Adverse drug reaction to antiparkinson agents in Idiopathic Parkinson Disease: a prospective observational study in a Movement Disorder outpatient clinic

Background: Parkinson disease (PD) generally requires therapy for prolonged periods often with multiple drugs; drug-related adverse effects often add to the existing morbidity. Although, such ADRs are common, comprehensive information about their incidence, severity, and ultimate health effects are not available. The objective of the study was to analyze the pattern of occurrence of Adverse Drug Reactions (ADRs) in patients receiving anti-parkinson agents (APA) in a tertiary care hospital. We also aimed to assess the causality, severity and preventability of these ADRs.Methods: This prospective, observational study with 6 month follow up was conducted among consecutive PD patients receiving anti parkinson agents attending the Movement disorder clinic of Neurology department between April 1st 2011 and September 30th 2012. Tools used were ADR Reporting form of National Pharmacovigilance centre, WHO causality scale, Hartwig and Siegel scale to assess severity and Schumock and Thornton scale to assess preventability of ADRs. Descriptive statistics was used and the values were expressed in numbers and percentages.Results: ADRs were experienced in 87 patients (82.1%) out of 106 patients and most of these patients were on combination therapy (66%). No gender difference in distribution of ADRs was observed. The most common reactions were sedation, dizziness, dry mouth and fatigue. The drug usage was in the order of pramipexole (58.4%), levodopa+carbidopa (55.7%), trihexyphenidyl (28.3%), entacapone (5.7%) and amantadine (7.5%). Majority of the ADRs were mild level 1 (71.1%). ADR was maximum with entacapone. Majority of ADRs belonged to the causality possible ADR category. All the ADRs came under the definitely or probably preventable category.Conclusions: ADRs with antiparkinsonian drugs is common but mild and preventable

A large Indian family with rearrangement of chromosome 4p16 and 3p26.3 and divergent clinical presentations

BACKGROUND: The deletion of the chromosome 4p16.3 Wolf-Hirschhorn syndrome critical region (WHSCR-2) typically results in a characteristic facial appearance, varying intellectual disability, stereotypies and prenatal onset of growth retardation, while gains of the same chromosomal region result in a more variable degree of intellectual deficit and dysmorphism. Similarly the phenotype of individuals with terminal deletions of distal chromosome 3p (3p deletion syndrome) varies from mild to severe intellectual deficit, micro- and trigonocephaly, and a distinct facial appearance.METHODS AND RESULTS: We investigated a large Indian five-generation pedigree with ten affected family members in which chromosomal microarray and fluorescence in situ hybridization analyses disclosed a complex rearrangement involving chromosomal subregions 4p16.1 and 3p26.3 resulting in a 4p16.1 deletion and 3p26.3 microduplication in three individuals, and a 4p16.1 duplication and 3p26.3 microdeletion in seven individuals. A typical clinical presentation of WHS was observed in all three cases with 4p16.1 deletion and 3p26.3 microduplication. Individuals with a 4p16.1 duplication and 3p26.3 microdeletion demonstrated a range of clinical features including typical 3p microdeletion or 4p partial trisomy syndrome to more severe neurodevelopmental delay with distinct dysmorphic features.CONCLUSION: We present the largest pedigree with complex t(4p;3p) chromosomal rearrangements and diverse clinical outcomes including Wolf Hirschorn-, 3p deletion-, and 4p duplication syndrome amongst affected individuals.<br/

Electrophysiological study in neuromuscular junction disorders

This review is on ultrastructure and subcellular physiology at normal and abnormal neuromuscular junctions. The clinical and electrophysiological findings in myasthenia gravis, Lambert-Eaton myasthenic syndrome (LEMS), congenital myasthenic syndromes, and botulinum intoxication are discussed. Single fiber electromyography (SFEMG) helps to explain the basis of testing neuromuscular junction function by repetitive nerve stimulation (RNS). SFEMG requires skill and patience and its availability is limited to a few centers. For RNS supramaximal stimulation is essential and so is display of the whole waveform of each muscle response at maximum amplitude. The amplitudes of the negative phase of the first and fourth responses are measured from baseline to negative peak, and the percent change of the fourth response compared with the first represents the decrement or increment. A decrement greater than 10% is accepted as abnormal and smooth progression of response amplitude train and reproducibility form the crux. In suspected LEMS the effect of fast rates of stimulation should be determined after RNS response to slow rates of stimulation. Caution is required to avoid misinterpretation of potentiation and pseudofacilitation

Impact of BH3-mimetics on Human and Mouse Blood Leukocytes: A Comparative Study.

BH3-mimetics are small molecule inhibitors that neutralize the function of anti-apoptotic BCL-2 family members. BH3-mimetics have recently gained a lot of popularity in oncology because of their success in cancer treatment. However, BH3-mimetics might have a broader clinical application. Here, we established an ex vivo flow cytometric assay allowing the comparison of the impact of BH3-mimetics (ABT-199, ABT-263, WEHI-539, and S63845) on leukocyte populations of both, healthy human subjects and C57BL/6 J wild type mice. BH3-mimetics were added to freshly drawn blood that was diluted 1/2 in cell medium, and BH3-mimetics-mediated impact on leukocyte count was assessed by flow cytometry. Our results demonstrate that responses towards 1μM of BH3-mimetics can be identical as well as considerably different in leukocytes of humans and mice. For instance, the inhibition of BCL-2 by ABT-199 caused cell death in all types of lymphocytes in mice but was exclusively specific for B cells in humans. Moreover, inhibition of BCL-XL by WEHI-539 affected solely mouse leukocytes while targeting MCL-1 by S63845 resulted in efficient induction of cell death in human neutrophils but not in their mouse counterparts. Our ex vivo assay enables initial identification of analogies and differences between human and mouse leukocytes in response towards BH3-mimetics

Dementia clinic in general hospital settings

BACKGROUND: There is a need to develop specialised dementia care services in developing countries. MATERIALS AND METHODS: We used the existing infrastructure of a general hospital to start a weekly dementia clinic. RESULTS: We were able to support home-based care, even in patients with advanced disease. This new service gave us opportunity to train clinicians and researchers interested in dementia. CONCLUSION: It is feasible to start weekly dementia clinics using existing infrastructure in developing countries. Networking of such centres can generate a database capable of guiding service development

Changing facades of Vibrio cholerae: An enigma in the epidemiology of cholera

Cholera, caused by the Gram-negative bacterium Vibrio cholerae, has ravaged humanity from time immemorial. Although the disease can be treated using antibiotics along with administration of oral rehydration salts and controlled by good sanitation, cholera is known to have produced mayhems in ancient times when little was known about the pathogen. By the 21st century, ample information about the pathogen, its epidemiology, genetics, treatment and control strategies was revealed. However, there is still fear of cholera outbreaks in developing countries, especially in the wake of natural calamities. Studies have proved that the bacterium is mutating and evolving, out-competing all our efforts to treat the disease with previously used antibiotics and control with existing vaccines. In this review, the major scientific insights of cholera research are discussed. Considering the important role of biofilm formation in the V. cholerae life cycle, the vast availability of next-generation sequencing data of the pathogen and multi-omic approach, the review thrusts on the identification of suitable biofilm-inhibiting targets and the discovery of anti-biofilm drugs from nature to control the disease