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Biomedical subjects

K Nelson

Publications and source records attributed to K Nelson.

At least 163 records · Page 9Linked to original sources

Influence of two guar preparations on glucose and insulin levels during a glucose tolerance test in healthy volunteers.

Dietary fiber deficiency may be alleviated with an increase in fiber-rich foods or fiber in the form of guar. The efficacy of a solid guar preparation and a liquid form on glucose and insulin levels during a glucose tolerance test in 12 healthy volunteers was examined. The first half of the study tested the efficacy of a new guar preparation (GU-052, Steigerwald, Darmstadt, Germany). Six volunteers ingested 75 glucose and 12 g guar mixed in 450 ml water. The other 6 received the same drink without guar. Blood was withdrawn for the determination of glucose and insulin before ingesting the glucose solution and after 15, 30, 45, 60, 90, 120, 180, 210 and 240 min. One week later the groups were crossed over. The second half of the study tested the efficacy of GU-052 against a solid preparation consisting of 5 g guar and 1.13 g additive (Glucotard, Boehringer, Mannheim, Germany). Volunteers receiving GU-052 with the glucose drink showed no increase in plasma glucose. Volunteers without GU-052 reached a maximal plasma glucose value of 6.66 +/- 1.30 mmol/l 30 min after glucose ingestion from an initial value of 5.28 +/- 0.40 mmol/l. A second smaller peak was observed 120 min after glucose ingestion. A 2.5-fold increase from 16.17 +/- 4.30 to 40.10 +/- 19.00 microIU/ml in insulin concentration occurred in the volunteers ingesting GU-052, whereas a 6-fold increase from 19.33 +/- 12.20 to 114 +/- 48.8 microIU/ml insulin occurred in the volunteers without GU-052. A second peak in insulin at 120 min which occurred in the volunteers without GU-052 was not apparent when the volunteers ingested GU-052. The comparison of GU-052 and Glucotard showed that GU-052 maintained the glucose level, whereas Glucotard allowed the plasma glucose to reach 6.67 +/- 0.98 microIU/l. The increase in insulin was not as great with GU-052 as with Glucotard. This study shows that guar suppresses glucose and insulin levels during a glucose tolerance test. The guar form influences the efficacy.

Adult↗

Investigation of early surface delamination observed in retrieved heat-pressed tibial inserts.

The objective was to examine possible reasons for delamination observed in tibial inserts of the porous-coated anatomic (PCA) knee replacement. To date, 33 PCA inserts have been forwarded to the authors' labs. Of these 33, 52% showed severe delamination within four years of implantation. Visual, structural, and mechanical analyses were conducted and data compared on the heat-pressed PCA type and the common machined inserts. Twenty inserts of the two different types were examined. Visual data using polarized light microscopy showed the presence of a surface layer separated from the middle region of the heat-pressed inserts by a line of demarcation 250-580 microns beneath the articulating surface. This anomaly was not observed in machined inserts. Structural analysis showed the new heat-pressed inserts had increased crystallinity in the surface layer when compared to new machined inserts. The retrieved heat-pressed inserts showed increased crystallinity in the surface and middle regions. There was a slight increase in surface crystallinity in the retrieved machined inserts. Microhardness data showed that there was an increased hardness associated with the crystallinity seen on the heat-pressed inserts. Orthopedic surgeons should be aware of early delamination and surface failure in heat-pressed inserts.

Hardness↗

Characterization of high specific activity [16 alpha-123I]Iodo-17 beta-estradiol as an estrogen receptor-specific radioligand capable of imaging estrogen receptor-positive tumors.

16 alpha-[123I]Iodo-17 beta-estradiol (16 alpha-[123I]E2) has been characterized for use as a selective radioligand for estrogen receptor (ERc) that is capable of generating in situ images of ERc-positive tumors. High specific activity 16 alpha-[123I]E2 (7,500-10,000 Ci/mmol) was used in all determinations. Radiochemical purity was determined by thin layer chromatography, and the selectivity of radioligand for ERc was evaluated using size exclusion high performance liquid chromatography on ERc prepared from rodent uteri. Efficiencies of radioidination approaching 100% were achieved, and excellent receptor selectivity was obtained even when the efficiency of radioiodination was as low as 10%. Low radiochemical purity was always associated with poor selectivity for ERc. No new radioligand species was generated during the course of radiodecay; however, reduced binding over time, even when increased activity was used to compensate for radiodecay, indicated that the formation of a radioinert competitor does occur. 16 alpha-[123I]E2 demonstrated stable, high affinity binding to ERc and was concentrated by ERc-positive tissues. After injecting 16 alpha-[123I]E2 in vivo, images of ERc-containing tissues were obtained, including rabbit reproductive tract and dimethylbenzanthracene-induced tumors. The demonstrations of ERc selectivity and image formation both indicate that 16 alpha-[123I]E2 should have promise as a useful new radiopharmaceutical for imaging ERc-positive cancers.

Animals↗

Co-dergocrine mesylate inhibits the increase in plasma catecholamines caused by nifedipine in essential hypertension.

Co-dergocrine mesylate (Cod), which inhibits norepinephrine secretion by stimulating presynaptic dopamine receptors, and has no known metabolic side effect, has an additive antihypertensive effect to that of Nifedipine (Nif). Plasma norepinephrine, epinephrine, renin activity and aldosterone have been measured after acute administration of Nif and Cod alone and in combination to 18 patients with a diastolic blood pressure greater than 105 mmHg in a cross-over, randomized, double-blind study. Every patient received 4 mg Cod then 20 mg Nif, placebo then 20 mg Nif and 4 mg Cod then placebo. The second treatment was always given 1 h after the first medication. Blood pressure was measured before and every 15 min during the study period. Blood for measurement of catecholamines, aldosterone and renin activity was collected before medication, 1 h after the first dose and 90 min after the second treatment. Blood pressure was significantly lower (P less than 0.05) where Cod preceded Nif. Cod caused a significant decrease in plasma norepinephrine from 293 to 202 pg.ml-1 and in epinephrine from 67 to 55 pg.ml-1. The Nif-induced increase in norepinephrine from a pre-treatment value of 293 pg.ml-1 with preceding Cod to 331 pg.ml-1 was much less than the increase with placebo as premedication, from 284 to 440 pg.ml-1. Nif caused an increase in renin activity but no increase in aldosterone. Nif-related side effects, such as flushing and headache, occurred in 6 patients of whom 5 had no received Cod as premedication.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

Children's knowledge of cancer and its treatment: impact of an oncology camp experience.

Because pediatric oncology camps provide an opportunity for children who have had cancer to interact with their peers in an informal, recreational environment, this study was designed to determine (1) whether cancer and its treatment are discussed informally among the children, (2) what kinds of information are exchanged if such discussions take place, and (3) how these interactions might affect the children's knowledge and understanding of cancer and its treatment. The study included detailed, open-ended, structured interviews and observational accounts of the subjects before, during, and after camp. These interviews and observations in a sample of 50 children revealed that the children engaged in informal discussion about cancer and its treatment, and that information on a variety of topics, ranging from medical procedures to prognosis, was exchanged. Despite the lack of formal instruction, there was a significant increase in the children's knowledge about cancer and its treatment. Age, sex, diagnosis, years since diagnosis, treatment status and times at camp were not found to be significant determinants of gain in knowledge. No control group was studied, but we believe that the data support the conclusion that attending a camp for children with cancer improves their knowledge of the disease and its treatment.

Adolescent↗

Influence of co-dergocrine mesilate/nifedipine compared to mefruside/nifedipine on circadian blood pressure in patients with essential hypertension.

This randomised, parallel group study was designed to compare the efficacy of nifedipine (40 mg once daily) combined with either the dopamine agonist, co-dergocrine mesilate (4 mg once daily) or the diuretic mefruside (25 mg once daily) in 40 patients with essential arterial hypertension and a diastolic blood pressure greater than 105 mmHg. Circadian blood pressure and heart rate were measured over 24 h every 15 min from 6 a.m. to 6 p.m. and every 30 min from 6 p.m. to 6 a.m. with an automatic, portable instrument (ICR 5300, Squibb) before and after a three-week treatment period. At the end of the three-week treatment period the mean value of all 24 h blood pressure measurements reflected highly significant decreases (2P less than 0.001), from 148/92 +/- 16/12 before treatment to 131/83 +/- 12/12 mmHg after treatment in the co-dergocrine mesilate/nifedipine group and from 145/92 +/- 16/10 before treatment to 129/84 +/- 10/6 mmHg after treatment in the mefruside/nifedipine group. Blood pressure reduction was still significant in both groups during the early morning hours at the end of the dosage interval. The efficacies of nifedipine combined with co-dergocrine mesilate or mefruside were comparable but side-effects were rated as more severe in the mefruside group. Therefore, the combination co-dergocrine mesilate/nifedipine may be preferable to the combination mefruside/nifedipine.

Adult↗

Intermolecular engagement of estrogen receptors indicated by the formation of a high molecular weight complex during activation.

After exposure to ligand at 0-4 degrees C, estrogen receptors from mouse uteri characteristically eluted between thyroglobulin (Mr 669,000) and ferritin (Mr 443,000) during size-exclusion HPLC. However, when preparations were warmed with ligand under mild activating conditions, most or all of the receptor was observed as a much larger complex, which eluted between dextran blue 2000 and thyroglobulin. Formation of the large complex required ligand, was inhibited by molybdate, and occurred even in 0.4 M KCl. Slower ligand dissociation characterized the large complex, indicating that activated receptors were included preferentially. This large complex did not form when charged cytosols were aged, concentrated, or precipitated, indicating that formation was not the result of random aggregation. After exposure to conditions commonly used for activation (25 degrees C, 60 min), most receptor existed as a very large, monodisperse complex of finite size, predicting an ordered structure for these large complexes that should be useful for defining the types of proteins which can interact with estrogen receptors. Formation of the large complex was not impeded or disrupted by EDTA, RNase, DNase I, thiourea, or mercaptoethanol; however, the capacity to form this large complex was not demonstrated by preparations that had been exposed to trypsin or by the small receptor forms obtained after salt extraction. Proteolytic sensitivity and lack of sensitivity to RNase or DNase indicate that interactions between receptors and other proteins are involved in peak A formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Changes in estrogen receptor, DNA ploidy, and estrogen metabolism in rat hepatocytes during a two-stage model for hepatocarcinogenesis using 17 alpha-ethinylestradiol as the promoting agent.

17 alpha-Ethylestradiol (EE2) was administered chronically to diethylnitrosamine (DEN)-initiated (200/mg/kg, i.p.) adult ovariectomized Sprague-Dawley rats, by means of Silastic implants at an estimated dose of 90 micrograms/kg/day. Isolated hepatocytes from DEN/EE2-treated animals exhibited a 2- to 3-fold increase in nuclear estrogen receptor (ER) levels throughout the promotion period. Furthermore, approximately 30-40% of the receptor was occupied when quantified by an exchange assay. For all groups the ER had a sedimentation coefficient of approximately 8S for unoccupied ER and a binding affinity for 17 beta-estradiol of 0.25 nM. An ER of lower affinity for estradiol was present in animals initiated with DEN and/or promoted with EE2. The increase in hepatocyte ER was associated with a 5.2-fold increase in gamma-glutamyl transpeptidase and 2.5-fold decrease in glucose-6-phosphatase activity at 20 weeks. EE2 treatment caused a 50% increase in the maximal binding capacity (Bmax) of hepatic epidermal growth factor receptors, but the equilibrium binding constant (Kd) did not change. Modulation of mitotic activity of hepatocyte subpopulations by EE2 treatment was indicated by an increase in the proportion of diploid hepatocytes and an increase in the number of hepatocytes undergoing DNA synthesis. In general, effects on ER, epidermal growth factor receptor, gamma-glutamyl transpeptidase and glucose-6-phosphatase were greater in DEN/EE2-treated animals than in rats receiving only EE2. Modification of receptor pathways associated with hepatocyte growth control, ER and epidermal growth factor receptor, may be contributing factors in the clonal expansion of preneoplastic cells during EE2 promotion of hepatocarcinogenesis.

Animals↗

[Piretanide in chronic and acute decompensated heart failure. Effect on hemodynamics and vasoactive hormones].

Eight patients with chronic heart failure classified as NYHA class II to III (group 1) and nine patients with acute decompensated heart failure classified as NYHA class IV (group 2) were treated with piretanide at a dosage of 12 mg administered intravenously. In both groups the level of prostaglandine PGE2 as well as plasma renine activity significantly increased prior to the onset of diuresis. The percentage increase was more pronounced in group 1 which had lower baseline values. With a time-lag, the norepinephrine plasma level also increased significantly. During the first 30 minutes there was only little effect on blood pressure, pulmonary artery pressure and cardiac output in patients with chronic heart failure (group 1). Only after 60 minutes there was a significant decrease in mean pulmonary artery pressure (from 39 +/- 17 to 33 +/- 18 mm Hg; p less than 0.05). In patients with acute decompensated heart failure (group 2) piretanide led to a significant reduction in mean pulmonary artery pressure (from 42 +/- 13 to 37 +/- 12 mm Hg; p less than 0.05) within 15 minutes after administration, i.e. even prior to the onset of diuresis. Thus, the administration of piretanide had a positive effect on hemodynamics in patients with chronic as well as in patients with acute decompensated heart failure. Significant improvement prior to diuresis onset, however, was only found in patients with acute decompensated heart failure. These effects may be explained by a stimulation of prostaglandines which promote vasodilation. They are increased by the diuresis.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

Stage I serous papillary carcinoma of the endometrium.

From 1973 to 1987, 16 patients with International Federation of Gynecology and Obstetrics (FIGO) Stage I serous papillary endometrial carcinoma were evaluated and treated at the University of Kentucky Medical Center (Lexington, KY). All patients were 60 years of age or older, and all were postmenopausal. Patients were treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy, and paraaortic lymph node sampling, and 38% were noted to have more extensive disease than appreciated clinically. Nine patients were given adjuvant postoperative radiation. Seven patients (44%) developed recurrent cancer with liver, lung, and upper abdomen being the most common sites of spread. Prognosis was most directly related to the presence of lymph vascular space invasion and the depth of myometrial penetration. No patient with serous papillary carcinoma confined to the endometrium developed recurrent cancer. In contrast, the recurrence rate of patients having myometrial invasion was 70% (P less than 0.03). Hormonal therapy was of limited value in the treatment of recurrent disease. This data suggests the need for adjuvant systemic therapy in the treatment of patients with Stage I serous papillary carcinoma of the endometrium who have myometrial invasion.

Aged↗

2,3,7,8-Tetrachlorodibenzo-p-dioxin enhancement of N-methyl-N'-nitro-N-nitrosoguanidine-induced transformation of rat tracheal epithelial cells in culture.

The abilities of various dioxins to induce toxicity or transformation of rat tracheal epithelial cells in culture were examined. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was not cytotoxic and did not induce transformation as measured by the induction of growth-altered, preneoplastic cells (termed enhanced growth variants). However, TCDD enhanced the transformation of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-initiated rat tracheal epithelial cells. Other dioxin congeners with 0 to 3 chloro substitutions were inactive in enhancing MNNG transformation. TCDD was most effective at a concentration of 0.3 nM and when treatment was administered immediately after MNNG exposure. The dose-response curves for enhancement of MNNG-induced transformation and induction of aryl hydrocarbon hydroxylase activity by TCDD were similar. These results are consistent with the hypothesis that the enhancement of cell transformation by TCDD is mediated through the TCDD receptor. TCDD also enhanced transformation when the cells were treated before MNNG treatment. The ability of 12-O-tetradecanoylphorbol-13-acetate (TPA) to enhance MNNG-induced rat tracheal epithelial transformation was also examined. In contrast to the findings with TCDD, the number of transformed colonies was increased only by pretreatment with TPA followed by MNNG. TPA-pretreatment enhanced equally the number of normal cells forming colonies and the total number of transformed colonies after selection; therefore, the transformation frequency (transformants per total surviving colonies) was unchanged by TPA. In contrast, TCDD treatment enhanced the transformation frequency in MNNG-exposed cultures since the number of transformed colonies increased while the number of total colonies remained constant. Thus, TCDD appears to act by a different mechanism than TPA. TCDD enhancement of MNNG-induced transformation may be attributed to a promotional effect, a comutagenic action, or a modulation of cell proliferation and/or differentiation mediated through the TCDD receptor.

Animals↗

Malformations due to presumed spontaneous mutations in newborn infants.

We conducted hospital-based surveillance of congenital malformations to determine the rate of apparently spontaneous single mutations leading to recognized phenotypes. Through surveillance of 69,277 infants with gestational ages of at least 20 weeks, we identified 48 infants (0.07 percent) with major malformations, with phenotypes that suggested that the malformations were due to single mutant genes. Family studies suggested that 11 of these infants (10 with autosomal dominant disorders and 1 with an X-linked condition) were affected as the result of a new (spontaneous) genetic mutation. The spontaneous mutation rates per gene were 0.7 x 10(-5) and 1.44 x 10(-5) for the disorders in which one and two infants were affected, respectively. In addition, 5 of the 10 infants with autosomal recessive malformations had negative family histories, but we were unable to infer the presence of spontaneous mutations in these cases. Because the family history was negative in 44.4 percent of the infants with disorders considered due to autosomal or X-linked genes, counseling should include the understanding that genetic disorders often occur unexpectedly among children of healthy parents.

Congenital Abnormalities↗

Influence of guar on serum lipids in patients with hyperlipidaemia.

The antihyperlipidaemic effect of a guar preparation which absorbs a particularly large amount of water has been examined in 13 patients with Type II hyperlipidaemia. A 30-day pre-treatment phase was followed by 60 days of treatment with 4 g guar dissolved in 200-ml liquid at each meal-time (total guar 12 g/day), and a 60-day post-treatment observation period. Routine other clinical blood tests were performed 30, 15 or 0 days before treatment, 15, 30 and 60 days after the start of treatment, and 30 and 60 days after its end. Total cholesterol fell by 0.85 mmol.l-1, from a pre-treatment concentration of 7.4 mmol.l-1 to a treatment value of 6.5 mmol.l-1, and LDL-cholesterol fell by 0.64 mmol.l-1, from 5.5 mmol.l-1 to a treatment value of 4.8 mmol.l-1. There was no significant change in triglyceride and VLDL concentrations during the study. A slight but significant fall in HDL-cholesterol was seen. The sole adverse effect was occasional intestinal discomfort.

Cholesterol↗