Rabies virus quasispecies: implications for pathogenesis

Passage of the mouse-adapted rabies virus strain CVS-24 (where CVS is challenge virus standard) in BHK cells results in the rapid selection of a dominant variant designated CVS-B2c that differs genotypically and phenotypically from the dominant variant CVS-N2c present in mouse-brain- or neuroblastoma-cell-passaged CVS-24. The glycoprotein of CVS-B2c has 10 amino acid substitutions compared with that of CVS-N2c. Because CVS-B2c can be reproducibly selected in BHK cells, it is likely to be a conserved minor subpopulation of CVS-24. CVS-N2c is more neurotropic in vitro and in vivo than CVS-B2c, which replicates more readily in nonneuronal cells in vitro and in vivo. These characteristics appear to be relevant to the pathogenicity of the two variants. CVS-N2c is more pathogenic for adult mice than CVS-B2c. In contrast, CVS-B2c is more pathogenic for neonatal mice. These differences in pathogenicity are reflected in the selection pattern when mixtures of CVS-N2c and CVS-B2c were used to infect neonatal and adult mice. Although CVS-N2c was highly selected in adult mice, no selection for either variant was seen in neonates, suggesting that certain aspects of development, such as maturation of the nervous and immune systems, may contribute to the selection process. We speculate that the existence of different variants within a rabies virus strain may facilitate the virus in overcoming barriers to its spread, both within the host and between species.     

Swyer James syndrome following Mycoplasma pneumoniae pneumonia: report of one case

Systemic vasculopathy in patients with neurofibromatosis type 1 is rare. We describe a case of unusual cerebral and renal involvement in a young, 29-year-old patient, who died of a cerebral ischemic attack one year after our observation.     

In vivo radiofrequency thermal balloon angioplasty of porcine coronary arteries: histologic effects and safety

The purpose of this study was to assess the safety and histologic effects of radiofrequency thermal balloon angioplasty in the coronary vasculature of normal pigs. Radiofrequency thermal balloon angioplasty was performed in 30 coronary arteries of 16 nonatherosclerotic pigs. Heated inflations were performed at either 50 degrees, 60 degrees, or 70 degrees C for 30 or 60 seconds, and were compared with five nonheated inflations in five additional arteries. All balloon inflations were performed at 2 atm pressure with a balloon/vessel diameter ratio of 1.2 to 1. Heart rate, arterial pressure, and left ventricular pressure were monitored continuously for each animal. A 12-lead ECG, coronary angiography, and two-dimensional transthoracic echocardiography were performed before and 1 hour after each balloon inflation. Each animal was subsequently put to death for postmortem cardiac examination. Heated inflations were well tolerated in 28 of the 30 arteries without significant adverse effects. During one inflation, ventricular fibrillation occurred because of prolonged ischemia from an occlusive guiding catheter. In another artery, a heated inflation resulted in a dissection with a transient decrease in distal coronary flow. Histologic examination revealed a significant increase in wall thinning and elastic fiber straightening with heating at 70 degrees C for both 30 and 60 seconds, and a significant increase in intracoronary thrombus with heating at 70 degrees C for 60 seconds. Depth of periarterial myocardial heat necrosis paralleled the increase in temperature, with an average depth of 166 microns at 50 degrees C, 312 microns at 60 degrees C, and 1031 microns at 70 degrees C. In vivo, radiofrequency coronary angioplasty can be performed relatively safely without significant electrical, hemodynamic, or ischemic changes beyond those seen with conventional nonthermal angioplasty. The extent of heat-induced vessel wall thinning, elastic tissue straightening, intracoronary thrombus formation, and periarterial myocardial necrosis are all related to balloon temperature or duration of heating.     

Autonomous epicardial and endocardial boundary detection in echocardiographic short-axis images

An autonomous endocardial and epicardial boundary detection (ABD) method is reported. One hundred ten cycles from 55 clinical studies were selected retrospectively. Image sequences were digitized at 512 x 480 pixel resolution. The point-by-point boundary positions of the ABD and the areas enclosed were compared with positions and enclosed areas drawn by three independent observers. Correlation coefficients for epicardial end-diastolic (ED) and end-systolic (ES) areas, endocardial ED and ES areas, muscle area, and fractional area change were 0.970, 0.976, 0.951, 0.985, 0.887, and 0.878, respectively. Bland-Altman analysis showed negligible biases with standard deviations comparable to those of the observers. The mean difference between the ABD border and the consensus observer border positions in 64 directions falls within the mean range of interobserver border positions, suggesting that shape is also well defined by the ABD.     

The clinical complexity of splenic vein thrombosis

Upper gastrointestinal hemorrhage secondary to splenic vein thrombosis is a curable form of localized portal hypertension when treated with splenectomy. A high index of suspicion is necessary in order to promptly diagnose and treat this underrecognized condition that is most commonly caused by inflammation or neoplasm of the pancreas. The triad of isolated gastric varices, splenomegaly, and normal hepatic function is classic; it is not uncommon, however, for patients to have only some or even none of these conditions. Mesenteric angiography with venous phase imaging is the gold standard of diagnosis. Ultrasound and CT may identify splenic vein thrombosis, but are most helpful in delineating concomitant upper abdominal pathology. Early recognition and intervention allow associated underlying conditions to be treated under the same anesthetic with minimal morbidity and mortality.     

Antiasthmatic activity of the second-generation phosphodiesterase 4 (PDE4) inhibitor SB 207499 (Ariflo) in the guinea pig

We evaluated the airway activity of the novel phosphodiesterase type 4 inhibitor SB 207499 [Ariflo; c-4-cyano-4-(3-cyclopentyloxy-4-methoxyp henyl-r-1-cyclohexane carboxylic acid)], in the guinea pig. Ovalbumin (OA)-induced contractions of guinea pig isolated tracheal strips were inhibited by SB 207499 with an EC50 of 1 microM but had little or no effect on exogenous agonist-induced contraction, which suggests that its effect on OA-induced contraction in vitro is primarily due to inhibition of mediator release from mast cells. In anesthetized guinea pigs, SB 207499 inhibited OA-induced bronchoconstriction with i.v. and p.o. ID50 values of 1.7 and 17 mg/kg, respectively. At 1, 3 and 6 hr after SB 207499 (30 mg/kg p.o.), OA-induced bronchospasm was inhibited by 92%, 70% and 58%, respectively, corresponding to elevated plasma concentrations of 1.62 +/- 0.19, 1.65 +/- 0.29 and 0. 93 +/- 0.24 microg/ml, respectively, of SB 207499. SB 207499 also inhibited house dust mite-induced bronchoconstriction (ID50 = 0.9 mg/kg i.v. and 8.9 mg/kg p.o.). In contrast to its lack of bronchorelaxant activity in vitro, SB 207499 inhibited bronchospasm induced by i.v. leukotriene D4 (LTD4) [ID50 = 3 mg/kg i.v.]. The bronchorelaxant effect of i.v.-administered SB 207499 was at least additive with that of salbutamol in reversing infused histamine-enhanced airway tone, but it did not alter base line or enhance salbutamol-induced cardiovascular effects. In conscious guinea pigs, SB 207499 (10 or 30 mg/kg p.o.), 1 hr before antigen or LTD4 challenge, markedly reduced bronchospasm and subsequent eosinophil influx as measured by bronchoalveolar lavage 24 hr after provocation. SB 207499 administered after OA or LTD4 challenge also reduced airway eosinophilia measured at 24 hr after OA challenge or 96 hr after LTD4 challenge. These results, coupled with the broad anti-inflammatory activity of SB 207499 previously described (Barnett et al., 1998), suggest that SB 207499 will be useful in the treatment of asthma and other inflammatory disorders.