Pharmacology of the AC AT Inhibitor Avasimibe (CI‐1011)

Avasimibe is a novel orally bioavailable ACAT inhibitor, currently under clinical development (phase III trials). It was safe when administered to rats, dogs, and humans. In vitro studies in human macrophages demonstrated that avasimibe reduces foam cell formation not only by enhancing free cholesterol efflux, but also by inhibiting the uptake of modified LDL. The concentration‐dependent reduction in cellular cholesteryl ester content in these cells was not accompanied by an increase in intracellular free cholesterol, which is in agreement with a good safety profile for avasimibe. In the liver, avasimibe caused a significant reduction in the secretion of apo B and apo B‐containing lipoproteins into plasma. Avasimibe induced cholesterol 7α‐hydroxylase and increased bile acid synthesis in cultured rat hepatocytes, and its administration to rats did not produce an increase in lithogenicity index of the bile. The hypolipidemic efficacy of the compound was demonstrated in cholesterol‐fed as well as in non‐cholesterol‐fed animals. In these models, plasma cholesterol levels were reduced, mainly due to the decrease in the non‐HDL cholesterol fraction. Clinical data are scarce, but in a study performed in 130 men and women with combined hyperlipidemia and hypoalphalipoproteinemia, avasimibe, 50–500 mg/day, significantly reduced plasma total triglyceride and VLDL‐cholesterol. Although total cholesterol, LDL‐cholesterol, and HDL‐cholesterol were unchanged, it must be stressed that animal data suggest that avasimibe may have direct antiatherosclerotic activity in addition to its cholesterol‐lowering effect. Avasimibe treatment can also contribute to increase plaque stability, as it reduces the accumulation of lipids in the arterial wall, inhibits macrophage infiltration into the media and reduces matrix metalloproteinase expression and activity. Moreover, avasimibe and statins have been shown to have synergistic effects, and the combination therapy may not only inhibit atherosclerotic lesion progression but also induce lesion regression, independently of changes in plasma cholesterol.     

The unusual association of three autoimmune diseases in a patient with Noonan syndrome.

We report on a 26-year-old female affected by Noonan syndrome (NS), a congenital disorder characterized by various phenotypic features and congenital anomalies) associated with a variety of autoimmune diseases, including systemic lupus erythematosus, celiac disease, and Hashimoto thyroiditis. Autoimmunity is seldom described in NS and the association between this congenital disease and three autoimmune disorders has not been previously reported. Should the occurrence of autoimmune disorders in NS be confirmed, a relevant clinical and laboratory evaluation of NS patients should be performed in order to clarify whether the immune system involvement represents only an occasional event or is a feature of the disease.     

ACTH in the plasma and cerebrospinal fluid in patients with multiple sclerosis

In 1984 and at the beginning of 1985 the authors carried out radioimmunoassays (SORIN-CIS kit) the plasma levels of ACTH in 116 multiple sclerosis patients (m-52, f-64) and in 10 cases this radioimmunoassay was done in the cerebrospinal fluid (m-5, f-5). The control group comprised 90 patients with ischialgia and neuroses. The normal value in the plasma was from 0 to 80.86 pg/ml, and in the fluid it was from 0 to 77.08 pg/ml. In multiple sclerosis patients the plasma ACTH level was from 0 to 286.9 pg/ml, in the cerebrospinal fluid from 0 to 89 pg/ml. The values of ACTH were significantly higher in multiple sclerosis patients, mainly in males. In the fluid the level of ACTH was significantly higher in the studied patients. No significant differences in ACTH levels were found between males and females with multiple sclerosis, and in the control group this level was higher in females. Raised ACTH level was found mainly in multiple sclerosis with lung duration of the disease (10 years) at the time of exacerbations. The authors continue studies on the axis hypothalamus-hypophysis-adrenals, on various hormones, prostaglandins, beta-endorphin, biochemical markers, cAMP, cCMP, arylosulphatase A and B MBC etc.     

Gaining insight into the Clinical Practice Guideline development processes: qualitative study in a workshop to implement the GRADE proposal in Spain

Background  

The GRADE method represents a new approach to grading the quality of evidence and strength of recommendations in the preparation of Clinical Practice Guidelines (CPG). In the context of a pilot study to assess the implementability of the system in Spain, we considered it relevant to gain an insight into the significance of the perceptions and attitudes expressed by the actual experts participating in the system try-out.     

Gestación heterotópica espontánea

Heterotopic pregnancy is the combination of intrauterine and ectopic pregnancy. This potentially fatal condition rarely occurs in spontaneous conception cycles and consequently its diagnosis requires a high index of suspicion. We report a case of heterotopic pregnancy in a 30-year old primipara with no known risk factors who presented with acute abdominal pain due to a spontaneous heterotopic pregnancy. The ectopic pregnancy was resected via laparoscopy. After surgery, the intrauterine pregnancy was uneventful.     

SEOM clinical guidelines for the treatment of follicular non-Hodgkin’s lymphoma

Follicular lymphoma (FL) is the second most common subtype of non-Hodgkin’s lymphoma (NHL) in the Western world. FL constitutes the most frequent indolent lymphoma, well characterized by its clinical presentation related to nodal involvement and its morphologic and biologic features. It is often managed as an incurable disease. However, several active therapeutic approaches from the ‘wait and watch” strategy to the allogeneic transplantation are available for management of patients with FL and clearly have changed the natural history of this disease, achieving a long-term disease-free survival. Therapeutic decision is mostly conditioned by patient’s characteristics, stage, histological grade, tumor burden, and risk-predicting factors. This article try to summarizes the diagnosis and treatment of this heterogeneous group of patients.