Superior vena caval abnormalities: their occurrence rate, associated cardiac abnormalities and angiographic classification in a paediatric population with congenital heart disease

Angiography of the superior systemic veins was performed on 510 patients with congenital heart disease. An analysis of these angiograms was carried out and a simple angiographic classification of superior vena caval anomalies is presented. Eleven per cent of cases had complete bilateral superior vena cavae, a frequency of occurrence higher than that previously reported. An analysis of associated congenital heart lesions revealed a higher than average association of bilateral superior vena cavae with atrioventricular septal defects and double-outlet right ventricle, but this was seen rarely in cases of transposition of the great arteries. Bilateral superior vena cavae also occurred very frequently (72%) in patients with situs abnormalities. Femoral vein catheterisation is likely to facilitate diagnosis and appropriate radiological signs are discussed.     

Dickkopf-4 is frequently down-regulated and inhibits growth of colorectal cancer cells

Like Dickkopf-1 (DKK1), DKK4 is a target of β-catenin/Tcf-4 in colorectal cancer. However, as a negative regulator of Wnt signalling its function in colorectal cancer cells is not well understood. We report that DKK4 is frequently down-regulated in colorectal cancer cell lines with deregulated β-catenin/Tcf-4 and in primary colorectal cancers. Exposure of cancer cells to DKK4 strongly inhibits basal β-catenin/Tcf-4 signalling activity, cancer cell growth and cell cycle progression. Therefore, loss of this negative feed-back loop provides Wnt factor expressing cancer cells with a growth advantage. Our data demonstrate that DKK4 is an important negative regulator of colon cancer cell growth.     

Interest of a loading dose of milnacipran in endogenous depressive inpatients. Comparison with the standard regimen and with fluvoxamine

A multicenter controlled study was designed to test the hypothesis that a loading dose of an antidepressant could shorten the latency of its clinical efficacy. Three parallel groups of about 40 endogenous depressive inpatients received either a loading dose of milnacipran (300 mg daily for 2 weeks and 150 mg daily during the 2 following weeks), the standard regimen of milnacipran in severe depression (200 mg daily for 4 weeks), or fluvoxamine (200 mg daily for 4 weeks). The duration of the study was 4 weeks, with assessments at baseline and after 4, 9, 14, 21, and 28 days of therapy by means of Montgomery and Asberg depression scale (MADS), the Hamilton depression scale, the Clinical Global Impressions (CGI), and a checklist of symptoms and side-effects. Results showed very similar evolution in the 3 treatment groups. In addition, the level of side-effects did not exhibit significant differences among the treatment groups, except for excitement-nervousness and akathisia which were more frequently reported with fluvoxamine. These results do not support the usefulness of a loading dose of an antidepressant such as milnacipran. They demonstrate however that milnacipran can be given at a 300 mg daily dose from the very first day of treatment with an excellent tolerance.     

Relationship between clinical and echocardiography-derived parameters and atrial activation as measured by the P-wave signal-averaged electrocardiogram

P-wave signal averaging is used in an attempt to detect patients at risk of atrial arrhythmias, particularly atrial fibrillation. Although many studies utilized this method, data on the relationship between clinical and echocardiographic variables and signal averaged P-wave parameters are sparse. Thus, we performed a prospective study to evaluate the influence of important clinical and echocardiographic variables on P-wave parameters. The study included 100 probands without demonstrable cardiac disease. P-wave signal averaging was performed after echocardiographic examination in all subjects. Overall P-wave duration averaged 122±16 ms and correlated significantly with age, left atrial and left ventricular end-diastolic diameter on univariate analysis (r=0.287, 0.393 and 0.375; p=0.004, <>;0.0001 and <>;0.0001, respectively). On multivariate analysis, however, age was the only independent factor affecting signal averaged P-wave duration (p=0.02). There were statistically significant differences in left atrial size and P-wave duration if probands were grouped according to their age. Conclusion There is a significant relationship between signal averaged P-wave duration and age. This may be due to increased atrial fibrosis in elderly subjects. These data should be considered when signal-averaged P wave duration is used as a risk stratifier in patients prone to atrial fibrillation.     

No increased risk of hypoglycaemic episodes during 48 h of subcutaneous glucagon-like-peptide-1 administration in fasting healthy subjects

Objective  It is uncertain whether the ability to avoid hypoglycaemia during fasting is preserved, and the risk of reactive hypoglycaemia after an oral glucose stimulus following a prolonged fasting period is increased at augmented glucagon-like peptide-1 (GLP-1) levels.
Design  A randomized, double-blind placebo-controlled cross-over study in eight healthy men to assess the safety, in terms of hypoglycaemia, of a continuously infused pharmacological dose of native GLP-1 during long-term fasting. After an overnight fast the fasting period continued for 48 h and was followed by a 3-h oral glucose tolerance test (OGTT). GLP-1(7-36 amide) or placebo was continuously infused subcutaneously and titrated to a dose of 4·8 pmol/kg per min.
Results  Two subjects in the GLP-1 group and one subject in the placebo group were withdrawn due to protocol specified plasma glucose (PG) ≤ 2·8 m m and neuroglycopaenic symptoms.
The infusion of GLP-1 resulted in pharmacological levels of intact GLP-1. During the fasting period PG, insulin and C-peptide levels declined and glucagon, GH and free fatty acid (FFA) levels increased with no differences between GLP-1 and placebo. During OGTT circulating levels of insulin and C-peptide were higher with GLP-1 infusion. However, PG was similar during GLP-1 vs. placebo infusions. GLP-1 infusion increased norepinephrine and cortisol levels during OGTT.
Conclusion  The counter-regulatory response during 48 h of subcutaneous GLP-1 infusion was preserved despite long-term fasting with no apparent increased risk of hypoglycaemic episodes. No reactive hypoglycaemia was observed when the fast was followed by an OGTT. Thus use of long-acting GLP-1 analogues may not increase the risk of hypoglycaemia.     

Solitary fibrous tumour of the oral cavity: clinicopathological and immunohistochemical characterization of three cases

Solitary fibrous tumour (SFT) is an uncommon mesenchymal neoplasm rarely located in the oral cavity. To characterize further oral SFT, we describe three new cases. Each tumour originated in the buccal mucosa of a middle-aged/elderly patient. Histological examination showed well-circumscribed tumours with densely cellular areas alternating with hypocellular areas in a variedly collagenous, vascular stroma. Mast cells were abundant. The spindle-shaped, neoplastic cells immunostained strongly for CD34 antigen and vimentin and weakly for bcl-2, but not for epithelial cell markers, alpha-smooth muscle actin, or neurofilament or S-100 proteins. Compatible with the virtual absence of mitoses and of marked nuclear atypia, the overall frequency of proliferating cells expressing Ki-67 was low. The expression of CD34 was useful in the differential diagnosis. The consistent location in the cheek and expansion of one tumour after local trauma does not preclude a traumatic element in the development of oral SFT.