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Biomedical subjects

A Schneider

Publications and source records attributed to A Schneider.

At least 19 recordsLinked to original sources
PubMed2007

The partial 5-hydroxytryptamine1A receptor agonist buspirone does not antagonize morphine-induced respiratory depression in humans.

Based on experiments in rats, serotonin receptor 5-hydroxytryptamine (5-HT)(1A) agonists have been proposed as a potential therapeutic strategy for the selective treatment of opioid-induced respiratory depression. We investigated the clinical applicability of this principle in healthy volunteers. Twelve subjects received 0.43 mg/kg morphine (30 mg for 70 kg body weight) administered intravenously (i.v.) over approximately 2 h. At the start of the morphine infusion, they received in a randomized, double-blind cross-over design 60 mg p.o. buspirone or placebo. Respiratory depression (hypercapnic challenge) and pain (electrical stimuli: 5 Hz sinus 0-20 mA; chemical stimuli: 200 ms gaseous CO(2) pulses applied to the nasal mucosa) were assessed at baseline, at the end of the morphine infusion, and a third time after antagonizing the opioid effects by i.v. administration of 2 mg naloxone. The linear relationship between the minute ventilation and the CO(2) concentration in the inspired air of 1.07+/-0.27 l/mm Hg CO(2) at baseline conditions became shallower (0.45+/-0.23 l/mm Hg CO(2)) after morphine administration (P<0.001), indicating respiratory depression, which was significantly reversed by naloxone (0.95+/-0.43 l/mm Hg CO(2); P=0.001). Co-administration of buspirone had no effect on morphine-induced respiratory depression (slope 0.45+/-0.23 l/mm Hg CO(2) under morphine plus placebo versus 0.38+/-0.25 l/mm Hg CO(2) under morphine plus buspirone; P=0.7). Significant morphine-induced analgesia was observed in both pain models and was reversed by naloxone but unaffected by buspirone. Buspirone significantly increased the nausea induced by morphine (P=0.011). Oral co-administration of a high dose of the clinically available 5-HT(1A) agonist buspirone cannot be advised as a remedy for opioid-induced respiratory depression. This is indicated by its lack of anti-respiratory depressive effects and by the buspirone-associated increase of morphine-induced nausea.

Adult↗
PubMed2007

[Portal vein embolization preparation for major hepatic resection: a new standard in liver surgery].

Preoperative portal vein embolization (PVE) is increasingly used for operative treatment of patients scheduled to undergo liver resection when the volume of the future remnant liver appears to be insufficient. Portal vein embolization should be considered when the prospective postoperative liver volume is less than 20 % or less than 40 % in patients with known liver cirrhosis. Our own results (n = 28) demonstrated an average volume increase in segments II and III of 280 +/- 95 ml to 420 +/- 98 ml within 6 weeks after selective percutaneous- transhepatic embolization of the portal vein branches (IV)-V-VIII. Thus, an expanded right resection of the liver could be performed in all patients without major complications. None of the patients suffered from clinically relevant liver insufficiency within the first few postoperative months.

Bile Duct Neoplasms↗
PubMed2007

Anti-CD45RB monoclonal antibody prolongs renal allograft survival in cynomolgus monkeys.

Previously, an anti-CD45RB monoclonal antibody (mAb) has been shown to induce murine allograft tolerance. The present study was performed to assess the ability of an anti-human CD45RB mAb to prevent rejection in a monkey MHC-mismatched kidney transplant model. The recipients were allocated into the following treatment groups: (1) isotype control IgG; (2) mouse anti-human CD45RB IgG1 (6G3); (3) human-mouse chimeric anti-CD45RB-IgG1 (C6G3-IgG1); (4) human-mouse chimeric anti-CD45RB-IgG2 (C6G3-IgG2); (5) tacrolimus at a subtherapeutic dose and (6) tacrolimus and C6G3-IgG1 in combination. Monotherapy with anti-CD45RB mAb significantly prolonged renal allograft survival to a median survival of 21 days. Adding a subtherapeutic dose of tacrolimus improved the efficacy of the anti-CD45RB mAb, achieving a median survival of 85 days, whereas a subtherapeutic dose of tacrolimus alone only moderately prolonged survival to 27 days. Treatment with anti-CD45RB mAb resulted in an alteration of the CD45RB(hi) : CD45RB(lo) cell ratio in the peripheral blood. We have, for the first time, demonstrated that an anti-human CD45RB mAb (6G3) can prolong graft survival. Induction with an anti-CD45RB mAb improves the efficacy of tacrolimus in the prevention of rejection. These encouraging results indicate that an anti-CD45RB mAb may be valuable in future clinical transplantation.

Animals↗
PubMed2006

Evaluation of different protocols for gene transfer into non-obese diabetes/severe combined immunodeficiency disease mouse repopulating cells.

PURPOSE: Although gene transfer with retroviral vectors has shown distinct clinical success in defined settings, efficient genetic manipulation of hematopoietic progenitor cells remains a challenge. To address this issue we have evaluated different transduction protocols and retroviral constructs in the non-obese diabetes (NOD)/severe combined immunodeficiency disease (SCID) xenograft model. METHODS: An extended transduction protocol requiring 144 h of in vitro manipulation was compared to a more conventional protocol requiring 96 h only. RESULT: While pretransplantation analysis of cells transduced with a retroviral vector, expressing the enhanced green fluorescent protein (EGFP) marker gene, demonstrated significantly higher overall transduction rates for the extended protocol (33.6 +/- 2.3 vs. 22.1 +/- 3.8%), EGFP expression in CD34+ cells before transplantation (4.0 +/- 0.9 vs. 11.6 +/- 2.5%), engraftment of human cells in NOD/SCID bone marrow 4 weeks after transplantation (4.5 +/- 1.7 vs. 36.5 +/- 9.4%) and EGFP expression in these cells (0 +/- 0 vs. 11.3 +/- 2.8%) were significantly impaired. When the 96 h protocol was used in combination with the spleen focus forming virus (SFFV)/murine embryonic stem cell (MESV) hybrid vector SFbeta11-EGFP, high transduction rates for CD45+ (41.0 +/- 5.3%) and CD34+ (38.5 +/- 3.7%) cells prior to transplantation, as well as efficient human cell engraftment in NOD/SCID mice 4 weeks after transplantation (32.4 +/- 3.5%), was detected. Transgene expression was observed in B-lymphoid (15.9 +/- 2.0%), myeloid (36.5 +/- 3.5%) and CD34+ cells (10.1 +/- 1.5%). CONCLUSION: Our data show that CD34+ cells maintained in cytokines for multiple days may differentiate and loose their capacity to contribute to the haematological reconstitution of NOD/SCID mice. In addition, the SFFV/MESV hybrid vector SFbeta11-EGFP allows efficient transduction of and gene expression in haematopoietic progenitor cells.

Animals↗
PubMed2006

The frequency of inappropriate tablet splitting in primary care.

INTRODUCTION: We assessed the frequency and determinants of tablet splitting in primary care in Germany and evaluated the quality of information on divisibility in the Summary of Product Characteristics (SPCs) and in the Package Leaflet (PL) as legal sources of information for health care providers and patients. METHODS: We performed a cross-sectional questionnaire survey among patients of 59 general practitioners in the German Federal State Saxony-Anhalt in 2005 in order to collect detailed information on all drugs of patients maintained on more than three drugs. RESULTS: The response rate was 82.1% (n=905) and 3,158 drugs (tablets and dragées) were included in the analyses. Of all drugs, 24.1% were split (762 of 3,158): 8.7% of all split tablets were unscored (66 of 762) and 3.8% of all split tablets were not allowed to be split (29 of 762). Tablets of the higher price categories and higher strengths were twice as likely to be split. Only 22.5% of the SPCs (9 of 40) of the split unscored tablet brands contained explicit information on divisibility and only 36.4% of the PLs (8 of 22) of the split brands that were not allowed to be split stated that splitting was not appropriate. CONCLUSION: The splitting of tablets in primary care is a frequent habit likely driven by medical and economic considerations. Almost 1% of all tablets are split that must not be fragmented. However, the SPC and PL provide only limited information on divisibility stressing the need to improve this information promptly to avoid medication errors.

Aged↗
PubMed2006

Change of procalcitonin predicts clinical outcome of febrile episodes in patients with hematological malignancies.

BACKGROUND: Procalcitonin (PCT) was widely investigated in febrile neutropenia as an indirect marker of infection. Many institutions also use PCT as a tool to monitor the course of a febrile episode because increases in PCT values during the febrile episode were associated with development of complications. However, to date, no study systematically evaluated the accuracy of decreasing PCT values in predicting favorable outcomes of a febrile episode. The aim of this study was to evaluate the changes in PCT values after resolution of fever with regard to their predictive value of stable defervescence. MATERIALS AND METHODS: PCT was studied prospectively in 94 febrile episodes of 35 patients with hematological malignancies. RESULTS: Sixty-seven episodes were associated with an increased level of PCT at the beginning. In these episodes, stable resolution of fever was significantly correlated with a decrease in PCT values. The best cut-off level to predict freedom from recurrence of fever for at least 5 days was <70% of the maximum PCT value on the second afebrile day. Out of 44 patient episodes with a subsequent decrease to <70%, only two patients had recurrent fever within the next 5 days, revealing a negative predictive value of 95%, p<0.001. CONCLUSION: Our study supports the value of PCT as a reliable tool to predict clinical outcome in febrile neutropenia.

Aged↗
PubMed2006

Early, sustained efficacy of adeno-associated virus vector-mediated gene therapy in glycogen storage disease type Ia.

The deficiency of glucose-6-phosphatase (G6Pase) underlies life-threatening hypoglycemia and growth retardation in glycogen storage disease type Ia (GSD-Ia). An adeno-associated virus (AAV) vector encoding G6Pase was pseudotyped as AAV8 and administered to 2-week-old GSD-Ia mice (n = 9). Median survival was prolonged to 7 months following vector administration, in contrast to untreated GSD-Ia mice that survived for only 2 weeks. Although GSD-Ia mice were initially growth-retarded, treated mice increased fourfold in weight to normal size. Blood glucose was partially corrected by 2 weeks following treatment, whereas blood cholesterol normalized. Glucose-6-phosphatase activity was partially corrected to 25% of the normal level at 7 months of age in treated mice, and blood glucose during fasting remained lower in treated, affected mice than in normal mice. Glycogen storage was partially corrected in the liver by 2 weeks following treatment, but reaccumulated to pre-treatment levels by 7 months old (m.o.). Vector genome DNA decreased between 3 days and 3 weeks in the liver following vector administration, mainly through the loss of single-stranded genomes; however, double-stranded vector genomes were more stable. Although CD8+ lymphocytic infiltrates were present in the liver, partial biochemical correction was sustained at 7 m.o. The development of efficacious AAV vector-mediated gene therapy could significantly reduce the impact of long-term complications in GSD-Ia, including hypoglycemia, hyperlipidemia and growth failure.

Animals↗
PubMed2006

Cholangioscopic characterization of dominant bile duct stenoses in patients with primary sclerosing cholangitis.

BACKGROUND AND STUDY AIMS: Primary sclerosing cholangitis (PSC) is associated with the development of cholangiocarcinoma in up to 10 % of patients. Cholangiography or endoscopic tissue sampling does not reliably distinguish between cholangiocarcinoma and a benign dominant bile duct stenosis. The aim of the present study was to assess the value of cholangioscopy for distinguishing between benign and malignant dominant stenoses in PSC patients. PATIENTS AND METHODS: Fifty-three PSC patients with dominant bile duct stenoses were prospectively studied. Transpapillary cholangioscopy and endoscopic tissue sampling were carried out in addition to endoscopic retrograde cholangiography (ERC). The cholangiography and cholangioscopic findings were classified as malignant or benign by the investigators. A final diagnosis of malignant stenosis was based on positive histology and/or cytology, whereas a benign condition was assumed in cases of negative tissue sampling and uneventful extended clinical follow-up. RESULTS: Twelve PSC patients (23 %) had dominant bile duct stenoses caused by cholangiocarcinoma, whereas 41 of the 53 patients (77 %) had benign dominant bile duct stenoses. Cholangioscopy was significantly superior to ERC for detecting malignancy in terms of its sensitivity (92 % vs. 66 %; P = 0.25), specificity (93 % vs. 51 %; P < 0.001), accuracy (93 % vs. 55 %; P < 0.001), positive predictive value (79 % vs. 29 %; P < 0.001), and negative predictive value (97 % vs. 84 %; P < 0.001). Transpapillary cholangioscopy is more sensitive and specific for characterizing malignant bile duct stenosis in comparison with endoscopic brush cytology. CONCLUSIONS: Transpapillary cholangioscopy significantly increases the ability to distinguish between malignant and benign dominant bile duct stenoses in patients with PSC.

Adolescent↗
PubMed2006

Long-term mortality after intracerebral hemorrhage.

OBJECTIVE: To characterize long-term mortality following intracerebral hemorrhage (ICH) in two large population-based cohorts assembled more than a decade apart. METHODS: All patients age > or = 18 hospitalized with nontraumatic ICH in the Greater Cincinnati/Northern Kentucky area were identified during 1988 (Cohort 1) and from May 1998 to July 2001 and August 2002 to April 2003 (Cohort 2). Mortality was tabulated using actuarial methods and compared with a log-rank test. RESULTS: There were 183 patients with ICH in Cohort 1 and 1,041 patients in Cohort 2. Patients in Cohort 1 were more likely to be white (p = 0.024) and undergo operation for their ICH (p = 0.002), whereas patients in Cohort 2 were more commonly on anticoagulants (p < 0.001). Among patients in Cohort 1, mortality at 7 days, 1 year, and 10 years was 31, 59, and 82%. Among patients in Cohort 2, mortality at 7 days and 1 year was 34 and 53%. Mortality rates did not differ between cohorts by log-rank test (p = 0.259). CONCLUSIONS: Intracerebral hemorrhage (ICH) mortality did not improve significantly between study periods. Operation for ICH became less frequent, whereas anticoagulant-associated ICH became more common.

Cerebral Hemorrhage↗
PubMed2006

Clinical and functional characteristics of the human Arg59Ter insulin-like growth factor i receptor (IGF1R) mutation: implications for a gene dosage effect of the human IGF1R.

CONTEXT: Signaling via the IGF-I receptor (IGF-IR) is crucial for normal prenatal and postnatal growth. The heterozygous IGF-IR mutation Arg59Ter resulted in reduced IGF-IR expression and represents haploinsufficiency of the human IGF1R gene. OBJECTIVE: We studied clinical and in vitro aspects of a human IGF1R gene dosage effect. We provide detailed clinical data on the two half-brothers and their mother with the Arg59Ter mutation. Arg59Ter and control fibroblasts were examined for functionality of IGF-I and insulin-stimulated receptor phosphorylation and signal transduction. RESULTS: The two brothers presented with primary microcephaly, mild mental retardation, and intrauterine as well as postnatal growth deficits. After GH therapy (30 microg/kg.d) for 24 months, the growth deficit in the propositus decreased by +1.0 sd. There was no clinical evidence for impaired glucose tolerance or hypoglycemia in all Arg59Ter subjects. In vitro, IGF-IR-deficient Arg59Ter cells expressed less IGF-IR and unchanged insulin receptor (IR) protein. Receptor autophosphorylation and phosphorylation of downstream protein kinase B/Akt exhibited resistance to IGF-I but showed an augmented response to insulin in Arg59Ter cells. Decreased IGF-IR content was accompanied by a reduction of IGF-IR/IR receptor hybrids, and therefore, increased levels of IR/IR homodimers probably explain increased insulin-stimulated receptor autophosphorylation and Akt phosphorylation. CONCLUSIONS: In vivo and in vitro IGF-I resistance in Arg59Ter subjects and fibroblasts indicates a human IGF1R gene dosage effect involving not only the IGF-IR, but also IGF-IR/IR hybrids. The abundance of both the IGF-IR protein and IGF-IR/IR hybrid receptors may have an impact on human growth, organ function, and glucose metabolism.

Body Weight↗
PubMed2006

Serum gamma-glutamyltransferase is a predictor of incident coronary events in apparently healthy men from the general population.

OBJECTIVE: To investigate whether serum gamma-glutamyltransferase (GGT) is an independent predictor for incident coronary events in initially healthy men from the general population. METHODS AND RESULTS: The study was based on 1878 men (aged 25-64 years) who participated in the first MONICA Augsburg survey 1984/1985, and who were free of coronary heart disease at baseline. Up to 2002 a total of 150 incident acute coronary events occurred. Baseline levels of GGT were higher in men who experienced an event than in event-free men (28.4+/-2.0 units/l versus 22.4+/-2.1 units/l, p 0.0002). GGT was highly correlated with other cardiovascular risk factors. In a Cox proportional hazards model after age adjustment hazard ratios (HR) for incident myocardial infarction across GGT quartiles (<13, 13 to <20, 20 to <35, and >/=35 units/l) were 1.0, 1.84, 2.02, and 3.08 (p for trend 0.0001). Further adjustment for hypertension, TC/HDL ratio, diabetes, smoking, physical activity, alcohol intake, education years and BMI attenuated the association; comparing the highest versus lowest quartile of GGT the HR for a first-ever coronary event was then 2.34 (95% CI, 1.23-4.44). CONCLUSIONS: Serum GGT is a strong predictor of acute coronary events in apparently healthy men from the general population, independent of other risk factors for cardiovascular disease.

Adult↗
PubMed2006

[Acute femoral artery thrombosis after thrombin injection of a pseudoaneurysm].

HISTORY: A 64-year old woman was admitted because of unstable angina pectoris. The coronary angiogram revealed two-vessel coronary disease with predominantly subtotal stenosis of the right coronary artery, which was treated by primary coronary stenting. The post-interventional clinical course after closure of the right femoral artery was complicated by the development of a complex pseudoaneurysm: its ultrasound-guided compression was unsuccessful. INVESTIGATIONS: The clinical findings included a marked superficial hematoma in the right groin without any evidence of an abscess, confirmed by color duplex ultrasonography. TREATMENT AND COURSE: 24 hours later a successful percutaneous ultrasound-guided thrombin injection of the pseudoaneurysm was performed without any problems regarding the injection into the aneurysm. A small area within the aneurysm remained perfused and was treated by additional ultrasound-guided compression. A few minutes after the compression complete thrombosis of the right superficial femoral artery occurred with acute critical ischemia of the right leg, probably due to leakage of thrombin into the femoral artery at the sheath puncture. The immediate therapy, including interventional recanalization of the right femoral superficial artery and subsequent fibrinolysis, produced a complete reperfusion of the right femoral superficial and popliteal artery. The fibrinolytic therapy resolved the thrombosis of the pseudoaneurysm. The remainder of the perfused pseudoaneurysm was treated surgically after one week without problems. CONCLUSION: This case demonstrates a so far rarely published complication of the displacement of thrombin from an intervention ally treated pseudoaneurysm into the right superficial femoral artery through a broad compound channel after ultrasound-guided compression.

Aneurysm, False↗
PubMed2006

Primary tumour genetic alterations and intra-tumoral heterogeneity are maintained in xenografts of human colon cancers showing chromosome instability.

Evaluation of the role of clonal heterogeneity in colon tumour sensitivity/resistance to drugs and/or in conferring metastatic potential requires an adequate experimental model in which the tumour cells maintain the initial genetic alterations and intra-tumoral heterogeneity through maintenance of the genetic clones present in the initial tumour. Therefore, we xenografted subcutaneously into nude mice seven human colonic tumours (from stages B1 to D) that showed chromosome instability and transplanted them sequentially for up to 14 passages. Maintenance after xenografting of the genetic alterations present in the initial tumours was scored by allelotype studies targeting 45 loci localized on 18 chromosomes. We show that xenografting does not alter the genetic or the histological profiles of the tumours even after 14 passages. Screening of the entire genome of one tumour by comparative genome hybridization also showed overall stability of the alterations between the initial and the xenografted tumour. In addition, intra-tumoral heterogeneity was maintained over time, suggesting that no clonal selection occurred in the nude mice. The observation that some loci showed partial allelic imbalance in the initial tumour but loss of heterozygosity after the first passage in nude mice when all the normal cells were lost may allow identification of interesting genetic defects that could be involved in tumour expansion. Thus, sequential xenografts of colon tumours will provide a powerful model for further study of tumour clonality and for the identification of genetic profiles responsible for differential resistance to therapeutic treatments. Our data also suggest that tumour expansion can result from alterations in several distinct genetic pathways.

Allelic Imbalance↗
PubMed2006

[Regulated hypothermia after cardiac arrest. A glimpse into the future].

The introduction of therapeutic mild hypothermia after cardiac arrest allows the neuronal damage caused by global cerebral ischemia to be advantageously influenced for the first time. Currently, hypothermia is induced by external or internal cooling of the patient (forced hypothermia). However, this results in activation of counter-regulation mechanisms which could be possible risk factors for the patient. The aim of this article is to give a review of possible, but at present only experimental, methods which could allow the body temperature set point to be decreased pharmacologically (regulated hypothermia). Various classes of substances will be discussed based on their effect on thermoregulation and their performance in animal experiments on cerebral ischemia.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2006

[Testicular metastasis of a metachronous small cell neuroendocrinic prostate cancer after anti-hormonal therapy of a prostatic adenocarcinoma. Case report and literature review].

Secondary malignant testicular tumors are rare, with the exception of infiltrations by lymphomas and leukemias. Metastases are sometimes found in cancers of the lung, gastrointestinal tract, kidney, skin and prostate. Less than about 200 cases of testicular metastasis of prostate cancer have been described in the literature. This is this a very small number in comparison to the high incidence of prostate cancer and the vast number of orchiectomies for operative hormone deprivation in advanced cases. The testicle metastases described are mostly unilateral and are often found as ductal carcinoma of the prostate. In our case, the testicular metastasis from a small cell prostate carcinoma appeared 2.5 years after androgen deprivation of an adenocarcinoma of the prostate.

Aged↗
PubMed2006

Complications in laparoscopic myomectomy.

BACKGROUND: An increasing number of patients with fibroids wish to retain their uterus without improving fertility. We evaluated the rate of complications in our teaching hospital and its association with patients' age. METHODS: Chart records of 351 patients were evaluated according to patients' age. RESULTS: A total of 654 fibroids were removed. Mean size of fibroids was 5.3 cm; mean duration of surgery was 113.2 min. Blood transfusion was necessary in one patient. The intraoperative complication rate was 2.6% and postoperative complications occurred in 5.7% of patients. Sonographic evaluation showed a hyperechogenic scar in 29.2%. A total of 57.1% pregnancies ended in term infants. No uterine rupture was reported. As a sign of contentment, 87% of patients would choose the same procedure again. Indication for myomectomy in elder women was more often associated with uncertain sonographic findings due to intraligamentary localization. CONCLUSION: Morbidity was low. Age had no impact. Laparoscopic myomectomy can be offered to all women.

Adult↗
PubMed2006

[Inhalative application devices for patients suffering from asthma bronchiale].

Asthma is a chronic inflammatory disorder of the airways. It is caused by infiltration of eosinophils, mast cells, and CD4+ -T-lymphocytes which leads to variable airway obstruction. The core element of therapy is to control inflammation, which is best possible with inhaled steroids, the so-called controller drugs. Cromones are only second line therapeutic agents because they are not powerful enough for optimal inflammation control. Reliever drugs like beta2-agonists or anticholinergic agents serve as a symptomatic medication because they only lead to bronchial dilatation. The inflammation in COPD is caused by neutrophils, macrophages and CD8+ -T-lymphocytes. This kind of inflammation causes an irreversible airway obstruction accompanied by destruction of the lung parenchyma. By the majority, only symptomatic medication is effective for COPD, like anticholinergic agents and beta2-agonists. About 10-20% of patients with COPD are showing improvement when treated with inhaled steroids. However, the best treatment result is only guaranteed by optimal application of the medication. The most important barrier is an insufficient coordination between manual use of the inhaling system and inhalation. Various attempts are made to solve this problem, thus leading to a huge variety of application systems. However this also leads to confusion of patients and doctors because it is difficult to choose the optimal system and to use it in the most efficient way. This article provides an overview of the different application systems and compiles important details to facilitate the optimal application of inhalation therapy by the patient.

Administration, Inhalation↗