[Cryoanalgesia. Pain relief following local application of cold].
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Biomedical subjects
Publications and source records attributed to K Birch.
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Due to the ubiquitous nature of airborne endotoxin, an understanding of pulmonary alterations which follow inhalation of environmentally realistic concentrations of purified bacteria derived lipopolysaccharide (LPS) is important. Using LPS derived from Enterobacter agglomerans, a bacterium found in cotton and cotton mill dust, aqueous aerosols (effective LPS concentration 4 micrograms/m3) were generated and used to expose either normal hamsters (N = 6) or those rendered endotoxin tolerant by pre-ip injection of 0.1 LD50 LPS. Control groups (normal--N = 6; tolerant--N = 6) received saline aerosol only. At 6 hr after 5-hr aerosol exposure, lungs of all animals were fixed, processed for light and transmission electron microscopy, and subject to qualitative and to multitiered morphometric analysis using standard point counting techniques. Qualitative evaluation of TEM micrographs from LPS aerosolized-nontolerant hamsters showed endothelial alteration (focal disruption, subendothelial space formation, and cytoplasmic blebbing) but volume and number of endothelial cells were not changed indicating only slight, focal endothelial damage. Quantitatively, septal capillary blood space in nontolerant, LPS aerosolized hamsters showed increased Vv of PMNs and platelets. These changes were not seen in tolerant induced-LPS aerosolized hamsters. Independent of tolerization treatment, LPS inhalation led to a decrease in fixed lung volume and an increase in numerical density of endothelial pinocytotic vesicles. It is concluded that the inhalation of realistic, environmental levels of bacterial endotoxin may induce significant changes in distal lung and may be important in the pathogenesis of byssinosis and adult respiratory distress syndrome.
In 23 diabetic patients, the disappearance from subcutaneous tissue of 125I-labelled short-acting insulin and of 133Xe (measuring subcutaneous blood flow (SBF] were registered simultaneously. Alterations in the SBF were produced either by orthostatic changes or by application of local heat or cold. The insulin absorption rate was related to the SBF in a curvilinear way with an almost linear relation at SBF below 2-3 ml . (min . 100 g)-1, whereas at SBFs above the value the insulin absorption rate increased less than proportional to SBF. Capillary diffusion capacity of the injected insulin was 0.0145-0.0874 ml . (min . 100 g)-1; indicating that insulin is absorbed in a polymeric form. This was supported by studies of insulin diffusion in agar gel at 37 degrees C, showing that insulin in the normal pharmacological concentration diffuses as a molecule of about 46,000 MW. In conclusion, the absorption of short-acting soluble insulin is curvilinearly related to the SBF. This can be explained by a diffusion-limited transport of insulin in the interstitial space, and increasing transcapillary transport of insulin at increasing blood flow rates caused by recruitment of capillaries, thus increasing exchange surface area and decreasing diffusion distance.
To compare the metabolic control and the pharmacokinetics of infused insulin using an insulin pump (Auto-Syringe AS 6C) which provides the basal rate in pulses every 2-10 min with a pump (Medix Syringe Driver 209) providing the basal rate in pulses every 15-60 min, 6 C-peptide negative diabetic patients received, in random order, identical, but individual, insulin treatment during one 4-day period using the Auto-Syringe pump and another 4-day period using the Medix pump. On the fourth day of each period, blood glucose and plasma-free insulin were estimated every 30 min for 7 hr and every 5 min for the next hour. Plasma-free insulin was significantly higher on 3 time points out of the 26 possible when using the Medix pump, but this was not reflected in the blood glucose concentrations which were similar in the 2 periods. The results indicate that, from a metabolic and pharmacokinetic point of view, insulin pumps working with larger intervals between the basal rate pulses are just as good as the more technically advanced and hence often more expensive pumps which provide the basal rate in more and smaller pulses.
Subcutaneous blood flow (SBF), measured by the 133Xenon local clearance technique, and absorption of subcutaneously injected 125I-labelled short-acting insulin from the femoral and abdominal regions were studied in 17 diabetic patients during supine and sitting position. Sitting up induced vasoconstriction with a 28.7-47.0% fall in SBF and a 19.2-43.6% fall in the insulin absorption rate. These findings imply that the SBF of the thighs and abdomen participate in the cardiovascular adjustments to postural changes. The change in the insulin absorption rate during the change of position probably contributes to the great day-to-day variation of insulin absorption. Furthermore, the observation stresses the importance of well defined experimental conditions in insulin absorption studies.
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The absorption of 125I-labelled porcine, bovine and human neutral protamine Hagedorn (NPH) insulins was compared in 40 diabetic patients after subcutaneous injections in the thighs using doses of 6 and 24 IU (40 IU/ml). Furthermore, the absorption of porcine NPH insulin was compared with bovine NPH insulin and porcine lente type insulin in the same dose (6 IU). All these intermediately acting insulins showed similar absorption rates when administered in the same dose. However, an increase in the injected dose from 6 to 24 IU resulted in a decrease of approximately 30% in the absorption rate of all NPH insulins.
To assess the effects of improved glycaemic control on the right and left ventricular ejection fraction (RVEF and LVEF), we performed radionuclide angiocardiography at rest and during exercise in nine insulin-dependent diabetics with a diabetes duration between 2 and 35 years (mean 12 years) and in 10 control subjects. The diabetics were investigated before and after 7 days' treatment with continuous subcutaneous insulin infusion (CSII). The diabetics had a significantly smaller rise in exercise-induced LVEF during normoglycaemia than in the hyperglycaemic state. In contrast to the control subjects, the diabetics, independent of glycaemic control, did not increase the end-diastolic volume and did not decrease the end-systolic volume during exercise. Our data indicate a preclinical abnormal left ventricular function in young diabetics without long-term diabetic complications. The dysfunction seems unrelated to changes in the loading of the heart and appears to be caused by decreased contractile reserve of the myocardium.
The aim was to study the effect of dose on subcutaneous absorption of semisynthetic human Lente-type insulin (Monotard HM) in IDDM patients. The absorption was evaluated by measurements of residual radioactivity of 125-I labelled insulin at the injection sites. In 9 patients, on consecutive days, 6, 12, 24 and 36 IU of Monotard HM was given subcutaneously. The residual radioactivity was measured up to 49 hr after injections. A dose-dependent absorption was found with significantly decreasing absorption rates for increasing doses. The times for 50% of initial activity to disappear were (doses given in parentheses): 9.0 hr (6 IU), 8.9 hr (12 IU), 10.9 hr (24 IU), 14.8 hr (36 IU).
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Twenty diabetic patients received a constant subcutaneous infusion of 125I-labelled short-acting insulin (1.12 U/h) into the anterior abdominal wall. Measurement of the size of the insulin depot at the infusion site was performed by measuring the radioactivity and by using a calibration bolus to transform count rate to units of insulin in the depot. By the 133Xenon technique, local subcutaneous blood flow rate was measured on the contralateral side of the anterior abdominal wall. From the start of the infusion the SC depot built up slowly, but did not reach steady-state by 6 h. After 24 h of infusion, the size of the depot ranged between 2.7 and 10.9 U (5.2 +/- 0.5 U, mean +/- SE). The size of this steady-state depot was inversely correlated with SC blood flow. After stopping the infusion, insulin disappeared according to first order kinetics without any lag period. The insulin disappearance rate from the depot was positively correlated with the blood flow in a curvilinear fashion. The results suggest that the relationship between blood flow and the size of the insulin depot is best explained by a predominantly blood flow limited removal of insulin at low rates of blood flow, with increasing limitation by diffusion at higher rates.
We studied the reliability of the Chemstrip system in the self-monitoring of blood glucose by diabetic patients. A total of 453 blood glucose values obtained by 38 diabetic patients using Chemstrip were compared with the glucose values of the same blood samples measured with a conventional laboratory method. We found a definite tendency at concentrations less than 320 mg/dl for patient-read Chemstrip values to be too low. Also, we found a wide range in laboratory values corresponding to a given patient-read Chemstrip value. However, a better agreement between Chemstrip and laboratory values was obtained when the Chemstrips were read by trained staff. We recommend, therefore, that the use of Chemstrip in the self-monitoring of blood glucose can be restricted to patients who have shown competence in the use of Chemstrip during prior testing.