Yet Another Doctor Blog On The Internet

Posttraumatic headache in military personnel and veterans of the iraq and afghanistan conflicts.


To report and discuss a case of fatal cerebral hemorrhage following a switch from atorvastatin to simvastatin in a patient taking warfarin.

Statins inhibit proliferation of various human cancer cell lines in vitro. As human embryonic stem cells (hESCs) possess neoplastic-like properties we have evaluated the role of various statins on karyotypically normal hESCs (HES3 and BG01), abnormal hESCs (BG01V) and breast adenocarcinoma cells (MCF-7) to evaluate whether the mode of action of the statins was via a stemness pathway.

This was a 16-week, double-blind, double-dummy, randomized, multicenter study involving eight medical centers in six Asian countries or areas. After a 6-week, diet-controlled, placebo lead-in period, 157 patients with low-density lipoprotein cholesterol (LDL-C) of between 160 and 250 mg/dL and serum triglyceride (TG) of less than 400 mg/dL were randomized to receive 10 mg of either atorvastatin (n = 79) or simvastatin (n = 78). After 8 weeks of treatment, all patients had the dose of study medication increased to 20 mg, irrespective of LDL-C concentration. Data obtained by monitoring lipid profiles, adverse events, and laboratory tests during the 16 weeks of study were used to assess the efficacy and safety of both treatments.

The receptor tyrosine kinase, c-kit (Steel Factor (SF) receptor) controls survival, proliferation, chemotaxis, and secretion of proinflammatory cytokines in mast cells (MCs). Activation of c-kit results, amongst others, in induction of the PI3K and MEK/Erk pathways. Comparison of two MEK inhibitors, the specific, widely used U0126 and the more selective PD0325901, in different MC models revealed severe differences on SF-induced expression of proinflammatory cytokines IL-6 and TNF-α as well as the transcription factor Krüppel-like factor 2 (KLF2). Expression of the latter in MCs was not investigated so far. Whereas SF-induced expression of IL-6, TNF-α, and KLF2 was unaltered by U0126, it was significantly augmented by PD0325901. The effect of PD0325901 was corroborated by a second selective MEK inhibitor, PD184352 (Cl-1040), indicating the presence of MEK/Erk-based negative feedback mechanism(s) downstream of c-kit activation. Further analysis of KLF2 production revealed a positive function of PI3K. Depending on additional stimuli (e.g. antigen, IGF-1, LPS, thapsigargin), SF-triggered KLF2 expression was differentially modified, most likely controlled by the respective ratio between MEK/Erk and PI3K pathway activation. Moreover, the statin, simvastatin, was demonstrated to upregulate expression of KLF2 in MCs. In conclusion, data obtained by solely using the MEK inhibitor U0126 have to be carefully corroborated by using more selective inhibitors, such as PD0325901 or PD184352. SF-induced expression of the transcription factor KLF2 and its regulation by the MEK/Erk and PI3K pathways could impact on physiological as well as pathophysiological MC functions.

The present study suggested that simvastatin, in vivo, had no effect on apoM levels in the hyperlipidemic mouse model. ApoM serum levels in mice were significantly correlated to the animal's age, whereas in cell cultures simvastatin does inhibit apoM expression in the HepG2 cells. The mechanism behind it is not known yet.

Patients were included if they were taking simvastatin or atorvastatin with regular lipid management and follow-up laboratory results. Patients were required to remain on the same milligram-per-day dose at least 6-8 weeks before and after tablet-splitting initiation and have cholesterol values drawn at least 6 weeks after initiation of both whole-tablet and half-tablet dosing. Patients were excluded if they had a triglyceride level > 400 mg/dL or were noncompliant on the basis of pharmacy records and provider notes. MEASUREMENT OUTCOMES: The primary end points were changes in total cholesterol and LDL cholesterol values before and after the patient was switched to half-tablet therapy.

This trial extends the observation of the beneficial angiographic effects of lipid-lowering therapy to normocholesterolemic patients. The implications of the neutral angiographic effects of angiotensin-converting enzyme inhibition are uncertain, but they deserve further investigation in light of the positive clinical benefits suggested here and seen elsewhere.

In order to evaluate a hypothesized protective effect of the use of HMG Co-A reductase inhibitors (statins) on the development of Type 2 diabetes, we conducted a nested case-control study based on data from the UK-based General Practice Research Database (GPRD).

The goal of this study was to examine prospectively the effects of rosuvastatin, atorvastatin, simvastatin, and pravastatin across dose ranges on non-HDL-C, apo B, apo A-I, and total cholesterol (TC):HDL-C, low-density lipoprotein cholesterol (LDL-C):HDL-C, non-HDL-C:HDL-C, and apo B:apo A-I ratios in patients with hypercholesterolemia (LDL-C > or =160 mg/dL and <250 mg/dL and triglycerides <400 mg/dL) in the Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin (STELLAR) trial.