The conduction system in transplanted hearts.

This is a serial section examination of the conduction system (CS) in six patients who died seven months, 11 months, two years four months, four years two months, 11 years, and 16 years eight months following cardiac transplantation. The heart was hypertrophied and enlarged in all. There was myocarditis of varying degree in all cases with arteriosclerosis and arteriolosclerosis. These findings were more dominant in the atria than in the ventricles. In the CS, myocarditis with fibrosis was found in all in the approaches to the sinoatrial (SA) node, the SA node, the atria, the atrioventricular (AV) node, and the bundle and bundle branches, to a varying degree. When compared with the endomyocardial biopsy findings, the autopsied cases revealed more myocarditis and fibrosis than those estimated to be present in the biopsy specimen. In summary, this study demonstrates that there are fibrotic changes in the CS with the persistence of inflammatory phenomena of the myocardium and the CS to a varying degree in transplanted hearts. This is accompanied by the ubiquitous coronary artery disease affecting not only the large coronaries but also the small vessels. The pathologic changes in and around the CS may be responsible for arrhythmias and sudden death in some cases of cardiac transplantation.     

Conduction system examination in a case of spontaneous heart block in a dog

This is a serial-section study of the conduction system in a 2-year-old boxer with electrocardiographic evidence of complete A-V block. The following findings were present: a lack of communication between the atria and the A-V node, atrophy of the A-V node, and tenuous connections between the A-V node and the A-V bundle. These were accompanied by acute degenerative changes in the conduction system. These changes are considered to be the result of arteriolosclerotic heart disease.     

Anatomic substrate for preexcitation in idiopathic myocardial hypertrophy with fibroelastosis of the left ventricle

Serial section of the conduction system and both atrioventricular (A-V) rims was performed in three patients who died with known preexcitatlon and idiopathic myocardial hypertrophy with fibroelastosis proved at autopsy. All three patients had type B preexcitation and a leftward and inferior 20 ms vector, suggesting a right free wall anomalous pathway. Patient 1 had no arrhythmia, Patient 2 died suddenly and Patient 3 had recurrent paroxysmal supraventricular tachycardia. Electrophysiologic study in Patients 1 and 3 revealed a bidirectionally conducting anomalous pathway with short refractoriness. Patient 1 had no, and Patient 3 had easily inducible A-V reentrant paroxysmal supraventricular tachycardia. Electrophysiologic study in Patient 3 revealed an anterior right free wall or anteroseptal anomalous pathway, manifested by the shortest stimulus-delta interval with pacing of the right anterior atrium. No electrophysiologic studies were performed in Patient 2.In Patient 1 serial section revealed a large right free wall anomalous pathway with myocardial disarray on the ventricular side of the anomalous pathway. In Patient 2, there were two small anomalous pathways in the right free wall. In Patient 3, no anomalous pathway was found in the right free wall; however, the right atrium was connected to the infundibular septum anterior to the membranous septum. This anomalous pathway had continuity with an anterior A-V nodal-like structure.In summary, (1) all three patients anatomically had a right-sided anomalous pathway (as predicted on electrocardlography in all three and electrophyBiologically in Patients 1 and 3). (2) In Patient 2, myocardial disarray in the Kent bundle may have prevented paroxysmal supraventricular tachycardia. (3) In Patient 3, histologic study revealed an anterior septal anomalous pathway on the right side with an anterior A-V nodal-like structure. Because the anomalous pathway did not show any A-V nodal properties, the significance of this structure is not clear. (4) The relation of the right-sided anomalous pathway to the left-sided fibroelastosis is not known.     

Duodenal necrosis as the presenting manifestation of polyarteritis nodosa

Polyarteritis nodosa involves necrotising vasculitis of small and medium-sized arteries. Multiple organ systems are involved. A non-specific and slow course of disease is common. Gastrointestinal involvement is characterised by abdominal pain, nausea and vomiting. Bowel infarction and perforation, cholecystitis and hepatic infarction are well known complications. However, bowel infarction as the presenting symptom of the disease is rare. The case of a 20-year-old male with necrosis of the duodenum heralding polyarteritis nodosa is reported. The patient made a slow recovery after extensive abdominal surgery and a stormy course. The postoperative management and treatment of polyarteritis nodosa are discussed. A high index of suspicion and prompt multidisciplinary approach are needed in order to improve survival in these rare but potentially fatal conditions. Received: 15 May 2001 / Accepted: 5 February 2002     

PDGF-A, PDGF-B, TGFbeta, and bFGF mRNA levels in patients with essential thrombocythemia treated with anagrelide

Plasmatic levels of PDGF-AB, TGFbeta1, and bFGF are increased in patients with essential thrombocythemia (ET) while intraplatelet levels are low for PDGF, normal for TGFbeta, and elevated for bFGF. To evaluate the contribution of gene expression to the dysregulated cytokine levels, we studied platelet PDGF-A, PDGF-B, TGFbeta1, and bFGF mRNA in ET patients before and during anagrelide treatment. We found decreased PDGF-A and PDGF-B, increased TGFbeta1, and normal bFGF mRNA levels. During treatment, mRNA levels remained decreased for PDGF-A, were increased for PDGF-B and normal for TGFbeta1. In untreated patients, protein expression of PDGF paralleled its mRNA levels while different patterns of RNA and protein were found for TGFbeta1 and bFGF.     

Improved transient silencing of gene expression in the mosquito female Aedes aegypti

Gene silencing using RNA interference (RNAi) has become a widely used genetic technique to study gene function in many organisms. In insects, this technique is often applied through the delivery of dsRNA. In the adult female Aedes aegypti, a main vector of human-infecting arboviruses, efficiency of gene silencing following dsRNA injection varies greatly according to targeted genes. Difficult knockdowns using dsRNA can thus hamper gene function analysis. Here, by analysing silencing of three different genes in female Ae. aegypti (p400, ago2 and E75), we show that gene silencing can indeed be dsRNA sequence dependent but different efficiencies do not correlate with dsRNA length. Our findings suggest that silencing is likely also gene dependent, probably due to gene-specific tissue expression and/or feedback mechanisms. We demonstrate that use of high doses of dsRNA can improve knockdown efficiency, and injection of a transfection reagent along with dsRNA reduces the variability in efficiency between replicates. Finally, we show that gene silencing cannot be achieved using siRNA injection in Ae. aegypti adult females. Overall, this work should help future gene function analyses using RNAi in adult females Ae. aegypti, leading toward a better understanding of physiological and infectious processes.