Pancreatic cancers require autophagy for tumor growth

Macroautophagy (autophagy) is a regulated catabolic pathway to degrade cellular organelles and macromolecules. The role of autophagy in cancer is complex and may differ depending on tumor type or context. Here we show that pancreatic cancers have a distinct dependence on autophagy. Pancreatic cancer primary tumors and cell lines show elevated autophagy under basal conditions. Genetic or pharmacologic inhibition of autophagy leads to increased reactive oxygen species, elevated DNA damage, and a metabolic defect leading to decreased mitochondrial oxidative phosphorylation. Together, these ultimately result in significant growth suppression of pancreatic cancer cells in vitro. Most importantly, inhibition of autophagy by genetic means or chloroquine treatment leads to robust tumor regression and prolonged survival in pancreatic cancer xenografts and genetic mouse models. These results suggest that, unlike in other cancers where autophagy inhibition may synergize with chemotherapy or targeted agents by preventing the up-regulation of autophagy as a reactive survival mechanism, autophagy is actually required for tumorigenic growth of pancreatic cancers de novo, and drugs that inactivate this process may have a unique clinical utility in treating pancreatic cancers and other malignancies with a similar dependence on autophagy. As chloroquine and its derivatives are potent inhibitors of autophagy and have been used safely in human patients for decades for a variety of purposes, these results are immediately translatable to the treatment of pancreatic cancer patients, and provide a much needed, novel vantage point of attack.     

Solitary angiokeratoma of the tongue treated with diode laser

Angiokeratoma is a muco-cutaneous disorder that is usually associated with a number of metabolic disorders. Involvement of the tongue with solitary angiokeratoma, without a systemic or metabolic disease, is very rare. To the best of our knowledge, we report the second case of solitary angiokeratoma of the tongue arising in a 16-year-old woman who was treated with diode laser (810 nm) in our department. This case was partially presented as poster presentation at the 12th Congress of the BaSS, 12–14 April 2007, Istanbul, under the auspices of the Balkan Stomatological Society. An erratum to this article can be found at     

Deep brain stimulation in movement disorders

Deep brain stimulation (DBS) is used for advanced and medically intractable patients with Parkinson's disease (PD), essential tremor (ET), and dystonia who meet strict criteria after a detailed motor, cognitive, and psychiatric evaluation. The potential targets are the ventral intermediate nucleus (VIM) of the thalamus for tremor, the globus pallidus interna (GPI) and the subthalamic nucleus (STN) for PD, and GPI for dystonia. The optimal target for PD has not been determined yet, although STN DBS has been performed more frequently in recent years. The mechanism of DBS effect is believed to be associated with disruption of pathological network activity in the cortico-basal ganglia-thalamic circuits by affecting the firing rates and bursting patterns of neurons and synchronized oscillatory activity of neuronal networks. Good candidates should be free of dementia, major psychiatric disorders, structural brain lesions, and important general medical problems. Although the risk for complications with DBS is less than with lesioning techniques, there is still a small risk for major complications associated with surgery. Bilateral procedures are more likely to cause problems with speech, cognition, and gait.     

P wave dispersion in patients with rheumatoid arthritis: its relation with clinical and echocardiographic parameters

P wave dispersion (PWD) is a sign for the prediction of atrial fibrillation (AF). The aim of this study was to assess P wave dispersion and its relation with clinical and echocardiographic parameters in patients with rheumatoid arthritis (RA). Thirty RA patients (mean age 49 ± 10 years) and 27 healthy controls (mean age 47 ± 8 years) were included in the study. We performed electrocardiography and Doppler echocardiography on patients and controls. Maximum and minimum P wave duration were obtained from electrocardiographic measurements. PWD defined as the difference between maximum and minimum P wave duration was also calculated. Maximum P wave duration and PWD was higher in RA patients than controls (P = 0.031 and P = 0.001, respectively). However, there was no significant difference in minimum P wave duration between the two groups (P = 0.152). There was significant correlation between PWD and disease duration (r = 0.375, P = 0.009) and isovolumetric relaxation time (r = 0.390, P = 0.006). P wave duration and PWD was found to be higher in RA patients than healthy control subjects. PWD is closely associated with disease duration and left ventricular (LV) diastolic dysfunction.     

A rare cause of sudden vision loss in a young male: papillary fibroelastoma of the aortic valve

Cardiac papillary fibroelastoma (CPF) is a rare cardiac neoplasm predominantly affecting the cardiac valves. Although it is most commonly an incidental finding, it can result in life-threatening complications, such as coronary and cerebral embolism, acute valvular dysfunction, and sudden death. In this report, we describe a case of a patient with aortic valve papillary fibroelastoma, which presented with sudden vision loss due to branch retinal artery occlusion. To the best of our knowledge, this is the third case of CPF-related retinal artery embolism in English literature.     

Is there any relation between insulin resistance and cognitive function in the elderly?

BACKGROUND: Vascular risk factors are blamed as being involved in the pathogenesis of cognitive dysfunction in the elderly. Alzheimer's disease or vascular-type dementia could be part of a metabolic syndrome. The aim of this study was to evaluate whether there is any relation between insulin resistance and cognitive status of the elderly regarding normal, mild cognitive impairment (MCI), Alzheimer's disease (AD), vascular dementia (VaD) and mixed dementia.METHODS: 267 elderly patients admitted to an outpatient geriatrics clinic were evaluated medically and cognitively in this study. The patients were diagnosed using ARDRA and DSM-IV criteria for AD; NINDS-AIREN and DSM-IV criteria for VaD; and Petersen criteria for MCI. Insulin resistance was calculated using both the homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) formulas.RESULTS: The mean values of HOMA and QUICKI scores were 2.79 (SD+/-3.56) and 0.346 (SD+/-0.036) for the normal group, 2.81 (SD+/-3.06) and 0.354 (SD+/-0.047) for AD group, 2.20 (SD+/-1.82) and 0.360 (SD+/-0.048) for VaD group, 2.87 (SD+/-1.81) and 0.339 (SD+/-0.038) for mixed dementia group, 2.79 (SD+/-2.81) and 0,349 (SD+/-0.042) for MCI group, respectively. There were no statistically significant differences between HOMA and QUICKI scores of all the groups.CONCLUSION: This is the first study of the possible relation between insulin resistance and cognitive function in people categorized according to five forms of cognitive status. Unfortunately the results do not allow generalizations. Further prospective cohort studies that follow a normal cognitive group and MCI patients with and without insulin resistance are necessary.     

Alcohol Ablation Therapy of an Atypically Located Symptomatic Bronchogenic Cyst: A Case Report

Bronchogenic cyst is a rare developmental lesion. It is usually asymptomatic and most frequently located in the middle mediastinum and lung parenchyma. It can cause symptoms only when infected or pressing on neighboring structures. The MRI findings in a 34-year-old woman with an 8 months history of back pain were evaluated and revealed a cystic lesion in the left paravertebral area. The histopathologic evaluation of the material aspirated with CT guidance was reported to be bronchogenic cyst. A simultaneous alcohol ablation was accomplished. After the procedure the patient’s pain disappeared and the follow-up MRI scan 1 year later revealed no relapse. Paravertebrally located bronchogenic cysts are very rare and only 3 cases were found to be reported in the medical literature prior to this one. While aspiration alone is sufficient for diagnosis, it is insufficient to treat the lesion and prevent the recurrences. This paper reports a paravertebral bronchogenic cyst which was symptomatic despite of its small size. CT-guided aspiration was accomplished and simultaneous alcohol ablation was carried out to prevent recurrences.     

Osteoblast adhesion on novel machinable calcium phosphate/lanthanum phosphate composites for orthopedic applications

Lanthanum phosphate (LaPO(4), LP) was combined with either hydroxyapatite (HA) or tricalcium phosphate (TCP) to form novel composites for orthopedic applications. In this study, these composites were prepared by wet chemistry synthesis and subsequent powder mixing. These HA/LP and TCP/LP composites were characterized in terms of phase stability and microstructure evolution during sintering using X-ray diffraction (XRD) and scanning electron microscopy (SEM). Their machinability was evaluated using a direct drilling test. For HA/LP composites, LP reacted with HA during sintering and formed a new phase, Ca(8)La(2)(PO(4))(6)O(2), as a reaction by-product. However, TCP/LP composites showed phase stability and the formation of a weak interface between TCP and LP machinability when sintered at 1100 degrees C, which is crucial for achieving desirable properties. Thus, these novel TCP/LP composites fulfilled the requirements for machinability, a key consideration for manufacturing orthopedic implants. Moreover, the biocompatibility of these novel LP composites was studied, for the first time, in this paper. In vitro cell culture tests demonstrated that the LP and its composites supported osteoblast (bone-forming cell) adhesion similar to natural bioceramics (such as HA and TCP). In conclusion, these novel LP composites should be further studied and developed for more effectively treating bone related diseases or injuries.