Fritz S. Keck

The function of a hydrogen peroxide-detecting electroenzymatic glucose electrode is markedly impaired in human sub-cutaneous tissue and plasma

Electroenzymatic glucose sensors implanted into sub-cutaneous (s.c.) tissue of human subjects and experimental animals exhibit lower sensitivities to glucose than in buffer solutions before implantation. The mechanism of the decrease of sensitivity is not known. Sensors used in this study were fabricated from platinum wires (diameter 0.125 mm) with covalently bound glucose oxidase at the tip of the wire. After coating the tip with polyurethane, wires were placed into 27 gauge steel needles. Sensors were operated potentiostatically at 700 mV against Ag/AgCl pseudo-reference electrodes. These sensors were implanted s.c. in 6 diabetic patients for 7 h. In 4 patients, sensors were responsive to successive increases of plasma glucose levels. Mean sensitivity to glucose in s.c. tissue was 29% of in vitro sensitivity. In 2 patients there was a sudden decrease of sensor currents, unrelated to glucose, shortly after implantation. Sensors were inhibited in human plasma to a similar extent. When sensors were exposed to native plasma and to plasma ultrafiltrate (mol. wt. < 10 kDa) for 10 h, identical decreases of signals were found. Exposure to dialysed plasma (mol. wt. > 12 kDa) caused much less decrease of sensor signals. Losses of sensor sensitivities to glucose in s.c. tissue and in plasma were totally reversible upon re-exposure of sensors to buffer solutions. We conclude that sensor inactivation in plasma and possibly in s.c. tissue is caused by low molecular weight substances not retained by the polyurethane membrane.

Left ventricular function at rest and during exercise in acute hypothyroidism.

The effect of hypothyroidism on left ventricular function at rest and during exercise was studied in nine patients without demonstrable cardiovascular disease who had had total thyroidectomy and ablative radioiodine treatment for thyroid cancer. Radionuclide ventriculography and simultaneous right heart catheterisation were performed while the patients were hypothyroid two weeks after stopping triiodothyronine treatment (to permit routine screening for metastases) and while they were euthyroid on thyroxine replacement treatment. When the patients were hypothyroid, cardiac output, stroke volume, and end diastolic volume at rest were all lower and peripheral resistance was higher than when they were euthyroid. Pulmonary capillary wedge pressure, right atrial pressure, heart rate, left ventricular ejection fraction, and the systolic pressure:volume relation of the left ventricle, which was used as an estimate of the contractile state, were not significantly different when the patients were hypothyroid or euthyroid. During exercise, heart rate, cardiac output, end diastolic volume, and stroke volume were higher when the patients were euthyroid than when they were hypothyroid. Again, pulmonary capillary wedge pressure, ejection fraction, and the systolic pressure:volume relation were similar in both thyroid states. The data suggest that the alterations in cardiac performance seen in short term hypothyroidism are primarily related to changes in loading conditions and exercise heart rate; they do not suggest that acute thyroid hormone deficiency has a major effect on the contractile properties of the myocardium.

Doppler echocardiographic evaluation of left ventricular diastolic function in acute hypothyroidism

OBJECTIVE Left ventricular diastolic dysfunction Is an important cause of symptomatic heart failure. Previous studies suggest that thyroid dysfunction affects left ventricular diastolic function but the underlying mechanisms remain controversial. The study was undertaken to assess the influence of acute hypothyroidism on left ventricular diastolic function and to elucidate possible underlying mechanisms by means of Doppler echocardiography in a group of athyreotic patients, whose thyroid state depended only on external thyroid hormone supply and could therefore easily be controlled.

The first experimental diabetes mellitus

SummaryIn the history of diabetes research, surgically induced experimental diabetes is usually associated with the names of Minkowski and von Mering on the basis of their investigations in 1889. However, temporary diabetes mellitus had already been induced 200 years previously by Johann Conrad Brunner (1653–1727) in an experiment in dogs. According to present-day knowledge, this temporary diabetes mellitus must be ascribed to subtotal pancreatectomy and reversible traumatic damage to the remaining endocrine pancreas. The brilliant experimenter Brunner did not associate the symptoms he produced with diabetes. Diabetes research would possibly have taken a different course had he done so.

Effects of hypothyroidism on bronchial reactivity in non-asthmatic subjects.

The effect of hypothyroidism on non-specific bronchial reactivity was studied in 11 patients without pulmonary disease (mean age 40 (SD 13) years) who had had a total thyroidectomy and radioiodine treatment for thyroid cancer 41 (36) months before the study. All patients when mildly hyperthyroid while having long term thyroxine replacement treatment and once when hypothyroid two weeks after stopping triiodothyronine for the purpose of screening for metastases. Bronchial reactivity was assessed by measuring specific airways conductance (sGaw) after increasing doses of inhaled carbachol (45-1260 micrograms). The dose producing a 35% decrease in sGaw (PD35) was determined from the cumulative log dose-response curve by linear regression analysis. Mean baseline sGaw values were similar when the patients were hypothyroid and when they were hyperthyroid (1.35 (0.36) and 1.41 (0.56) s-1 kPa-1). The interstudy coefficients of variation of baseline sGaw were higher in the thyroid patients than in a euthyroid control group (14% versus 8%). Geometric mean PD35 was lower when the patients were hypothyroid (97 micrograms) than when they were mildly hyperthyroid (192 micrograms). It is concluded that acute hypothyroidism increases non-specific bronchial reactivity in nonasthmatic subjects.

Evidence for Peripheral Autoregulation of Thyroxine Conversion

The reciprocal changes of triiodothyronine (T3) serum concentrations and (SC) and thyroxine (T4) SC observed in patients with varying degrees of primary hypothyroidism are well known. T3 SC are often still within normal limits, when T4 SC have already reached low-normal or subnormal levels. The patients do not have clinical evidence of hypothyroidism at that time (1). Considering the other extreme of the spectrum, most athyroid patients have a negative TRH test only if T4 SC are raised to levels beyond the normal range by large doses of T4. This is associated with T3 SC in the upper normal range. These patients do not appear to be clinically hyperthyroid (2). These findings suggest that a non-thyroidal mechanism accounts for the reciprocal changes in T4 SC and T3 SC. The purpose of this clinical study was to clarify the role of these non-thyroidal mechanisms in regulating T3.

[Acute factitious hyperthyroidism--moderate clinical symptoms in 3 cases under beta-blocker treatment].

The clinical and laboratory findings are described in three patients who ingested large amounts of L-thyroxine (two cases) and L-thyroxine together with L-triiodothyronine and who were treated with propranolol. Serum concentrations of thyroxine (maximum values 75 micrograms/dl, 64 micrograms/dl, and 20 micrograms/dl, respectively; normal range 4-12 micrograms/dl), triiodothyronine (maximum values 837 ng/dl, 453 ng/dl, and 566 ng/dl, resp.; normal range 80-180 ng/dl), reverse triiodothyronine (maximum values 235 ng/dl, 190 ng/dl, and 65 ng/dl, resp.; normal range 10-40 ng/dl) as well as free thyroxine equivalent and free triiodothyronine equivalent were monitored daily until they reached the normal range. Statistical analysis of the kinetics of these parameters indicated that the extreme thyroxine conversion was directed toward reverse triiodothyronine, partly due to the treatment with the beta-adrenergic blocker propranolol. The striking discrepancy between the high concentrations of the active hormones and the moderate clinical symptoms was most likely caused by peripheral effects of propranolol.SummaryThe clinical and laboratory findings are described in three patients who ingested large amounts ofl-thyroxine (two cases) andl-thyroxine together withl-triiodothyronine and who were treated with propranolol. Serum concentrations of thyroxine (maximum values 75 µg/dl, 64 µg/dl, and 20 µg/dl, respectively; normal range 4–12 µg/dl), triiodothyronine (maximum values 837 ng/dl, 453 ng/dl, and 566 ng/dl, resp.; normal range 80–180 ng/dl), reverse triiodothyronine (maximum values 235 ng/dl, 190 ng/dl, and 65 ng/dl, resp.; normal range 10–40 ng/dl) as well as free thyroxine equivalent and free triiodothyronine equivalent were monitored daily until they reached the normal range. Statistical analysis of the kinetics of these parameters indicated that the extreme thyroxine conversion was directed toward reverse triiodothyronine, partly due to the treatment with the β-adrenergic blocker propranolol. The striking discrepancy between the high concentrations of the active hormones and the moderate clinical symptoms was most likely caused by peripheral effects of propranolol.

Acute hypothyroidism has no effect on pulmonary vascular resistance

SummaryThe 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<0.01] and systolic pulmonary artery pressure [18±3 mmHg vs 23±2 mmHg,p<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<0.01], mean pulmonary artery pressure [25±6 mmHg vs 30±6 mmHg,p<0.02], and systolic pulmonary artery pressure [36±6 mmHg vs 44±8 mmHg,p<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. The data do not suggest that thyroid hormones play a role in the regulation of pulmonary vascular resistance.

Continuous Registration of Peritoneal and Subcutaneous Glucose Content by a Combined Microdialyis/Enzymatic Glucose Measuring Device

This chapter describes continuous registration of peritoneal and subcutaneous glucose content by a combined microdialyis/enzymatic glucose measuring device. A glucose sensing device for continuous registration of dissolved glucose in body fluids was obtained by combining the micro-dialysis technique with amperometric glucose sensor based on the glucose oxidase method. In 16 rats commercially available, needle type micro-dialysis probes were simultaneously inserted into the abdominal wall and into the peritoneal cavity over 6 h. The probes were steadily perfused with saline at flow rate of 5 μl/min, the glucose concentration in the microdialysis outlet was continuously measured by an ex vivo flow chamber. Blood glucose concentration was exogenously varied by intravenous glucose, and insulin application, resp., between 25, and 600 mg/dl, the blood glucose concentration changing rates obtained ranged between 0, and 400 mg/dl/30 min. It is found that glucose concentration in the plasma, and the peritoneal fluid was measured using the Beckkman analyzer.

Left Ventricular Diastolic Function in Acute Hypothyroidism

The thyroid state is an important determinant of cardiac performance. This study examines the effects of acute hypothyroidism on left ventricular diastolic function.