Beiträge zur Pathologie und Therapie der Toxischen Erkrankungen im Säuglings- und Kindesalter

Ohne Zusammenfassung     

Causes of Death and Risk Factors for Mortality in Patients With Severe Chronic Obstructive Pulmonary Disease

ObjectiveThe objective of this study was to assess the causes of death and risk factors for mortality in a cohort of patients with severe chronic obstructive pulmonary disease (COPD).Patients and methodsWe studied 203 patients with severe COPD (forced expiratory volume in 1 second [FEV₁] <50%), who were attended in our respiratory department day hospital (2001-2006). Clinical variables were recorded on inclusion, and clinical course and causes of death were retrospectively reviewed.ResultsThe mean (SD) age of patients was 69 (8) years and the mean FEV₁ was 30.8% (8.2%). One-hundred and nine patients died (53.7%); death was attributed to respiratory causes in 72 (80.9%), with COPD exacerbation being the most frequent specific cause within this category (48.3%). During follow-up, 18.7% required admission to the intensive care unit (ICU). Survival at 1, 3, and 5 years was 80%, 53%, and 26%, respectively. The multivariate analysis showed that mortality was associated with age, stage IV classification according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), cor pulmonale, and hospital admission during the year prior to inclusion. Need for admission to the ICU during follow-up was a factor independently associated with higher mortality.ConclusionsMortality in patients with severe COPD was high and exacerbation of the disease was one of the most frequent causes of death. Age, GOLD stage, cor pulmonale, prior admission to hospital, and need for admission to the ICU during follow-up were independent predictors of mortality.     

Usefulness of the N-Terminal Fraction of Brain Natriuretic Peptide for Deciding When to Refer Patients With Sleep Apnea-Hypopnea Syndrome to the Cardiologist

Introduction and objectiveWhen sleep apnea-hypopnea syndrome (SAHS) and cardiovascular disease occur concurrently, prognosis is affected. Echocardiography can detect structural cardiac abnormalities but using this technique in all patients would place a heavy burden on resources. The objective of this study was to investigate whether the N-terminal fraction of brain natriuretic peptide (NT-proBNP) can be used as a marker for silent heart disease.Patients and methodsNT-proBNP concentration was measured in the 114 consecutive patients with SAHS who underwent echocardiography before starting treatment. Left and right ventricular systolic and diastolic function, as well as structural abnormalities, were studied. Correlations between NT-proBNP concentration and the abnormalities detected were investigated. A receiver operating characteristics (ROC) curve was plotted for NT-proBNP concentration and cardiac abnormalities.ResultsData for 98 patients were finally analyzed. NT-proBNP concentration was significantly correlated with ventricular septal thickness (r=0.63), posterior wall thickness (r=0.45), and left ventricular enddiastolic diameter (r=0.51) (P<.0001 for all correlations). The area under the ROC curve was significant (0.870; 95% confidence interval, 0.801-0.939; P<.0001). Assuming that specificity would be more useful for clinical practice, we calculated that NT-proBNP concentrations below 100 and 200 pg/mL could rule out structural abnormalities with a reliability of 90% and 100%, respectively.ConclusionsNT-proBNP concentration was strongly correlated with echocardiographic abnormalities and so could be a useful tool for identifying patients who should be referred to the cardiologist.     

Curative Laparoscopic Resection for Pancreatic Neoplasms: A Critical Analysis from a Single Institution

Laparoscopic pancreatic surgery (LPS) has seen significant development but much of the knowledge refers to small and benign pancreatic tumors. This study aims to evaluate the feasibility, safety, and long-term outcome of the laparoscopic approach in patients with benign, premalignant, and overt malignant lesions of the pancreas. This study, currently, is the largest single center experience worldwide. One hundred twenty-three consecutive patients underwent laparoscopic pancreatic surgery from April 1998 to April 2007, 20 patients with cysts or pseudocysts for acute and chronic pancreatitis, laparoscopic pancreatic drainage was performed, and were excluded from the analysis. The 103 patients were divided based on preoperative diagnosis: group I, inflammatory tumors for chronic pancreatitis (eight patients); group II, cystic pancreatic neoplasms (29 patients); group III, intraductal papillary mucinous neoplasms (10 patients); group IV, neuroendocrine pancreatic tumors (NETs) (43 patients); and group V ductal adenocarcinoma (13 patients). The median tumor size was 5.3 cm. Pathologic data include R ₀ or R ₁ resection (transection margins on the specimen were inked). Perioperative data, postoperative complications, and resection modalities were compared using statistical analysis. Long-term outcomes were analysed by tumor recurrence and patient survival. The overall conversion rate was 7%. Laparoscopic distal pancreatic resection was performed in 82 patients (79.6%). Laparoscopic spleen-preserving distal pancreatectomy (Lap SPDP) was performed in 52 patients (63.7%), but with splenic vessels preservation in 22% and without splenic vessels preservation in 41.5%. Laparoscopic en-bloc splenopancreatectomy (Lap SxDP) was performed in 30 patients (36.6%) and laparoscopic enucleation (Lap En) in 20 patients (19.4%). There was no mortality. The overall complication rate was 25.2, 16.7, and 40% after Lap SPDP, Lap SxDP, and Lap En, respectively. The overall morbidity rate was significantly higher (p > 0.05) in the group of Lap SPDP without splenic vessels preservation comparing with Lap SPDP with splenic vessels preservation because of the occurrence of splenic complications (20.6%). The overall pancreatic fistulas was 7.7, 10, and 35% after Lap SPDP, Lap SxDP, and Lap En, respectively; the severity of fistula was significantly higher in the Lap En group (p > 0.05). The mean hospital stay was within 1 week in all groups, except in the group of ductal adenocarcinoma, which is 8 days. In this series, 27 patients (26.2%) had malignant disease. R ₀ resection was achieved in 90% of ductal adenocarcinoma and 100% for other malignant tumors. The median survival for ductal adenocarcinoma patients was 14 months. This series demonstrates that LPS is feasible and safe in benign-appearing and malignant lesions of the pancreas.     

Measurement of the residual radioactivity induced in the front foil of a target assembly in a modern medical cyclotron.

The levels of residual radioactivity induced in Havar foils at the entrance of a high-pressure 18O-enriched water target used for the production of 18F- in a medical cyclotron with 16 MeV protons have been determined using high-resolution gamma-ray spectrometry. Whole body and skin dose rates arising from exposure to these foils during their periodic replacement have been estimated. The results indicate that irradiated foils do not represent a significant radiological hazard for the cyclotron operating staff and that no waste disposal difficulties should be encountered after an appropriate 'cooling' period of 2 years.     

The R7 subfamily of RGS proteins assists tachyphylaxis and acute tolerance at mu-opioid receptors.

Members of the R7 subfamily of regulators of G-protein signaling (RGS) proteins (RGS6, RGS7, RGS9-2, and RGS11) are found in the mouse CNS. The expression of these proteins was effectively reduced in different neural structures by blocking their mRNA with antisense oligodeoxynucleotides (ODNs). This was achieved without noticeable changes in the binding characteristics of labeled beta-endorphin to opioid receptors. Knockdown of R7 proteins enhanced the potency of antinociception promoted by morphine and [D-Ala(2), N-MePhe(4), Gly-ol(5)]-enkephalin (DAMGO)-both agonists at mu-opioid receptors. The duration of morphine analgesia was greatly increased in RGS9-2 and in RGS11 knockdown mice. The impairment of R7 proteins brought about different changes in the analgesic activity of selective delta agonists. Knockdown of RGS11 reduced [D-Ala(2)]deltorphin II analgesic effects. Those of RGS6 and RGS9-2 proteins caused [D-Ala(2)]deltorphin II to produce a smoothened time-course curve-the peak effect blunted and analgesia extended during the declining phase. RGS9-2 impairment also promoted a similar pattern of change for [D-Pen(2,5)]-enkephalin (DPDPE). RGS7-deficient mice showed an increased response to both [D-Ala(2)]deltorphin II and DPDPE analgesic effects. A single intracerebroventricular (i.c.v.) ED(80) analgesic dose of morphine gave rise to acute tolerance in control mice, but did not promote tolerance in RGS6, RGS7, RGS9-2, or RGS11 knockdown animals. Thus, R7 proteins play a critical role in agonist tachyphylaxis and acute tolerance at mu-opioid receptors, and show differences in their modulation of delta-opioid receptors.     

Preparation of bupivacaine-loaded poly(epsilon-caprolactone) microspheres by spray drying: drug release studies and biocompatibility.

Poly(epsilon-caprolactone) microspheres containing bupivacaine were prepared by the spray-drying process. The average size of drug loaded microspheres was less than 3 microm in diameter, and the percentage of entrapment efficiency was 91 +/- 3%. In vitro drug release kinetic in phosphate buffer at 37 degrees C showed a hyperbolic profile, with a burst-effect during the first hour. Subcutaneous injection of bupivacaine-loaded microspheres in the back of rats caused an increase in drug concentration in plasma. Maximum bupivacaine concentration in plasma was 237 +/- 58 ng/ml at 105 h, and drug was detected in plasma for 16 days. The half-life time of the drug was increased by more than 125 times with regard to that of the drug administered in a solution by intraperitoneal injection. After 30 days of injection, a mass formed by microspheres surrounded by a thin fibrous capsule was observed. Small blood vessels and multinucleate foreign body giant cells with macrophagic function around microspheres were detected. After 60 days of injection a subcutaneous mass was also observed, which was formed of more degraded dispersed microspheres in conjunctive tissue, which had a normal structure. Thus, bupivacaine-loaded poly(epsilon-caprolactone) microspheres could be considered as a device to be used in the treatment of severe pain that is not responsive to opioids for example in cancer-related syndromes or in intractable herpetic neuralgia.     

Hepatic stellate cell activation in liver transplant patients with hepatitis C recurrence and in non-transplanted patients with chronic hepatitis C.

The pathogenic mechanisms of accelerated graft fibrosis in hepatitis C recurrence after liver transplantation (LT) are not well established. The aim of the study was to assess whether a greater activation of hepatic stellate cells (HSC), the major collagen-producing cells in the liver, can occur in these patients as compared to non-LT patients with chronic hepatitis C. We determined the amount of activated HSC by computer-based morphometric analysis of alpha-smooth muscle actin (alphaSMA)-positive cells and the hepatic TGFbeta(1) expression by immunohistochemistry in 46 LT patients with hepatitis C recurrence, 35 non-LT patients with chronic hepatitis C, and 16 controls. Hepatic alphaSMA and TGFbeta(1) expression was higher in LT patients with hepatitis C recurrence than in controls and was correlated with fibrosis stage and progression rate. No significant difference in alphaSMA and TGFbeta(1) expression was observed between LT and non-LT patients with hepatitis C, with the exception of a higher transforming growth factor beta-1 (TGFbeta(1)) expression in non-LT patients in the early stages of fibrosis. LT patients receiving cyclosporine (CsA) or tacrolimus (FK) had a similar fibrosis progression rate and alphaSMA and TGFbeta(1) expression. In conclusion, the accelerated fibrosis observed in LT patients with hepatitis C recurrence does not seem to be related to a greater amount of activated HSC and TGFbeta(1) expression in the grafts of these patients as compared to non-LT patients with chronic hepatitis C. In LT patients, the amount of activated HSC and TGFbeta(1) expression correlated with fibrosis stage and progression, without any apparent influence of the type of calcineurin inhibitor administered.