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E F Pfeiffer

Publications and source records attributed to E F Pfeiffer.

At least 73 records · Page 4Linked to original sources

Liver thiol content under varying glucoregulatory states in rats.

The influence of varying glucoregulatory states as induced by fasting, feeding and intravenous glucose infusion on liver thiol content has been assessed in the male rat. As expected, increasing the serum glucose levels from 131 +/- 7 mg/dl to 343 +/- 12 mg/dl (mean +/- S.E.) caused a corresponding increase in serum insulin responses. Rising from 3.2 +/- 0.4 mumol/g w.w. in the fasted group to a peak value of 6.3 +/- 0.4 mumol/g (P less than 0.01) in the group infused by 10% glucose solution, hepatic non protein bound sulphydryl groups (NP-SH) were closely related to serum glucose levels up to 244 +/- 11 mg/dl. When higher glucose doses were infused. NP-SH values fell steadily, they even inclined below the level of the fasted rats after infusion of 30% and 40% glucose solutions (1.3 +/- 0.4 mumol/g w.w., P less than 0.05 and 0.7 +/- 0.3, P less than 0.01, resp.), mean serum glucose levels being 291 +/- 12 and 343 +/- 13 mg/dl, resp. Hepatic protein bound thiols were not affected by any of the glucoregulatory states experimentally induced. The data demonstrate that the glucoregulatory state influences hepatic NP-SH content divergently. The study suggests that under physiological conditions liver NP-SH content covariates positively with serum insulin and glucose levels.

Animals↗

The glucose sensor: the missing link in diabetes therapy.

This review considers the present state of the implantable glucose sensor from the point of view of technical models available today. Chemical analysis behind the practical experiences under both in vitro and in vivo conditions are described (Abel, Fischer, Brunstein and Ertle 1988; Brückel, Kerner, Zier, Steinbach and Pfeiffer 1988a; Brückel, Kerner, Zier, Steinbach and Pfeiffer 1988b; Steinbach, Kerner, Zier, Dolderer and Pfeiffer 1987). Amperometric enzymatic glucose sensors are used by the majority of laboratories, providing satisfactory results of glucose determinan in solution and in the laboratory. Up to 4 days of reliable values were recorded by measuring glucose in vivo, in practical terms, in the subcutaneous tissue in animals. However, also in this first period of foreign-body reactions, enough encapsulation obviously occurs to neutralize the majority of the sensors implanted. In first experiments in humans, the results are even worse. Generally, decreasing activity was observed in less than 24 h. Therefore, continuous blood glucose monitoring by portable glucose sensors used the same principle in a flow-through chamber; the sensor of our own make was employed in a number of clinical conditions. When one of the available insulin pumps effecting continuous subcutaneous insulin infusions was connected, the algorithms worked out for the big AEP under bedside conditions were also of use in a slightly modified fashion for the subcutaneous insulin application. Renouncing the computer-mediated automated regulation of the insulin delivery is possible when the patient is constantly reading his blood glucose values and operates the insulin infusion pulses in association with meals. Continuous glucose monitoring by portable instruments is the only and irreplaceable prerequisite for unprejudiced evaluation of the various strategies for substitution of the insulin deficiency in any form of diabetes.

Biosensing Techniques↗

Non-human primate pancreas as a substrate for the detection of islet-cell antibodies in human sera.

In an effort to find out if the use of non-human primate pancreas may improve the sensitivity of the islet cell antibody (ICA) test, the sera from patients with type 1 diabetes (insulin-dependent IDDM) and controls were investigated by indirect immunofluorescence (IFL) on both human and baboon substrates. The mean titers of positives were insignificantly higher (1:24.9) on baboon as compared to human tissue (1:22.3). Of 50 sera from IDDM patients positive for ICA on human tissue, 47 were also positive on baboon pancreas. Of 40 ICA-negative IDDM sera two were judged positive on baboon substrate. ICA were positive on human/baboon pancreas in 3/4 out of 50 first-degree relatives of IDDM patients, 2/2 of 50 sera from patients with autoimmune diseases, 0/0 of 50 sera from type 2 diabetics and 2/1 of 100 mixed hospital controls. A disadvantage of baboon pancreas for ICA testing by IFL is the high background fluorescence given by the exocrine pancreas. With baboon tissue, three highly positive results would have been missed with undiluted sera which are usually used in this assay. It is therefore suggested that human pancreas should still be preferentially used for ICA determination, but baboon tissue may be a valuable substitute.

Animals↗

Acute hypothyroidism has no effect on pulmonary vascular resistance.

The effect of acute hypothyroidism on the pulmonary circulation was studied in 9 nonobese athyreotic patients by right heart catheterization at rest and during exercise. The patients were studied while they were hypothyroid 2 weeks after ceasing triiodothyronine treatment and while they were euthyroid on replacement therapy. At rest, pulmonary blood flow [4.0 +/- 0.6 l/min vs 5.8 +/- 1.0 l/min, p less than 0.01] and systolic pulmonary artery pressure [18 +/- 3 mmHg vs 23 +/- 2 mmHg, p less than 0.01] were lower when the patients were hypothyroid than when they were euthyroid. The mean and diastolic pressures in the pulmonary artery and the pulmonary capillary pressures were not different among the groups. Likewise, thyroid hormone levels had no significant effect on pulmonary vascular resistance [100 +/- 25 dyn-s-cm-5 vs 90 +/- 23 dyn-s-cm-5]. With supine exercise, pulmonary blood flow [10.1 +/- 1.6 l/min vs. 13.2 +/- 2.0 l/min, p less than 0.01], mean pulmonary artery pressure [25 +/- 6 mmHg vs 30 +/- 6 mmHg, p less than 0.02], and systolic pulmonary artery pressure [36 +/- 6 mmHg vs 44 +/- 8 mmHg, p less than 0.01] were lower when the patients were hypothyroid. The diastolic pulmonary artery pressure and the pulmonary capillary pressure were similar in both thyroid states. Again, thyroid deficiency had no effect on pulmonary vascular resistance [81 +/- 23 dyn-s-cm-5 vs 76 +/- 24 dyn-s-cm-5]. The lower systolic pressures in the pulmonary artery seen in hypothyroidism are probably due to the decreased systolic volume load of the pulmonary circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

In vivo measurement of subcutaneous glucose concentrations with an enzymatic glucose sensor and a wick method.

An amperometric enzyme electrode and a wick technique were used for measurement of glucose in sc. tissue of sheep. When wicks were left implanted long enough to equilibrate with interstitial fluid, sc. glucose could have been reproducibly determined with the necessary accuracy. It was demonstrated that sc. tissue glucose concentrations in sheep are about 30% higher than in whole blood and are on the level of plasma glucose. This allows interpretation of sc. glucose sensor currents since results of in vitro-calibrations cannot be transferred to in vivo conditions. When an enzymatic sensor was implanted in the sc. compartment, the sensor signals were closely related to changes of blood glucose. These in vivo experiments indicate that short term glucose-monitoring with an subcutaneously implantable glucose sensor is feasible and so may provide a possible access to glycemic control. Further experiments will have to show, if glucose-controlled insulin infusions based on the output of a sc. glucose sensor will be able to maintain stable normoglycemia.

Animals↗

[Stress testing of long-term type I diabetic patients with radionuclide ventriculography].

Left ventricular function was assessed by means of radionuclide ventriculography in 42 patients with long-standing (13 +/- 5 yrs) insulin-dependent diabetes mellitus and in eleven healthy age matched control subjects. Only diabetics were included in the study without diabetes related cardiac risk factors such as hypertension and CAD in order to evaluate diabetes specific changes of cardiac function. No differences were seen between diabetics and controls concerning heart rate and functional parameters of left ventricle in systole and diastole. The rapid filling period was not prolonged. According to our radionuclide data there is no evidence of diabetes related impairment of ventricular function in young patients with long-standing type-1-diabetes mellitus.

Adult↗

[Reversible germ cell toxicity following aggressive chemotherapy in patients with testicular tumors: results of a prospective study].

The impact of aggressive chemotherapy on reproductive and endocrine gonadal function was prospectively studied in 44 patients with germ cell tumors. Diagnostic procedures to determine gonadal toxicity consisted of hormone determinations, semen analyses, interviews with a standardized questionnaire, and gonadal histology. After chemotherapy all patients showed elevated serum levels of follicle-stimulating hormone (FSH) and azoospermia due to germ cell and stem cell loss. Recovery of spermatogenesis, as indicated by normalization of serum FSH levels and sperm density, occurred in 77% of the patients 25-60 months after cessation of chemotherapy. In all patients serum testosterone and luteinizing hormone (LH) values remained within normal limits after therapy indicating resistance of Leydig cells to cytotoxic drugs. Three patients fathered four healthy children after completion of chemotherapy. These data suggest significant reproductive dysfunction in all men treated for germ cell tumors. However, most patients showed late and complete recovery of spermatogenesis. In contrast, endocrine gonadal function was unaffected after chemotherapy in all patients. FSH and LH are feasible markers to assess drug-induced gonadal toxicity.

Adolescent↗

[Clinical and laboratory chemical studies of the incidence and extent of diabetic cheiropathy in childhood and adolescence].

Diabetic cheiropathy is often not diagnosed because of a paucity of symptoms. In the present study, 100 type I diabetic patients and 20 controls were investigated. The age of patients ranged from seven to 26 years, the duration of diabetes was one to 23 years. Extension of hands by "prayer position", a hand-print and angle determinations of joints were considered for the determination of diabetic cheiropathy. The presence of cheiropathy was unrelated to the duration of diabetes. However, it was well correlated with the quality of blood sugar control and it was often associated with diabetic retinopathy: Diabetic cheiropathy was detected in 53 (53%) of the diabetic patients, and in 26 (49%) of them diabetic retinopathy was also diagnosed. Only three patients had a retinopathy without cheiropathy. On the basis of our results, diabetic cheiropathy is a surprisingly common feature in young type I-diabetics. It is not to be considered as a late complication but rather a sequel of badly controlled diabetes mellitus.

Adolescent↗

Immunocytochemical localization of prolactin-like antigenic determinants in the neuroendocrine system of the honeybee (Apis mellifica).

In the brain of the adult worker bee (Apis mellifica) prolactin-like (PRL) immunoreactive cells were localized in the lateral neurosecretory cell region and the subesophageal ganglion by means of the PAP procedure. These cells emit nerve fibers which pass through the neuropile of the brain to the corpora cardiaca where a great number of immunoreactive axon terminals is present. Test with antisera against rat pituitary prolactin and human luteinizing hormone were negative. These results indicate that hPRL material is produced in neurosecretory cells of the bee brain and transferred via axons to the corpora cardiaca for storage and subsequent release into haemolymph.

Animals↗

Eye muscle antibodies in endocrine exophthalmos. Clinical and serological observations.

Serum samples were obtained from 65 patients with endocrine exophthalmos class I-V. In 33/65 patients who were treated either with prednisone or with ciclosporin, blood was sampled before, during and after therapy. Antibodies against eye muscle were determined during the course of immunosuppressive therapy in order to have an objective parameter of the therapeutic effect. To ascertain the specificity of the reaction both eye and abdominal muscles were used as antigens in an ELISA system. Both IgG and IgM antibodies were detected. In 45/65 patients (71%) eye muscle antibodies were positive before starting therapy. Antibodies were mostly detected in patients with active disease. Patients with exophthalmos of recent onset always had IgM antibodies whereas patients with chronic exophthalmos were mostly IgG positive. Patients with relapse showed mostly IgG but also IgG and IgM positivity in 2 cases. In 58% of cases only IgG antibodies were found whereas in 34% both IgG and IgM were detected and in 8% only IgM antibodies. There was no association between antibodies directed against eye muscle and thyroid microsomal and thyroglobulin antibodies or with the state of thyroid function. Furthermore there was no correlation between exophthalmos classes and eye muscle antibody binding activity. The antibody level declined during therapy with prednisone or with ciclosporin but rose again 8-12 weeks after stopping the drug in patients with progressive disease.

Adolescent↗

Adipogenic activity in sera from obese children before and after weight reduction.

The adipogenic and mitogenic potentials of sera obtained from obese children before and after weight reduction and from lean control subjects were studied in clonal 3T3 L1 fibroblasts. The sera from the lean (n = 14) and obese (n = 12) children under habitual diet contained similar adipogenic activity. However, when the obese children underwent a weight-reduction program for 3 wk (600 kcal/d), the potential of their sera to stimulate glycero-phosphate dehydrogenase, an index of adipogenic activity, was significantly reduced by 32% (p less than 0.01). Similarly, the mitogenic activity of these sera decreased significantly (202 +/- 15 vs 231 +/- 27 micrograms per dish, p less than 0.01). Testing pooled sera from the different groups in cultured rat adipocyte precursor cells gave similar results. This study suggests that human childhood-onset obesity is not accompanied by increased circulatory factors involved in the formation of new fat cells. The adipogenic and mitogenic activity of sera from obese children may be influenced by long-term dietary restriction.

Adipose Tissue↗

Acute hypothyroidism slows the rate of left ventricular diastolic relaxation.

The effect of acute thyroid hormone deficiency on left ventricular diastolic filling was studied by radionuclide ventriculography with simultaneous right heart catheterization in nine athyreotic patients without cardiovascular disease. The patients were studied when they were hypothyroid and when they were euthyroid on replacement therapy. Peak filling rate and the time to peak filling were used to characterize diastolic function. The time to peak filling was defined as the interval from end-systole on the radionuclide time-volume curve to the time of occurrence of peak filling. The peak filling rate was determined in absolute terms from the normalized radionuclide peak filling rate and from the end-diastolic volume, which was derived from the radionuclide ejection fraction and from the thermodilution stroke volume. In all patients, the values for peak filling rate were lower in the hypothyroid than in the euthyroid state (287 +/- 91 mL/s vs. 400 +/- 118 mL/s, delta = 41 +/- 13%, p less than 0.01). Peak filling always occurred during the first half of the diastolic interval. The time to peak filling was not significantly affected by the thyroid state (170 +/- 10 ms vs. 159 +/- 21 ms, delta = 7 +/- 10%). Left ventricular filling pressure as reflected by the pulmonary capillary wedge pressure and end-systolic volume were similar in both thyroid states (6 +/- 2 mmHg vs. 8 +/- 2 mmHg (1 mmHg = 133.32 Pa) and 32 +/- 11 mL vs. 32 +/- 7 mL, respectively). The data suggest that the rate of active diastolic relaxation is decreased in short-duration hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Promoting effect of glucocorticoids on the differentiation of human adipocyte precursor cells cultured in a chemically defined medium.

Stromal-vascular cells obtained from adult human subcutaneous adipose tissue were cultured in a chemically defined serum-free medium. In the presence of 0.2 nM triiodothyronine and 0.5 microM insulin, up to 25% of the cells were able to undergo terminal adipose differentiation within 18 d, as assessed by lipid accumulation and the expression of lipoprotein lipase (LPL) and glycerol-3-phosphate dehydrogenase (GPDH) activities. Addition of cortisol resulted in a potent dose-dependent stimulation of the adipose differentiation process. Cortisol could be replaced by dexamethasone and partly by aldosterone, but not by sex steroids. The proportion of differentiated cells was dependent upon the age of the donor; when isolated from young adults, up to 70% of the stromal-vascular cells expressed the adipocyte phenotype as compared with 5-10% when the cells were isolated from the oldest subjects. An inverse relationship was observed between the age of the 27 normal-weight donors and the extent of GPDH expression after maintenance of the cells for 18 d in chemically defined medium supplemented with insulin, triiodothyronine, and cortisol (r = -0.787, P less than 0.001). It is concluded that adult human adipose tissue still contains precursor cells that are able to undergo adipose differentiation in vitro. This improved culture system may offer the opportunity to characterize other adipogenic factors as well as antiadipogenic factors involved in the control of adipose tissue growth.

Adipose Tissue↗

Method for rapid separation of 3,5,3'-triiodothyroacetic acid in human serum by fast protein liquid chromatography.

The 3,5,3'-triiodothyroacetic acid (TRIAC) has been approved as a valuable agent in the management of hyperthyroidism secondary to inappropriate secretion of thyrotropin. We have developed a fast protein liquid chromatography (FPLC) method for separation and quantification of TRIAC. Serum samples charged with TRIAC were extracted with methanol/ammonium acetate, the supernatants were evaporated to dryness, reconstituted in NaOH and injected on a reversed phase column for chromatography. For separation an isocratic elution method (methanol water; 0.1% trifluoroacetic acid) was used. The area under the curve (ml%) was compared with those of the calibration curves. Recoveries were 70 +/- 10.8%. TRIAC was eluted in 2.33 ml. Conclusively, the present method shows that TRIAC can be measured by FPLC and may be applied to the measurement of TRIAC in pharmacological studies.

Chromatography, High Pressure Liquid↗

Determination of islet cell antibodies using an ELISA system with a preparation of rat insulinoma (RIN A2) cells.

An enzyme-linked immunosorbent assay (ELISA) was established for the detection of islet cell antibodies in human sera. The antigen was prepared from rat insulinoma (RIN A2) cells. Cells were dissociated in lysis buffer and the lysate was centrifuged at 100,000 x g. The supernatant was used to coat microtiter ELISA plates (10 micrograms protein/ml in PBS pH 7.2). Non-specific binding sites on the plates were blocked with 2% PBS-BSA. Human test sera were preabsorbed on separate plates using 2% PBS-BSA and incubated on precoated plates at an optimal dilution of 1/10 in 60 mM PBS for 60 min at 37 degrees C. Phosphatase-labeled anti-human IgG serum and phosphatase substrate were applied and the reaction was stopped by adding 3 M NaOH. Out of 90 sera from type I diabetic patients, 47 (52.2%) reacted in the new ELISA whereas none of 15 type II diabetics, 50 sera containing non-islet specific antibodies or 100 normal controls were positive. In the same group of patients, ICA were positive in 63.3%. When both, the ELISA and conventional ICA testing were applied, the number of positives was increased to 83%. The ICA-ELISA with the above described antigen preparation provides a well standardized and reproducible test method which is highly specific for type I diabetes. It may therefore be useful for large screening procedures.

Adult↗