PubMed Health⌕ Search

Biomedical subjects

P Bach

Publications and source records attributed to P Bach.

At least 19 recordsLinked to original sources
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↗
PubMed2005

[Survival and pattern of failure in palliative endobronchial HDR -- brachytherapy using iridium 192 in recurring bronchial carcinoma].

To evaluate the impact of palliative high dose rate brachytherapy on survival and a pattern of failure, we performed a matched pair study. 94 patients with tumor recurrence after external beam radiation received endobronchial brachytherapy. They were followed prospectively and matched retrospectively with 94 comparable patients who had not received brachytherapy. Matched parameters were age, gender, smoking behaviour, histology, tumor stage, EBRT-dose and fractionation. The leading cause of death in both groups was generalized tumor growth. In the combined therapy group, fatal hemorrage was 27.7 %, two and a half times higher than in the EBRT group with 10.6 %, whereas respiratory insufficiency in the brachytherapy group was 6.4 % and 11.7 % in the EBRT group. A complete remission after brachytherapy yielded a 10.5 months longer mean survival. Patients dying from fatal hemorrhage after endobronchial brachytherapy lived on average 10.2 months longer than matched EBRT patients dying from the same cause. Analyzing the time-course of fatal hemorrage in the brachytherapy group we conclude that - because of its early onset in the first 10 months after induction of therapy roughly 20 % of the deaths can be attributed to a radiation damage. In those patients who died after 10 months the major cause of fatal hemorrhage was the natural course of sqamous cell carcinoma with prolonged survival.

Brachytherapy↗
PubMed2002

Cytokine profiles in peripheral blood mononuclear cells and lymph node cells from piglets infected in utero with porcine reproductive and respiratory syndrome virus.

The aim of the present study was to investigate at 2, 4, and 6 weeks after birth cytokine expression by peripheral blood mononuclear cells and bronchial lymph node cells from piglets infected in utero with porcine reproductive and respiratory syndrome virus (PRRSV). Technically, by flow cytometry we were able to measure gamma interferon (gamma-IFN), tumor necrosis factor alpha (TNF-alpha), interleukin-4 (IL-4), and IL-8 levels. In general, we found increases in the percentages of IL-4-, gamma-IFN-, and TNF-alpha-producing lymphocytes in the infected piglets compared to the percentages in the uninfected control animals, while there was a decrease in the percentage of IL-8-producing monocytes. We believe that these findings reflect a general lymphocyte activation stage that is created due to the infection and that occurs in combination with impairment of the monocyte function, possibly due to the ongoing viral replication in these cells. Single-cell bronchial lymph node preparations exhibited very much the same cytokine profiles as peripheral blood mononuclear cells except for a lack of IL-8 production. When the levels of the individual cytokines in the three groups of PRRSV-infected piglets were compared, the levels of cytokine expression at 4 weeks diverged from those at 2 and 6 weeks, in that there was a significant decrease in the numbers of lymphocytes producing gamma-IFN and TNF-alpha. This tendency was also observed among blood monocytes and lymph node macrophages. Possible reasons for this temporary immunosuppression in the piglets at 4 weeks are discussed.

Animals↗
PubMed2000

Type and position of promoter elements in retroviral vectors have substantial effects on the expression level of an enhanced green fluorescent protein reporter gene.

PURPOSE: Although gene transfer with retroviral vectors has already been applied to patients as part of clinical protocols, low expression of transgenes in target cells still remains a problem. Therefore, we compared various retroviral vectors using different promoters and backbones for expression of the enhanced green fluorescent protein (EGFP) reporter gene in fibroblasts and CD34+ cells. METHODS: The N2A retroviral vector was used to test expression from the herpes simplex virus thymidine kinase promoter (vector N2A-TK-EGFP), a human phosphoglycerate kinase promoter (vector N2A-PGK-EGFP), and the SV40 promoter (vector N2A-SV-EGFP). Additional constructs used the spleen focus-forming virus (SFFV) long terminal repeat (LTR) as promoter and expressed EGFP alone (vector SFbeta1-EGFP) or EGFP and a downstream (vector SFbeta1-EGFP-IRES) or upstream (vector SFbeta1-IRES-EGFP) internal ribosomal entry site. RESULTS: For NIH 3T3 cells the fluorescence-activated cell sorting analysis revealed that the most active internal promoter was the SV40 promoter in the vector N2A-SV-EGFP (mean fluorescence intensity, MFI, 66.7 +/- 0.4), followed by N2A-PGK-EGFP (26.3 +/- 1.8 MFI), and N2A-TK-EGFP (4.8 +/- 0.1 MFI). Expression from the SFbeta1-EGFP vector (82.6 +/- 6.7 MFI) and the SFbeta1-EGFP-IRES vector (102.8 +/- 6.2 MFI) was higher than from SFbeta1-IRES-EGFP vector (15.5 +/- 1.8 MFI). In human CD34-positive cells, the EGFP expression from all vectors was considerably lower than in fibroblasts with the SFbeta1-EGFP vector still being four- to fivefold more active than the internal promoters tested. CONCLUSION: The SFFV LTR seems to allow a high expression of transgenes, as long as the transgene is not expressed downstream of an internal ribosomal entry site. Internal promoters may be useful for targeted gene expression in specific cell types, but the reduced level of expression from some internal promoters has to be taken into consideration.

3T3 Cells↗
PubMed1994

Ultrasonic evaluation of bladder neck position and mobility: the influence of urethral catheter, bladder volume, and body position.

The influence of urethral catheter, bladder volume, and body position on the ultrasonic assessment of bladder neck position and mobility was evaluated in 24 incontinent women. The bladder neck position was described by two independent parameters: BS-distance, from the bladder neck to the lower tip of the symphysis pubis, and the rotation angle between the BS-line and the symphyseal middline. Catheterisation resulted in apposition of the bladder neck towards the symphysis pubis, seen as a significant shortening of the BS-distance in postmenopausal women without estrogen replacement. The rotation angle was unaffected. Increasing the bladder volume to symptomatically full resulted in increased capacity to withhold, since the rotation angle decreased 6.6 degrees. Examination in the sitting position, compared to the supine resulted in bladder neck descent to a "lower level," and the rotation angle increased in average 16 degrees. Bladder neck mobility was unaffected by catheterisation and body position. Vaginal ultrasonic evaluation of bladder neck suspension is recommended to be performed without a catheter, with a comfortably full bladder in a convenient, but standardised examination position.

Adult↗
PubMed1994

Changes in rabbit corneal epithelial membrane permeability caused by locally applied Pseudomonas aeruginosa cytotoxin: a microfluorometric examination in vivo.

The effects of a pore-forming protein from Pseudomonas aeruginosa on the rabbit cornea were tested in vivo by measuring intraepithelial carboxyfluorescein accumulation. Carboxyfluorescein diacetate and subsequently the P. aeruginosa cytotoxin were applied by means of contact lenses with a spherical cavity on the concave surface. This allowed the application of defined concentrations of carboxyfluorescein diacetate and cytotoxin on a defined area of the corneal epithelium. Starting at 0.5 microM, cytotoxin increased the epithelial cell membrane permeability for the intracellular carboxyfluorescein within 1 min. At higher concentrations cells were shed from the epithelium. Corresponding morphological changes of the cellular structure of the corneal epithelium were observed and documented by fluorescence photomicrography. The healing process of toxified corneal epithelium appeared to be complete within 3 days. The data presented here indicate the possible role of cytotoxin-induced changes in epithelial permeability in P. aeruginosa infections. In this context, the role of soft contact lenses as a possible cytotoxin reservoir is discussed.

ADP Ribose Transferases↗
PubMed1994

Application of nuclear analytical techniques using long-life sealed-tube neutron generators.

The new range of sealed-tube neutron generators developed by SODERN appears to be appropriate for the industrial environment. The main characteristics are the high emission stability during the very long lifetime of the tube, flexible pulsed mode capability, safety in operation with no radiation in "off" state, and the easy transportation of equipment. Some applications of the neutron generators, called GENIE, are considered: high-sensitivity measurement of transuranic elements in nuclear waste drums, bulk material analysis for process control, and determination of the airborne pollutants for environmental monitoring.

Air Pollutants, Radioactive↗
PubMed1994

[Minimally invasive surgery in persistent pneumothorax and pneumocystis carinii infection].

The most frequent pulmological complication of AIDS is pneumocystis carinii pneumonia (PCP), which in 2% of cases will cause a spontaneous pneumothorax. Every AIDS patient who develops a pneumothorax is highly suspicious for a pneumocystis carinii pneumonia too. We describe the case of an AIDS patient who suffered from pneumothorax caused by PCP. Conventional tube thoracostomy with continuous suction and tetracycline pleurodesis were unsuccessful. The patient recovered however after resection of PCP cysts in the apical upper lobe and talcum pleurodesis by means of minimally invasive surgery.

AIDS-Related Opportunistic Infections↗
PubMed1992

A comparison of electrophysiologically guided antiarrhythmic drug therapy with beta-blocker therapy in patients with symptomatic, sustained ventricular tachyarrhythmias.

BACKGROUND: Antiarrhythmic drug therapy guided by invasive electrophysiologic testing is now widely used in patients with symptomatic, sustained ventricular tachyarrhythmias. METHODS: We conducted a prospective, randomized trial in 170 patients to investigate whether this approach would improve long-term outcome. Patients whose arrhythmia was inducible by programmed electrical stimulation were assigned to treatment with electrophysiologically guided drug therapy based on serial testing (61 patients) or with metoprolol (54 patients). Electrophysiologically guided therapy consisted of serial testing of antiarrhythmic agents to identify the first one that rendered the arrhythmia noninducible. The 55 patients whose arrhythmia was noninducible during the initial electrophysiologic test were also treated with metoprolol. RESULTS: During a mean (+/- SD) follow-up period of 23 +/- 17 months, recurrent, nonfatal arrhythmia occurred in 44 patients and sudden death due to cardiac factors in 27. The incidence of symptomatic arrhythmia and sudden death combined was virtually the same in the two groups with inducible arrhythmia after two years of observation (electrophysiologically guided therapy vs. metoprolol therapy, 46 percent vs. 48 percent). The outcome was more favorable in the patients with noninducible arrhythmia at base line (75 percent had neither adverse event) than in those with inducible arrhythmia who were assigned to metoprolol therapy (P = 0.009 by log-rank test). Only 6 of the 29 patients (21 percent) with inducible arrhythmia that became noninducible during drug therapy had recurrent arrhythmia or sudden death, as compared with 21 of the 32 patients (66 percent) with arrhythmia that continued to be inducible (P less than 0.001). A multivariate regression analysis identified continued inducibility of the arrhythmia as an independent predictor of recurrent arrhythmia or sudden death (relative risk, 7.3; 95 percent confidence interval, 2.3 to 23.2; P less than 0.001). CONCLUSIONS: As compared with metoprolol therapy, electrophysiologically guided antiarrhythmic drug therapy did not improve the overall outcome of patients with sustained ventricular tachyarrhythmias. However, effective suppression of inducible arrhythmia by antiarrhythmic drugs was associated with a better outcome than was lack of suppression.

Adrenergic beta-Antagonists↗
PubMed1992

Influence of assay methods on serum concentrations of digoxin during FAB fragment treatment.

The treatment of digoxin intoxication has been revolutionized by digoxin specific antibody fragments (Fab). Serum digoxin concentrations may be inaccurate after this treatment. We report a case of digoxin intoxication where the results of serum concentration determinations were strikingly disparate depending on the assay used. To investigate this discrepancy we compared serum samples spiked with digoxin from 0-50 ng/mL in the presence of increasing concentrations of digoxin specific Fab-fragments. Samples were measured using the Abbott TDx assay with and without ultrafiltration of the sample and the Dade-Stratus radial partition assay. The TDx assay was statistically reduced by the Fab-fragments although the magnitude of the effect was small. The radial partition assay was dramatically affected by the addition of Fab-fragments. The predicted non-Fab bound concentration correlated highly with the measured concentration. When samples were ultrafiltered prior to TDx assay, the measured concentration was dramatically depressed but the regression of predicted non-Fab bound concentration versus observed had a significantly lower slope than for the radial partition assay. We hypothesize that this difference is due to serum protein binding in addition to Fab-fragment binding. We conclude that the radial partition assay gives the best approximation of digoxin concentration remaining unbound to Fab-fragments. Ultrafiltration followed by TDx assay gives an acceptable approximation.

Antigen-Antibody Reactions↗
PubMed1992

[Anti-arrhythmia and pro-arrhythmia effects of oral cibenzoline therapy in sustained ventricular tachycardia].

The efficacy and safety of the new class-I antiarrhythmic drug cibenzoline was assessed in 12 patients with spontaneous and inducible ventricular tachycardia. Programmed ventricular stimulation, 24-h ambulatory electrocardiogram (ECG), and continuous ECG monitoring were performed without antiarrhythmic drugs and after oral administration of 254 +/- 80 mg of the substance. Oral cibenzoline suppressed the induction of tachycardia in only one patient. Induction of tachycardia was more difficult in two patients, unchanged in four patients, and easier in two patients. Cycle length of induced tachycardia and QT-interval corrected for frequency were not changed significantly; effective refractory period of the right ventricle was prolonged. Twenty-four hours of ambulatory monitoring during cibenzoline treatment (n = 9) showed no significant increase in the frequency of ventricular premature complexes. However, spontaneous sustained ventricular tachycardia developed in three patients after initiation of cibenzoline treatment. In two patients, termination of induced ventricular tachycardia was significantly more difficult under cibenzoline; several DC-shocks were required to terminate the tachycardia. Thus, the use of oral cibenzoline in patients with sustained spontaneous and inducible ventricular tachycardias showed a low antiarrhythmic efficacy at programmed stimulation and a high incidence of spontaneous ventricular tachycardia.

Adult↗
PubMed1988

[Therapy of paroxysmal atrial fibrillation. Cardiac glycosides alone or combined with anti-arrhythmia agents?].

In a prospective study 45 patients with paroxysmal atrial fibrillation were randomly assigned to one of three groups (of 15 patients each): group I received oral digoxin, three times 0.125 mg up to twice 0.25 mg daily; group II oral digoxin twice 0.125 mg and quinidine hydrogen sulphate 750-1000 mg daily; group III oral digoxin three times 0.125 mg and flecainide 200-300 mg daily. During a mean observation period of 11 months digoxin alone was significantly less effective (P less than 0.05) in reducing or suppressing paroxysms of atrial fibrillation than digoxin plus quinidine or flecainide. Flecainide with digoxin was more effective than the drug regimen in groups I and II (P less than 0.05). Two patients each in groups I and III had side effects, eight in group II. The results suggest that, at the chosen dosage, flecainide produces fewer side effects than quinidine.

Administration, Oral↗
PubMed1988

Electrophysiologic and antiarrhythmic effects of carocainide in humans.

Electrophysiologic and antiarrhythmic effects of the new benzofurane derivative carocainide given intravenously have been studied in normal patients (Group I) and in patients with paroxysmal supraventricular tachycardias (Group II). In normal patients (n = 10), carocainide increased sinoatrial conduction time, PR, PA, AH, and HV interval, QRS duration, as well as QT and QTc intervals. Sinus rate and sinus node recovery time were not influenced and refractory periods of right atrium, AV node, and right ventricle were unchanged. Like class I-C antiarrhythmic drugs, carocainide causes an increase of QRS duration without significant lengthening of the QT interval. In patients of Group II (n = 12), the ability of carocainide to interrupt supraventricular reentrant tachycardia was studied. In 11 of 12 patients (11 patients with regular atrioventricular reentrant tachycardia incorporating an accessory pathway, one patient with AV node reentry), sustained tachycardia was stopped by intravenous injection of carocainide in a dose of 3.5 mg/kg body weight. No major adverse effects were seen during or after administration of the drug. Carocainide was effective in the short-term treatment of supraventricular tachycardias. Further studies must show whether these promising effects can also be obtained during long-term oral treatment.

Adult↗
PubMed1986

Electrophysiologic and antiarrhythmic efficacy of oral sotalol for sustained ventricular tachyarrhythmias: evaluation by programmed stimulation and ambulatory electrocardiogram.

Programmed ventricular stimulation and ambulatory electrocardiography were performed both before and during oral sotalol therapy in 39 patients with ventricular tachyarrhythmia inducible by programmed stimulation (sustained ventricular tachycardia [n = 31], ventricular fibrillation [n = 3], nonsustained ventricular tachycardia [n = 5]). Oral sotalol was started at 80 mg twice daily and the dose thereafter was then gradually increased until a mean daily dose of 300 mg (range 160-480) was reached. In 12 of 34 patients with inducible sustained ventricular tachycardia or fibrillation the arrhythmia was suppressed; in 19 patients it was not and in 3 the spontaneous arrhythmia recurred. Reproducibly inducible nonsustained ventricular tachycardia was suppressed by sotalol in all five patients with this arrhythmia. Thus, a favorable electrophysiologic response was obtained in 17 (44%) of 39 patients. Arrhythmia suppression correlated with the type of arrhythmia (unsustained or sustained) induced during the control period (p less than 0.05), and nonresponders had a higher incidence of previously ineffective drug trials (p less than 0.05). In 22 patients treated long term with sotalol suppression of arrhythmia inducibility on programmed stimulation predicted freedom from recurrences (16 of 17), whereas continued inducibility indicated drug failure (5 of 5) (p less than 0.005). Serial ambulatory electrocardiograms performed in 37 of the 39 patients did not correlate with the results of electrophysiologic testing. For the patients on long-term treatment, invasive testing was superior to electrocardiographic monitoring in predicting outcome. These data indicate that in daily doses of 160 to 480 mg oral sotalol is a very useful agent in patients presenting with sustained ventricular tachycardia or fibrillation, and its efficacy is fairly well predicted by programmed stimulation.

Adult↗