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.     

Echocardiographically guided closure of a patent foramen ovale during pregnancy after recurrent strokes

BACKGROUND: Stroke during pregnancy and puerperium is a severe complication that causes high morbidity and mortality. A patent foramen ovale (PFO) allowing paradoxical embolism is one identified risk factor. CASE: A 25-year-old pregnant woman with PFO suffered from recurrent cerebral embolism. To prevent recurrent cerebral embolism during pregnancy, delivery, and puerperium, interventional closure of the PFO was performed without fluoroscopy under echocardiographic guidance. The postinterventional course was uneventful. CONCLUSION: Percutaneous transvenous closure of a PFO during pregnancy is feasible without the use of fluoroscopy.     

Effect of diethylcarbamazine citrate on Brugia malayi infections in cats following daily, weekly, or monthly administration

Cats with patent infections of Brugia malayi were treated by intraperitoneal injection of diethylcarbamazine citrate (DEC) for 6 consecutive days, weekly for 6 consecutive weeks or monthly for 3 months. Each cat received a total of 100 mg DEC per kg. At necropsy 7 months after infection, no living worms were recovered from any of eight cats treated weekly and only one of nine cats treated daily had a single living Brugia. Five of nine cats treated monthly and six of eight untreated controls had one or more living worms. Cats treated weekly showed a larger decline in microfilariae than those of the other treated groups. The mean microfilariae level of untreated controls increased 2-fold. At necropsy, gross appearance of regional lymphatics in daily and weekly treated cats resembled those of uninfected controls more closely than those in cats treated monthly or untreated. Differences in degree of histological changes between groups of infected cats were not apparent. Weekly administration of DEC appeared to be the most effective regimen; monthly treatment was less effective.     

Factors influencing the change in cerebral hemodynamics in pediatric patients during and after corrective cardiac surgery of congenital heart diseases by means of full-flow cardiopulmonary bypass

BACKGROUND: The pathophysiology of hypoxic-ischemic brain injury in relation to extracorporeal circulation is multifactorial and can be interpreted, in part, as possible alteration in cerebral perfusion and inadequate oxygen delivery to the brain cells. The aim of this study was to evaluate influencing factors on the change in cerebral blood flow velocity (CBFV) patterns determined by transcranial Doppler sonography (TCD) in infants who undergo corrective cardiac surgery by means of full-flow cardiopulmonary bypass (CPB). METHODS: Included in the study were 67 neonates, infants, and children with a median age of 4 months (0.1-70 months), median weight of 4.8 kg (2.5-18.8 kg), and with cyanotic and noncyanotic congenital heart disease (CHD), who underwent surgical correction of CHD by means of CPB [flow rate 144 +/- 47 ml/kg body weight (BW)] and the alpha-stat strategy. The patients were divided into three groups with respect to the minimum rectal temperature during perfusion: deep hypothermic CPB (<18 degrees C) n=18, moderate hypothermic CPB (22-35 degrees C) n=29, normothermic CPB (36 degrees C) n=20. Continuous determination of mean flow velocity (Vmean) in the middle cerebral artery (MCA) by TCD provided qualitative on-line information on cerebral perfusion. The pulsatility index (PI) was calculated in accordance with the formula: Maximum flow velocity - end - diastolic flow velocity/ Mean flow velocity and was used as a parameter for the qualitative assessment of cerebrovascular resistance after the end of CPB. RESULTS: The Vmean was significantly increased 15 min after cross-clamping in the normothermic group (p=0.03) and decreased in the moderate hypothermic group (p=0.02) and deep hypothermic group (p=0.009). The postoperative Vmean values correlated significantly with age (r=0.79, p<0.0001), weight (r=0.75, p<0.0001), bypass time (r=-0.51, p=0.0006), and minimum rectal temperature (r=0.60, p=0.0001). Mean arterial pressure and hemoglobin concentration, but not pCO2, seem to significantly influence the change in Vmean after the termination of CPB (r=0.5, p=0.001; r=-0.55, p=0.002, respectively). In comparison with the values at the start of CPB, the Vmean was significantly decreased after the end of CPB in the hypothermic and moderate hypothermic groups and still significantly elevated in the normothermic group. The age-independent PI was increased after termination of bypass in all groups (p<0.05) and still slightly elevated after the end of operation in the hypothermic group (p=0.05). CONCLUSIONS: The changes in CBFV patterns before, during, and after the termination of CPB were dependent on age, weight, perfusion pressure, and degree of hypothermia during CPB.     

Iloprost als inhalative bzw. intraven?se Langzeitbehandlung von Patienten mit Prim?rer Pulmonaler Hypertonie – Register der Berliner Arbeitsgruppe für Pulmonale Hypertonie – – Register der Berliner Arbeitsgruppe für Pulmonale Hypertonie –

Wir berichten über 81 Patienten mit Prim?rer Pulmonaler Hypertonie bzw. Pulmonaler Hypertonie assoziiert mit einer Kollagenose oder Leberzirrhose, bei denen die Diagnose seit 22±32 Monate bekannt war. Die H?modynamik bei Erstvorstellung war durch einen mittleren rechtsatrialen bzw. pulmonalarteriellen Druck von 8,6±5 bzw. 58,9±17 mmHg, einen Cardiac Index von 1,8±0,6 l/min/m² und einen pulmonalvaskul?ren Widerstand von 1574±787 dyn×s×cm^-5 gekennzeichnet. Bei jeweils einem Drittel der Patienten wurden restriktive und obstruktive Ventilationsst?rungen dokumentiert. Spirometrisch konnten bei der Mehrzahl der Patienten endexspiratorische Ver?nderungen im Sinne einer „small airways disease“ erfasst werden. Zus?tzlich zeigten zwei Drittel aller untersuchten Patienten eine Diffusionsst?rung. Die spiroergometrisch gemessene kardiopulmonale Leistungsf?higkeit war bei 46 Prozent der Patienten hochgradig eingeschr?nkt.     

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.