Temperature and blood flow measurements in and around 7,12-dimethylbenz(a)anthracene-induced tumor and Walker 256 carcinosarcomas in rats.

By means of an implanted transmitter, a circadian rhythm of temperature was found both in 7,12-dimethylbenz(a)anthracene-induced tumors and in Walker 256 carcinosarcomas. There was no significant difference in the temperatures of the two tumors. The temperature was lowest in periods of rest, and the temperature difference between light and dark periods was about 1 degree. Both tumors were found to have a higher temperature than that of s.c. tissue. External temperature measurements of the skin covering the 7,12-dimethylbenz(a)anthracene-induced tumor by thermistor probe and by thermography showed a temperature 1-2 degrees below the temperature of surrounding skin areas. In the 7,12-dimethylbenz(a)anthracene-induced tumors the blood flow was low, which should correspond to a relatively small heat production, although the temperature was relatively high. Blood flow in skin overlying tumor was high, presumably a perifocal hyperemic reaction, although the temperature was relatively low in this area. Thus tissue temperatures was not indicative of blood flow.

Absorption and miscibility of regular porcine insulin after subcutaneous injection of insulin-treated diabetic patients.

The absorption and miscibility of subcutaneously injected 125I-regular porcine insulin was examined in 20 insulin-treated diabetic patients. The disappearance half-life (t1/2) was 2.1 +/- 0.8 h (SD) after injection of regular insulin (40 U/ml) and 2.3 +/- 0.7 h when mixed with porcine NPH insulin (NS). A significant inverse relation was demonstrated between insulin concentration and absorption, as t1/2 was 1.8 +/- 0.7 h (P less than 0.05) when using 20 U/ml. The interindividual coefficients of variation for absorption of regular insulin were 30.9-41.6% and independent of the presence of NPH insulin. The intrapatient variability, however, was much smaller, 14.5-23.6%.

Assessment of cadmium telluride detector system for measurement of muscle blood flow during dynamic exercise in man.

We have used a miniature cadmium telluride detector in the assessment of muscle blood flow during dynamic exercise in man following local injection of 133Xenon. The results obtained were compared with those using a conventional sodium iodide detector. There was no significant difference between the results obtained with the two detectors. The reproducibility of results was greater with cadmium telluride than with sodium iodide. The cadmium telluride system has the advantage of being small, lightweight and portable and enables measurements to be made during dynamic exercise.

Local variation in cutaneous and subcutaneous blood flow measured by CdTe(C1) minidetectors in normal and psoriatic skin.

The accuracy of the 133Xe washout method and the validity of newly developed cadmium telluride CdTe(Cl) minisemiconductor detectors were estimated by performing comparative, simultaneous measurements of both cutaneous (CBF) and subcutaneous (SBF) blood flow using 2 conventional scintillation sodium iodide NaI(Tl) and CdTe(Cl) detectors over the same radioactive depot in each of 10 individuals. The accuracy of the 133Xe washout method was found to be 13-15% (C.V.) for the CBF measurements and 9-12% (C.V.) for the SBF measurements. The CdTe(Cl) detectors, which have a weight of 20 g and were attached directly over the radioactive depot, may replace stationary NaI(Tl) detectors placed 20 cm from the depot for measurements of both CBF and SBF. Two CdTe(Cl) detectors were used for estimations of the local variation in CBF and SBF within a distance of 5 cm in normal skin of 10 individuals. The C.V. was 7% for the CBF measurements and 18% for the SBF measurements. Measurements of CBF and SBF were performed in 6 psoriatic patients who, after about 1 week of antipsoriatic treatment with beech tar, developed typical Woronoff rings. The local CBF differed significantly from the center of psoriatic plaques to the margin, in the Woronoff ring, and in nonlesional skin. In contrast, SBF was remarkably equal within the plaque and in the Woronoff ring. The color of the Woronoff ring cannot be ascribed to a local cutaneous vasoconstriction. Cutaneous blood flow in chronic stable, lesional psoriatic skin was significantly lower than previously published values for active lesional psoriatic skin, but significantly higher than CBF in normal individuals. Measurements of CBF in tetrahydrofurfuryl nicotinic acid (Trafuril)-treated skin showed higher values than measurements of CBF in the postischemic hyperemia period both in normal and in lesional psoriatic skin. Trafuril induced a significant increase of CBF in both lesional and nonlesional skin. The high CBF rates in lesional psoriatic skin are not due to a maximally, passively dilated vascular bed.

Kinetics of subcutaneous NPH insulin in diabetics.

Kinetics of subcutaneous NPH insulin were studied in newly diagnosed insulin-dependent diabetics. Using a biotelemetric technique with small Geiger-Müller detectors applied to the skin surface, the disappearance of 125I-NPH insulin fron subcutis was monoexponential with a mean half-life of 6.6 +/- 3.3 (SD) hr. A model is presented to compare the disappearance rates of subcutaneous 125I-NPH insulin and the calculated plasma appearance insulin curve derived from the actual plasma insulin concentration measurements, assuming a one-compartment model and first-order kinetics. Areas under the absorption- and appearance-time curves calculated from external measurements and from plasma insulin concentrations were identical. There was a strong correlation between plasma concentrations and absorbed amounts of labeled insulin (r = 0.8782, P less than 0.001), as there was between the blood glucose-lowering effects and percent absorbed insulin per hour (r = 0.7659, P less than 0.001). Our results indicate that the disappearance rate of iodine-labeled insulin was a relevant biological expression of insulin absorption from subcutis and a reliable noninvasive method of quantitative determination of insulin concentration in blood.

Portable detectors for 125I-insulin absorption measurement during subcutaneous infusion with portable pumps.

Programmed subcutaneous insulin infusion is a promising method for normalisation of the blood glucose concentration in insulin-dependent diabetics. To evaluate insulin availability the absorption rate from the depot is usually measured intermittently by radioactively-labelled insulin and stationary scintillation detectors. Small portable detectors are an alternative, however, and continuous absorption measurements could be made during normal life conditions. Contrary to conventional single injection therapy, the insulin depot initially expands during infusion treatment, changing the geometry during measurements. In the present study the methodological aspects and geometrical dependences were investigated. Simulated studies were made with various plane disc 125I sources in Perspex phantoms as well as 125I-insulin absorption studies in short-term subcutaneous infusion experiments with anaesthetised rabbits. Results from portable, end-window Geiger-Müller (GM) detectors fixed above the depots and close to the surfaces of phantom or skin were compared with results obtained by a conventional stationary NaI(Tl) detector 15 cm from the phantom or skin surface. With a 125I-insulin infusion site at 5 mm depth in the subcutaneous tissue of rabbits, an overall linear proportionality was found between the results obtained with a NaI(Tl) detector and a GM detector raised 15 mm above the skin surface inside the detector housing.

A semiconductor silicon PIN diode matrix detector for measurement of 133Xe washout in small regional skin areas.

Local variations in microvascularization are expected in lesions and lesion-free skin of patients with pressure sores. To investigate these variations, methods for studies of the regional blood flow rate within small skin areas are needed. Regional blood flow can be estimated by measuring the washout of 133Xe from the tissue. This study describes a 2 x 12 Si PIN diode matrix detector capable of 133Xe detection, and equipped with a collimator to improve the spatial resolution. Thus the regional blood flow in subcutaneous skin areas down to about 2 cm2 can be investigated when the atraumatic epicutaneous labelling technique is used. The capability of the matrix detector and its collimator is described by laboratory investigations. In pilot investigations three normal subjects and three paraplegics with pressure sores were studied. In each individual study the detector matrix was divided into six square areas containing four diode detectors each. Thus six 133Xe disappearance rate constants from adjacent subcutaneous tissue could be determined simultaneously.

A portable, pre-programmable insulin infusion system in diabetes mellitus.

A miniaturized portable pump has been developed in order to study the effects of pre-programmed insulin infusion patterns on the blood glucose levels in juvenile-onset, insulin-requiring diabetics. Six diabetics undergoing 7 insulin infusion periods of up to 4 days were studied. The mean blood glucose was 7.0 +/- 2.3 (SD) mmol/l and the mean amplitude of glycemic excursions was 5.0 +/- 1.4 mmol/l. Success in achieving normoglycemia will depend on choosing the correct dose of insulin for infusion.

A portable, Preprogrammable insulin infusion system with 16 rates.

An external, portable, programmable pump has been developed for long-term therapeutic i.v. insusion of drugs. The impulse-controlled system consists of a 250 g CMOS-electronic unit and an electromechanical infusor (200 g) containing a 10 ml disposable syringe. The infusion pattern during the 24-h cycle is manually programmed in 16 steps from 24 to 384 microliter per 0.5 h. The coefficient of variation of the infusate is less than 2% per 0.5 h. An alarm circuit monitors the pump speed and the reservoir volume. The infusion system can operate continuously for 7 days with a 1 Ah, 5.4 volt battery.

Circadian variations in 32P uptake of DMBA-induced mammary tumour and Walker carcinosarcoma in rats.

The 32P uptake in a mammary tumour induced by DMBA and in the Walker 256 carcinosarcoma was measured by external GM -tubes. The uptake was significantly higher than in the skin. During exposure to a synchronized light regime a circadian variation was present in the 32P uptake of the hormone-dependent DMBA-induced tumour. The maximal 32P uptake was in the dark period, in which the highest temperature in the tumour has also been found (Møoller and Bojsen, 1975). In the hormone-independent Walker 256 carcinosarcoma there was no periodicity in 32P uptake. No variation in 32P uptake was registered in the skin of normal controls or in tumour-bearing rats.

The immediate effect of TSH on renal iodide excretion rate in rabbits.

The renal iodide excretion rate was determined in unrestrained female rabbits by means of conventional clearance technique or continuous monitoring of the whole body disappearance of iv injected 125I-iodide using an implanted Geiger-Muller detector. The immediate effect of pharmacological doses of bovine TSH was studied by both methods and a significant decrease in iodide excretion rate was recorded following the administration of a single TSH dose of 4 IU. The effect of TSH lasted 3-6 h. Injection of 10-20 mug TRH caused a transient delay in iodide disappearance (30-50 min) while 2-20 mug triiodothyronine iv or sc had no immediate effect on the iodide disappearance.

The diurnal variation in renal iodide excretion rate in rabbits.

The diurnal variation in renal iodide excretion rate was determined in unrestrained female rabbits by means of either a conventional clearance technique or a continuous monitoring of the whole body disappearance of iv injected 125I-iodide using an implanted Geiger-Muller detector. A distinct diurnal rhythm was detected in the disappearance rate of 125I-iodide. A slow disappearance rate occurred from 12 p.m. to 6 a.m. (darkness from 5 p.m. to 5 a.m.). The values of iodide excretion rate obtained by both methods were consistent like in humans with an excretion fraction of 0.3 for iodide in rabbits. In rabbits weighing 3-4 kg the renal iodide excretion rates were 5-7 ml/min during the rapid phase and 3-4 ml/min during the slow phase.

Storage telemetric system for detection of radionuclide tracers in humans.

An external-storage telemetric device for continuous detection and registration of radionuclide tracers in humans is described. The weight of the system is 600 g. A pocket-sized ECG cassette tape recorder with 24-h continuous registration constitutes the storage unit. Two end-window GM detectors (Philips 18515) are used as surface detectors. Both gamma- and beta-emitters are detected by this equipment. The linear range is 100 counts/s. Renal excretion of [125I]iodide during 30 h in a normal person is shown. The disappearance rates are 0.1 h-1 during the day and 0.05 h-1 during the night. The coefficient of variation of the individual slopes has been calculated to less than 5%. A comparison with the analog radiotelemetric equipment is shown. The storage telemetric equipment can be applied outside the hospital, when the patient is ambulatory.

The glomerular filtration rate in unrestrained rabbits determined by means of an implanted telemetrical device.

An implanted radio-telemetrical device, which consists of a Geiger-Müller detector, a high voltage supply and a FM transmitter, incapsulated in araldite (weight 130 g) was used to measure the body disappearance rate of 125I-iothalamate following a single i.v. bolus in unrestrained and undisturbed rabbits. The disappearance curve is practically monoexponential from 10 to 60 minutes after administration of the indicator and the disappearance rate constant (Ke) is closely correlated to the "final slope" of the plasma disappearance curve of 125I-iothalamate (kp) r=0.99). A linear correlation was also found between Ke and GFR measured simultaneously by constant infusion clearance technique, using an indicator not detected by the Geiger-Müller detector (51Cr-EDTA) (r=0.98). The ratios between the renal clearances of 125I-iothalamate, 51Cr-EDTA and inulin were determined by constant infusion clearance technique in a separate series of experiments since no data were available in the present literature. The results show that GFR can be determined by means of the telemetrical method and in a series of experiments in undisturbed rabbits GFR was found to be on average 4.7 ml . min-1 . kg-1 (expressed as inulin clearance). Using the same technique in lightly pentobarbital anesthetized rabbits GFR was on average 3.5 ml . min-1 . kg-1.

Biotelemetric detection of the disappearance of subcutaneously injected 125I-NPH insulin.

A biotelemetric method with Geiger-Müller (GM) detectors fixed to the skin surface was used for continuous registration of the disappearance rate of subcutaneously injected 125I-NPH insulin. Methodological problems concerning counting geometry were investigated by comparing the disappearance of radioactivity, measured the GM- and NaI-detectors, respectively, and by scanning of the radioactive source. The size and position of the subcutaneous depot was unchanged throughout the study. Movement artifacts could be avoided. The coefficient of variation for distribution of ratios between count rates for GM- and NaI-detectors was 3.0% +/- 1.1 (SD) (range 0.9-4.0%) over periods of 24 h. It is concluded that the biotelemetry technique proved to be a clinically useful procedure for insulin absorption studies.

Improvement of glucose homeostasis in insulin-dependent diabetics using a miniature insulin infusion pump with a fixed profile.

Glucose homeostasis was studied in nine longstanding insulin-dependent diabetic patients using a portable pump for intravenous insulin infusion. The 24 h infusion dose was calculated from the conventional SC insulin treatment. The range of basal infusion rates was 2.5 to 15 mU/min and peak delivery rates were raised up to 16-fold from start of main meals for 30-60 minutes. Mean blood glucose improved from 12.0 +/- 2.4 to 6.4 +/- 1.0 mmol/l (SD) during infusion (p less than 0.01). Glucose excretion decreased from 23 g/24 h (range 1-42) to 4 g/24 h (range 0-14) (p less than 0.01). Mean amplitude of glycaemic excursions was significantly improved during infusion (from 8.9 +/- 4.8 to 4.7 +/- 0.9 mmol/l; p less than 0.01). No severe hypoglycaemic episodes or other adverse reactions were seen.

Clinical factors influencing the absorption of 125I-NPH insulin in diabetic patients.

Clinical factors which might influence the absorption of subcutaneously injected 125I-NPH insulin were studied in 101 diabetics. The disappearance curve was monoexponential after a delay period of 1.5 +/- 0.8 h (mean +/- SD). Lipohypertrophy significantly prolonged insulin absorption (half life (T1/2) = 11.2 +/- 3.1 h, p = 0.0001). Low bicarbonate levels increased the absorption (T1/2 3.9 +/- 2.3 h, p less than 0.05). Lean diabetics had a faster absorption (6.2 +/- 1.9 h) than normal weight diabetics (7.5 +/- 2.0 h, p less than 0.02). Sex, age, diabetes duration and injection depth did not influence T1/2. The half life was significantly inversely correlated to the resting subcutaneous blood flow (r = 0.882, p less than 0.01). The overall interindividual coefficient of variation for insulin absorption in nonketotic diabetics was 27.4%. Also considerable intra-patient day-to-day variation was found (24.5%), and between different injection sites (30.2%). These variations emphasize the drawbacks of conventional insulin therapy in the management of insulin-requiring diabetics.