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Biomedical subjects

W Simon

Publications and source records attributed to W Simon.

At least 19 recordsLinked to original sources

Age related rejoining of broken chromosomes in human leukocytes following X-irradiation.

One theory of aging is that the ability to repair DNA or chromosome damage decreases with age. This study made use of a method which allows the measurement of chromatid repair in interphase nuclei, the technique of premature chromosome condensation. The number of excess chromosome fragments per cell remaining after 24 h of incubation at 37 degrees C was determined and used as a measure of the ability of leukocytes to repair. The leukocytes from male donors of several ages were used and the cells from older donors showed greater residual damage and, therefore, less repair.

Adolescent

Growth fraction in breast carcinoma determined by Ki-67 immunostaining: correlation with pathological and clinical variables.

The growth fractions (GF) of 151 mammary carcinomas were determined in situ by Ki-67 immunoperoxidase staining. A mean value of 14.6% Ki-67-positive tumor cells, with a standard deviation of 11.1, was found. Tumors of histological grades 1 and 2 had a mean GF of 13.1% which was significantly lower (p less than 0.05) than that of grade 3 tumors (mean GF 17.3%). The 14 patients in whom distant metastases appeared after primary staging had a significantly higher (p less than 0.05) GF (21.3%) than the other patients (13.9%). No significant correlation was found between GF and concentration of hormone receptors, lymph node status, tumor size, or patient's age. Our results suggest that immunostaining with Ki-67 could be used as an additional tool to detect breast carcinoma patients with a high risk of developing metastases.

Adenocarcinoma

[Chemical sensors in medical use: ion-selective electrodes, limitations and potentials].

The electrolyte concentrations of potassium and sodium, for example, are routinely analyzed in diluted serum and plasma. In contrast, electrolyte activities are quantified by ISEs directly in undiluted whole blood and plasma and promise to be highly informative. Nevertheless, some drawbacks, such as the interaction between the biological matrix and the ISE surface, limit the accuracy of measurements. A symmetrical measuring arrangement allows one to localize and quantify the known sources of errors. These are minimized by adequate techniques. The membrane composition for sodium selective electrodes is optimized in particular. The interpretation of ISE values as compared to FAES (flame atomic emission spectroscopy) is closely related to the water concentration of the samples. Comparisons between ISE and FAES results obviously allow one to evaluate the water concentration of samples, as is shown by a linear regression plot.

Calibration

Lifetime of neutral-carrier-based liquid membranes in aqueous samples and blood and the lipophilicity of membrane components.

On the basis of previously reported correlations between the lipophilicity of membrane components, their partition coefficient between the membrane and the sample, and the lifetime of corresponding neutral-carrier-based sensors, the lipophilicities of ionophores and plasticizers in analytically relevant ion-selective electrodes, ISFETs, and optodes are analyzed and reported. Equations for the estimation of the lifetimes of liquid membranes in continuous-flow systems are presented, and the experimental determination of the lipophilicity values by thin-layer chromatography (TLC) is described. The required lipophilicities for the lifetimes of liquid membranes over 30 24-h days for different applications in aqueous solutions as well as in blood are presented. A comparison of the experimental results of lifetime measurements with calculated theoretical values is given. The experimental results of the determination of the lipophilicity by TLC are compared with the lipophilicities estimated on the basis of Hansch parameters.

Animals

Improvement of local control by regional hyperthermia combined with systemic chemotherapy (ifosfamide plus etoposide) in advanced sarcomas: updated report on 65 patients.

From July 1986 to 1990, 65 patients with deep-seated, advanced sarcomas (43 soft-tissue sarcomas, 12 Ewing's sarcomas, 7 chondrosarcomas and 3 osteosarcomas) were entered in a protocol involving regional hyperthermia (RHT) combined with systemic ifosfamide and etoposide. RHT was produced by an electromagnetic deep regional heating device (BSD Medical Corporation, Salt Lake City, Utah). Of these patients, 62% (40 patients) had received ifosfamide-containing drug regimens before entering the RHT study, 26% (17 patients) were pretreated by surgery and/or radiation and 12% (8 patients) were treated primarily. A total of 426 RHT treatments (mean 6.6 RHT/patient) were applied predominantly within the pelvic region (82%) bearing relative large tumours (mean volume 500 cm3). For systemic chemotherapy, all patients received ifosfamide (1.5 g/m2, days 1-5), etoposide (100 mg/m2, days 1, 3, 5) and 2-mercaptoethanesulphonic acid (mesna; 300 mg/m2 x 4, days 1-5) with RHT only given on days 1 and 5 in repeated cycles every 4 weeks. Detailed thermal mapping by invasive thermometry was performed in all patients. In 61 patients evaluable for tumour control the overall objective response rate including 9 complete responders (CR), 4 partial responders (PR) and 8 patients with favourable histological response (FHR) was 34% (95% confidence limits, 23%-46%). Following CR, the patients are alive and remain disease-free (mean disease-free survival 15.6 months). Of the patients with PR and FHR, 3 died from metastatic and/or local disease after 4, 17, and 39 months, and 1 patient died from other disease (acute myelocytic leukemia) after 27 months. The other 8 patients remain stable at 29, 25, 17, 11, 10, 8, 7, and 6 months. Twenty-two patients revealed no change and 18 patients showed local tumour progression (PD). Side-effects of RHT were tolerable and there was no indication of enhanced bone marrow toxicity due to the addition of RHT to the systemic chemotherapy. By analysis of temperature parameters, the time-averaged temperatures of all RHT treatments calculated for 20% (T20), 50% (T50) or 90% (T90) of measured tumour sites differed significantly between responders (CR + PR + FHR) and non-responders (PD), respectively (T20, P = 0.001; T50, P = 0.0005; T90, P = 0.0001). the data further support a strong potential for ifosfamide plus etoposide combined with RHT in pretreated patients with advanced sarcomas.

Adolescent

Characterization of sodium-selective optode membranes based on neutral ionophores and assay of sodium in plasma.

Plasticized poly(vinyl chloride) membranes that incorporate a highly lipophilic sodium-selective neutral ionophore (ETH 4120) and novel H(+)-selective chromo-ionophores, lipophilic isologs of Nile Blue, are used in the competitive binding of Na+ and H+ for a reversible, optical determination of sodium activities in buffered solutions at different selected pH values. These optode membranes are used to assay total sodium concentrations in pH-buffered human blood plasma.

Electrodes

Neutral ionophore-based selective electrode for assaying the activity of magnesium in undiluted blood serum.

The concentration of free, ionized magnesium in undiluted blood serum can be determined potentiometrically with a new magnesium-selective carrier in polymeric membrane electrodes (by weight 66% plasticizer, approximately 33% polyvinyl chloride and approximately 1% ionophore). However, discrimination of calcium by the new ionophore-added membrane is not sufficient to keep calcium interference to less than 1%. To correct for the interference by calcium, we determine the calcium activity of the serum sample with a calcium-selective electrode and calibrate the magnesium-selective electrode with standard solutions containing calcium in the concentrations found. In this way we determined the free ionized magnesium in five plasma samples from five different persons and found it to be within the range expected for magnesium in undiluted serum.

Amides

Intracellular magnesium ion selective microelectrode based on a neutral carrier.

A magnesium ion selective microelectrode based on a synthetic neutral carrier is presented. The selectivity of Mg2+ over Na+, K+, H+, and Ca2+ is sufficient for assays of intracellular magnesium ion activities. The microelectrodes with an optimized membrane composition have a resistance of about 5 x 10(10) omega and a 90% response time of less than or equal to 3 s for a tip diameter around 1 microns. The lifetime of the microelectrode cell assembly is longer than 1 week and the emf drift after equilibration is less than or equal to 0.3 mV/h.

Animals

A new double-barrelled, ionophore-based microelectrode for chloride ions.

A new Cl- selective microelectrode based on the ionophore 5,10,15,20-tetraphenyl-21H,23H-porphin manganese(III) chloride is presented which discriminates better against HCO3- and several organic anions than electrodes containing the Corning 477913 ion-exchanger. Using a redesigned construction procedure, fine-tip double-barrelled microelectrodes were produced which had slopes of -52.4 +/- 0.6 mV (SE, n = 24), resistances of about 7.10(11) omega and a selectivity coefficient log KpotCLHCO3 of -1.40 +/- 0.03. Some electrodes showed a small unexplained sensitivity to pH greater than 7.6. When used to puncture cells of isolated S3 segments of rabbit renal proximal tubule during perfusion with HCO3- Ringer solution, the electrodes gave a membrane potential of -69.8 +/- 1.5 mV and an intracellular Cl- activity, [Cl-]i, of 35.3 +/- 2.6 mmol/l. Upon switching bath and lumen perfusions to Cl- -free solutions the "residual" [Cl-]i dropped to 1.20 +/- 0.03 mmol/l, while in similar measurements with ion-exchanger electrodes the "residual" [Cl-]i dropped only to 10.9 +/- 0.5 mmol/l. These observations demonstrate the superiority of the new electrode and prove that previously determined high [Cl-]i values in Cl- -free ambient solutions reflect interference problems rather than non-exchangeable intracellular chloride.

Animals

Extra- and intracellular hydrogen ion-selective microelectrode based on neutral carriers with extended pH response range in acid media.

A series of new neutral hydrogen ion carriers suitable for application in H+-selective microelectrodes is presented. One carrier (ETH 1907) proves to be superior to tridodecylamine currently very much in use. Microelectrodes based on ETH 1907 in an optimized membrane composition exhibit a linear dynamic response function from pH 2 to 9 extended into the acidic range, a response time less than or equal to 5 s, and a resistance of about 35 G omega for a tip diameter of about 1 micron. This makes the electrode suitable for measurements at normal physiological intracellular pH as well as in acid physiological media. Measurements using this microelectrode in proximal tubule cells of isolated perfused frog kidney are presented.

Animals

NH4+ ion-selective microelectrode based on the antibiotics nonactin/monactin.

A liquid-membrane microelectrode (less than or equal to 1 micron tip diameter) using macrotetrolide antibiotics as ion-selective components is described. The electrode shows selectivities of NH4+ over K+, Na+ and H+ of 3.8, 100 and 150, respectively. The stability and reproducibility of the sensor signal and the response time are determined in solutions with a typical intracellular ion background. The microelectrode does not suffer from significant interference by inorganic and organic inhibitors and lipophilic cations, but high concentrations of lipophilic anions may interfere considerably.

Anti-Bacterial Agents

Upper and lower time limits in the decision to recommend marrow transplantation for patients with chronic myelogenous leukaemia.

Long-term survival of patients with chronic myelogenous leukaemia (CML) requires marrow transplantation from a histocompatible donor. The optimal timing of the transplant is difficult to determine because of the high peritransplant mortality of 20-35% and the existence of a group of patients who can have the disease controlled by drug treatment for prolonged periods. We have developed a mathematical model implemented with a computer program which calculates lower and upper time limits for the timing of marrow transplantation. The lower time limit for transplantation is derived from the loss of life expectancy with delay, and the upper time limit is calculated by comparing the transplant survival probability with the probability of surviving an additional year without a transplant. Thus, an objective basis is provided for bracketing the most appropriate time for transplantation. This analysis suggests that the decision to transplant can be postponed in some patients for periods longer than may generally be recommended.

Adult