Cardiac Sarcoidosis – Arrhythmias, Inflammation and Anti-Inflammatory Drug Therapy.

Cardiac Sarcoidosis – Arrhythmias, Inflammation and Anti-inflammatory Drug Therapy.

Filed under: Drug and Alcohol Rehabilitation

Indian Pacing Electrophysiol J. 2012 Nov; 12(6): 234-6
Bhargava K

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EMA/CO for High-Risk Gestational Trophoblastic Neoplasia: Good Outcomes With Induction Low-Dose Etoposide-Cisplatin and Genetic Analysis.

Filed under: Drug and Alcohol Rehabilitation

J Clin Oncol. 2012 Dec 10;
Alifrangis C, Agarwal R, Short D, Fisher RA, Sebire NJ, Harvey R, Savage PM, Seckl MJ

PURPOSEPatients with high-risk (International Federation of Gynecology and Obstetrics score ? 7) gestational trophoblastic neoplasia (GTN) frequently receive etoposide, methotrexate, and dactinomycin alternating weekly with cyclophosphamide and vincristine (EMA/CO). Between 1979 and 1995, overall survival (OS) with this regimen at our institute was 85.4% with a significant proportion of early deaths (< 4 weeks). Here, we determine whether survival rates have improved in a more recent patient cohort (1995 to 2010). PATIENTS AND METHODSPatients receiving EMA/CO were identified using the Charing Cross GTN database. Genetic analysis identified nongestational trophoblastic tumors (nGTTs). The use of induction low-dose etoposide 100 mg/m(2) and cisplatin 20 mg/m(2) (EP; days 1 and 2 every 7 days) since 1995 to reduce early deaths before commencing EMA/CO was noted.ResultsFour hundred thirty-eight patients received EMA/CO between 1995 and 2010. Six patients had nGTTs, 140 had high-risk disease, and 250 had relapsed/resistant low-risk GTN. OS was 94.3% in high-risk patients (90.4% including nGTTs) and 99.6% in the low-risk group, with a median follow-up time of 4.2 years. All patients with nGTT and seven patients with high-risk GTNs died as a result of drug-resistant disease. EP induction chemotherapy was given to 23.1% of high-risk patients (33 of 140 patients) with a large disease burden, and the early death rate was only 0.7% (n = 1; 95% CI, 0.1% to 3.7%) compared with 7.2% (n = 11 of 151 patients; 95% CI, 4.1% to 12.6%) in the pre-1995 cohort. CONCLUSIONOS after EMA/CO for high-risk GTN has increased by nearly 9%. This reflects a more accurate estimate of OS by excluding nGTTs (3.9%) in patients with atypical presentations using genetic diagnosis. Low-dose induction EP in selected individuals also allows near complete elimination of early deaths. The latter should be considered routinely in high-risk GTN. HubMed – drug


Carbidopa/levodopa dose elevation and safety concerns in Parkinson’s patients: a cross-sectional and cohort design.

Filed under: Drug and Alcohol Rehabilitation

BMJ Open. 2012; 2(6):
Brodell DW, Stanford NT, Jacobson CE, Schmidt P, Okun MS

Sinemet, a combination drug containing carbidopa and levodopa is considered the gold standard therapy for the treatment of Parkinson’s disease (PD). When approved by the Food and Drug Administration (FDA) in 1988, a maximum daily dosage limit of 800 mg (eight tablets) of the 25/100 carbidopa/levodopa formulation was introduced. Overall, the FDA approval was a historic success; however, the pill limit has been hardcoded into many online medical record systems. This study investigates the 800 mg threshold by using a prospectively collected database of patient information.A retrospective cohort study: (Part I) cross-sectional, (Part II) longitudinal.PD patients at a Movement Disorders Center in a large academic, tertiary medical setting.An analysis was performed using carbidopa/levodopa at dosages below and above the 800 mg threshold. A secondary analysis was then performed using two consecutive clinic visits to determine the effects of crossing the 800 mg threshold. Comparisons were made on standardised scales.There was no significant difference in motor, mood and quality-of-life scores in patients consuming below and above the 800 mg carbidopa/levodopa threshold, though a mild worsening in dyskinesia duration was noted without worsening in dyskinesia pain and disability. In PD patients who crossed the 800 mg threshold between two consecutive clinic visits, a significant improvement in depressive symptoms and quality-of-life measures was demonstrated, and in these patients there was no worsening of motor fluctuations or dyskinesia.The data suggest that PD patients have the potential for enhanced clinical benefits when eclipsing the 800 mg carbidopa/levodopa threshold. Many patients will likely need to eclipse the 800 mg threshold and pharmacies and insurance companies should be aware of the requirements that may extend beyond approval limits.
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?III spectrin regulates the structural integrity and the secretory protein transport of the Golgi complex.

Filed under: Drug and Alcohol Rehabilitation

J Biol Chem. 2012 Dec 11;
Salcedo-Sicilia L, Granell S, Jovic M, Sicart A, Mato E, Johannes L, Balla T, Egea G

A spectrin-based cytoskeleton is associated with endomembranes including the Golgi complex and cytoplasmic vesicles but its role remains poorly understood. Using new generated antibodies to specific peptide sequences of the human ?III spectrin, we here show its distribution in the Golgi complex, where it is enriched in the trans-Golgi and trans-Golgi network (TGN). The use of a drug-inducible enzymatic assay that deplete the Golgi-associated pool of PI4P as well as the expression of PH domains of Golgi proteins that specifically recognize this phosphoinositide both displaced ?III spectrin from the Golgi. However, the interference with actin dynamics using actin toxins did not affect the localization of ?III spectrin to Golgi membranes. Depletion of ?III spectrin using siRNA technology and the microinjection of anti-?III spectrin antibodies into the cytoplasm lead to the fragmentation of the Golgi. At ultrastructural level, Golgi fragments showed swollen distal Golgi cisternae and vesicular structures. Using a variety of protein transport assays, we show that the ER-to-Golgi and post-Golgi protein transports were impaired in ?III spectrin-depleted cells. However, the internalization of the Shiga toxin subunit B to the ER was unaffected. We state that ?III spectrin constitutes a major skeletal component of distal Golgi compartments, where it is necessary to maintain its structural integrity and secretory activity, and unlike actin, PIP4 appears to be highly relevant for the association of ?III spectrin the Golgi complex.
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