Biomedical subjects
Publications and source records attributed to T Lindström.
The predominant d-wave pairing symmetry in high-temperature superconductors allows for a variety of current-phase relations in Josephson junctions, which is to a certain degree fabrication controlled. In this Letter, we report on direct experimental observations of the effects of a nonsinusoidal current-phase dependence in YBCO dc SQUIDs, which agree with the theoretical description of the system.
OBJECTIVE: To evaluate a dose titration model for recombinant human GH substitution in adult patients with GH deficiency, aiming at normal plasma levels of IGF-I. DESIGN AND METHODS: Eighteen patients participated and a start dose of 0.17 mg GH/day was used except by two men who started with 0.33 mg/day. To demonstrate a clear GH effect the patients were first titrated, with steps of 0.17 mg GH/day every 6-8 weeks, to IGF-I levels in the upper range of age-adjusted reference values. The GH dose was then reduced 1 dose step and kept for a further 6 months. For comparison we investigated 17 healthy control subjects. RESULTS: Plasma IGF-I was increased after 2 weeks on the start dose and did not increase further for up to 8 weeks. Women had significantly lower GH sensitivity than men measured as net increment of IGF-I on the start dose of GH. GH sensitivity was not changed by age. The plasma IGF-I levels increased from 76.3+/-47.0 (s.d.) to 237+/-97 microg/l at the end of the study (P<0.001), and similar IGF-I levels were obtained in both sexes. The maintenance median GH dose was 0.33 mg/day in males and 0.83 mg/day in females (P=0.017). The GH dose correlated negatively with age in both sexes. Body weight, very low density triglycerides, lipoprotein(a) (Lp(a)), and fasting insulin increased, whereas insulin sensitivity index (QUICKI) decreased significantly. In comparison with the controls, the patients had lower fasting blood glucose, fasting insulin and Lp(a) levels at baseline, but these differences disappeared after GH substitution. The two groups had equal insulin sensitivity (QUICKI), but 2 h oral glucose tolerance test values of blood glucose and insulin were significantly higher in the patients at the end of the study. CONCLUSIONS: In conclusion our data suggest that the starting dose of GH substitution and the dose titration steps should be individualised according to GH sensitivity (gender) and the IGF-I level aimed for (age). The reduced insulin sensitivity induced by GH substitution could be viewed as a normalisation if compared with control subjects.
BACKGROUND: To study the effect on body weight and glycaemic control of two insulin treatment regimens in patients with Type 2 diabetes and moderate failure to oral hypoglycaemic agents. METHODS: Sixteen patients treated with oral hypoglycaemic agents (6 men and 10 women) were included in this open-label, randomized, parallel group study. Their age was 62 +/- 2 (mean +/- SEM) years (range 44-79 years), body weight 71.3 +/- 2.9 kg, body mass index (BMI) 24.6 +/- 0.8 kg/m(2). The patients were switched to insulin treatment with bedtime NPH insulin combined with daytime sulphonylurea (combination group) or twice daily injections of a premixed combination of regular human and NPH insulin (insulin twice daily group) with measurements as given below before and after 12 and 24 weeks of treatment. RESULTS: HbA(1c) was lowered from 8.3 +/- 0.3% to 7.0 +/- 0.2% in the insulin twice daily group (p<0.05) and from 8.3 +/- 0.3% to 6.8 +/- 0.5% in the combination group (p<0.03; ns between treatment groups). Body weight increased from 71.7 +/- 4.0 kg to 77.6 +/- 4.4 kg in the insulin twice daily group (p<0.001) and from 70.8 +/- 4.6 kg to 72.7 +/- 5.1 kg in the combination group (ns; p<0.02 between groups). The dose of insulin at 24 weeks in the insulin twice daily group was 45.8 +/- 4.2 U and 29.4 +/- 5.4 U in the combination group (p=0.03). Combination treatment reduced fasting and stimulated C-peptide levels. CONCLUSIONS: Both treatments improved glycaemic control to the same extent but the combination of bedtime NPH insulin and daytime sulphonylurea gave a very small increase of body weight over a 6 months period. We conclude that combination therapy is an attractive alternative when starting insulin treatment in patients with Type 2 diabetes as this is a critical period for weight gain in such patients.
The aim of this study was to investigate if the release of oxytocin and cortisol were different depending on levels of oral manipulation with feed or rumen fill in dairy cows. Blood samples and behavior of 12 rumen-fistulated cows were analyzed in 2 consecutive years during morning and afternoon periods when the cows were subjected to either (A) long duration of oral manipulation of feed with low rumen fill or (B) short duration of oral manipulation of feed but with filled rumen. The response areas under the curve for oxytocin in both years were larger in A than in B in the afternoons. There were peaks in oxytocin release at milking in the afternoon in both treatments. In B, the oxytocin concentration was higher after than before feeding, higher in B than in A after the non-oral rumen filling, and higher in B after than before the non-oral rumen filling in Year 1. The level of cortisol was higher in B than in A in the morning, lower in both treatments before than after milking in the afternoon, and there was a tendency for the cortisol level to be higher in A than in B after oral feeding. The B cows spent a shorter time eating and the A cows spent a shorter time ruminating. This study indicates that a long duration of oral manipulation of feed in cows, may, per se be linked to higher oxytocin but lower cortisol levels, compared with shorter oral feeding time and filled rumen.
OBJECTIVE: IGF-I levels in patients with type 1 diabetes without endogenous insulin production are low. Our aim was to examine whether the plasma insulin profile obtained by treatment with the insulin analogue lispro has a different effect on plasma concentrations of IGF-I and IGFBP-1 than that seen during treatment with conventional human insulin (regular insulin). DESIGN AND PATIENTS: Twelve patients with type 1 diabetes, age 47.8 +/- 2.4 years (mean +/- SEM), body mass index 26.5 +/- 1.0 kg/m2, diabetes duration 30.5 +/- 3.2 years participated in this open label randomized cross-over study. IGF-I and IGFBP-1 levels were measured at the end of 6 weeks treatment with each insulin being administered by a continuous subcutaneous insulin infusion. IGF-I was measured fasting while IGFBP-1, free insulin and blood glucose were measured fasting and repeatedly after a morning meal preceded by an insulin bolus dose. RESULTS: Lispro gave a marked insulin peak of 135 +/- 20 pmol/l 50 minutes after injection. After an initial rapid rise, human regular insulin reached a plateau of approximately 50 pmol/l. The plasma free insulin area under the curve (AUC) from 0710 h to 0910 h was more than twice as large on lispro as on regular insulin (P = 0.01). Plasma IGF-I concentration was 78.8 +/- 10.9 microg/l on lispro and 82.3 +/- 10.5 microg/l on human regular insulin (not significant). AUC for IGFBP-1 did not show a significant difference even when divided from 0710 h to 0910 h and from 0930 h to 1430 h. Blood glucose AUC after administration of the bolus was significantly lower during treatment with lispro (P = 0.006) but glycosylated haemoglobin (HbA1c) was 6.4 +/- 0.2% on both therapies. CONCLUSIONS: Our results indicate that the effect of lispro on IGF-I and IGFBP-1 in patients with type 1 diabetes does not differ from that of human regular insulin.
OBJECTIVE: To study whether administration of 1.25 and 5.0 mg ramipril daily, compared with placebo treatment, reduces the urinary albumin excretion rate (UAER) in normotensive patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Ramipril was administered double blind at two different doses (1.25 [n = 19] and 5.0 mg [n = 18]), and compared with placebo (n = 18) after a single-blind placebo period of 1-4 weeks. The patients (total, n = 55; women, n = 14) were followed for 2 years. To document an effect on the renin-angiotensin system, ACE activity and plasma-renin activity (PRA) were measured. In addition, 24-h ambulatory blood pressure (BP) was recorded at baseline and repeated after 1 and 2 years using a Spacelab 90207 ambulatory BP recording device (Spacelab, Redmont, CA). RESULTS: Both doses of ramipril were sufficient to reduce ACE activity and to increase PRA significantly as compared with placebo (P < 0.05 for both). On the other hand, neither ambulatory nor clinic BP was affected by either dose of ramipril compared with the placebo group. There was no progression of UAER in the placebo group during the 2 years of the study. Analysis of covariance showed no differences in UAER between the three treatment groups at year 1 (P = 0.94) or year 2 (P = 0.97), after adjusting for baseline. Furthermore, there were no statistically significant changes from baseline UAER within any of the three treatment groups. CONCLUSIONS: Treatment with ramipril did not affect microalbuminuria or clinic or ambulatory BP in this study. On the basis of the present study, we question the clinical use of ACE inhibitors in stably normotensive patients with type 1 diabetes and microalbuminuria in whom a concomitant reduction in BP is not demonstrated.
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The aim of the present experiment was to test the hypothesis that oral manipulation of feed is a behavioural need in cattle, irrespective of actual rumen load. Twelve rumen fistulated cows were used and subjected to four different treatments: low rumen content+long duration of eating (A), high rumen content+short duration of eating (B), high rumen content+long duration of eating (=positive control) (C) and low rumen content+short duration of eating (=negative control) (D). To obtain treatment A and B, rumen content was transferred by hand from cow A to B through the rumen fistulaes. Each treatment lasted for 3 days with 2 weeks of recovery between each new treatment. The experiment was repeated twice during two consecutive years. All cows were fed the same mixture of silage, concentrate and hay. The cows were videotaped under normal conditions (24h), and on the third day of the experiment. From these videotapes, the behaviours (frequency and duration per 24h) have been analysed.Time spent eating differed between the four treatments (P<0.001), with shortest eating-times in B and D. The cows with low rumen content (A and D) spent shorter time ruminating (P<0.001) than the cows with filled rumen (B and C). The B and D cows (short duration of eating) spent longer time (P<0.001) with behaviours related to feed-searching than the cows with long duration of eating (A and C). The C cows had fewer (P<0.001) bouts of behaviours related to feed-searching than the A, B and D cows. Time spent with stereotypies (tongue-rolling) was longer (P<0.01) in D than in the other treatments. There was a difference (P<0.001) between treatments in eating bouts. The A cows had more (P<0.05) eating bouts than the cows in B, C and D. The cows with low rumen content (A and D) had fewer ruminating bouts (P<0.001) than the cows with filled rumens (B and C). The number of bouts with stereotypies differed (P<0.01), the cows in D having the highest figures compared with all the other treatments.In conclusion, our results support the hypothesis that oral manipulation of feed is a behavioural need in cattle irrespective of rumen load. A low duration of feeding behaviours combined with a low rumen load, which is a common practice in certain categories of growing cattle or dry dairy cows, seriously impairs the welfare in cattle.
UNLABELLED: Our objective was to investigate the usefulness of human ultralente insulin as basal substitution overnight in patients with Type 1 diabetes treated with multiple insulin injection therapy by evaluating the free insulin and glucose profiles, the day-to-day variability and the impact of the time of injection. METHODS: Ten patients with Type 1 diabetes and with good metabolic control (mean HbAlc 6.0%), treated with regular human insulin before breakfast, lunch and dinner and human ultralente (Ultratard) before dinner or at bedtime, were studied. Plasma profiles of blood glucose and free insulin were measured on three occasions from 16.00 h until noon the next day. On two of these occasions Ultratard was injected before dinner and once it was injected at bedtime in randomized order. RESULTS: Injection of regular insulin before dinner resulted in a high insulin peak during the evening but no insulin peak was found that could be attributed to ultralente. The plasma concentration of free insulin at 03.00 h was 11.0+/-1.9 mU/L and it slowly decreased to 6.4+/-1.4 at 12.00 h after administration of ultralente at 17.00 h. There were no differences in the mean plasma insulin profiles compared to the other occasion when insulin was given at 17.00 h or at 22.00 h. On the other hand, the intra-individual day-to-day variability of mean insulin concentration during the night was considerable, often exceeding 50%. No differences were noted in the mean blood glucose profiles between the three occasions. CONCLUSION: Human ultralente insulin gives an insulin profile suitable for overnight substitution, but the great day-to-day variability limits its usefulness. It can be injected before dinner or at bedtime without any change in the insulin profile during the night.
OBJECTIVES: To evaluate how a snack influences the blood glucose profile during treatment with preprandial regular human insulin. DESIGN: In a randomized study a mid-morning snack either was or was not served. Insulin was given 30 min before the usual breakfast of the patients. Plasma free insulin and blood glucose were repeatedly determined for 5 h. SETTING: Outpatient clinic at a university hospital. SUBJECTS: Twenty patients with type 1 diabetes treated with multiple injections of regular insulin (Actrapid) and eight non-diabetic subjects. INTERVENTIONS: A mid-morning snack either was or was not served 2 h after the usual morning insulin injection. MAIN OUTCOME MEASURES: A difference in the blood glucose profile after a mid-morning snack. RESULTS: With a snack there was no difference in blood glucose fasting and at 12.30 h, whilst without a snack there was a decrease of almost 4 mmol L-1, several patients experienced low blood glucose and three had hypoglycaemia. An extended peak of free insulin was reached 30 min after the insulin injection with a slow decrease to the fasting level after 5 h. After the insulin injection a significant decrease in blood glucose occurred within 30-45 min. CONCLUSIONS: A snack 2 h after the insulin injection results in a smoother blood glucose profile and reduces the risk of hypoglycaemia in patients with type 1 diabetes treated with preprandial regular human insulin. Furthermore, the recommended interval of 30 min between insulin injection and a meal may be too long.
AIMS: To study whether changes in endogenous insulin secretion at the same glycaemic control affect the plasma concentrations of lipoproteins in patients with Type 2 diabetes mellitus. METHODS: Fifteen patients, age 59+/-2 years (mean +/- SEM), body weight 86.3+/-3.0kg, body mass index 29.6+/-0.9 kg/m2 were treated with sulphonylurea and insulin in combination or with insulin alone in a randomized, double-blind, crossover study. All patients were treated with a multiple daily injection regimen with the addition of glibenclamide 10.5 mg daily or placebo tablets. RESULTS: During combination therapy, the dose of insulin was 25% less (P < 0.002) and there was a 29% increase in plasma C-peptide concentration (P = 0.01). Plasma levels of free insulin were not changed. Plasma levels of sex hormone-binding globulin (SHBG) and insulin-like growth factor-binding protein (IGFBP)-1 were lowered. There were no differences in the 24-h blood glucose profiles or HbA1c (6.0+/-0.2 vs. 6.3+/-0.2%; P = 0.16). Body weight was similar. There was a significant decrease in plasma LDL cholesterol (3.04+/-0.24 vs. 3.41+/-0.21 mmol/l; P = 0.04), apolipoprotein A1 and of lipoprotein(a) but an increase in VLDL-triglycerides (1.36+/-0.31 vs. 0.96+/-0.16 mmol/l; P = 0.02) during combination therapy. The ratio between LDL cholesterol and apolipoprotein B concentrations was significantly lower during combination therapy (P < 0.01). CONCLUSIONS: Combination therapy with insulin and sulphonylureas increases portal insulin supply and thereby alters liver lipoprotein metabolism when compared with insulin therapy alone.
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OBJECTIVE: To compare the effects of unreamed and reamed intramedullary nailing on the systemic production of prostacyclin and thromboxane A2 as assessed, respectively, by determinations of urinary 2,3-dinor-6-ketoprostaglandin F1alpha and 11-dehydrothromboxane B2 excretion. METHODS: Ten otherwise healthy patients with closed and simple tibial shaft fractures were treated with unreamed intramedullary nailing, and 10 otherwise healthy patients with closed and simple tibial shaft fractures were treated with reamed intramedullary nailing. Urine was collected preoperatively and during the next 5 postoperative days. The samples were stored at -70 degrees C until assayed at the end of the study. RESULTS: In the unreamed group, urinary 2,3-dinor-6-ketoprostaglandin F1alpha and 11-dehydrothromboxane B2 excretion remained stable and at a significantly lower levels compared with the reamed group during the entire study period (p < 0.021). In the reamed group, the alteration in urinary 2,3-dinor-6-ketoprostaglandin F1alpha excretion preoperatively and on the first postoperative day was nearly significant (p=0.075), and the increase in urinary 11-dehydrothromboxane B2 excretion was significant (p=0.020). The proportional increase compared with baseline, however, was 1.6 times greater for 11-dehydrothromboxane B2 than for 2,3-dinor-6-ketoprostaglandin F1alpha. CONCLUSION: Only reamed intramedullary nailing elevates urinary 2,3-dinor-6-ketoprostaglandin F1alpha and 11-dehydrothromboxane B2 concentrations and their ratio (thromboxane A2/prostacyclin production) in patients with simple tibial shaft fractures.
We evaluated the effect of hyperbaric oxygen (HBO2) therapy on tibialis posterior (TPA), dorsalis pedis (DPA), and sum (TPA + DPA) arterial peak signals, as well as transcutaneous oxygen (PtcO2) tension and leg skin temperature (T) after intramedullary nailing of tibial shaft fractures. Twenty consecutive patients with closed and simple tibial shaft fractures treated with reamed intramedullary nailing were assigned randomly to HBO2 or control groups. HBO2 therapy was given postoperatively at 2.5 atm abs pressure for 90 min daily for a total of five treatments. The first HBO2 therapy was given 1 h after the operation. In both groups, measurements were performed preoperatively, 30 min and 6 h postoperatively, and on the following 5 days. There was a statistically significant improvement in TPA values in the nailed legs in the HBO2 treatment group after the first postoperative day, and these values remained at a significantly higher level until the end of the study when compared to the nailed legs in the control group. Further, there was a statistically significant improvement in PtcO2 values in the nailed legs in the HBO2 group after the third HBO2 treatment. However, there were no statistically significant differences in DPA and TPA + DPA values within or between the nailed legs in HBO2 and control groups. HBO2 therapy seemed to decrease the skin temperature of the nailed legs, but this alteration was not statistically significant. In addition to the clearly documented advantages in the management of crush injuries and compartment syndromes, HBO2 therapy has a positive effect on the perfusion parameter (TPA) and PtcO2 in patients with low energy, intramedullary nailed simple tibial shaft fractures. The improvement in TPA and PtcO2 values may result from the vasoconstrictive and edema reductive effect on HBO2 with concomitant inhibition of inflammatory reactions with slight cooling.
BACKGROUNDS AND AIMS: To measure noninvasively the effect of circulative changes caused by fracture and intramedullary nailing on tibialis posterior (TPA), dorsalis pedis (DPA) and sum (TPA + DPA) arterial peak signals, transcutaneous oxygen tension (PtcO2) as well as local skin temperature (T) in patients with tibial shaft fractures. PATIENTS, MATERIAL AND METHODS: A total of thirty tibias consisting of ten closed, reamed, intramedullary nailed simple tibial shaft fractures (Type AO A), ten contralateral tibias and as controls, ten intact tibias of healthy volunteers. The measurements took place one day before and immediately after nailing, six hours later and during five days postoperatively. The values were compared to those of contralateral legs and to control legs. RESULTS: In the nailed legs the mean TPA and PtcO2 remained at a significantly lower level compared to the contralateral legs throughout the study (p < 0.003 in both cases). However, the alterations in DPA and TPA + DPA were not statistically significant. Additionally, skin temperature on the fracture site was averagely 3 degrees C warmer than that of the contralaterals (p < 0.001). All the measured parameters were statistically significantly higher in control legs compared to contralateral legs. There were no statistically significant differences between pre- and postoperative values in any measured parameters. CONCLUSION: The changes in the local tissue perfusion variables measured in the present study reflect rather the injury mechanism itself than the effect of reaming and intramedullary nailing in simple tibial fractures. Additionally, arterial circulation was reduced in the contralateral legs.
The objective was to evaluate the effect of insulin treatment on circulating islet amyloid polypeptide (IAPP). Twelve patients with NIDDM and secondary failure were studied on oral agents and then switched to insulin treatment. Fasting and postprandial IAPP concentrations were measured on oral treatment and on insulin treatment. In 5 of the patients no postprandial concentrations were determined. In the 7 patients who were investigated both fasting and postprandially the fasting IAPP concentration was 6.5 +/- 1.2 pmol l(-1) (mean +/- SEM) during oral treatment with a rise to 13.5 +/- 3.1 90 min after breakfast (p = 0.028). On insulin treatment HbA1c decreased from 8.6 +/- 0.5 to 7.5 +/- 0.4% (p< 0.03) and plasma C-peptide concentration was significantly lowered (p< 0.01). There was a close correlation using simple regression between the per cent change of IAPP concentration and the per cent change of C-peptide concentration during this period (r = 0.88; p< 0.01). In the total patient material of 12 patients there was a significant correlation using simple regression analysis between per cent change of IAPP concentration and per cent change of C-peptide concentration using all 48 measurements available (r = 0.58: p< 0.001). These data suggest that secretion of IAPP is lowered when endogenous insulin secretion is lowered by administration of exogenous insulin in patients with NIDDM. Thus, if IAPP secretion has a pathogenetic role in the development of beta cell failure in NIDDM, insulin treatment might delay this deterioration.
This prospective study investigates the effect of injury and surgery of cartilage and bone on serum group II phospholipase A2 (PLA2-II) and C-reactive protein (CRP) levels. Serum concentrations of PLA2-II and CRP were measured before and after the operation in nine patients with closed tibial shaft fractures treated by nailing, 11 patients with fractures of lateral tibial plateau treated by bone grafting, and 19 patients with ruptured anterior cruciate ligament treated by reconstruction. The postoperative PLA2-II and CRP values were statistically significantly higher than the pre-operative values in the tibial plateau fracture and ligament rupture groups, whereas the increase in the PLA2-II values in the tibial fracture group was not statistically significant. The highest values of both parameters were found on the second postoperative day. The changes in the PLA2-II and CRP values were parallel in the lateral condyle fracture and in anterior cruciate ligament rupture groups. PLA2-II behaves as an acute phase reactant in the serum of patients undergoing acute and elective knee surgery.
OBJECTIVE: To study relationships between leptin and factors regulating body composition as well as metabolic risk factors. Furthermore, to study the effects of GH on leptin. DESIGN: Cross-sectional and population-based. Regarding the effects of GH, prospective and interventional. PATIENTS: One hundred and eleven women and 107 men, 20-70 years old, randomly selected from the population registry in the community of Linköping, Sweden. Ten GH-deficient subjects were given GH until normalization of IGF-I levels. MEASUREMENTS: Venous blood was drawn in the fasting state. Serum leptin and hormones were analysed by immunoassay. RESULTS: In the population sample the natural logarithm of leptin (in(leptin)) correlated with body mass index (BMI) (men, r = 0.67), P < 0.0001; women, r = 0.71, P < 0.0001). The median value of leptin was 4.6 micrograms/l in men and 12.3 micrograms/l in women (P < 0.0001). Levels of in(leptin) did not correlate with plasma neuropeptide Y (men, P = 0.13; women, P = 0.35). In men only there was an inverse relationship between in(leptin) and testosterone (r = -0.46, P < 0.0001, after correction for BMI standardized r = -0.26, P = 0.03) as well as IGF-I (r = -0.20, P = 0.048). Although BMI was similar, smoking men had higher leptin levels than non-smoking men (median, 6.6 and 4.2 micrograms/l, respectively; Mann-Whitney; P = 0.006). In the GH-deficient subjects leptin levels were elevated and, although GH treatment did not change BMI, leptin levels decreased (median before GH, 21 micrograms/l and after 15 micrograms/l, respectively; P = 0.017). CONCLUSION: Serum leptin concentration is closely associated with BMI in the population with a gender difference in absolute levels and a strong negative correlation with testosterone in men. Serum leptin is elevated in GH deficiency and lowered by GH substitution.