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Biomedical subjects

V Schwarz

Publications and source records attributed to V Schwarz.

At least 19 recordsLinked to original sources

Photodynamic therapy of locoregional breast cancer recurrences using a chlorin-type photosensitizer.

Chest wall recurrences are a frequent problem in patients treated by mastectomy for breast cancer. Surgery and ionizing radiation are established treatment modalities in these cases. Photodynamic therapy (PDT) provides an alternative treatment modality using a photosensitizer and laser light to induce selective tumor necrosis. PDT was performed as compassionate use in 7 patients aged 57.6 years (+/-12.6 SD). A total of 89 metastatic skin nodes were treated in 11 PDT sessions. As photosensitizer meta-tetra(hydroxyphenyl)chlorin (m-THPC) was applied intravenously. Patients (n = 3) photosensitized with a drug dose of 0.10 mg/kg bodyweight were irradiated 48 hr after drug application at a lightdose of 5 J/cm(2). Patients (n = 4) were illuminated by an optical dose of 10 J/cm(2) 96 hr after photosensitization with 0.15 mg/kg. Laser light at a wavelength of 652 nm was generated by a diode laser and applied by a front lens light diffuser using a fluence rate of 20--25 mW/cm(2). PDT using m-THPC resulted in complete response in all patients. Response to treatment did not differ when using the 2 different drugdose protocols. Healing time depended mainly on the size of the illumination field but not on the lightdose. Pain score usually raised 1 day after PDT and lasted at higher levels for about 10 days. Healing time usually ranged between 8--10 weeks. Photodynamic technique offers a minimal-invasive, outpatient treatment modality for recurrent breast cancer on the chest wall with few side effects, high patient's satisfaction and with possible repetitive application.

Antineoplastic Agents↗

Polymers with thiol groups: a new generation of mucoadhesive polymers?

PURPOSE: To improve the mucoadhesive properties of polycarbophil by the introduction of sulfhydryl groups. METHODS: Mediated by a carbodiimide, cysteine was covalently bound to polycarbophil (PCP) forming amide bonds between the primary amino group of the amino acid and the carboxylic acid moieties of the polymer. The amount of covalently attached cysteine and the formation of disulfide bonds within the modified polymer were determined by quantifying the share of thiol groups on the polymer conjugates with Ellman's reagent. The adhesive properties of polycarbophil-cysteine conjugates were evaluated in vitro on excised porcine intestinal mucosa by determining the total work of adhesion (TWA). RESULTS: Depending on the weight-ratio of polycarbophil to cysteine at the coupling reaction, e.g., 16:1 and 2:1, 0.6+/-0.7 micromole and 5.3+/-2.4 micromole cysteine, respectively, were covalently bound per g polymer. The modified polymer displayed improved internal cohesive properties due to the formation of interchain disulfide bonds within the polymer in aqueous solutions at pH-values above 5. Adhesion studies revealed strongly improved adhesive properties. Whereas the TWA was determined to be 104+/-21 microJ for the unmodified polymer, it was 191+/-47 microJ for the polymer-cysteine conjugate 16:1 and 280+/-67 microJ for the polymer-cysteine conjugate 2:1. CONCLUSIONS: Polymers with thiol groups might represent a new generation of mucoadhesive polymers displaying comparatively stronger adhesive properties.

Acrylic Resins↗

Solvent composition and viscosity effects on the kinetics of CO binding to horse myoglobin.

Ligand binding to myoglobin in aqueous solution involves two kinetic components, one extramolecular and one intramolecular, which have been interpreted in terms of two sequential kinetic barriers. In mixed solvents and sub-zero temperatures, the outer barrier increases and the inner barrier splits into several components, giving rise to fast intramolecular recombination. The nature of these barriers and their relation to structural relaxation are examined using the effect of solvent composition and viscosity on the kinetics of CO binding to horse myoglobin in 60% ethylene glycol/water, 75% and 90% glycerol/water, 80% and 92% sucrose/water solutions. Measurements of the corresponding solvent structural relaxation rates by frequency resolved calorimetry allow us to discriminate between solvent composition and viscosity-related effects. The outer kinetic barrier controlling ligand entry and release depends on the viscosity consistent with Kramers-Stokes law of activated escape in the presence of friction. At high cosolvent concentration, we observe deviations from Stokes law, implying a smaller microviscosity at the protein-solvent interface as compared to the bulk. The inner barrier and its coupling to structural relaxation appears to be independent of viscosity but changes with solvent composition. As a possible explanation, we discuss the role of distal water molecules in the formation of the effective inner barrier. At low temperatures, this barrier has a distributed height, depending only slightly on the nature of the cosolvent and temperature at low cosolvent concentrations. In contrast, myoglobin embedded in a sucrose glass (92% sucrose/water) exhibits a temperature-dependent and bimodal enthalpy distribution. This result demonstrates that the exchange between protonation states of His64, A0 left and right arrow A1, can take place in the glass and at temperatures as low as 80 K.

Animals↗

Comparison of serological and DNA PCR-SSP typing results for HLA-A and HLA-B in 421 Black individuals: a Collaborative Transplant Study report.

In a recent study, we observed a discrepancy rate of 8.5% between the results of molecular and serological HLA class I typing in Caucasian kidney donors and recipients. In the present study we addressed the question how often black individuals are mistyped using the serological technique. 421 Blacks whose HLA typing results were reported to the Collaborative Transplant Study (CTS) were typed retrospectively for HLA-A and -B using a PCR-SSP method. 78 of the 421 individuals (18.5%) showed a discrepancy for HLA-A and 107 individuals (25.4%) for HLA-B. 36.3% of all individuals tested showed either an HLA-A or an HLA-B discrepancy. 13.1% of the discrepancies at the HLA-A locus were due to antigen misassignments and 4.8% were due to missed antigens. HLA-B discrepancies were caused in 15.7% by antigen misassignments and in 10.5% by missed antigens. These results demonstrate an impressive advantage of the PCR-SSP method for HLA-A and HLA-B locus typing over serological typing in black individuals. The high typing discrepancy rate observed in Blacks provides a strong argument for replacing serological typing by the DNA method. It is likely that this will improve the HLA matching correlation in clinical transplantation in Blacks.

Black People↗

Prospective evaluation of pretransplant blood transfusions in cadaver kidney recipients.

BACKGROUND: A beneficial effect of pretransplant transfusions on graft survival was demonstrated in the early 1970s. In the mid-1980s, however, retrospective studies showed that transfusions had lost their graft-protective effect in the cyclosporine era. During the last 10 years, deliberate transfusion pretreatment of transplant patients has been discontinued. METHODS: Within a collaborative project of 14 transplant centers, prospective recipients of cadaver kidney grafts were randomized to receive either three pretransplant transfusions or transplants without transfusions. RESULTS; The graft survival rate was significantly higher in the 205 transfusion recipients than in the 218 patients who did not receive transfusions (at 1 year: 90+/-2% vs. 82+/-3%, P=0.020; at 5 years: 79+/-3% vs. 70+/-4%, P=0.025). Cox regression analysis showed that this effect was independent of age, gender, underlying disease, prophylaxis with antilymphocyte antibodies, and preformed lymphocytotoxins. CONCLUSIONS; Transfusion pretreatment improves the outcome of cadaver kidney transplants even with the use of modern immunosuppressive regimens.

Blood Transfusion↗

Interaction of heart-rate fluctuations and respiration in 12 to 14-year-old children during sleeping and waking.

Our study was designed to investigate and quantitatively characterise the interaction of breathing and instantaneous heart rate. Comparisons were made during consciousness at rest, and during non-REM sleep. 31 12-14-year-old healthy children were subjected to a 24-h polygraphic electrocardiogram, respirogram, electrooculogram and actogram measurements. The data were analysed by means of power spectral analysis and coherence spectra. The peak frequency of high-frequency heart rate fluctuations was always clearly related to the breathing frequency, i.e., respiratory sinus arrhythmia is present in both states. Moving squared coherence analysis demonstrates the stability of the cardiorespiratory coupling to remain constant during wakefulness or non-REM sleep. However, coherence increases from waking state to non-REM sleep. The lower coherence during waking state may be explained by greater additional central and peripheral influences on the cardiorespiratory coupling or by increased non-linear properties of the transfer system due to operating point shifting.

Adolescent↗

Maximal lactate steady state during the second decade of age.

Maximal lactate steady state (MLSS) presumably corresponds to the highest constant workload that can be performed by oxidative metabolism. The anaerobic and, to a minor extent, the oxidative metabolism have been reported to be affected by age. The second decade of life is the key period in the change in energy metabolism between children and adults. The aim of this study was to evaluate the effects of age on MLSS in 34 male subjects (age: 15.4 +/- 2.8 yr, range: 11-20 yr; height: 171.8 +/- 14.9 cm, range: 134-191 cm; body mass: 59.6 +/- 15.5 kg, range: 27-90 kg) performing an incremental load test to determine maximal workload and several constant load tests for MLSS measurement on a cycle ergometer. MLSS (4.2 +/- 0.7 mmol.l-1, range: 2.8 to 5.5 mmol.l-1) and MLSS intensity related to maximal workload (66.5 +/- 7.7%, range: 50-84%) were independent of age. MLSS heart rate (180.1 +/- 10.1 min-1, range: 156-208 min-1) decreased (P < 0.01) with increasing age, whereas absolute (157.2 +/- 54.8 W, range: 65-240 W) and relative MLSS workload (2.6 +/- 0.5 W.kg-1, range: 1.5 to 4.1 W.kg-1) and absolute (236.9 +/- 79.0 W, range: 100-350 W) and relative maximal workload (3.9 +/- 0.6 W.kg-1, range: 2.7 to 5.5 W.kg-1) increased (P < 0.001) with age. The age independence of MLSS supports the theory that neuromuscular factors may contribute to the frequently observed changes in response to given exercise with physical maturity more than changes in oxidative metabolism and/or glycolysis.

Adolescent↗

[Sleep structure in relation to respiration and heart rate in children in puberty].

The different expression of respiratory sinus arrhythmia in REM- versus nonREM-sleep indicates a dependence of cardiorespiratory interaction on patterns of sleep. Investigations of the intensity of respiratory entrainment on heart rhythmicity during various stages of sleep will provide an insight into the coupling of cardiorespiratory interaction and sleep patterns. 42 healthy children (12 to 15 years old) were polygraphically investigated over 24 h. An ECG, EOG, and actogram were performed, respiratory movements were observed, and the skin temperature was taken. The power spectra of the instantaneous heart rate and the respirograms were calculated. The analysis of coherence was carried out to determine how pronounced the cardiorespiratory interaction is. REM-sleep, nonREM-phases, and wakefulness were compared. The spectral parameters of instantaneous heart rate show differences between both stages of sleep and the waking state. Due to a dependence of spectral power on breathing patterns, drawing quantitative conclusions is not possible. The analysis of coherence provides more information about sleep patterns within the cardiorespiratory interaction. It is very pronounced during non-REM-sleep (0.80 +/- 0.07; mean +/- standard deviation). Heart rhythmicity proceeds independent of breathing during REM-sleep (0.52 +/- 0.11). The coupling is weaker than during wakefulness (0.64 +/- 0.09).

Adolescent↗

[Correlation between respiration and heart rate in 12- to 14-year-old children during sleep and wakefulness].

The coupling of respiratory and cardiac rhythm is determined by interactions of oscillating brain stem centers and external physical and psychical influences. Not well known are effects of sleep and wakefulness which will be investigated over the day. From the ECG and respirogram of 42 healthy children (11 female, 31 male, 12 to 14 years) during 24 h the time series of instantaneous heart rate (HR) and respiratory rhythm and from this by FFT the density spectra of power, the maximal power and related frequency in the respiratory range were ascertained. Differences between nonREM sleep and wakefulness and the strength of coupling were determined by coherence analysis. In all probands the maximal power of HR and of the coherence were higher during nonREM sleep than in wakefulness. Both values were stable during each state. The maximum related frequencies of HR and respiration shifted parallel between sleep and wakefulness. The results mean augmentation in nonREM sleep following to improved transfer of respiratory activity to the control of HR. The increased coherence hints at a stronger linear coupling which is stable during each state. The changes of cardiorespiratory coupling may be effected by stronger non-linear parts in the interactions during wakefulness.

Adolescent↗

Non-Hodgkin's lymphoma after kidney or heart transplantation: frequency of occurrence during the first posttransplant year.

The incidence of non-Hodgkin's lymphoma was analysed in over 70,000 kidney transplant recipients and over 10,000 heart, heart-lung or lung transplant recipients. An increased incidence of lymphomas during the first posttransplant year was observed in cadaver kidney recipients as compared to related kidney recipients, in thoracic organ recipients as compared to kidney recipients, in heart-lung recipients as compared to heart or lung recipients, in patients transplanted in North America as compared to patients transplanted in Europe, in patients receiving cyclosporine in combination with azathioprine as compared to patients with other immunosuppressive regimens, and in patients receiving ATG/ALG or monoclonal OKT3 for rejection prophylaxis.

Germany↗

[Effect of HLA compatibility on kidney transplantation].

The influence of the HLA system on the success rate of kidney transplantations was evaluated in a worldwide collaborative study. The results confirm the influence of the HLA chromosome on transplants from related donors. Moreover, a highly significant effect of compatibility for the HLA-A, -B, -DR antigens was observed in cadaver transplants (p < 0.0001). The great importance of a good quality of tissue typing was emphasized by a) the observation that a significant influence of compatibility for the HLA-A, -B antigens was evident only if donors and recipients were typed for 'split' specificities and not when they were typed for 'broad' antigens, and b) an improved effect of HLA-DR compatibility when serological typing errors were corrected by molecular (DNA) typing. Computations show that kidney allocation according to the best possible HLA compatibility results in a gain of 800 transplant function years per 1,000 transplantations over a 10-year period.

Cadaver↗

Current status of HLA matching in renal transplantation. The Collaborative Transplant Study.

The impact of HLA compatibility on the success rate of kidney transplants was studied in over 80,000 recipients of primary transplants. The transplants were done from 1982 to 1991 at over 300 transplant centers in 43 countries. The results show that matching the HLA chromosomes in related donor transplants has a striking influence. It is also important that matching for individual HLA antigens in cadaver transplants provides a highly significant improvement in graft survival (P less than 0.0001). After 5 years, matched grafts have a survival rate approximately 20% higher than completely mismatched grafts. The matching effect is particularly strong in presensitized and second graft recipients. There is now direct evidence that even if it is necessary to transport well-matched kidneys a long way, they have a significantly higher success rate than locally transplanted poorly matched kidneys. New data based on molecular technology show that the precise identification of HLA-DR antigens by DNA typing further improves the success rate of HLA-matched transplants.

Follow-Up Studies↗

Outcome after emergency surgery for cancer of the large intestine.

The data for 77 patients with colorectal cancer who underwent emergency surgery for acute intestinal obstruction (57 patients) or perforation (20 patients) within 24 h of admission were evaluated. The patients were older and had more advanced disease than patients undergoing elective surgery for colorectal cancer. Emergency surgery for carcinoma of the right colon consisted of primary resection in 95 per cent of cases and was followed by a 28 per cent mortality rate. Perforated tumours of the left colon and rectum were managed by primary resection in 82 per cent of cases with a 22 per cent mortality rate. In contrast, obstructing tumours of the left colon and rectum were treated by primary resection in 38 per cent of cases with a 6 per cent mortality rate, and by primary decompression in 62 per cent of cases with a 25 per cent mortality rate. The overall postoperative mortality rate was 23 per cent and increased with advanced tumour disease, perforation and peritonitis. Cardiac decompensation and intraabdominal sepsis were the major causes of death. Although the long-term survival rate following emergency surgery was worse than after elective surgery, improvements in outcome should be achieved by better management of the initial emergency situation.

Adult↗

[Plasma lipoprotein fractions in high-dose medroxyprogesterone acetate therapy in metastatic breast cancer].

Metabolic disorders induced by synthetic gestagens have been discussed under the aspect of single endocrine parameters or the carbohydrate or lipid metabolism. In order to obtain more complex information a prospective study of 26 patients was performed, who were treated with 1,000 mg medroxyprogesterone acetate (MPA) per day over a period of 5 weeks as a second-line therapy of breast cancer. Before treatment and afterwards once a week the serum concentrations of MPA, androstenedione, DHEA-S, cortisol, prolactin, insulin, c-peptide, glucose, cholesterol, triglycerides, phospholipids and the lipoprotein fractions (VLDL, IDL, LDL, HDL) were analyzed. Besides the reduction of the androgens and changes in the glucose regulation significant effects on the lipoprotein metabolism were observed, leading to the conclusion that under high-dose gestagen therapy very complex interactions of the endocrine and metabolic system occur.

Antineoplastic Agents↗

Tumor recurrence and options for further treatment after resection of liver metastases in patients with colorectal cancer.

The aim of this study was to evaluate the pattern of recurrence and its impact on therapy in patients undergoing liver resection for colorectal metastases. Within 7 years 105 patients were operated on; 75 patients were followed up for at least 2 years postoperatively with a median follow-up of 30 months (range 24-93 months). The median time interval when patients were free of tumor recurrence was only 9 months. The initial recurrence site was the liver in 47% and the other sites were extrahepatic in 39%. Seventy-one percent of the patients developed disseminated metastases as the disease progressed. The median survival time after diagnosis of tumor recurrence was 14 months and was significantly affected by the type of treatment used for the recurrence. Surgical resection was followed by a 23-month median survival, while systemic and intra-arterial chemotherapy led to a 14- and 15-month median survival time, respectively. Untreated patients had a median survival of only 4 months. It is concluded that liver resection for colorectal secondaries leads to a very limited number of disease-free survivors after 5 years. As a few patients may profit from a surgical treatment even in cases of recurrence, surgery should not be regarded as useless.

Adult↗

[Anthropogenetics and suitability for sports of children and adolescents].

Methods, tests and criterions for selection of children and adolescents talented for sport are described. A review is given on the author's investigations on the genetic conditionality of the prerequisites for performances in sport based on twin studies and on the developmental stability of the selection criterions tested.

Adolescent↗