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Biomedical subjects

R Straub

Publications and source records attributed to R Straub.

At least 73 records · Page 4Linked to original sources
PubMed1999

Prevalence of beta2-toxigenic Clostridium perfringens in horses with intestinal disorders.

The incidence of a new, yet unassigned toxin type of Clostridium perfringens containing the genes for the alpha-toxin and the recently described beta2-toxin in horses with intestinal disorders is reported. The study included 18 horses suffering from typical typhlocolitis, 7 horses with atypical typhlocolitis, 16 horses with other intestinal disorders, and 58 horses without intestinal disease. In total, 20 samples of ingesta of the small and large intestines, five biopsy specimens of the intestinal wall, and 74 fecal samples were analyzed bacteriologically. C. perfringens isolates were typed for the presence of the alpha-, beta-, beta2-, and epsilon-toxin and enterotoxin genes by PCR, including a newly developed PCR for the detection of the beta2-toxin gene cpb2. beta2-Toxigenic C. perfringens was detected in samples from 13 of 25 (52%) horses with typical or atypical typhlocolitis, with a particularly high incidence in specimens of ingesta and biopsy specimens (75%), whereas only 6 of 16 specimens from horses with other intestinal diseases yielded beta2-toxigenic C. perfringens. No beta2-toxigenic C. perfringens was found in the samples from the 58 control horses, of which only one fecal sample contained C. perfringens type A. Among the samples from the 15 horses with fatal cases of typical and atypical typhlocolitis 9 (60%) were positive for beta2-toxigenic C. perfringens, whereas samples from only 4 of the 10 (40%) animals with nonfatal cases of infection were positive. We found an interesting correlation between the antibiotic-treated horses which were positive for beta2-toxigenic C. perfringens and lethal progression of the disease. No C. perfringens strains isolated in this study contained genes for the beta- and epsilon-toxins and enterotoxin. The high incidence of beta2-toxigenic C. perfringens in samples of ingesta, biopsy specimens of the intestinal wall, and feces from horses suffering or dying from typhlocolitis together with the absence of this organism in healthy horses provides strong evidence that beta2-toxigenic C. perfringens play an important role in the pathogenesis of typhlocolitis.

Animals↗
PubMed1999

Application of the ADEPT strategy to the MDR resistance in cancer chemotherapy.

New prodrugs consisting of a beta-D-glucuronic acid linked to a MDR reversal agent (verapamil, quinine or dipyridamole) through a self-immolative spacer were synthesized. Four of them were selected for their reduced cytoxicity and beta-glucuronidase enzymatic efficient hydrolysis. Combined use of these prodrugs with a beta-D-glucuronyl-spacer-doxorubicin (HMR1826) according to an ADEPT strategy restored in vitro the sensibility of a MDR resistant strain.

Animals↗
PubMed1998

Prodrugs of anthracyclines for use in antibody-directed enzyme prodrug therapy.

A series of new prodrugs of daunorubicin and doxorubicin which are candidates for antibody-directed enzyme prodrug therapy (ADEPT) is reported. These compounds (25a,b,c and 32a,b,c) have been designed to generate cytotoxic drugs after activation with beta-glucuronidase. As expected, recovery of the active drug was observed after enzymatic cleavage by Escherichia coli beta-glucuronidase as well as by a fusion protein which has been obtained from human beta-glucuronidase and humanized CEA-specific binding region. The six prodrugs are highly stable and are more than 100-fold less cytotoxic than doxorubicin against murine L1210 cell lines. The ortho-substituted phenyl carbamates 25a,b,c are better substrates for beta-glucuronidase than the corresponding para-substituted analogues. After taking into account additional factors such as stability in plasma and kinetics of enzymatic cleavage, we selected the o-nitro prodrug 25c for clinical trials.

Animals↗
PubMed1998

Physiological and emotional response to psychological stressors in psychiatric and psychosomatic disorders.

Deviations from emotional and physiological homeostasis in humans occur under episodic, chronic, or traumatic stress experiences. These dysregulations can provoke emotional and physical disturbances that may result in stress-related psychiatric or psychosomatic disorders. This brief review discusses a variety of both naturally occurring and experimental stressors and the complexity of intervening variables on cardiovascular and hormonal dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis. In addition to the type, intensity, and duration of the stressor, subject variables such as dispositional factors (e.g., age and sex), personality traits, and coping styles are considered. Finally, emotional and physiological stress responses to naturally occurring stressors and psychological challenge tests in depressed patients and anxiety disorder patients are presented and discussed. Stressors in humans induce emotional arousal, which leads to physiological activation of the central nervous system, an increase of hormones of the HPA axis, and coping reactions on the psychological and behavioral level. Depending on the type, intensity, and duration of the stressor, on personal and psychosocial resources of the individual, stressful situations may provoke emotional and physical disturbances. These dysfunctions may result in psychosomatic or psychiatric disorders. The following brief review intends to discuss a variety of stressors that have been examined in humans in order to gain insight into the complex relationship between physiological and behavioral stress reactions and the occurrence or maintenance of stress related psychosomatic and psychiatric disorders.

Anxiety↗
PubMed1998

Elucidation of the mechanism enabling tumor selective prodrug monotherapy.

Elucidation of the mechanism enabling tumor selective PMT in vivo with appropriate glucuronyl-spacer-doxorubicin prodrugs, such as HMR 1826, is important for the design of clinical studies, as well as for the development of more selective drugs. Enzyme histochemistry, immunohistochemistry, and the terminal deoxytransferase technique were applied using human cryopreserved cancer tissues, normal human, monkey, and mouse tissues, and human tumor xenografts to examine mechanisms underlying the selectivity of successful PMT with HMR 1826. It could unambiguously be shown by enzyme histochemistry that necrotic areas in human cancers are the sites in which lysosomal beta-glucuronidase is liberated extracellularly in high local concentrations. The cells responsible for the liberation of the enzyme are mainly acute and chronic inflammatory cells, as shown by IHC. Furthermore, it could be demonstrated that beta-glucuronidase liberated in necrotic areas of tumors can activate HMR 1826, resulting in increased doxorubicin deposition in human tumor xenografts or in human lung cancers subjected to extracorporal perfusion, compared to chemotherapy with doxorubicin. Additionally, the doxorubicin load to normal tissues was significantly reduced compared to chemotherapy with doxorubicin. Surprisingly, the increased doxorubicin deposition in tumors also resulted in strong antitumor effects also in cancers resistant to maximum tolerated doses of systemic doxorubicin. Finally, toxicity studies in mice and monkeys revealed an excellent tolerability of HMR 1826, up to a dose of 3 g/m2 (monkeys). These data suggest that HMR 1826 is a promising candidate for clinical development.

Animals↗
PubMed1998

[Verification of MR thermometry by means of an in vivo intralesional, fluoroptic temperature measurement for laser-induced thermotherapy ov liver metastases].

PURPOSE: To evaluate the correlation of MR-measured changes of signal intensity and invasive fluoroptic temperature measurements during MR-guided LITT of liver metastases. MATERIALS AND METHODS: In 15 patients with proven liver metastases of colorectal carcinoma, MR-guided LITT was performed with a percutaneous approach in a multiapplicator technique. Two temperature sensitive T1-weighted sequences (FLASH-2D- and TurboFLASH-sequences) were used to map the spatial and temporal distribution of Nd:YAG laser effects. Parallel fluoroptic temperature measurements were carried out by means of an inserted probe in a distance of 5-26 mm (mean: 14 mm) from the laser applicator. RESULTS: In both sequences a gradually increasing signal loss could be documented during laser application which proved to be reversible after cessation of energy deposition. the percentage of decrease in signal intensity correlated directly with the measured increase of temperature. Invasive fluoroptical evaluation of temperature distribution after 10 min exposure time showed at 5 mm distance from the applicator an increase of temperature of 35 degrees C, in 10 mm distance a mean increase of 9 degrees C +/- 1.7, in 15 mm a mean increase of 7 degrees C +/- 1.6 and in 20 mm a mean increase of 3 degrees C +/- 0.5. This is evidence of thermal tissue damage up to 3 cm in diameter with laser monoapplication. The qualitative evaluation revealed a reproducible correlation of the extent of signal loss around the applicator and the finally induced degree of necrosis. CONCLUSION: Invasive fluoroptical temperature measurements prove the diagnostic reliability of MR thermometry for the online monitoring of LITT of liver metastases.

Adult↗
PubMed1998

Internally cooled power laser for MR-guided interstitial laser-induced thermotherapy of liver lesions: initial clinical results.

PURPOSE: To evaluate experimentally and clinically an internally cooled power laser system for percutaneous treatment of liver metastases, with magnetic resonance (MR) imaging guidance, to increase the volume of coagulative necrosis with single laser beam applications. MATERIALS AND METHODS: The power laser system consisted of standard cannulation paraphernalia and a specially designed 7-F protective catheter for cooling the laser tip during treatment to avoid carbonization. A microdome laser beam applicator with a laser tip diameter of 0.95 mm kept the entire device as small as possible. After the unit was tested in 40 porcine livers, 532 laser beam applications (mean power, 27.5 W [range, 22.1-30.0 W]; mean application time, 19.8 minutes [range, 14-30 minutes]) were performed with MR guidance in 127 patients with 318 liver metastases. The safety of the procedure and the volume of induced necrosis were evaluated. RESULTS: In vitro, cuboid areas of coagulative necrosis with a mean greatest diameter of 4.3 cm +/- 0.5 (SD) were demonstrated after single applications. In vivo, MR thermometry allowed accurate demarcation of changes induced by heat, with a mean diameter of necrosis of 3.3 cm +/- 1.4. No carbonization or vaporization of tissue or damage of equipment occurred during treatment. CONCLUSION: This power laser system can increase the volume of laser-induced necrosis in liver metastases with a single application, thereby simplifying and accelerating the treatment of larger lesions.

Animals↗
PubMed1997

Mucus quality on horse tracheal epithelium: microscopic grading based on transparency.

The aim of this ex-vivo study on excised tracheas of healthy horses was to characterise the microscopic heterogeneity of mucus quality by a visual grading system based on transparency and to determine whether differences in mucus quality, assessed by a visual grading system, influence tracheal mucus velocity (TMV). Small pieces of each trachea were mounted into a humidified chamber under a microscope. Mucus quality was visually subdivided into four grades (MG) and ciliary beat frequency and TMV were determined. Mucus on excised horse tracheal epithelium does not form a homogenous layer. We observed flakes and streams of a great heterogeneity, which by the characteristic of transparency can be qualified and quantified. Visual characterisation of mucus was able to explain a considerable part of TMV variation. Therefore, it can be considered as a suitable non-invasive method for the evaluation of mucus quality and transport effectiveness.

Animals↗
PubMed1997

Magnetic resonance imaging--guided abdominal interventional radiology: laser-induced thermotherapy of liver metastases.

The aim of this study was to evaluate the clinical benefit of magnetic resonance imaging--guided laser-induced thermotherapy (LITT) for the minimally invasive treatment of liver metastases, with regard to survival rates and local tumor control. Magnetic resonance--guided LITT under local anesthesia was carried out in 134 consecutive patients aged 28-84 (mean age 69), with a total of 383 liver metastases. The major groups were liver metastases from colorectal cancer (88 patients) and liver metastases from breast cancer (20 patients), as well as metastases of miscellaneous primary tumors (26 patients). A total of 1048 laser applications were carried out. Cumulative survival times were calculated using the Kaplan-Meier method. All of the patients tolerated the procedure under local anesthesia well, and no severe complications or side effects were observed. During the follow-up period, 29 of the 134 patients treated died. The mean survival time was 35 months in the colorectal cancer group, 30 months in the breast cancer group, and 34 months in the group with miscellaneous primary tumors. The statistical assessment of the equality of survival distribution showed no significant differences between the three groups (Breslow test P = 0.35, Tarone-Ware test P = 0.49). These results suggest that in patients with liver metastases, local tumor destruction using minimally invasive percutaneous LITT under local anesthesia results in improved clinical outcomes, independently of the type of primary tumor.

Abdomen↗
PubMed1997

Ultrasound spirometry in the horse: a preliminary report on the method and the effects of xylazine and lobeline hydrochloride medication.

A new computerised ultrasound-based spirometry system according to Buess et al. (1995) modified by a double flow measurement facility was used to study pulmonary function in healthy horses and horses affected with subclinical and manifest chronic bronchiolitis (CB). The horses were first evaluated at rest without any medication. On another occasion all horses were tested following i.v. administration of xylazine (0.4 mg/kg) and following i.v. administration of lobeline hydrochloride (l.hy.; 0.2 mg/kg) to evaluate the effect of xylazine and l.hy. on different spirometric variables. Ultrasound-based spirometry proved to be an easily applicable method for lung function testing, even in difficult horses. However, there existed a pronounced physiological variation for all measured lung function parameters and no significant differences between healthy horses and horses with chronic bronchiolitis could be found except for the expiratory tidal volume (VTE p < 0.05). Individually, a marked decrease of variability from breath to breath following either xylazine and l.hy. administration could be observed for all parameters, except the flow-time-ratio (Tpef./ Texp.) and the flow-volume-ratio (Vpef./Vexp).

Animals↗
PubMed1996

Electrodermal activity (EDA) and suicidal behavior.

There may be a connection between suicidal tendencies, electrodermal activity (EDA), disorders of impulse control, and neurobiochemistry (in the sense of a "psychobiology of suicidal tendencies"). The EDA values obtained during a psychobiological habituation experiment involving 11 female patients with personality disorders (PA; ICD-10) and histories of suicide attempts were compared with those of age-paralleled nonsuicidal depressive patients and depressive patients with histories of suicide attempts. They were also compared with EDA values in female schizophrenics with and without histories of suicide attempts. The PA group showed significant differences in all EDA values compared with nonsuicidal depressives, but no significant differences compared with other groups.

Adolescent↗
PubMed1996

[Depression and electrodermal response measures in a habituation experiment. Results from over 400 depressed inpatients].

Depressed inpatients of the Weissenau Depression Treatment Unit take part in an over ten years unchanged psychophysiological habituation experiment with auditive stimuli to study their electrodermal reactivity. An overview on EDA-results of about 400 inpatients (ICD-9: 296.1/300.4/309.1, without delusional depression and without bipolar affective psychosis) is given. Women compared to men and also endogenous (ICD-9: 296.1) compared to psychogenic depression (ICD-9: 300.4/309.1) show significantly more non- and hypo-response.

Adult↗
PubMed1995

[Electrodermal reactivity in schizophrenic women with so-called basic symptoms].

Studies on electrodermal reactivity in a psychophysiological habituation experiment with schizophrenic patients often show a high number of "non" - or "hypo-responsiveness". There is not enough evidence to explain non-response as anticholinergic drug effect of antipsychotic medication; results in the literature suggest that hyporesponsiveness can be regarded more as a psychopathological phenomenon of a distinct subgroup of subsigns of schizophrenia which are called negative symptoms or basic disturbances. For the measurements of so-called basic symptoms we used two German self-report questionnaires, the "Frankfurter Befindlichkeitsskala für schizophren Erkrankte (FBS)" by Süllwold and Herrlich (1987) and the "Günzburger Selbstbeurteilungsskala für Basissymptome bei Schizophrenen (GSBS)" by Schüttler and co-workers (Blumenthal et al., 1989). The FBS includes two factors, a so-called "hyper" - and a "hypo"-syndrome; the GSBS consists of three categories which are named "Potential-reduktion", "kognitive Denkstörungen" and "kognitive Wahrnehmungsstörungen". We expected a relationship between "non" - oder "hypo-responsiveness" of the electrodermal reactivity in a habituation experiment with acoustic stimuli and higher values in the "FBS hypo-syndrome" respectively the "GSBS Potentialreduktion" (reduction of energy, drive, apathy, depressive mood etc.). 40 female inpatients, mean age 35.5 years with the ICD-9 diagnoses 295.x (n = 34) and 397.0 (n = 6) were investigated in this study. All the inpatients were treated with antipsychotic medication at the time of the study (usually the third week of inpatient stay in a closed acute treatment ward for females after reduction of acute psychopathology).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Folate deficiency, anticonvulsant drugs, and psychiatric morbidity.

The folic acid (FOA) level was determined in serum and erythrocytes in 100 epileptic patients and 100 control patients using a luminescence assay. A lowered FOA concentration in serum, erythrocytes, or both was observed in 15% of the epileptic patients and in 2% of the control group. In the epileptic patients, the FOA in the serum and in the erythrocytes was significantly lower than that in the control group. Patients receiving carbamazepine monotherapy had a significantly lower FOA level in the erythrocytes than did patients receiving phenytoin monotherapy. The FOA level showed a negative correlation to the duration of epilepsy. None of the patients with lowered FOA had a normal mental status. The course of the supplementation treatment with 5 mg folinic acid (or FOA) of four patients with FOA deficiency could be monitored psychopathometrically. All four patients showed an improvement in their well-being and the majority of measured variables of the cognitive performance.

Adult↗
PubMed1994

Determination of beta-lactam residues in milk using perfusive-particle liquid chromatography combined with ultrasonic nebulization electrospray mass spectrometry.

The introduced electrospray (ESP) technique combined with quadrupole mass spectrometry (MS) was applied for the trace residue detection (10 ppb) of commonly administered beta-lactam antibiotics in bovine milk. Because of the widespread use of penicillin G, ampicillin, amoxicillin, cephapirin, cloxacillin, and ceftiofur in veterinary medicine, these six popular drugs were chosen to develop a fast and reliable microcolumn liquid chromatographic (micro-LC) separation method for residue-containing milk extracts. Furthermore, the analytes were selected to test the chromatographic behavior of a novel stationary phase, a perfusive-particle column packed with derivatized porous polystyrene divinylbenzene. The effects of mobile phase additives on separation and ESP ionization efficiency were investigated. The ionization of the eluted analytes took place either in a conventional ESP interface with a capillary shield allowing flow rates up to 40 microL/min or in the latest model of the ultrasonic nebulization ESP interface. The perfusive-particle column, although not optimized for the separation of small molecules, exhibited sufficient resolution of the antibiotics for its routine usage, especially when considering the remarkable time-saving advantage compared with ordinary reversed phase micro-LC columns. The application of the novel ultrasonic nebulization interface lowered detection limits and improved the stability of the signals over a much wider flow rate range than possible for ionization with the ESP system equipped with the conventional needle.

Animals↗