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     

Constitutional thinness: unusual human phenotype of low bone quality

CONTEXT: Low fat mass and hormonal or nutritional deficiencies are often incriminated in bone loss related to thinness. Constitutional thinness has been described in young women with low body mass index (BMI) but close-to-normal body composition, physiological menstruation, no hormonal abnormalities, and no anorexia nervosa (AN) psychological profile. OBJECTIVE: Our objective was to determine whether constitutional thinness is associated with impaired bone quality. DESIGN, SETTING, AND PARTICIPANTS: This was an observational, cross-sectional study on 25 constitutionally thin and 44 AN young women with similar low BMI (<16.5 kg/m2) and 28 age-matched controls. MAIN OUTCOME MEASURES: Femoral and lumbar spine bone mineral density by dual-energy x-ray absorptiometry, distal tibia and radius bone architecture and breaking strength by three-dimensional peripheral quantitative computed tomography, and bone turnover markers were determined. RESULTS: Constitutionally thin subjects displayed a higher percentage of fat mass than AN subjects but had similar lumbar and femoral bone mineral density, which were significantly lower than in controls (P < 0.001). Constitutionally thin subjects displayed more markedly impaired trabecular and cortical bone parameters in the distal tibia than in the radius. AN bone structure was impaired only in subjects with a long history of disease. Calculated breaking strength was decreased in constitutional thinness and long-standing AN in both the radius and the tibia. Bone markers in constitutionally thin subjects were similar to those of controls. Osteoprotegerin to receptor activator of nuclear factor kappa B ligand ratio was higher in constitutionally thin subjects than in controls or AN women. CONCLUSIONS: Young women with constitutional thinness present an unexpectedly high prevalence of low bone mass (44%) associated with small bone size, overall diminished breaking strength, but normal bone turnover. Mechanisms related to insufficient skeletal load and/or genetics are proposed to explain this new phenotype of impaired bone quality.     

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.     

Brain structure in asymptomatic FMR1 premutation carriers at risk for fragile X-associated tremor/ataxia syndrome

Fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset movement disorder affecting FMR1 premutation carriers, is associated with cerebral and cerebellar lesions. The aim of this study was to test whether computational anatomy can detect similar patterns in asymptomatic FMR1 premutation carriers (mean age 46.7 years) with qualitatively normal -appearing grey and white matter on brain MRI. We used a multimodal imaging protocol to characterize brain anatomy by automated assessment of gray matter volume and white matter properties. Structural changes in the hippocampus and in the cerebellar motor network with decreased gray matter volume in lobule VI and white matter alterations of the corresponding afferent projections through the middle cerebellar peduncles are demonstrated. Diffuse subcortical white matter changes in both hemispheres, without corresponding gray matter alterations, are only identified through age × group interactions. We interpret the hippocampal fimbria and cerebellar changes as early alterations with a possible neurodevelopmental origin. In contrast, progression of the diffuse cerebral hemispheric white matter changes suggests a neurodegenerative process, leading to late-onset lesions, which may mark the imminent onset of FXTAS.