Search PubMed⌕ Search

Biomedical subjects

U Fischer

Publications and source records attributed to U Fischer.

At least 253 records · Page 14Linked to original sources

Insulin therapy on the peritoneal route: effects on glucose control in experimental insulin dependent diabetes.

To quantitate the degree of glycemic control in relation to insulin doses required on the peritoneal route of administration, insulin dependent diabetic dogs instrumented with chronic peritoneal and venous catheters and with access devices for serial peritoneal injections, were treated with regular insulin at random order as follows: (1) subcutaneous injections, (2) peritoneal injections, (3) continuous intravenous infusion, (4) continuous peritoneal infusion. Metabolic profiles were taken over 24 h after an average duration of treatment of 2 weeks and were compared to data obtained in nondiabetic animals. Insulin doses and postprandial increase in peripheral insulinemia were higher and glycemic control was worse on peritoneal vs. subcutaneous injection therapy. Glycemic control and insulin doses were identical between peritoneal and intravenous infusion regimes. Hyperinsulinemia was only seen during nighttime in intravenously infused animals. It is concluded that in accordance with the fast pharmacokinetics of peritoneally administered insulin, sufficient glycemic and insulinemic control can only be obtained on the peritoneal route, when the insulin is applied by means of pumps.

Alanine↗

KADIS--a computer-aided decision support system for improving the management of type-I diabetes.

Despite the introduction of new therapeutic aids such as insulin pumps and injectors, blood glucose test tapes, particular insulin formulations, and the physiological basis-bolus principle of insulin dosage regimes, the metabolic care of most insulin-dependent patients is still insufficient. One potential tool of further improving the results in diabetes treatment consists in the application of computer-aided procedures to estimate individually optimal regimes. Employing a validated mathematical model of the glucose/insulin metabolic control system and individual sets of data from patients' self-monitoring, a software package was developed on a micro-computer which allowed both the retrospective analysis of data resulting from the therapeutic process, and the prospective simulation of the outcome of alterations in the regime in terms of glycaemia and insulinaemia. The two parts of the programme provide either for the patient or for the physician an interactive mode of working with the computer. The system is now being validated by means of a long-term follow-up study in type-I diabetic patients. It may be used mainly in diabetic outpatient centers and as a tool of educating, training, and motivating patients.

Computer Simulation↗

Recombinants from a proviral bovine leukemia virus genome corresponding to the 3' region transactivate viral LTR in NIH3T3 and non-infected FLK cells.

Bovine leukemia virus (BLV), like human T-cell leukemia viruses, Types I and II, contains three open reading frames at the 3' end of its genome. The longest open reading frame encodes a transactivator protein which is generated by a doubly-spliced mRNA. A series of co-transfection experiments, using proviral BLV pX expression plasmids under the control of the Moloney leukemia virus LTR and the indicator plasmid containing the assayable lac Z gene under the control of BLV LTR, revealed that both NIH3T3 cells and non-infected fetal lamb kidney cells are able to express an active transactivator protein.

Animals↗

[Studies on the mobility of soft tissue marks of the lower face].

The mobility of soft tissue points used for measuring the rest vertical dimension was assessed in 29 probands with full dentitions and 24 edentulous subjects. A video-aided procedure was used for recording the measuring pictures. Similar results were obtained with fully dentulous and edentulous subjects. For the upper jaw the point of the nose was the mark undergoing the least fluctuations, due to the action of the mimic muscles. For the lower jaw the least mobile skin area was between the labiomental sulcus and the gnathion.

Adult↗

A model-based system for the individual prediction of metabolic responses to improve therapy in type I diabetes.

Despite recent achievements such as home glucose monitoring and intensified injection regimens or insulin pumps, the metabolic care in diabetic patients is still mostly insufficient. One approach of further improving the management is the application of computer-aided procedures to estimate individually the optimal regimes. To accomplish this, a model-based strategy was developed which permits the prospective assessment of the metabolic outcome. This strategy comprises the following components: (1) a validated model of the physiological glucose-insulin regulatory system; (2) a procedure for identifying the metabolic situation of a given patient in terms of the model parameters; (3) methods of estimating the pharmacokinetics of insulin and its effect on glycemia, the absorption profiles of ingested glucose equivalents, and the effect of exercise as expressed in equivalents of insulin action; (4) computer procedures of prospective simulation of glycemic profiles around the day under the influence of selected or proposed therapeutic regimes. The entire method has been validated in C-peptide negative type I diabetic patients by comparing experimental results with theoretical predictions from model-based simulations over up to one year. This model-based simulation may be applied by ambulatory patients together with their physicians as a decision-support system in selecting appropriate individually suited regimes.

Blood Glucose↗

[Continuous intracorporeal glucose measurement using enzyme electrodes].

An enzyme electrode (GOD, Pt-Ag/AgCl) is introduced for amperometric measurement of the intracorporal glucose concentration in the subcutaneous tissue. Changes of the glucose concentration in the peripheral blood (PG) were induced by glucose- respectively insulin-infusion in healthy dogs. PG was compared with values found by out means of a sensor implanted in the necks of the dogs (SG). The regression equation SG = 0.81 PG - 1.39 was calculated by analysing 62 steady state levels. The regression delta SG = 0.83 delta PG + 0.22 submitted for the deviation of the normoglycemic base-level. A sensibility loss of the sensor of about 10% appears after an implantation duration of 7.5 hours in medium. Conclusions for the further development of the sensors follows especially with the in vivo functions (biocompatibility, diminution, sterilisation).

Animals↗

Analysis of genomic clones of the murine U1RNA-associated 70-kDa protein reveals a high evolutionary conservation of the protein between human and mouse.

We have isolated and characterised two overlapping lambda EMBL3 clones carrying sequences of the gene for the murine U1RNA-associated 70-kDa protein. The two clones cover around 23 kb of the 70-kDa protein gene including its 3' end. Southern blot hybridisation revealed the existence of a single copy of the 70-kDa protein gene in the mouse genome. The 23-kb-long portion of the 70-kDa protein gene is divided into eight exons. While most of the exons are quite small and are widely scattered throughout the DNA sequence, the last one consists of about 830 bp and encodes 226 amino acids of the 70-kDa protein, including the C-terminus. The predicted amino acid sequence of the region of the 70-kDa protein encoded by the genomic clones reveals high conservation of structure when it is compared with the sequence of the human 70-kDa protein. Interestingly, all deletions, additions and substitutions are localised exclusively within the C-terminus of the protein, accounting for a 5'-3' polarity with respect to protein conservation. Moreover, the analysis of the genomic sequences predicts the existence of multiple subclasses of mRNAs that may arise by alternative pre-mRNA splicing. A 72-bp alternative exon harboring an in-frame termination codon was also found in the mouse 70-kDa gene and shows, surprisingly, 100% nucleotide identity to its human counterpart.

Amino Acid Sequence↗

Automated feedback control of subcutaneous glucose concentration in diabetic dogs.

The subcutaneous tissue is generally considered as a potential site for the monitoring of intracorporal glucose concentration by means of implanted sensors. We studied the suitability of using the resulting signal from the interstitial glucose concentration as an input in a feedback-controlled system for insulin administration. Miniaturized glucose electrodes (amperometric glucose oxidase sensors for the measurement of hydrogen peroxide) were implanted in insulin-dependent diabetic dogs. The output of these sensors was fed into the controller of a bedside-type artificial B cell. Insulin was infused by the device intravenously on the basis of a proportional-differential algorithm. The glucose patterns were compared to identical experiments where feedback control was accomplished on the basis of paracorporal blood glucose measurement using the same algorithm. Normoglycaemia was restored and maintained in both sets of experiments and oral glucose loads were well compensated for. It is concluded that the apparent subcutaneous glucose concentration is appropriate as an input signal for an artificial B cell.

Animals↗

Whole body glucose metabolism in experimental insulin-dependent diabetes after initiation or termination of insulin administration.

To investigate the kinetics in glucose metabolism, diabetic dogs were infused with double labelled glucose either when they were connected to an artificial beta cell after overnight insulin withdrawal (study I) or when they were disconnected from insulin supply after excellent metabolic control (study II). Fourteen hours after the last insulin injection, the animals had three-fold elevated rates of appearance Ra and of disappearance Rd of glucose in relation to non-diabetic controls; the metabolic clearance rate was reduced, glucose carbon recirculation was slightly elevated, and the % lactate from glucose was not altered. Glucosuria contributed approximately 30% to the elevated glucose turnover. In study I, Ra was normalized within 45 min after insulin supply but Rd increased transiently before returning to normal. In study II, plasma insulin was zero 30 min after termination of insulin supply. Ra increased immediately; Rd decreased slightly but increased thereafter. Lactate was elevated under all conditions. Its production from glucose increased slightly after initiation of insulin action. Glucose carbon recirculation was reduced to subnormal values when the animals were euglycemic but hyperinsulinemic.--It is concluded that even short intervals of relative lack of insulin action followed by restoration of glucose homeostasis, may induce wasting of substrates.

Animals↗

Wick technique: reference method for implanted glucose sensors.

The control of function of experimentally implanted glucose sensors needs an independent reference method. Employing saline-impregnated cotton threads, an implanted wick-technique was adopted in dogs to obtain analytical specimen from the subcutaneous interstitial fluid compartment. By measuring the contents of potassium, calcium, and hemoglobin, the centrifuged wick fluid was validated to contain the interstitial concentrations of solutes after an equilibration time of approximately 15 min. Between 2 and 25 mmol/L, the steady state subcutaneous glucose concentration is nearly identical to circulating glycemia. Slow alterations, as during an oral glucose tolerance test, (OGTT) are well paralleled by the levels in the wick fluid. During alterations, however, a distinct delay is observed. The wick-based glucose levels are mirrored by the output of electrochemical sensors implanted at the same site. This method may be used in checking implanted sensors that can otherwise not be calibrated in situ.

Animals↗

In situ calibration of implanted electrochemical glucose sensors.

A feasible and reliable method of in situ checking and calibration of implanted glucose sensors is required to compensate for alterations in the overall sensitivity of the "sensor plus subcutaneous fluid glucose compartment" system. In a study on nondiabetic dogs, the linear regression analysis of paired plasma glucose/sensor current data is validated as a potential basis of recalibration of intracorporal glucose sensors. These sensors were amperometric glucose oxidase/hydrogen peroxide electrodes of which the in vitro response time to square alterations in the ambient glucose concentration T95 was less than 5 min. The method presented may be incorporated into the data handling system of portable glucose monitors or of miniaturized artificial beta-cells. For its performance, no steady state glycaemia but a minimum alteration in the intracorporal glucose concentration is needed. The latter can be provided both by tests or by fluctuations as they occur spontaneously during the course of the day.

Animals↗

Oxygen tension at the subcutaneous implantation site of glucose sensors.

To elucidate potential influences of the average tissue pO2 on the function of implanted glucose sensors, non-miniaturized polarographic oxygen electrodes and glucose oxidase/H2O2 glucose electrodes were implanted in the subcutaneous tissue of spontaneously breathing normal and diabetic dogs. There was no appreciable run-in phenomenon of oxygen sensors but normally a pronounced initial decrease in current after implantation of glucose sensors. The subcutaneous pO2 amounted to an average of 7 kPa in air-breathing animals with no difference between normal and insulin-dependent diabetic dogs. It showed oscillations of approximately +/- 2 kPa but the mean was stable over the maximum duration of experiments of 16 h. Induced alterations of tissue pO2 between less than 2 and greater than 20 kPa (as verified by measurements of arterial pO2) were not followed by alterations in the current of nearby implanted glucose sensors. It is concluded that the frequently observed instabilities and losses in sensitivity of the system "implanted glucose sensor in situ + tissue glucose compartment" are not caused by alterations in tissue pO2.

Animals↗

Intraindividual comparison of pharmacokinetics of insulin after intravenous, portal, subcutaneous and peritoneal administration.

To compare the kinetics of praehepatic and of posthepatic administered insulin, short term insulin deprived diabetic dogs were sequentially injected with 200 mU/kg of a monocomponent porcine insulin using either the intravenous, portal, subcutaneous or peritoneal route. After peritoneal insulin was applied, the peripheral plasma insulin levels increased immediately, their maxima were in the same range as after subcutaneous injection but the duration of elevation was shorter. There were portal-peripheral insulin-quotients greater than 1 after peritoneal and portal insulin administration but quotients less than 1 after subcutaneous and intravenous application. The time constant of insulin elimination was identical regardless of whether the praehepatic or the posthepatic route was used for application. The effectiveness of the administered insulin dose on blood glucose was found to be dependent on the posthepatic elevation of plasma insulin and its duration. The decrease in glycemia was initially identical in all tests but, on the whole, it was smaller after the two intravascular routes were used because of the shorter duration of elevated insulin levels. It is concluded that in an optimized management of insulin-dependent diabetes, the regime (doses and intervals or algorithms) must be adapted to the pharmacokinetic implications of the employed route of application.

Animals↗

[The value of lymphography of malignant testicular tumors].

Between 1965 and 1968, 6500 lymphograms were performed at the University of Göttingen. Amongst these, there were 412 patients with malignant testicular tumours. In 81 patients the results of lymphography could be checked histologically. There was agreement between the lymphographic and histological findings in 65 patients (80.3%), sensitivity of 98.1% (51 out of 52) and specificity of 48.3% (14 out of 29). In 50 patients CT was performed in addition. The findings agreed in 31 cases; in eight patients lymphangiography resulted in a false positive finding and CT was incorrect in 12 patients. In all patients with proven retroperitoneal metastases, one or the other method produced a correct diagnosis.

Adult↗