Sequential scintigraphy and orthoradiographic measurement of femoral shortening after femoral neck fracture

The objective of the study was to assess scintigraphic patterns and femoral shortening after femoral neck fracture in order to select predictive parameters for late complications. Eighty-eight patients with osteosynthesized femoral neck fractures were followed for 2 years with regular scintigraphic evaluations and orthoradiographic measurements of femoral length shortening. Four different patient categories were identified with regard to the late outcome: two different groups with uneventful healing and two different groups with late complications. Accordingly, a high scintigraphic uptake at 1 month may eiher point to an uneventful healing if combined with minor femoral shortening or indicate failure if combined with a high degree of femoral shortening. In contrast, low scintigraphic uptake may either reflect primary fracture healing if accompanied by minor femoral shortening or predict failure if a high degree of femoral shortening is present. Compared with using scintigraphy alone, combined scintigraphic evaluation and assessment of femoral shortening increased the accuracy for prediction of late failures from 80% to 93%. Early scintigraphic patterns after osteosynthesis of femoral neck fractures have to be validated with care. Radiographic assessment of femoral shortening, which is less invasive, gives better prognostic accuracy and should therefore be preferred for this purpose.     

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.     

Relation between tobacco use and urinary excretion of thromboxane A2 and prostacyclin metabolites in young men

BACKGROUND. Cigarette smoking is a risk factor for cardiovascular disease. The present study addressed the effect of tobacco use on the formation of two eicosanoids, thromboxane A2 and prostacyclin, which have been implicated in both acute and chronic cardiovascular disorders. METHODS AND RESULTS. In 577 randomly sampled 18-19-year-old men, the urinary excretion of the 2,3-dinor metabolites of thromboxane A2 and prostacyclin (Tx-M and PGI-M, respectively) was analyzed and related to the subjects' self-reported use of tobacco. Sixty-five percent of the subjects used no tobacco, 7.5% were cigarette smokers, 22% used wet (oral) snuff, and the rest reported a mixed use of tobacco. The urinary excretion of Tx-M was higher (p less than 0.001) in cigarette smokers than in those not using tobacco (180 versus 128 pg/mg creatinine) and was correlated (r = 0.35, p less than 0.05) with the daily cigarette consumption. Snuff users had no increase in their urinary excretion of Tx-M, despite urinary cotinine levels comparable to those in the cigarette smokers (1,210 and 1,560 ng/ml, respectively). The excretion of PGI-M did not differ between non-tobacco users, cigarette smokers, and snuff users. CONCLUSIONS. We conclude that cigarette smoking, but not the use of snuff, facilitates the formation of thromboxane A2. We propose that such an increased formation reflects platelet activation in the absence of vascular injury and that it may be of significance for the subsequent development of cardiovascular disease.     

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.     

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.