Effect of inhaled prostacyclin in combination with almitrine on ventilation-perfusion distributions in experimental lung injury

BACKGROUND: Inhaled prostacyclin and intravenous almitrine have both been shown to improve pulmonary gas exchange in acute lung injury (ALI). This study was performed to investigate a possible additive effect of prostacyclin and almitrine on pulmonary ventilation-perfusion (VA/Q) ratio in ALI compared with inhaled prostacyclin or intravenous almitrine alone. METHODS: Experimental ALI was established in 24 pigs by repeated lung lavage. Animals were randomly assigned to receive either 25 ng.kg(-1).min(-1) inhaled prostacyclin alone, 1 microg.kg(-1).min(-1) almitrine alone, 25 ng.kg(-1).min(-1) inhaled prostacyclin in combination with 1 microg.kg(-1).min(-1) almitrine, or no specific treatment (controls) for 30 min. For each intervention, pulmonary gas exchange and hemodynamics were analyzed and VA/Q distributions were calculated using the multiple inert gas elimination technique. The data was analyzed within and between the groups by analysis of variance for repeated measurements, followed by the Student-Newman-Keuls test for multiple comparison when analysis of variance revealed significant differences. RESULTS: All values are expressed as mean +/- SD. In controls, pulmonary gas exchange, hemodynamics, and VA/Q distribution remained unchanged. With prostacyclin alone and almitrine alone, arterial oxygen partial pressure (PaO2) increased, whereas intrapulmonary shunt (QS/QT) decreased (P < 0.05). Combined prostacyclin and almitrine also increased PaO2 and decreased QS/QT (P < 0.05). When compared with either prostacyclin or almitrine alone, the combined application of both drugs revealed no additional effect in gas exchange or VA/Q distribution. CONCLUSIONS: The authors conclude that, in this experimental model of ALI, the combination of 25 ng.kg(-1).min(-1) prostacyclin and 1 microg.kg(-1).min(-1) almitrine does not result in an additive improvement of pulmonary gas exchange or VA/Q distribution when compared with prostacyclin or almitrine alone.     

Desflurane confers neurologic protection for deep hypothermic circulatory arrest in newborn pigs

BACKGROUND: Cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA), as used for infant heart surgery, carry a risk of ischemic neurologic injury. Volatile anesthetics have neuroprotective properties against both global and focal ischemia at normothermia. The authors examined the hemodynamic and neuroprotective effects of desflurane in a piglet CPB-DHCA model. METHODS: Twenty piglets aged 5-10 days received a desflurane- (6-9% expired) or fentanyl-based anesthetic before and during CPB (before and after DHCA). DHCA lasted 90 min at 19 degrees C brain. Cardiovascular variables (heart rate, arterial pressure, blood gases, glucose, brain temperature) were monitored. On postoperative day 2, neurologic and histologic outcomes were determined. RESULTS: Cardiovascular variables before, during, and after CPB were physiologically similar between groups. The desflurane group had better neurologic performance (P = 0.023) and greater postoperative weight gain (P = 0.04) than the fentanyl group. In neocortex, the desflurane group had less tissue damage (P = 0.0015) and fewer dead neurons (P = 0.0015) than the fentanyl group. Hippocampal tissue damage was less in the desflurane group (P = 0.05), but overall, neuronal cell counts in the CA1 sector of the right hippocampus were similar to those in the fentanyl group. CONCLUSIONS: Desflurane-based anesthesia yields hemodynamics during CPB with DHCA that are similar to those with fentanyl-based anesthesia. However, desflurane-based anesthesia improves neurologic and histologic outcomes of CPB-DHCA in comparison with outcomes with fentanyl-based anesthesia.     

Benzo[a]pyrene at an environmentally relevant dose is slowly absorbed by, and extensively metabolized in, tracheal epithelium

While tobacco smoke has been conclusively identified as a lung carcinogen, there is much debate over which smoke constituent(s) are primarily responsible for its carcinogenicity. Previous studies in our laboratory suggested that highly lipophilic carcinogens are slowly absorbed in the thicker epithelium of the conducting airways, potentially allowing for substantial local metabolism. The bioactivation of polycyclic aromatic hydrocarbons in airway epithelium may, hence, be important in tobacco smoke-induced carcinogenesis. In the present study, the hypothesis of slow absorption and substantial local metabolic activation of highly lipophilic carcinogen in airway epithelium was tested in dogs. A single dose of tritiated benzo[a]pyrene (BaP) dissolved in a saline/phospholipid suspension was instilled in the trachea, just anterior to the carina. At intervals of a few minutes up to 30 min over a 3-h period, blood samples were drawn from the azygous vein, which drains the area around the point of instillation, and from the systemic circulation. Tissue samples were taken at the end of the experiment. The concentration of BaP with depth into the tracheal mucosa was determined with autoradiography. BaP was slowly absorbed into the trachea with a half-time of approximately 73 min, which is consistent with diffusion-limited passage through the epithelium and lead to local doses in the tracheal epithelium that were more than a 1000-fold those of other tissues. The long retention of BaP in the epithelium provided the local metabolizing enzymes with high substrate levels over a long period, resulting in extensive metabolism. At 3 h after the exposure, 23% of the BaP-equivalent activity remained in the tracheal mucosa. Of this fraction, 13% was parent compound, 28% was organic extractable, 31% was water-soluble, and 28-7% of the instilled dose was bound to tracheal tissues. These results explain the tendency of highly lipophilic carcinogens, such as BaP, to induce tumors at the site of entry and, furthermore, indicate that the highly lipophilic components of tobacco smoke and polluted air may be the most important contributors to lung tumors of the conducting airways.      

Die klinische Bedeutung der Isocitratdehydrogenase (ICDH) im Serum bei gesunden und kranken Kindern

Zusammenfassung Bei 312 erkrankten Kindern im Alter bis zu 12 Jahren wurde die Aktivität der Isocitratdehydrogenase (ICDH) im Serum ermittelt, um deren mögliche diagnostische Bedeutung für die Pädiatrie festzustellen. Dem Krankengut wurde ein Normalkollektiv von 176 gesunden Kindern gegenübergestellt.Die Normalwerte der ICDH-Aktivität im Serum bei Neugeborenen liegen zwischen 1,88 und 8,76 mU mit einem Mittelwert von 4,8±2,2 mU; bei Kindern bis zu 12 Jahren zwischen 0 und 5,13 mU mit einem Mittelwert von 2,21±0,91 mU. In 80% der Fälle von akuter Virushepatitis zeigte die Serum-ICDH Aktivitätserhöhungen bis zu 59,6 mU/ml, wobei das Ausmaß der Erhöhungen der ICDH bei akuter Virushepatitis keinen sicheren Schluß auf Schwere und Prognose der Erkrankung zuläßt. Der diagnostische Wert der ICDH bei Erkrankungen im Kindesalter liegt vor allem in den akuten Krankheitsverläufen (akute Virusmyokarditis oder Virushepatitis). Im Liquor cerebrospinalis gesunder Kinder war keine Aktivität nachweisbar, im pathologischen Liquor fanden sich unterschiedliche Erhöhungen, die keinen differentialdiagnostischen Rückschluß erlaubten.D 29.     

Urinary albumin excretion and transcapillary escape rate of albumin in malignancies

Transcapillary escape rate of albumin was determined in 22 patients with different malignancies. In addition, urinary albumin excretion rate was measured in 24-h urine samples using a sensitive immunoassay. Increased urinary albumin excretion was defined as ≥20 μg/min according to conventional standards. Renal glomerular filtration and tubular function was estimated by⁵¹Cr-EDTA plasma clearance and urinary beta 2-microglobulin, respectively. Median urinary albumin excretion rate was 15.0 μg/min (range 6–510 μg/min) and the frequency of increased urinary albumin excretion was 41%. This agrees with other studies showing increased albuminuria in several types of malignant diseases. Patients with advanced disease (tumour, node, metastasis (TNM) stage II–IV) had a significantly higher urinary albumin excretion rate than patients with localized disease (TNM stage I). Serum creatinine, glomerular filtration rate and urinary beta 2-microglobulin were all within normal limits. Median transcapillary escape rate of albumin was 5.5%/h (range 2–8%/h) and this level is comparable with values in healthy subjects. There was no significant difference in transcapillary escape rate between patients with elevated urinary albumin excretion and the normoalbuminuric group. Median value of the absolut outflux of albumin was 10.6 g/h with similar levels in patients with increased urinary albumin excretion and patients with normoalbuminuria. Our results indicate a high prevalence of minor glomerular dysfunction with a slightly elevated urinary albumin excretion in patients with malignancies. The normal endothelial function, as estimated by the transcapillary escape rate of albumin, suggests an overal unaffected capillary permeability and increased urinary albumin loss appears to be an isolated renal phenomenon in cancer patients.     

Sonographic imaging of foramen ovale electrodes.

OBJECTIVE: In patients with medically intractable partial epilepsy of mesiotemporal origin, video electroencephalographic monitoring with foramen ovale electrodes is necessary to plan neurosurgical interventions. Imaging of these electrodes after implantation hitherto required conventional radiography, magnetic resonance imaging, or computed tomography of the skull. These methods are expensive. Therefore, the aim of our work was to show the capability of more cost-effective transcranial B-mode sonography for visualization of the electrodes. METHODS: In this pilot study, a 42-year-old female patient with implanted foramen ovale electrodes was examined transtemporally with a 2-MHz sector transducer to visualize the intracranially implanted electroencephalographic recording device. RESULTS: Foramen ovale electrodes could be detected easily in the patient, and bedside monitoring of explantation was possible. CONCLUSIONS: We were able to show the applicability of transcranial B-mode sonography for visualization of foramen ovale electrodes in preoperative electroencephalographic monitoring of patients with epilepsy. Further evaluation of this method in additional patients will follow.     

Low-sodium, high-potassium diet: feasibility and acceptability in a normotensive population

Sixty-nine normotensive volunteers participated in an eight-week study to test the feasibility and acceptability of two low-sodium (less than 70 mEq), high-potassium (greater than 100 mEq) diets. The diet groups differed only in the use of KCl salt substitute. Both dietary groups were able to reduce sodium and increase potassium intake compared to the control group. Urine sodium excretion decreased in the diet groups but no change was observed in potassium. Potassium chloride salt substitute was not used as recommended, suggesting its unacceptability.     

Treatment of distal ureteral stones in the horse riding position

From August 1986 through March 1987, 102 patients with 110 distal ureteral stones were treated in 110 sessions with the standard Dornier HM-3 lithotriptor in the so-called horse riding position. The majority of the patients (70 of 110, 63.7%) were treated for distal stones alone, whereas in a third (40 of 110, or 36.3%) treatment was performed for distal and upper stone localization during the same session. Additional treatment besides extracorporeal shock wave lithotripsy was necessary in 12.7% of the patients. Of the 110 patients 89.4% were without residual stones after a mean of 17.3 days. This modified position of the patient, which is specific to the Dornier HM-3 lithotriptor, makes possible treatment of distal ureteral stones with results comparable to those of endoscopic management but with less major complications (4.7%). A total of 7 patients had anal blood loss in the early postoperative period. Rectal bleeding ceased within 36 hours after treatment. The position also allows for treatment of stones at other, more proximal locations without great modifications to the position during the same session.     

Synthesis of retrovirus-like particles in testicular teratocarcinomas

Two lines of evidence led to the investigation of human teratocarcinoma cells in vitro for oncogenic retroviruses: the observation by electron microscopy of retrovirus-like particles budding from the syncytial trophoblasts of human placentas, and the demonstration that teratocarcinoma patients before treatment show a high serum antibody reactivity against envelope proteins of mammalian retroviruses. In all 5 teratocarcinoma cell lines studied so far, retrovirus-like particles have been detected by electron microscopy. The production of these human teratocarcinoma-derived (HTD)-particles is enhanced by induction procedures known to be effective in animal virus model systems. In parallel, virus induction also increases the level of chorionic gonadotropin in the culture supernatant, demonstrating syncytial trophoblast-like cells in the heterogeneous cell population of teratocarcinomas which could be responsible for HTD-particle production. The origin of these virus-like particles--endogenous or exogenous--as well as their role in the pathogenesis of teratocarcinomas is not known so far. The potential value of serum antibody reactivity in teratocarcinoma patients as a diagnostic marker is discussed.     

Bacillus calmette-guerin versus chemotherapy for the intravesical treatment of patients with carcinoma in situ of the bladder: a meta-analysis of the published results of randomized clinical trials

PURPOSE: We determined the short-term and long-term efficacy of bacillus Calmette-Guerin (BCG) and chemotherapy in the treatment of patients with carcinoma in situ (CIS). MATERIALS AND METHODS: A meta-analysis was performed on published results of randomized clinical trials comparing intravesical BCG to intravesical chemotherapy. RESULTS: Nine randomized trials including 700 patients with CIS compared BCG to either mitomycin C (MMC), epirubicin, adriamycin, or sequential MMC/adriamycin. Of 298 patients on BCG 203 (68.1%) had a complete response compared with 158 of 307 patients on chemotherapy (51.5%), a reduction of 47% in the odds of nonresponse on BCG (OR 0.53, p =0.0002). Based on a median followup of 3.6 years, 161 of 345 patients on BCG (46.7%) had no evidence of disease compared with 93 of 355 patients on chemotherapy (26.2%), a reduction of 59% in the odds of treatment failure on BCG (OR 0.41, p <0.0001). Although the long-term benefit of BCG was smaller in trials with MMC, BCG was superior to MMC in trials with maintenance BCG (OR 0.57, p =0.04). The reduction of 26% in the risk of progression on BCG (p =0.20) is consistent with the reduction of 27% (p =0.001) previously reported in a larger superficial bladder cancer meta-analysis. CONCLUSIONS: Intravesical BCG significantly reduces the risk of short and long-term treatment failure compared with intravesical chemotherapy. Therefore, it is considered to be the intravesical agent of choice in the treatment of CIS.