Superior vena cava syndrome and syncope in an implantable cardioverter defibrillator recipient.

We describe the case of a recipient of an implantable cardioverter defibrillator with multiple syncopal episodes due both to superior vena cava obstruction and electrical instability. These complications occurred in the presence of two transvenous implantable cardioverter defibrillator leads. The patient has been managed conservatively with anticoagulants and new antiarrhythmic drugs with improvement in both his clinical problems.     

Differential assessment of angiogenic activity and of vascular survival ability (VSA) in breast cancer

Recent reports provide evidence that some growth factors behave as inhibitors of the apoptosis of the endothelial cells, bringing forward the concept of vascular survival as a post-angiogenesis process. At least two different vasculature development processes occur within a tumor: the angiogenic (formation of new vessels) and the vascular survival pathway, which is devoted to the preservation of the newly-formed vessels in layers that lose contact with the adjacent normal tissue. We developed a method to assess these processes in tissue samples. We noted that differences among tumors may exist not only in the tumor angiogenic activity (TAA) but also in the vascular survival ability (VSA). One third of the highly angiogenic breast cancer cases examined had a poor ability to maintain high vessel density in inner tumor areas. Both parameters are independently related to prognosis, while VSA was directly related to tumor dimensions and node involvement. Patients with high TAA and VSA had a particularly poor prognosis. It is suggested that although cancer angiogenic activity is important for the local invasion and dissemination into vessels and lymphatics, the VSA may be important for the effective formation of viable tumor foci in lymph nodes or distant organs. Recognition and quantification of the vascular survival ability in human tumors may significantly improve the prognostic value of the assessment of tumor vasculature, and may help to stratify patients for clinical trials with novel anti-angiogenic or angiotoxic drugs. Elucidation of the pathways may provide additional targets for antiangiogenic therapy. This revised version was published online in July 2006 with corrections to the Cover Date.     

'Invading edge vs. inner' (edvin) patterns of vascularization: an interplay between angiogenic and vascular survival factors defines the clinical behaviour of non-small cell lung cancer

Neo-angiogenesis during neoplastic growth involves endothelial mitogenic and migration stimuli produced by cancer or tumour stromal cells. Although this active angiogenesis takes place in the tumour periphery, the process of vessel growth and survival in inner areas and its clinical role remain largely unexplored. The present study compared the microvessel score (MS) as well as the single endothelial cell score (ECS) in the invading edge and in inner areas of non-small cell lung carcinomas (NSCLCs). Three different patterns of vascular growth were distinguished: the edvin (edge vs. inner) type 1, where a low MS was observed in both peripheral and inner tumour areas; the edvin type 2, where a high MS was noted in the invading front but a low MS in inner areas; and the edvin type 3, where both peripheral and inner tumour areas had a high MS. The ECS was high in the invading edge in edvin type 2 and 3 cases and was sharply decreased in both types in inner areas, suggesting that endothelial cell migration is unlikely to contribute to the angiogenic process in areas away from the tumour front. Expression of the vascular endothelial growth factor (VEGF) and of thymidine phosphorylase (TP) was associated with a high MS in the invading edge. VEGF was associated with a high MS in inner areas (edvin 3), while TP expression was associated with edvin type 2, showing that VEGF (and not TP) contributes to the preservation of the inner vasculature. Both edvin type 2 and 3 cases showed an increased incidence of node metastasis, but edvin type 3 cases had a poorer prognosis, even in the N1-stage group. The present study suggests that tumour factors regulating angiogenesis and vascular survival are not identical. A possible method is reported to quantify these two parameters by comparing the MS in the invading edge and inner areas (edvin types). This observation may contribute to the evaluation of the effectiveness of different therapeutic approaches, namely vascular targeting vs. anti-angiogenesis.     

Tumour angiogenesis: vascular growth and survival

Angiogenesis starts at the edge of a malignant epithelial tumour concurrently with tumour cell invasion and stromatogenesis, i.e. the formation of specific connective tissue stroma amenable to easy penetration by endothelial and tumour cells. However, as the tumour continues its growth, the edge becomes the inner tumour area, and a new invading tumour front is formed by the multiplying malignant cells which outflank the initial edge. This process, which repeats itself again and again, forms the "relay race" model of tumour vascular growth and regression. At the heart of the tumour unfavourable environmental conditions prevail -- hypoxia, acidity, lack of nutrients, failure of waste removal, and apoptosis rather than proliferation. Blood vessels and tumour cells are greatly decreased, but do not vanish, as tumour cells are shifting to anaerobic glycolysis, and blood vessels are turning into anti-apoptotic pathways -- vascular survival ability (VSA). Thus, assessing vascular density (VD) by simply counting "hot spots" at the edge of a tumour, where conditions are most favourable, is futile; it may reflect tumour angiogenic activity (TAA), but is not representative of genuine tumour vasculature. By combining vessel counts at the invading tumour front with those of the inner tumour areas a complete picture of tumour VD can be achieved. The thus formed four patterns of vascularization, designated as "edvin" (edge vsinner tumour area), are: edvin 1: low TAA/low VSA; edvin 4: high TAA/high VSA; edvin 2: low TAA/high VSA; and edvin 3: high TAA/low VSA. It is expected that this scheme will prove useful in the field of chemoradiotherapy and anti-angiogenic treatment.     

Activating mutations of ras family genes in prostatic-cancer

ras family genes (H-, K- and N-ras) encode for a 21 kD membrane protein which possesses GTPase activity and participates in a signal transduction pathway. Activating mutations of the ras family genes occur at codons 12, 13 and 61 and have been detected in a variety of human tumours, including colonic, bladder and pancreatic cancers. Prostatic cancer is among the most common malignancies throughout the world and a major cause of death from cancer in males. Data reported on the implication of the ras family genes in the development of the disease are conflicting. The aim of this study was to determine the incidence of mutations at codon 12 of H-ras, codon 12 of K-ras and codon 61 of N-ras proto-oncogenes, in a Greek population with prostatic cancer. Our analysis revealed that 4 out of 20 (20%) samples harboured a K-ras codon 12 point mutation, 1 out of 20 (5%) specimens contained mutations at codon 12 of the H-ras and 1 out of 20 (5%) at codon 61 of the N-ras, indicating a role for the ras genes in the development of the disease.     

c-erbB-2 related aggressiveness in breast cancer is hypoxia inducible factor-1alpha dependent.

c-erbB-2-positive breast carcinomas are highly aggressive tumors. In vitro data on breast cell lines showed that c-erbB-2 enhanced translational efficiency of hypoxia inducible factor-1alpha (HIF1alpha) production (Laughner et al., Mol Cell Biol 2001;21:3995-4005). We investigated the clinical correlate of this observation to assess whether c-erbB-2 expression was related to HIF1alpha expression, angiogenesis, and prognosis. A series of 180 breast carcinomas of known c-erbB-2 status (90 c-erbB-2-positive and 90 c-erbB-2-negative carcinomas) were stained immunohistochemically for HIF1alpha and CD31 endothelial cell antigen. c-erbB-2 positivity was clearly related to HIF1alpha protein expression and high angiogenesis. However, prognosis was decreased only in cases with simultaneous c-erbB-2 and HIF1alpha expression. If activation of c-erbB-2 in humans results in overexpression of HIF1alpha independently of conditions of hypoxia, as occur in experimental studies, this interaction may represent a main pathway conferring clinical aggressiveness to c-erbB-2-positive breast tumors.     

A fatal case of Ludwig's angina and mediastinitis caused by an unusual microorganism, Gemella morbillorum

We present a case of Ludwig's angina in a 48-y-old immunocompetent male caused by an unusual pathogen, Gemella morbillorum. The infection was complicated with mediastinitis and despite aggressive management of the disease the patient died after 12 d of hospitalization. This is the first reported case of Ludwig's angina caused by G. morbillorum and emphasizes that the disease remains a potentially lethal infection.     

Coronary and peripheral blood flow changes following biventricular pacing and their relation to heart failure improvement.

AIMS: To study the effect of cardiac resynchronization therapy (CRT) on coronary and peripheral arterial circulation and to assess whether their changes are related to the improvement in patients' functional capacity and prognostically important biochemical markers. METHODS AND RESULTS: Twenty-five patients were studied (New York Heart Association classes III and IV, left ventricular ejection fraction <35%, QRS>120 ms, mean age 66 +/- 2.1 years). Coronary blood flow (CBF), forearm blood flow (FBF), and their reserve were measured by transoesophageal echocardiography (in cm/s) and venous occlusion plethysmography (in mL/100 mL/min) at baseline and following 3 months of CRT. N-terminal-pro-brain natriuretic peptide (Nt-pro-BNP) and serum adhesion molecules, sICAM-1 and sVCAM-1 levels were also assessed. CRT induced a non-significant increase in resting CBF (baseline vs. CRT: 52.1 +/- 5.5 vs. 58.2 +/- 3.6, P: NS), whereas hyperaemic CBF was increased by CRT (baseline vs. CRT: 67.8 +/- 6.8 vs. 79.8 +/- 6.2, P < 0.05). Significant increases were observed in resting FBF (baseline vs. CRT: 1.6 +/- 0.2 vs. 2.6 +/- 0.2, P < 0.05) and hyperaemic FBF (baseline vs. CRT: 2.1 +/- 0.2 vs. 3.2 +/- 0.3, P < 0.05). The per cent difference in hyperaemic FBF was related to the per cent change in Nt-pro-BNP (r = -0.71, P < 0.05) and the per cent improvement in exercise duration (r = 0.80, P < 0.05). CONCLUSION: CRT induces favourable changes in coronary and peripheral arterial function. Changes in peripheral blood flow are related to patients' improvement and may be prognostically significant.     

Burnout Evaluation and Potential Predictors in a Greek Cohort of Mental Health Nurses

Background

Job burnout is one of the most serious occupational health hazards, especially, among mental health nurses. It has been attributed among others to staff shortages, health service changes, poor morale and insufficient employee participation in decision-making.