Lymphatic patterns of cats infected with Brugia malayi and streptococcus

Approximately 50% of the hind legs of cats infected with Brugia malayi and insulted with a beta haemolytic streptococcus became elephantoid in appearance after four to six weeks. This condition was found to be reversible. Collateral lymphatic vessels were seen by lymphography in most of the Brugia-streptococcus-infected legs. The popliteal draining systems in two of three cats, which harboured no worms, appeared normal by lymphography at 18 weeks.     

HEART: an automated beat-to-beat cardiovascular analysis package using Matlab

A computer program is described for beat-to-beat analysis of cardiovascular parameters from high-fidelity pressure and flow waveforms. The Hemodynamic Estimation and Analysis Research Tool (HEART) is a post-processing analysis software package developed in Matlab that enables scientists and clinicians to document, load, view, calibrate, and analyze experimental data that have been digitally saved in ascii or binary format. Analysis routines include traditional hemodynamic parameter estimates as well as more sophisticated analyses such as lumped arterial model parameter estimation and vascular impedance frequency spectra. Cardiovascular parameter values of all analyzed beats can be viewed and statistically analyzed. An attractive feature of the HEART program is the ability to analyze data with visual quality assurance throughout the process, thus establishing a framework toward which Good Laboratory Practice (GLP) compliance can be obtained. Additionally, the development of HEART on the Matlab platform provides users with the flexibility to adapt or create study specific analysis files according to their specific needs.     

The angiotensin II receptor blocker candesartan improves survival and mesenteric perfusion in an acute porcine endotoxin model

BACKGROUND: Blockade of the angiotensin II type 1 (AT1) receptor has been demonstrated to ameliorate splanchnic hypoperfusion in acute experimental circulatory failure. This study focused on hemodynamic changes and survival in pigs treated with AT1 blockade prior to or during acute endotoxinemia. METHODS: Escherichia coli lipopolysaccharide endotoxin was infused in anesthetized and mechanically ventilated pigs. Systemic, renal, mesenteric and jejunal mucosal perfusion as well as systemic oxygen and acid-base balance were monitored. The selective AT1 receptor blocker candesartan was administered prior to as well as during endotoxinemia. Control animals received the saline vehicle. RESULTS: Pre-treatment with candesartan resulted in higher survival rate (83%, 10 out of 12 animals) compared with 50% (6 of 12) in control animals and 27% (3 of 11) in animals treated during endotoxinemia. Pre-treatment with candesartan resulted in higher cardiac output, mixed venous oxygen saturation, arterial standard base-excess, portal venous blood flow during endotoxin infusion compared with controls and animals treated during endotoxinemia. No adverse effects were found on neither systemic nor renal circulation. CONCLUSION: The favorable results of AT1 receptor blockade prior to endotoxinemia are lost when blockade is established during endotoxinemia demonstrating the importance of the renin-angiotensin system and its dynamic involvement in acute endotoxinemic shock.     

Pharmacodynamics and pharmacokinetics of inhaled iloprost, aerosolized by three different devices, in severe pulmonary hypertension

BACKGROUND: Inhalation of iloprost, a stable prostacyclin analog, is an effective therapy for pulmonary hypertension with few side effects. This approach may, however, be handicapped by limitations of currently available nebulization devices. We assessed whether the physical characterization of a device is sufficient to predict drug deposition and pharmacologic effects. METHODS: We investigated the effects of a standardized iloprost aerosol dose (5 micro g; inhaled within approximately 10 min) in 12 patients with severe pulmonary hypertension in a crossover design employing three well-characterized nebulizers. The nebulizers use different techniques to increase efficiency and alveolar targeting (Ilo-Neb/Aerotrap [Nebu-Tec; Elsenfeld, Germany], Ventstream [MedicAid; Bognor Regis, UK], and HaloLite [Profile Therapeutics; Bognor Regis, UK]). Measurements were performed using a Swan-Ganz catheter and determination of arterial iloprost plasma levels. RESULTS: During inhalation of iloprost, the pulmonary vascular resistance decreased substantially (baseline, approximately 1,250 dyne.s.cm(-5); decrease, - 35.5 to - 38.0%) and pulmonary artery pressure decreased substantially (baseline, approximately 58 mm Hg; decline, - 18.4 to -21.8%), whereas the systemic arterial pressure was largely unaffected. Cardiac output and mixed venous and arterial oxygen saturation displayed a marked increase. The pharmacodynamic profiles with the three devices were superimposable. Moreover, rapid entry of iloprost into the systemic circulation was noted, peaking immediately after termination of the inhalation maneuver, with very similar maximum serum concentrations (158 pg/mL, 155 pg/mL, and 157 pg/mL), and half-lives of serum levels (6.5 min, 9.4 min, and 7.7 min) for the three nebulizers, respectively. Interestingly, the "half-life" of the pharmacodynamic effects in the pulmonary vasculature (eg, decrease in pulmonary vascular resistance, ranging between 21 and 25 min) clearly outlasted this serum level-based pharmacokinetic half-life. CONCLUSIONS: A standardized dose of aerosolized iloprost delivered by different nebulizer types induces comparable pharmacodynamic and pharmacokinetic responses. Pulmonary vasodilation, persisting after disappearance of the drug from the systemic circulation, supports the hypothesis that local drug deposition largely contributes to the preferential pulmonary vasodilation in response to inhaled iloprost.     

Hearing aid troubleshooting based on patients' descriptions

Clinical audiologists were surveyed to determine the terms that their patients use to describe their reaction to hearing aid fitting problems. From this survey, a vocabulary of 40 frequently reported terms was developed. A second survey of hearing aid fitting experts was conducted to determine their methods of troubleshooting a hearing aid fitting when the patient reports one of the frequently reported terms. There was a high degree of agreement among the 24 experts. Principal components analysis resulted in ten components that explained 90.8% of the variance in the experts' responses. These results can be applied as an expert system for fine-tuning hearing aid fittings.     

Evolution of lymph thrombi in experimental Brugia malayi infections: a scanning electron microscopic study

Lymph thrombi in cats experimentally-infected with Brugia malayi were examined by scanning electron microscopy. A variety of morphological forms were noted and it appeared that thrombi undergo a maturation process characterized by at least three transitional phases. Initially, the thrombus consists of erythrocytes encased in fibrin (Phase I). Phase II thrombi are characterized by the appearance of phagocytic cells and fibroblasts on the surface of the thrombus. At the end of the maturation process, the thrombus surface consists solely of fibroblasts or endothelial cells, perhaps derived from the vessel wall (Phase III). Occlusion of the lymphatic lumen by thrombi and the accompanying inflammatory response triggered by B. malayi infection may be a major factor in the pathogenesis of lymph stasis in this disorder.     

Blocked B cell differentiation and emigration support the early growth of Myc-induced lymphomas.

Avian leukosis virus induces lymphoma in chickens after proviral integration within the c-Myc gene, and subsequent expansion of Myc-overexpressing lymphocytes within transformed bursal follicles. The clonal expansion of these follicles allowed us to examine how Myc influences cell differentiation, growth, and apoptosis in lymphoid progenitors soon after the onset of Myc overexpression. Immunohistochemical analysis of developmental markers established that Myc overexpression consistently blocks lymphocyte differentiation at a late embryonic stage. Myc-transformed follicles also grow much more rapidly than normal follicles. This rapid growth is not mediated by suppression of apoptosis, as normal and Myc-transformed follicles showed similar rates of cell death by TUNEL immunohistochemical analysis of cells undergoing DNA degradation. Measurements of DNA synthesis and mitotic index showed modest effects of Myc to increase lymphocyte proliferation, as normal lymphocytes already divide rapidly. The major mechanism mediating rapid growth of transformed follicles instead involved failure of myc-overexpressing lymphocytes to emigrate from transformed follicles, while normal lymphocytes actively emigrate after hatching, as measured by BrdU pulse-chase labeling and immunohistochemical measurements. This failure to undergo the normal program of differentiation and subsequent bursal retention of lymphocytes accounts for most of the growth of transformed follicles, while Myc-induced proliferation makes a smaller contribution.