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Biomedical subjects

P C Scriba

Publications and source records attributed to P C Scriba.

At least 19 recordsLinked to original sources

The relationship between insulin binding, insulin activation of insulin-receptor tyrosine kinase, and insulin stimulation of glucose uptake in isolated rat adipocytes. Effects of isoprenaline.

We have studied the relationship between insulin activation of insulin-receptor kinase and insulin stimulation of glucose uptake in isolated rat adipocytes. Glucose uptake was half-maximally or maximally stimulated, respectively, when only 4% or 14% of the maximal kinase activity had been reached. To investigate this relationship also under conditions where the insulin effect on activation of receptor kinase was decreased, the adipocytes were exposed to 10 microM-isoprenaline alone or with 5 micrograms of adenosine deaminase/ml. An approx. 30% (isoprenaline) or approx. 50% (isoprenaline + adenosine deaminase) decrease in the insulin effect on receptor kinase activity was found at insulin concentrations between 0.4 and 20 ng/ml, and this could not be explained by decreased insulin binding. The decreased insulin-effect on kinase activity was closely correlated with a loss of insulin-sensitivity of glucose uptake. Moreover, our data indicate that the relation between receptor kinase activity and glucose uptake (expressed as percentage of maximal uptake) remained unchanged. The following conclusions were drawn. (1) If activation of receptor kinase stimulates glucose uptake, only 14% of the maximal kinase activity is sufficient for maximal stimulation. (2) Isoprenaline decreases the coupling efficiency between insulin binding and receptor-kinase activation, this being accompanied by a corresponding decrease in sensitivity of glucose uptake. (3) Our data indicate that the signalling for glucose uptake is closely related to receptor-kinase activity, even when the coupling efficiency between insulin binding and kinase activation is altered. They thus support the hypothesis that receptor-kinase activity reflects the signal which originates from the receptor and which is transduced to the glucose-transport system.

3-O-Methylglucose

Clinical evaluation of decision support system for insulin-dose adjustment in IDDM.

OBJECTIVE: We developed a wallet-sized learning memory decision support system that helps patients with insulin-dependent diabetes mellitus adjust their insulin dosages. RESEARCH DESIGN AND METHODS: To determine the efficacy of the support system, we designed a randomized clinical trial with patients participating in a program in a diabetes education center. Patients were assigned to two groups of 21 patients each. All patients performed self-monitoring of blood glucose (SMBG) and were treated with multiple daily injections of insulin. Each of the patients was examined over a 32-day period. The basic educational program, i.e., practical advice in SMBG, diet, and exercise under homelike conditions, was identical in both groups. The only difference was that the first group used the computer for adjusting the insulin dose, whereas the second group received recommendations from the education team. RESULTS: The baseline HbA1 levels (9.8 +/- 1.6 vs. 9.9 +/- 1.6%) of both groups did not differ significantly. Mean blood glucose over the last 2 wk of the study was higher (P less than 0.01) in the second group (8.4 +/- 1.4 vs. 9.2 +/- 2.0 mM); the frequencies of hypoglycemic episodes were not different (1.7 vs. 2.3%). CONCLUSIONS: Metabolic control and safety were comparable in both groups. Thus, patients may benefit from such a system at home where no support by diabetes educators is available.

Adult

[Effect of demographic changes on the case rate and days of care for hospitalized internal medicine patients].

Using case categories at the Center for Internal Medicine of the Medical University at Lübeck and predictions of future population trends by the German Federal Statistical Office, likely future numbers of inpatients and days of hospital stay were calculated. Assuming other conditions remaining constant, an annual rise of 0.9% of medical cases is to be expected until the year 2005. An increase above this average is expected for cases of cardiovascular and respiratory disease and of malignant neoplasms, while it will be below average for renal or gastrointestinal diseases. These data are similar to comparable projections made, on the basis of Federal statistics, of hospital cases registered with local health insurance schemes. In addition they indicate an increase of 3% for all non-paediatric admissions up to 2005.

Age Factors

Thyroid growth stimulating activity in highly purified IgG-fractions of patients with nonimmune thyroid diseases.

Two different proliferation assays have been used to measure the proliferative potential of IgG-fractions from 57 patients with nontoxic goiter of an iodine-deficient area: primary human thyroid epithelial cells (TEC) and the thouroughly investigated FRTL-5 cell line. IgG-fractions from patients with nontoxic goiter (n = 30), nontoxic recurrent goiter (n = 8), toxic-nodular goiter (n = 15) and carcinoma of the thyroid (n = 4) were highly purified on DEAE-Sepharose and additionally Protein A-Sepharose in some cases. The two proliferation assays gave contradictory results: primary cultures of human thyroid epithelial cells (TEC) could not be stimulated by any of the patient's IgG-fractions nor by bTSH. The FRTL-5 cells, however, were stimulated with 10 microU/ml bTSH by 326% +/- 96% (range: 222% - 497%, p less than 0.001). In one experimental series, 72% of all patients exceeded mean + 2 SD of normal controls, when the stimulation index was referred to the effect of bTSH (NTG: 77%, Rec. G.: 88%, Tox. G.: 53%, Ca. thyroid: 75%). With a different method of calculation - stimulation index referred to the basal value - the number of patients above mean + 2 SD of normal controls decreased to 30% (NTG: 33%, Rec. G.: 12.5%, Tox. G.: 33%, Ca. thyroid: 25%). Statistical analysis, however, of results of different patient groups compared to the normal control group failed to show any significance.

Adolescent

Ultrasonography related to clinical and laboratory findings in lymphocytic thyroiditis.

The value of ultrasonography compared with established diagnostic procedures was investigated by reviewing medical records of 92 patients (88 women and 4 men, age 11-81 years, mean age 47) with lymphocytic thyroiditis. Clinical manifestations of the disease and serum antimicrosomal antibodies and TSH were determined in all patients. The thyroid was examined by ultrasound. Both lobes were aspirated by a fine needle under sonographic control and smears examined cytologically. A total of 27 (29.3%) patients had no clinical symptoms. Antimicrosomal antibodies were undetable in 12 (13%) patients, 16 (17.4%) had low titres 1:32-) 1:100, and 64 (69.6%) greater than or equal to 1:320. TSH (reference values 0.3-3.9 mU/1) was les than 0.3 in 4 (4.3%) 0.3-3.9 in 4) (44.6%) , 4-20 in 26 (28.3%), and greater than 20 in 21 (22.8%) patients. Ultrasound revealed a scattered sonolucent echo in 87 (94.6%) patients, and in 45 (48.9%) a normal thyroid volume (women less than 18, men less than 25 ml). Cytology alone was diagnostic in 84 (91.3%) patients, In conclusion, ultrasound can suggest lymphocytic thyroiditis. If antimicrosomal antibodies are undetectable or titres are not significant and/or clinical symptoms are uncertain, fine-needle aspiration can confirm the sonographic finding. Epidemiological studies including ultrasonography are necessary to obtain reliable data on the prevalence of lymphocytic thyroiditis.

Adolescent

[The development of drug utilization with special reference to demographic factors].

Possible influences of demographic changes in the Federal Republic of Germany on future expenditures for medication have been investigated using population models from the Federal Statistical Office and data concerning the structure of current drug expenditures of the health insurance system. In addition the former contribution of demographic changes to the development of drug expenditures has been estimated using retrospective analysis. The study demonstrates that a constant supply with medicines would require an increase of expenses of 0.6% per year until 2,000 AD due to demographic changes, assuming other conditions remain constant. Development since 1957, however, shows that demographic influences are of relatively low importance for the development of total drug expenditures. During the last decade the total growth of costs for medicines was 6 times higher than that which would have been expected due to demographic changes alone. Further comparisons with the growth rate of the gross national product (GNP) demonstrate that since 1975 growth of drug expenditures parallels growth of GNP. The price indices for pharmaceutical products and for cost of living developed in a parallel way during the same period of time.

Age Factors

Comparative study of hormonal counterregulation during GCIIS-guided hypoglycemia tests using human proinsulin and human insulin (recombinant DNA).

Counterregulatory effect following administration of biosynthetic human proinsulin (BHPI) and human insulin (BHI) were compared during hypoglycemia standardized by means of a glucose controlled insulin infusion system (GCIIS). A total of 0.148 +/- 0.010 U/kg of BHPI had to be given by the GCIIS in order to obtain a minimal blood glucose (BG) of 26 +/- 2 mg/dl (means +/- SEM) at 43 +/- 2 min. In contrast, 0.083 +/- 0.004 U/kg of BHI were sufficient to produce a minimal BG of 21 +/- 1 mg/dl (n.s.) at 35 +/- 1 min. (P less than 0.005). Moreover, BHPI infusion resulted in prolonged hypoglycemia and delayed blood glucose recovery. On a molar basis, the acute BG lowering effect of BHPI was about 13% that of BHI (BHPI 3.94 +/- 0.27 vs. BHI 0.51 +/- 0.03 nmol/kg). Serum proinsulin after BHPI reached its maximum of 19.4 +/- 2 pmol/ml at 20 min. and still exceeded basal values markedly at the end of the test period at 240 min. Serum insulin peaked at 10 min. (162 +/- 47 microU/ml) and had already returned to basal values (7.5 +/- 1 microU/ml) after 45 min. No severe side effects were observed and there was no need for glucose administration, but clinical symptoms of hypoglycemia were more pronounced after BHPI. Compared to BHI, BHPI produced a higher cortisol peak (252 +/- 16 vs. 168 +/- 10 ng/ml), a more pronounced secretion of ACTH and GH as well as a stronger decline of serum potassium (3.20 +/- 0.06 vs. 3.58 +/- 0.08 mmol/l). Counterregulatory prolactin secretion did not differ significantly. Urinary epinephrine secretion following hypoglycemia after BHPI exceeded that after BHI (10.3 +/- 4.8 vs. 3.0 +/- 0.5 ng/120 min.). Serum lactate increase after BHPI was more prolonged (1.68 +/- 0.24 vs. 0.37 +/- 0.14 mmol/l at 120 min.). BHPI-induced inhibition of lipolysis, as determined by free fatty acid patterns, was delayed and less pronounced. Our results indicate that the observed more distinct glucose counterregulation is due to prolonged hypoglycemia rather than to any specific BHPI action on the hypothalamic-pituitary axis. We regard this as a consequence of the prolonged circulating and biological half-life. A preferential proinsulin action on the liver may play an additional role. Whether this "depot effect" may be beneficial in the treatment of diabetes mellitus remains to be established.

Adrenocorticotropic Hormone

Parathyroid localization.

Twenty-nine consecutive patients with suspected primary hyperparathyroidism were examined preoperatively using ultrasound, sonographically guided fine needle aspiration, and aspirate immunostaining for PTH. In 25 patients, localization of enlarged parathyroid glands was successful. In 2 patients, the tumors were located retrosternally and, thus, could not be detected by ultrasound. One patient had a multinodular goiter which impeded localization. In 1 patient with renal osteodystrophy, 2 enlarged parathyroid glands in the neck were not visualized preoperatively. Cytology was not diagnostic, although some cytological features were suggestive of parathyroid cells. Immunostaining of the aspirated smears for PTH, however, correctly diagnosed all preoperatively localized lesions. Ultrasound should be the routine procedure of choice for preoperative localization of abnormal parathyroid glands in primary hyperparathyroidism. Fine needle aspiration and immunocytochemistry can supply confirmation, if necessary.

Adolescent

[Validity of scintigraphic and endocrinological methods in classifying autonomous adenomas of the thyroid (author's transl)].

The validity of various scintigraphic and endocrinological methods was assessed in order to classify confirmed autonomous adenomas (AA) and to differentiate AA from euthyroid and hyperthyroid goitres. Methods used included: Measurement of 131J-uptake 6, 24 and 48 hours after 131J-application, before and after suppression by T3, thyroid scanning, count-rate measurement in the AA and the paranodular tissue, and determination of T4. All patients received 131J-therapy (40,000 rads). In 8 out of 30 scintigraphically compensated autonomous adenomas (CAA) there was no TSH response to TRH. 12 cases showed a subnormal TSH response and 10 patients had a normal TSH response. T4-values were increased in only 2 cases. Out of 73 decompensated autonomous adenomas (DAA), 66 cases (90%) had no TSH response and 7 cases showed only a subnormal response. In 48% of DAA T4-levels turned out to be in the hyperthyroid range. Both, scintigraphic and endocrinological tests were found to agree in most cases of DAA. However, the diagnosis of CAA could only be proved on the basis of a scintigraphically confirmed suppressive effect of T3 on the paranodular tissue. Thus, in the individual case, separation of CAA from DAA turned out to be impossible using the results of TRH-test alone.

Adenoma

Improvement of the calcitonin radioimmunoassay.

A rapid and specific assay for human serum calcitonin is described. The total assay-time is under 24 h and uses double-antibody in combination with polyethylene glycol to separate bound and free hormone. The antibody has been checked for its affinity to human serum calcitonin by using a Scatchard plot. Geometric dilution of sera from patients with medullary thyroid carcinoma showed a linear relationship with measured values approximating those expected. The use of Florisil to extract human serum calcitonin from sera to make "human calcitonin-free"-serum for standards has been investigated. A series of 52 normal volunteers and 99 patients with medullary thyroid carcinoma or other possible calcitonin-metabolism disorders have been examined. Only the medullary thyroid carcinoma-patients showed significantly elevated results. In the other groups two patients with phaeochromocytoma and one patient from 29 with bronchial carcinoma had elevated serum calcitonin levels.

Calcitonin

A rapid and specific method for separation of bound and free antigen in radioimmunoassay systems.

This communication reports a method for increasing the speed of separation of bound and free antigen in radioimmunoassay systems with no loss in the specificity of binding. The technique uses a mixture of second antibody and polyethylene glycol. It is not species or antibody specific, and systems using specific first antibodies from rabbit, goat or sheep are all functional. Results for the assay of parathyrin, calcitonin and corticotropin are described here, although the system has been shown to work for triiodothyronine, thyroxin, thyrotropin, thyroxine binding globulin and transferrin. The time taken for the reaction between first and second antibody is in the order of seconds, and the stability of the complex is unchanged over a period of hours.

Adrenocorticotropic Hormone

Effects of obesity, total fasting and re-alimentation on L-thyroxine (T4), 3,5,3'-L-triiodothyronine (T3), 3,3',5'-L-triiodothyronine (rT3), thyroxine binding globulin (TBG), cortisol, thyrotrophin, cortisol binding globulin (CBG), transferrin, alpha 2-haptoglobin and complement C'3 in serum.

UNLABELLED: The effects of total fasting for 31 +/- 10 days followed by re-alimentation with an 800 calorie diet on thyroid function, i.e. T4,T3,rT3,RT3U (resin T3 uptake), and TSH, and on TBG levels in serum were studied sequentially in obese hospitalized patients (N=18). Additionally, cortisol, growth hormone, prolactin, parathyrin and free fatty acids were followed as hormonal and metabolic parameters, respectively. Further, CBG, transferrin, alpha 2-haptoglobin and complement C'3 were measured as representatives of other serum proteins. Results before fasting: T4, T3, TBG, cortisol, CBG, alpha 2-haptoglobin and complement C'3 of the obese patients were elevated when compared with healthy normal weight controls, whereas rT3, T4/TBG ratio, T3/TBG ratio, TSH, coritsol/cbg ratio, growth hormone, prolactin, parathyrin and transferrin of the obese group were normal. RT3U and fT4 index were decreased in the obese patients. Results during fasting: Significant decreases were observed during fasting for the following parameters -- T3, TBG, T3/TBG ratio, transferrin, alpha 2-haptoglobin complement C'3. rT3, T4/TBG ratio, RT3U, fT4 index and FFA increased. T4, tsh response to TRH stimulation, cortisol, CBG, cortisol/cbg ratio, parathyrin, growth hormone and prolactin did not change. Results during re-alimentation: T3, TBG, T3/TBG ratio, TSH response to TRH, transferrin, alpha 2-haptoglobin and complement C'3 increased. Conversely, fT3, RT3U, FFA, cortisol and cortisol/cbg ratio decreased whereas the other parameters did not change. CONCLUSIONS: 1) There is no evidence for primary hypothyroidism in obese patients during prolonged fasting and re-alimentation. 2) The rapid decrease of T3 and increase of RT3U after initiation of fasting are not fully explained by the observed slower decreases in TBG. 3) The alterations of T3, rT3 and RT3U resemble in their kinetics the changes in FFA levels. 4) Fasting reduced the levels of only certain serum proteins, interestingly TBG, transferrin, alpha 2-haptoglobin and complement C'3, all of which, except transferrin, are elevated in obesity. 5) The magnitude of the observed decreases does not suggest any clinically relevant deficiencies in serum proteins. 6) Re-alimentation reverses rapidly all observed changes.

Adult

Isolation, characterization and radioimmunoassay of corticosteroid-binding globulin (CBG) in human serum -- clinical significance and comparison to thyroxine-binding globulin (TBG).

Isolation of the corticosteroid-binding globulin CBG was achieved by 5 chromatographical steps on cortisol Sepharose, QAE-Sephadex A-50, Con A-Sepharose and hydroxylapatite. The purity of the isolated CBG was demonstrated in polyacrylamide gel electrophoresis, SDS electrophoresis, immunodiffusion and ultracentrifugation. Microheterogeneity was shown in isoelectric focusing by 5 bands in the pH range of 3.7--4.2, which could be reduced to one major band after neuraminidase treatment. The equimolar binding of cortisol to CBG was demonstrated by binding studies. The association constant for cortisol was 2.8 x 10(8)M-1, for progesterone 1.7 x 10(6)M-1. From analytical ultracentrifugation, the molecular weight was calculated on 50 700; the sedimentation coefficient was 3.6 S, the partial specific volume 0.690 ml/g, the Stokes radius 38 A and the frictional coefficient ratio 1.5. A specific radioimmunoassay for CBG was established using the purified CBG for immunization, radioiodination and for calibration standards. The normal range of CBG levels in human serum was 2.4--4.4 mg/100 ml (mean +/- 2 SD). Studies were performed to compare the levels of CBG and thyroxine-binding globulin (TBG). No sex differences but a significant biphasic age dependence were observed for both proteins. In pregnancy and under oestrogen treatment of women and men, CBG was demonstrated to be the more distinct indicator of oestrogenic activity as compared with TBG, whereas the sensitivity of TBG was more pronounced to supposedly antioestrogenic substances like Danazol, and in severe disease. No coincidence of genetic CBG and TBG deficiencies have been found so far.

Amino Acids