Effect of non-dopaminergic drug treatment on Levodopa induced dyskinesias in MPTP monkeys: Common implication of striatal neuropeptides

Dopamine denervation in Parkinson's disease and repeated Levodopa (L-DOPA) administration that induces dyskinesias are associated with an enhancement of basal ganglia neuropeptide transmission. Various adjunct non-dopaminergic treatments to Levodopa were shown to reduce and/or prevent dyskinesias. The aim of this study was to seek if non-dopaminergic drug treatments to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioned monkeys combined with L-DOPA to prevent dyskinesia were associated with changes of striatal neuropeptides. Chronic treatment with Ro 61-8048 a kynurenine hydroxylase inhibitor, docosahexaenoic acid (DHA) a polyunsaturated fatty acid (omega-3), naltrexone an opioidergic antagonist and CI-1041 an N-methyl-d-aspartate (NMDA) glutamate receptor antagonist with L-DOPA prevented dyskinesias to various extents except naltrexone whereas all MPTP monkeys treated with L-DOPA alone developed dyskinesias. Striatal preproenkephalin (PPE), preprodynorphin (PPD) and preprotachykinin A (PPT-A) mRNA levels were measured by in situ hybridization. An increase of PPE and PPD mRNA levels was observed in anterior caudate nucleus of L-DOPA treated MPTP monkeys compared to controls and to Saline-treated MPTP monkeys whereas PPT-A mRNA levels were unchanged. Striatal PPE and PPD mRNA levels remained elevated in L-DOPA plus naltrexone-treated MPTP monkeys, while co-treatment with DHA, CI-1041 or Ro 61-8048 prevented their increase to various extents. Maximal dyskinesias scores of MPTP monkeys correlated significantly with striatal PPE and PPD mRNA levels but not with PPT-A mRNA levels. These results show that drugs displaying a wide range of pharmacological activities can modulate L-DOPA induced dyskinesias and this activity is correlated with striatal PPD and PPE mRNA levels suggesting a convergent mechanism.     

Hepatitis C virus infection rates and risk factors in an Australian hospital endoscopy cohort

Objective: To determine the reservoir and risk factors of HCV infection in a hospital population.
Methods: The presence of anti-HCV in 2,119 endoscopy patients was related to putative risk factors for exposure using the SAS statistical package.
Results: Most of the 4.7% of anti-HCV positive patients had multiple risk factors for HCV exposure. The risk was significantly increased in patients; with a previous history of hepatitis (36.4 fold), past history of injecting drugs (IDU) (32.1 fold), those born in North Africa, Middle East and Mediterranean countries (4.3 fold), had been tattooed before 1980s (3.3 fold), from 1980s-1990s (5.9 fold), had acupuncture before 1980s (3.8 fold), had a blood transfusion (3.6 fold), had clotting factors or growth hormone (4 fold), had contact with someone diagnosed with hepatitis in 1990s (4.1 fold). Of the anti-HCV patients 38 had a history of IDU, 43 were migrants and 10 were both.
Conclusion: Anti-HCV prevalence was five times higher than predicted by the passive surveillance scheme and 20% of patients were unaware of their infection. Only one of these patients reported IDU. The evidence of HCV intersecting epidemics between developing and developed countries in Australia was strongly supported.
Implications: The study provides a rational basis for targeted programs to identify asymptomatic HCV carriers who might benefit from the new antiviral treatment.     

Paraspinal extramedullary hematopoiesis in patients with thalassemia intermedia

Ineffective erythropoiesis in patients with thalassemia intermedia drives extramedullary hematopoietic tumor formation in several parts of the body. Paraspinal involvement has received increasing attention due to the associated morbidity secondary to spinal cord compression. Although the history and physical examination may help narrow the differential diagnosis, radiographic imaging remains essential to confirm the existence of hematopoietic tissue. Characteristic appearance has been observed mainly on magnetic resonance imaging. Several treatment options have been described, including transfusion therapy, laminectomy, radiotherapy, and the use of fetal hemoglobin inducing agents that decrease the hematopoietic drive. However, the ideal management scheme remains controversial. Until large prospective trials evaluate the efficacy and safety of the available treatment options, both in single and in combination therapy, an individualized approach should be entertained.     

Radiological features of acute gastric volvulus in adult patients

ObjectiveTo evaluate the radiological features of acute gastric volvulus in adults and correlate these features with operative findings.Materials and MethodsThe clinical, radiological and operative findings of five adult patients (four males and one female with mean age of 50.4 years) who presented or referred to King Abdullah University hospital over 4 year’s period with symptoms of acute gastric volvulus were reviewed retrospectively. All patients underwent upper gastrointestinal barium study and two of them had computed tomographic (CT) scans preoperatively. The radiological features demonstrated on upper gastrointestinal barium exams and CT scans were analyzed and compared with operative findings.ResultsRadiological and operative findings revealed organo-axial gastric volvulus in all patients in our study. All of them had associated diaphragmatic defect or hiatal hernia. The upper gastrointestinal barium studies demonstrated the classic radiological features of organo-axial volvulus. CT done on two of our patients confirmed the diagnosis.ConclusionUpper gastrointestinal barium study is an accurate way to diagnose and characterize acute gastric volvulus in adult patients. CT scan can also be used to diagnose this clinical entity.     

Utilizing wavelet transform and support vector machine for detection of the paradoxical splitting in the second heart sound

Paradoxical splitting occurs when pulmonic valve (P2) closes before the aortic valve (A2). This causes second heart sound (S2) to be a single sound during inspiration and split during exhalation. Etiology delay in aortic closure: aortic stenosis, volume overload of left ventricle (LV), conduction defects in LV, and left bundle branch block (LBBB). In this article, a method was proposed in early detection of a reverse in the appearance of A2 and P2 within S2. This method is based on the time–frequency maps obtained with the continuous wavelet transform (CWT), namely, the Meyer wavelet. A number of patients with LBBB and others with fitted pacemakers were studied. The above method is combined with the support vector machine (SVM) and performance of this method is evaluated using classification accuracy (Ca), sensitivity (Se), specificity, positive, and negative predicted values. Results show that it is relatively easy to detect the reverse in A2 and P2 and the Ca and Se is 90.97 and 94.44%, respectively, for the sample of 42 patients whose data were collected from the Cardiology Department at Brighton and Sussex University Hospital in England.