsize several small molecule inhibitors of NAMPT and their potential therapeutic utilities in cancer and usher in some terra incognita of future researches on NAMPT in cancer.