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Biomedical subjects

M Becker

Publications and source records attributed to M Becker.

At least 73 records · Page 4Linked to original sources

[Nerve regeneration in autologous and allogeneic transplant of the sciatic nerve of the rat with and without immunosuppression by cyclosporin A].

The following experimental studies show different stages of regeneration and rejection in autologous and allogenic nerve grafts in 162 rats with and without immunosuppression with Cyclosporin A. Allografts were used in congenic rats differing only in major histocompatibility complex (MHC). Nerve regeneration was studied in autologous grafts with and without treatment with Cy A and with toxic doses of Cy A. No difference in nerve regeneration was seen in these groups. Allografts were transplanted between congenic rats type LEW 1 A and 1 U and vice versa with and without treatment with Cy A. Various degrees of rejection from slight to moderate were seen. Without Cy A-treatment, nerve grafts were totally destroyed after four weeks. With Cy A, nerve grafting resulted in complete regeneration.

Animals

Improved high-performance liquid chromatographic procedure for the determination of chlormethiazole levels following solid-phase extraction from plasma.

An improved high-performance liquid chromatographic method for the determination of chlormethiazole levels in plasma is described. The drug is extracted from plasma using commercially available reversed-phase extraction columns; recovery values obtained using Sep-Pak C18 and Bond Elut C1, C2, C4, C6, C8, C18 columns are compared. Separation was achieved by reversed-phase chromatography, using a mobile phase consisting of 0.025 M sodium acetate buffer, pH 4.5-acetonitrile (67:33) at a flow-rate of 1.6 ml/min in conjunction with a 15-cm Jones Chromatography Apex ODS column. The analytical column was protected by a Waters Assoc. Guard-Pak module containing a Guard-Pak CN insert. Using ultraviolet detection at 254 nm chlormethiazole levels in the region of 50 ng/ml can be measured with only 500 microliter of plasma.

Chlormethiazole

A phase II trial of diaziquone in patients with head and neck cancer.

Diaziquone (AZQ) is a lipophilic alkylating agent which crosses the blood-brain barrier and has marked antitumor activity in a broad spectrum of murine tumor systems. Myelosuppression has been the dose-limiting toxicity in phase I trials. In this study 36 patients with head and neck cancer received diaziquone. Thirty-one of these patients (28 male, 3 female) were evaluable for efficacy. The initial starting dose was 7 mg/m2/day X 5 days i.v. repeated every 28 days. Because of the severe myelosuppression encountered in the first four patients, the starting dose was decreased by 20% to 5.5 mg/m2/day X 5 days repeated every 28 days. The majority of patients were considered to be good-risk patients as evidenced by performance status (80% 0-1 Zubrod) and prior therapy. Even with this dosage reduction, myelosuppression (especially thrombocytopenia) was again the dose-limiting toxicity with 25% of patients experiencing granulocyte and platelet nadirs below 1000/mm3 and 50,000/mm3 respectively. Thirty-five percent of patients required a subsequent dosage reduction of 20% prior to receiving a second course of therapy. There was one complete (CR), four partial (PR) and three minor (MR) responses. All but the CR were of relatively short duration (mean of 30 days). The patient with a CR has remained disease-free for nearly 3 years. In this group of patients the activity of diaziquone as a single agent at this dose and schedule (CR + PR + MR = 26%; CR + PR = 16%) is less than that of methotrexate, bleomycin, and cis-platinum but is encouraging. Further trials utilizing combinations are warranted.

Adult

Circulating somatomedin-C levels and the effect of growth hormone-releasing factor on plasma levels of growth hormone and somatostatin-like immunoreactivity in obese children.

The effect of growth hormone-releasing factor (GRF) 1-44 on growth hormone and somatostatin release in plasma has been studied in 20 obese children. Twenty age and sex-matched children with normal weight served as controls. Mean peak growth hormone response in obese children after 1 microgram/kg body wt. GRF 1-44 was significantly lower than in controls (23.7 +/- 3.6 ng/ml vs. 41.1 +/- 3.0 ng/ml; P less than 0.01), as were mean integrated growth hormone response areas (1544 +/- 272 ng X ml-1 X 2 h vs. 2476 +/- 283 ng X ml-1 X 2 h; P less than 0.01). Mean plasma levels of somatostatin-like immunoreactivity did not change after GRF in both groups. Mean somatomedin-C levels in obese children were significantly higher compared to controls (1.6 +/- 0.4 U/ml vs. 0.86 +/- 0.4 U/ml; P less than 0.01). Somatomedin-C levels were not related to the integrated growth hormone responses. In conclusion there is no relation between somatomedin-C levels and the reduced growth hormone-releasing effect of GRF in obese children. GRF does not alter peripheral somatostatin-like immunoreactivity levels either in normal or obese children.

Adolescent

Effect of insulin-induced hypoglycemia on circulating levels of plasma growth hormone-releasing hormone and somatostatin in children.

In response to insulin-induced hypoglycemia (0.1 U insulin/kg body weight, i.v.) plasma levels of growth hormone-releasing hormone (GHRH), somatostatin (SLI), and growth hormone (GH) were measured by radioimmunoassay in 10 children with short stature. Insulin injection resulted in a significant increase in plasma GHRH values at 15 min (10.0 +/- 0.5 vs. 17.1 +/- 3.1 pg/ml; p less than 0.05) preceding the increase in plasma GH levels (1.5 +/- 0.4 vs. 13.6 +/- 1.2 ng/ml; p less than 0.001). SLI concentrations peaked between 15 and 60 min after insulin injection (20.9 +/- 1.2 vs. 47.1 +/- 6.2 pg/ml; p less than 0.01). No correlation was present between plasma GHRH or SLI levels and plasma GH concentrations. A significant negative correlation could be established between maximum increments of plasma GHRH and SLI levels (r = -0.843; p less than 0.01) in response to insulin injection. This finding suggests a possible relationship between these two hormones at peripheral level.

Adolescent

Plasma levels of growth hormone-releasing hormone and somatostatin in response to a mixed meal and during sleep in children.

Following a mixed meal, plasma levels of GHRH, GH, SRIH and insulin were measured in 7 prepubertal children with constitutional delay of growth and adolescence (CDGA) and in 3 children with proven GH-deficiency which responded to GHRH-injection. In children with CDGA, plasma levels of GHRH increased between 60 and 120 min (10.1 +/- 1.2 ng/l vs 25.5 +/- 4.4 ng/l; P less than 0.01). Although no GH increase occurred in patients with GH-deficiency, their plasma GHRH increases were comparable to those in CDGA children. No time relationship was present between circulating GHRH and GH, SRIH, or insulin, nor was there any correlation between their integrated hormone response areas. Sleep-induced plasma GHRH, GH and SRIH values were determined in 10 prepubertal children with CDGA. Spontaneous variations of plasma GHRH and GH values occurred with no temporal or quantitative relationship. SRIH values did not change during nocturnal sleep. In one child with GH-deficiency, comparable GHRH plasma fluctuations occurred, although GH values were all below 1 microgram/l. Our results support the concept that circulating GHRH does not only represent hypothalamic GHRH, but derives mainly from extrahypothalamic sources, possibly from the gastrointestinal tract.

Adolescent

[Therapy of constipation with wheat bran in infancy and early childhood].

In 22 infants and children aged 6 to 62 months (mean = 23 months) with severe constipation a commercially produced solid food containing 4.2 g wheat bran was used for 41 days. Acceptance was satisfactory, compatibility was reported to be good. In 86% of the children normal bowel movements appeared within 8.2 days of therapy. Blood levels of hemoglobin, calcium, phosphathase, alkaline phosphatase, iron, transferrin, total protein, cholesterol, and carotene were controlled in monthly intervals. Under wheat bran there was only a slight decrease of carotene concentrations by 13.5 mg/dl (p less than 0.05) and a minimal increase of alkaline phosphatase activity by 14.5 U/l (p less than 0.1). In 8 healthy infants aged 4.5-9 months (mean = 6.7 months) the bran preparation induced an increase of stool weight by 21.5% (p less than 0.05), whereas the frequency of bowel actions did not change. The results indicate that bran preparations may be used in severe constipation even in early childhood.

Child, Preschool

Characterization of a new tumor in NMRI-mice suitable for chemotherapeutic experiments.

The tumor was found in the peritoneum of a 6-months old female NMRI-mouse. Histologically it can probably be classified as a less-differentiated reticulum-cell sarcoma (histiocytic sarcoma). Following ip. or sc. transplantation metastases were only in some cases found. After im. inoculation of tumor brei lungs, livers, kidneys, spleens and lymph nodes were free of metastases, as a bioassay revealed. The im. transplantation was the most suitable technique for chemotherapeutic experiments: It resulted in a 100% take rate and a relatively narrow and well reproducible death range; tumor size and life span of the animals could be used as therapeutic parameters. The tumor was highly sensible against the cytostatic drugs Cyclophosphamide, Doxorubicin and Vincristine. A moderate activity showed CCNU, Cis-DDP and Bleomycin, while DTIC and a novel Benzochinonguanylhydrazon-derivative only reversibly influenced the tumor growth and not the life time of the animals. Liposomally encapsulated Daunorubicin and Bleomycin had in general similar effectiveness as the drugs in its free form. Because of its high sensitivity against a lot of cytostatics with different mechanisms of action the tumor can be recommended for the screening of novel antineoplastic substances.

Animals

High-performance liquid chromatographic determination of carbamazepine and carbamazepine 10,11-epoxide in plasma and saliva following solid-phase sample extraction.

A rapid, sensitive and simple to operate high-performance liquid chromatographic method for the simultaneous determination of carbamazepine (CBZ) and carbamazepine 10,11-epoxide (CBZ-EP) in plasma and saliva is described. The drug and its metabolite are extracted from both plasma and saliva using commercially available reversed-phase octadecylsilane bonded silica columns (Bond-Elut C18, 2.8 ml capacity). Separation of CBZ and CBZ-EP was achieved by reversed-phase chromatography, using a mobile phase consisting of acetonitrile-methanol-water (19:37:44) at a flow-rate of 1.8 ml/min in conjunction with a Nova-Pak C18 column. The analytical column, in Radial-Pak cartridge form, was used in combination with a Z-module RCSS and protected by a Guard-Pak precolumn module containing a Guard-Pak mu Bondapak C18 insert. Using ultraviolet detection at 214 nm, levels in the region of 50-100 ng/ml for CBZ and CBZ-EP can be measured with only 250 and 500 microliters of plasma and saliva, respectively. The method, which has been used to determine steady-state concentrations of the drug and its metabolite in paediatric patients receiving CBZ monotherapy, is also suitable for pharmacokinetic studies.

Carbamazepine

Solid-phase extraction of acetazolamide from biological fluids and subsequent analysis by high-performance liquid chromatography.

A sensitive, relatively fast and simple to operate high-performance liquid chromatographic method for the determination of acetazolamide in plasma and saliva is described. Quantitative extraction of the drug from both plasma and saliva was achieved using commercially available reversed-phase octadecylsilane-bonded silica column (Bond-Elut C18, 2.8 ml capacity). Acetazolamide and the internal standard are retained on the Bond-Elut C18 column and reproducibly recovered by elution with methanol. Liquid-liquid partition chromatography, carried out on a 30-cm mu Porasil column (10-microns porous silica) using a mobile phase consisting of dichloromethane-ethanol-water-glacial acetic acid (500:65:65:1), provided adequate separation with acceptable retention times. Acetazolamide levels in the region 50-100 ng/ml can be determined in 100 microliters of plasma or 200 microliters of saliva employing ultraviolet detection at 254 nm with a sensitivity of 0.005 absorbance units full scale. Although the method is primarily used to determine steady-state drug levels in paediatric patients, its general applicability is illustrated by the 24-h plasma and saliva concentration profiles obtained from a male volunteer following oral administration of acetazolamide.

Acetazolamide

The histocompatibility of a new bovine pericard graft.

An artificial defect of the umbilical area in ten calves was covered by a pericard graft whose new preparation method has been proved in bovine vessel grafts. Between 2 and 6 months postoperatively (p.o.) two animals at a time were euthanized to sample the graft and its surrounding tissue for histological investigations. On the one hand, there was an inflammatory foreign body type granulomatous reaction, but on the other hand this did not lead to rejection. Within the 6-month observation time the graft fibers were immigrated by the own young collagen fibers. We interpret this as a guide function of the graft fibers. Tiny focal calcifications appeared to be the effect of an intensive tissue irritation which may be caused by an incomplete edulcoration of the chemical substances used during preparation. We recommend a longer edulcoration time to prevent these reactions.

Animals

Biliary cholesterol saturation in non-obese women and non-obese men before and after puberty.

The lipid composition of gallbladder bile was determined in forty-seven normal, non-obese subjects (twenty females and twenty-seven males) without gallstones ranging in age from seven months to twenty-nine years. Before puberty, bile was undersaturated with cholesterol in both sexes to the same extent. After puberty a marked increase in cholesterol saturation was observed in females but not in males (138% vs 88%; P less than 0.01). A significant correlation between age and cholesterol saturation could be observed in females (r = 0.546; P less than 0.05) but not in males. In addition a significant correlation between absolute weight and cholesterol saturation in all females (r = 0.827; P less than 0.001) and those after puberty (r = 0.659; P less than 0.05) could be demonstrated. In neither sex was saturation related to body mass index or ideal body weight. These findings suggest that saturation of bile raises in women during puberty but not in men, and this sex-related difference in cholesterol saturation probably contributes to the more common occurrence of gallstones in women than in men.

Adolescent

[Circulating somatostatin concentrations in childhood. Studies in normal weight and obese children and patients with growth hormone deficiency].

At present in childhood there is only few information about the importance concerning circulating somatostatin concentrations. We therefore investigated the plasma somatostatin response to a mixed meal, an oral glucose load, pentagastrin injection and insulin hypoglycemia in normal weight and obese children and patients with growth hormone deficiency. Results in normal weight children: 1. Following a 800 kcal mixed meal (50% carbohydrate, 35% protein, 15% fet) peak values of plasma somatostatin were reached within 30-180 min (37.6 +/- 4.2 pg/ml vs. 58.5 +/- 3.4 pg/ml; p less than 0.05) in 6 children. 2. In response to oral glucose load of 1.75 g/kg bw glucose no alterations of plasma somatostatin levels were observed in 13 children 3. Injection of 6 micrograms/kg bw pentagastrin s.c. in 10 children resulted in maximal increase of somatostatin concentrations between 5 and 15 min (32.0 +/- 4.5 pg/ml vs. 69.1 +/- 7.4 pg/ml; p less than 0.01). 4. Injection of 0.1 IU/kg bw insulin in 7 children induced hypoglycemia and stimulated peak values of plasma somatostatin within 15-60 min (32.0 +/- 6.6 pg/ml vs. 57.4 +/- 6.4 pg/ml; p less than 0.01). - Results in obese children: Following mixed meal ingestion in 7 obese children plasma somatostatin response was comparable to controls. Although integrated insulin response over 180 min was higher in this group (9694 +/- 1363 microU/ml vs. 5054 +/- 651 microU/ml; p less than 0.05) the integrated somatostatin response (9038 +/- 1852 pg/ml) did not differ from controls (8614 +/- 876 pg/ml). After oral glucose load no changes in circulating somatostatin concentrations were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent