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Biomedical subjects

R Heinze

Publications and source records attributed to R Heinze.

At least 19 recordsLinked to original sources
PubMed2004

Rutkow PerFix-plug repair for primary and recurrent inguinal hernias--a prospective study.

Surgery of the groin hernia has become more a question of the applied tension-free, mesh technique. Whereas studies on laparascopic versus open tension-free hernia repair or open-mesh versus open-nonmesh repair have been performed sufficiently, data regarding the open tension-free plug-and-patch technique are rather poor. During the period from January 2001 to October 2003, we followed and filed 766 hernia repairs in the plug-and-patch technique of Rutkow. Follow up was during the hospital stay, 4 weeks, and minimally 12 months after operation. The main follow-up variables were complications, recurrence rate, and pain. The mean operating time was 37.8 +/- 15.85 (12-135) minutes. In 141 (19.3%) patients (n=730), the ilioinguinal nerve was resected. The 1 intraoperative complication that occurred was a severed small intestine. Length of hospital stay was 2.09 +/- 1.35 (0-17) days, work leave lasted for 15.3 +/- 12.42 (0-60) days, and return to normal daily activities was possible within 6.54 +/- 6.86 (0-35) days. Twenty-two (2.9%) patients (n=766) developed a postoperative hematoma as the most common complication, and a reoperation was required 17 (2.2%) times during the hospital stay. Early complications included hematoma (3.7%), seroma (3.5%), infection (0.2%), necrosis of 1 testicle (0.2%), persisting scrotal swelling (1.5%), persisting pain (0.9%), and hypoesthesia (2.4%). Within 4 weeks, 4 (0.9%) patients were reoperated for 1 seroma, hematoma, infection, and testicle necrosis. After 605.4 +/- 154.5 (365-1018) days, the following 19 (5.7%) patient complaints were noted: persisting pain (2.1%), hypoesthesia (1.8%), foreign-body feeling (0.6%), scrotal swelling (0.6%), and 1 (0.3%) mesh dislocation. Six (1.8%) reoperations have been performed. The overall recurrence rate was 1.8% (n=6), for primary 1.5% (n=4), and 3.3% (n=2) for recurrent hernias; 96.3% of the patients would agree to undergo the same operation a second time. Tension-free repair of the inguinal hernia by the plug-and-patch technique is a quick and secure method that simplifies hernia surgery without compromising the high-quality standards such as a low recurrence rate and low pain load of the patient. Patients had a fast recovery with a subsequent short work leave. The method is a simple, effective, and economical operation, suitable as a standard performed in local anesthesia on an out-patient basis.

Adult↗
PubMed2003

Cylindrospermopsin occurrence in two German lakes and preliminary assessment of toxicity and toxin production of Cylindrospermopsis raciborskii (Cyanobacteria) isolates.

Cylindrospermopsis raciborskii, a freshwater cyanobacterium of tropical origin, is not only increasingly found in (sub) tropical water bodies, but also in temperate regions. Since this species may produce potent toxins such as cylindrospermopsin (CYN) and paralytic shellfish poisons, its massive occurrence in water bodies used as drinking water sources or for recreation is of major concern. The proliferation of C. raciborskii in German water bodies has been documented for the past decade. We investigated the occurrence of CYN in field populations and isolates of C. raciborskii from two lakes, and assessed the toxicity of culture isolates using the mouse bioassay, primary rat hepatocytes and human derived cell lines. We show for the first time the occurrence of CYN in German water bodies. None of seven isolates of C. raciborskii contained CYN, however, all isolates were toxic to primary rat hepatocytes, human hepatoblastoma (HEP-G2) and human colon adenocarcinoma (CACO-2) cells. Methanolic extracts were more toxic than aqueous extracts. Three isolates tested in the mouse bioassay were toxic at a concentration of 800 mg kg(-1) showing liver and spleen damage and inflammation of the intestine. These results give strong evidence that the German isolates of C. raciborskii contain currently not identified or unknown toxins.

Alkaloids↗
PubMed2003

Medication use among older Australian veterans and war widows.

This study aimed to review the medications used by a group of Australian war veterans and widows, to identify type and number of medications used and potential inappropriate prescribing. Label details of 4304 medications used by 887 participants were recorded and classified according to the Anatomical Therapeutic Chemical code. The median number of regular medications being used was four (interquartile range 2-7), with a median of one other medication (interquartile range 1-2) being taken as needed. Over half (53%) the participants were taking four or more regular medications. There were 26 potential interactions among 25 people. Polypharmacy was a considerable problem for this group of older Australians.

Aged↗
PubMed2001

Limits for the detection of (poly-)phosphoinositides by matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS).

Matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been recently established as a powerful tool for the analysis of biomolecules. Here, MALDI-TOF MS was used for the detection of (poly-)phosphoinositides (PPI). PPI possess higher molecular weights than other phospholipids and a high phosphorylation-dependent negative charge. Both features affect the MALDI detection limits expressed as the minimum of analyte on the sample plate resulting in a signal-to-noise-ratio of S/N = 5. Using 2,5-dihydroxybenzoic acid (DHB) as matrix the detection limit for phosphatidylinositol (PI) is seven times higher than for phosphatidylcholine (PC) and further increases with increasing phosphorylation or in mixtures with other well-detectable phospholipids. For phosphatidylinositol-tris-phosphate (PIP3) in a mixture with PC, the limit is about 20 times higher than for PI. The consequences for the experimental conditions are discussed. It is advisable to pre-separate PPI from biological lipid mixtures prior to the application of MALDI-TOF MS.

Phosphatidylinositol Phosphates↗
PubMed2000

Co-occurrence of non-toxic (cyanopeptolin) and toxic (microcystin) peptides in a bloom of Microcystis sp. from a Chilean lake.

A cyanobacterial bloom occurring in 1998 in lake Tres Pascualas (Concepción/Chile) was found to be dominated by Microcystis sp. The bloom contained both non-toxic (cyanopeptolin-type) and hepatotoxic (microcystin-type) peptides. Cyanopeptolin structure of the non-toxic peptides (called cyanopeptolin VW-1 and VW-2, respectively) was revealed by matrix assisted laser desorption ionization mass spectrometry (MALDI-TOF-MS) of whole cells, showing dominant molecular ions at m/z = 975 and m/z 995, respectively. On post source decay (PSD), both cyanopeptolins showed fragments deriving from Ahp-Phe-MTyr (3-amino-6-hydroxy-2-piperidone), the characteristic partial structure of cyanopeptolins. The amounts of each of the two cyanopeptolins could only roughly be estimated to be >0.1% of bloom material dry weight. In addition the blooms contained microcystins (20 microg/g bloom dry weight as determined by RP-HPLC, 13 microg/g according to ELISA determination). MALDI-TOF-MS revealed several structural variants of microcystin: MCYST-RR (microcystin with Arg and Arg, indicated by m/z 1,038 and confirmed by PSD revealing a m/z = 135 fragment deriving from the Adda side chain, MCYST-FR (microcystin with Phe and Arg, indicated by m/z = 1,015). The presence of [Asp(3)]-MCYST-LR (microcystin with Leu and Arg, Asp non-methylated, indicated by m/z 981), and [Asp(3)]-MCYST-YR (microcystin with Tyr and Arg, Asp non-methylated, indicated by m/z 1,031) were likely. The relative amounts of the peptides varied between February, April, and May. Whole cell extracts from the bloom material revealed specific enzyme inhibitory activities. The serin-proteases trypsin, plasmin, elastase were inhibited, assumable due to the cyanopeptolins found. Elastase and the cysteine-protease papain were not inhibited, inhibitions of protein kinase and glutathione S-transferase (GST) were low. Strong inhibition was observed with protein-phosphatase-1, likely due to the microcystins present in the samples.

Bacterial Toxins↗
PubMed2000

Studies on the influence of a Se-restricted diet on the effects of long-term increased copper intake in guinea pigs.

Guinea pigs were exposed to Se-restriction/deficiency in combination with drinking water containing 200 or 300 mg Cu/l for 6-30 weeks. Under the influence of Se-restriction/deficiency Cu excretion by bile was diminished, the Cu content of the kidneys was increased and disturbances of liver function were seen in animals exposed for prolonged periods. Some parameters of the immune system, such as the phagocytic activity of peritoneal macrophages, mitogenicity of spleen lymphocytes and the amount of lymphatic spleen tissue were also adversely affected. These effects correlated in part with the liver damage and the copper content of the kidneys. Conclusion are drawn with respect to the Idiopathic Copper Toxicosis/Indian Childhood Cirrhosis.

Animals↗
PubMed1999

Microcystin in cyanobacterial blooms in a Chilean lake.

Cyanobacterial blooms dominated by Microcystis sp. occurred in lake Rocuant ("marisma", near Concepción/Chile) in February 1995 and 1996. In the bloom samples collected in both years the hepatotoxin microcystin was detected by RP-HPLC in both samples and in the sample of 1995 also by a toxicity assay using primary rat hepatocytes. In the bloom of 1995, the microcystin content of the dry bloom biomass was determined to be 130 micrograms/g on the basis of the RP-HPLC peak area and 800 micrograms/g on the basis of the rat hepatotoxicity assay, respectively. In the bloom of 1996, RP-HPLC analysis revealed a microcystin content of 8.13 micrograms/g bloom material dry weight. In this year no hepatotoxicity was measured using a concentration range up to 0.8 mg (d. w.) of bloom material per ml in the rat hepatotoxicity assay. This is the first report on the detection of microcystins in Chilean water bodies.

Animals↗
PubMed1999

Farnesylation of Ras is important for the interaction with phosphoinositide 3-kinase gamma.

The correct functioning of Ras proteins requires post-translational modification of the GTP hydrolases (GTPases). These modifications provide hydrophobic moieties that lead to the attachment of Ras to the inner side of the plasma membrane. In this study we investigated the role of Ras processing in the interaction with various putative Ras-effector proteins. We describe a specific, GTP-independent interaction between post-translationally modified Ha- and Ki-Ras4B and the G-protein responsive phosphoinositide 3-kinase p110gamma. Our data demonstrate that post-translational processing increases markedly the binding of Ras to p110gamma in vitro and in Sf9 cells, whereas the interaction with p110alpha is unaffected under the same conditions. Using in vitro farnesylated Ras, we show that farnesylation of Ras is sufficient to produce this effect. The complex of p110gamma and farnesylated RasGTP exhibits a reduced dissociation rate leading to the efficient shielding of the GTPase from GTPase activating protein (GAP) action. Moreover, Ras processing affects the dissociation rate of the RasGTP complex with the Ras binding domain (RBD) of Raf-1, indicating that processing induces alterations in the conformation of RasGTP. The results suggest a direct interaction between a moiety present only on fully processed or farnesylated Ras and the putative target protein p110gamma.

Animals↗
PubMed1999

Phase-related changes in right ventricular cardiac output under volume-controlled mechanical ventilation with positive end-expiratory pressure.

OBJECTIVE: To examine determinants of right ventricular function throughout the ventilatory cycle under volume-controlled mechanical ventilation with various positive end-expiratory pressure (PEEP) stages. DESIGN: Prospective observational animal pilot study. SETTING: Animal research laboratory at a university hospital. SUBJECTS: Eight healthy swine under volume- controlled mechanical ventilation. INTERVENTIONS: Flow probes were implanted in eight swine in order to continuously measure blood flow in the pulmonary artery and inferior vena cava. After a recovery phase of 14 days, the swine were subjected to various PEEP stages (0, 5, 10 cm H2O) during volume-controlled positive pressure ventilation. MEASUREMENTS AND MAIN RESULTS: Continuous flow measurement took place in the pulmonary artery and inferior vena cava. Data on standard hemodynamic parameters were additionally acquired. Respiration-phase-specific analysis of right ventricular cardiac output and of additional hemodynamic function parameters followed, after calculation of mean values throughout five respiration cycles. PEEP at 5 cm H2O led to significant decreases in inferior vena cava flow (4.1%), and in right ventricular cardiac output (5.2%); the respective decreases at PEEP 10 cm H2O were 13.9% and 18.3%. In the inspiration phase at PEEP 10 cm H2O, results revealed an overproportionally pronounced decrease in comparison with the expiration phase in inferior vena cava flow (-24.6% vs. -10%) and right ventricular cardiac output (-35% vs. -13.5%). This phenomenon is presumably caused by a PEEP-related increase in mean airway pressure by the amount of 10.7 cm H2O in inspiration. CONCLUSIONS: Increases in PEEP during volume-controlled mechanical ventilation leads to respiration-phase-specific reduction of right ventricular cardiac output, with a significantly pronounced decrease during the inspiration phase. This decrease in cardiac output should be taken into particular consideration for patients with already critically reduced cardiac output.

Airway Resistance↗
PubMed1998

A novel mitogenic signaling pathway of bradykinin in the human colon carcinoma cell line SW-480 involves sequential activation of a Gq/11 protein, phosphatidylinositol 3-kinase beta, and protein kinase Cepsilon.

The signaling routes connecting G protein-coupled receptors to the mitogen-activated protein kinase (MAPK) pathway reveal a high degree of complexity and cell specificity. In the human colon carcinoma cell line SW-480, we detected a mitogenic effect of bradykinin (BK) that is mediated via a pertussis toxin-insensitive G protein of the Gq/11 family and that involves activation of MAPK. Both BK-induced stimulation of DNA synthesis and activation of MAPK in response to BK were abolished by two different inhibitors of phosphatidylinositol 3-kinase (PI3K), wortmannin and LY 294002, as well as by two different inhibitors of protein kinase C (PKC), bisindolylmaleimide and Ro 31-8220. Stimulation of SW-480 cells by BK led to increased formation of PI3K lipid products (phosphatidylinositol 3,4,5-trisphosphate and phosphatidylinositol 3, 4-bisphosphate) and to enhanced translocation of the PKCepsilon isoform from the cytosol to the membrane. Both effects of BK were inhibited by wortmannin, too. Using subtype-specific antibodies, only the PI3K subunits p110beta and p85, but not p110alpha and p110gamma, were detected in SW-480 cells. Finally, p110beta was found to be co-immunoprecipitated with PKCepsilon. Our data suggest that in SW-480 cells, (i) dimeric PI3Kbeta is activated via a Gq/11 protein; (ii) PKCepsilon is a downstream target of PI3Kbeta mediating the mitogenic signal to the MAPK pathway; and (iii) PKCepsilon associates with the p110 subunit of PI3Kbeta. Thus, these results add a novel possibility to the emerging picture of multiple pathways linking G protein-coupled receptors to MAPK.

Bradykinin↗
PubMed1998

First report on the identification of microcystin in a water bloom collected in Belgium.

A toxic cyanobacterial bloom dominated by Microcystis aeruginosa occurred in 1995 in three adjacent ponds near Liège (Belgium) where at the same time conspicuous bird deaths were observed. The toxicity assay using primary rat hepatocytes indicated a high hepatoxicity. A 4 h incubation yielded a LD50 of 0.23 mg bloom material (dry weight)/ml cell culture medium. Toxicity was due to hepatotoxins of the microcystin class, microcystin-LR and-RR being the major microcystins present as determined by RP-HPLC absorption spectra, 1H NMR, and ESMS spectra. Additionally, the bloom sample contained small amounts of microcystin-YR. The microcystin content of the dry bloom biomass was 870 micrograms/g (on the basis of the hepatotoxicity assay) and 556 micrograms/g (on the basis of the RP-HPLC peak area). A higher yield of microcystins was obtained by acetic acid extraction instead of methanol extraction, whereas different extraction temperatures (20 degrees C, 40 degrees C) had no effect on the yield.

Animals↗
PubMed1998

Liver fibrosis in guinea pigs experimentally induced by combined copper and aflatoxin application.

Aflatoxin B1 alone (0.05 mg resp. 0.037 mg/kg/d), copper alone (6.6 mg/kg/d or 200 mg/l drinking water) or a combination of both was administrated orally for 6 months to young guinea pigs from the first/second day of life. In the copper group there were no pathomorphological changes. For the aflatoxin B1 group liver damage was established. In the combined group liver injury was more frequent and more severe compared to the aflatoxin B1 group. Compared with the copper group biliary copper excretion was diminished and the kidney copper content was elevated in the Afl. B1 + Cu group. While copper concentrations in bile and kidney correlated with other parameters, notably the pathological lesions of the liver, no such correlation was found for liver copper. Therefore in this experiment the degree of Cu accumulation was not decisive for the liver lesions. The livers' capacity for excreting Cu by bile seems to be a much more important factor. Histologically only the livers of the combined group exhibited degeneration, atrophy and steatosis of liver cells, and a fibrosis more or less pronounced. For childhood cirrhosis (ICC and ICT), a combined etiology--a liver damaging agent plus elevated alimentary copper--is a plausible hypothesis.

Aflatoxin B1↗
PubMed1998

Immunomagnetic enrichment of disseminated epithelial tumor cells from peripheral blood by MACS.

Disseminated epithelial tumor cells have been detected in the bone marrow and blood of cancer patients by means of immunocytochemical or immunofluorescent staining of cytocentrifuge slides, multiparameter flow cytometry, and reverse transcriptase-polymerase chain reaction. However, it is hardly possible using such methods to detect tumor cells at a frequency below 10(-6). To increase the sensitivity of these detection techniques we have developed a new technology for the enrichment of disseminated epithelial tumor cells from hematopoietic cell samples by high-gradient magnetic cell sorting (MACS). Cells are permeabilized and fixed and carcinoma cells are magnetically labeled specifically with an anti-cytokeratin 8 monoclonal antibody (mAb) directly conjugated to superparamagnetic microbeads. Magnetically labeled cells are enriched on high-gradient magnetic columns. Tumor cells are detected in the enriched cell fraction by flow cytometry, fluorescence microscopy, or immunocytochemisty. In this study we demonstrated the method using a model system in which five to 5,000 cells from a breast cancer cell line were seeded into blood cell samples from a healthy donor containing 1.2 x 10(8) leukocytes. Tumor cells were 10,477+/-4242 (n=25)-fold magnetically enriched, and 57.7%+/-16.9% (n=33) of the initially seeded tumor cells were recovered. Applying the method to 20-40 mL blood samples from patients with advanced carcinomas of the breast, prostate, colon, rectum, or lung, we were able to detect between one and 6.8 x 10(4) cytokeratin-expressing tumor cells in 21 of 34 patients. This corresponds to frequencies of tumor cells between 6.8 x 10(-9) and 1.1 x 10(-3) among nucleated cells in the original sample. Enriched tumor cells were further analyzed for expression of tissue-specific and prognostic markers such as breast mucin glycoproteins, erbB2, and CD44v6 for additional characterization and to confirm their tumor origin. The technique described could become a valuable tool for the quantification and molecular characterization of metastatic carcinoma cells in hematopoietic tissue, and may ultimately prove useful in the diagnosis, prognosis, and monitoring of patients with carcinoma.

Adult↗
PubMed1995

Subchronic application of humic acids and associated compounds provokes histological changes of goitre in the rat.

1. Different preparations of humic acids, a pyrogallol oxydation product (PYROP) and resorcinol were administered to male and female rats with the drinking water for 8 to 14 weeks. 2. By histometrical evaluation of the thyroid glands, an increase of the mean epithelial cell height of follicular epithelial cells was established in the 0.1% humic acid groups, 0.1% PYROP group and the 0.004% resorcinol groups. Females seemed to be more sensitive than males. Additionally, in some experiments, a decrease of the mean follicular diameter was found, which was the result of newly formed little follicles. The changes must be considered as a precursor of goitre. 3. In one of the experiments, in which circulating thyroid hormones were investigated, the serum thyroxine level in the male 0.1% humic acid group and the free thyroxine index in the female 0.1% humic group were diminished as compared to the control groups.

Animals↗
PubMed1989

[CO2-stunning of swine for slaughter from the anesthesiological viewpoint].

For investigations of CO2-stunning of feeder- and slaughter-pigs parameters of behaviour, blood-gas-analyses and electroencephalograms were chosen. The following results were obtained: 1. Blood-gas-analyses proved that the CO2-stunning does not produce unconsciousness due to a lack of oxygen. 2. The criterias of general anaesthesia: unconsciousness, muscle-relaxation and analgesia with total reversibility could be confirmed. 3. The violent convulsive symptoms were evaluated as reactions identical with the stage II of GUEDEL's scheme of anaesthesia. 4. Muscular agitation, which sometimes appeared a few seconds before the stage of excitation, was judged to belong either to the start of the excitation phase or to the end of Guedel's stage of analgesia, during which the sensitivity is decreased. Neither study of behavior nor objective measurements showed, during the first 10 to 20 seconds of exposure to the CO2, any sign of pain or suffering related to the Act for Prevention of Cruelty to Animals, and accordingly such suffering should not be ascribed to the CO2 stunning method.

Abattoirs↗
PubMed1988

A new multisensor pacing system using stroke volume, respiratory rate, mixed venous oxygen saturation, and temperature, right atrial pressure, right ventricular pressure, and dP/dt.

A new multisensor pacing device using respiratory rate (RR), stroke volume (SV), oxygen saturation (SO2), temperature (T), right atrial pressure (RAP), right ventricular pressure (RVP) and right ventricular dP/dt, has been developed. It consists of a 7F multisensor catheter and an external pacing unit. It allows simultaneous recording of the input signals and the corresponding data can be compared among the different parameters under identical conditions. Furthermore, several parameters can be combined in such a way as to form a new combination better suitable for rate responsive pacing. The response of each parameter to exercise was studied in 12 healthy volunteers (mean age: 28 years). Exercise testing was carried out using a bicycle ergometer, with workloads up to 200 W. The dynamic characteristics, response and sensitivity to changes of workloads of each parameter were analyzed and compared to one another. SO2 proved to be a quick responding parameter (less than 10 sec) with higher sensitivity in the low exercise range (less than 75 W), T, on the other hand, responded slowly (greater than 30 sec) to exercise changes and had the highest sensitivity in the exercise range beyond 75 W. RR displayed a slow response (greater than 30 sec) and an adequate sensitivity was only found in the upper exercise range (greater than 100 W). SV reacted rapidly to workload changes (less than 10 sec) but showed poor sensitivity at all exercise levels. RAP, RVP and dP/dt displayed quick responses and constantly good sensitivity throughout the workload range. Furthermore, respiratory rate was easily derived from the RAP curve. Special algorithms were developed for each parameter so that pacing rate would reproduce sinus rate behavior. We found that SO2 and all pressure parameter imitated sinus rate response quite well. When using parameter combinations, SO2 and T proved to be superior. Five patients (mean age 68 years) with third degree AV-block were stimulated temporarily using this system. Compared to fixed rate stimulation (VVI 70), exercise performance improved, using SO2 as the input parameter for rate response, by 25% to 50%.

Adult↗
PubMed1988

First clinical experience with an oxygen saturation controlled pacemaker in man.

This article describes the characteristics of a new implantable pacemaker controlled by right atrial oxygen saturation and reports the first clinical experience in man. During the observation period over 5 months, there was no evidence of malfunction due to tissue growth. The system's reaction to exercise changes proved to be quick (5 s to 17 s); decay times varied depending on the magnitude of the power previously performed. Under various exercise tests, the rate increase was linear to the stress load. Measurements of cardiac output showed the system's hemodynamic feedback and its potential self-optimization of pacing rate.

Aged↗