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Biomedical subjects

T Lindström

Publications and source records attributed to T Lindström.

29 records · Page 2Linked to original sources

Serum leptin concentrations in a normal population and in GH deficiency: negative correlation with testosterone in men and effects of GH treatment.

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.

Adult↗

A comparison a amitriptyline and maprotiline in the treatment of painful polyneuropathy in diabetics and nondiabetics.

OBJECTIVE: To compare amitriptyline and maprotiline in the treatment of painful polyneuropathy in diabetics and nondiabetics. DESIGN: A double-blind, crossover trial of treatment with amitriptyline, maprotiline, and placebo. Treatment was given in randomized order for periods of 4 weeks. Each period was separated by a 1-week washout. The final dose was 75 mg/day for both amitriptyline and maprotiline. PATIENTS: Thirty-seven patients with diabetic and nondiabetic painful polyneuropathy. OUTCOME MEASURES: The treatment effects were assessed by daily ratings of pain intensity on a 10-step verbal scale (0 = no pain and 10 = worst thinkable pain) and at the end of each treatment period by a global rating of the analgesic effect on a 5-step verbal scale (pain relief scale). For the assessment of depression, the Comprehensive Psychopathological Rating Scale (CPRS) was used. RESULTS: Using the global assessment of pain relief at the end of each treatment period, 22 of 33 patients reported reduced pain on amitriptyline treatment compared with 14 of 33 patients on maprotiline treatment and 8 patients on placebo treatment (p < .0001 and p < .05 for amitriptyline and maprotiline, respectively, against placebo). Amitriptyline was slightly better than maprotiline (p < .05) [tested by repeated measures analysis of variance (ANOVA)]. The order in which treatments occurred and the diagnosis of diabetes or nondiabetes did not have any significant effect on the global rating of pain relief. The mean values of the daily ratings of pain intensity showed that pain was more severe in the evenings than in the mornings and that diabetic patients reported worse pain than nondiabetics at baseline. The mean values of pain reduction as assessed with the 10-step verbal scale during the 4th week of treatment showed that amitriptyline and maprotiline were significantly better than placebo in relieving the pain (p < .0001 and p < .01, respectively, post hoc test according to Scheffé). However, there was no significant difference between the pain reduction of amitriptyline compared with maprotiline when assessing pain reduction with the 10-step verbal scale during the 4th treatment week. Nor was there a significant difference between diabetics and nondiabetics with regard to the effect of the drugs. The clinical effect was not significantly correlated to plasma concentration of either amitriptyline and its active metabolite nortriptyline or maprotiline in the global or daily assessments. The effect of treatment was not correlated to any particular pain quality nor to the intensity of pain. Depression was noted in three patients who completed the medication trial, but the effect of treatment of pain and depression did not clearly correlate. The adverse side effects of amitriptyline and maprotiline were common, and in 5 patients the medication had to be discontinued because of severe side effects. CONCLUSION: From the present results and the literature, it is concluded that tricyclic antidepressants with a pharmacologic profile similar to amitriptyline are the most effective drugs in the treatment of polyneuropathy pain in both diabetic and nondiabetic patients.

Adult↗

Leg tissue perfusion in simple tibial shaft fractures treated with unreamed and reamed nailing.

BACKGROUND: To compare the effects of unreamed and reamed intramedullary nailing on tibialis posterior, dorsalis pedis, and sum (tibialis posterior plus dorsalis pedis) distal arterial peak pulses. Additionally, leg skin temperature and transcutaneous oxygen tension were measured in patients with low energy, closed tibial shaft fractures. METHODS: The patients were randomized to unreamed and reamed groups, and intramedullary nailing without or with reaming was performed under spinal anesthesia. The measurements were carried out before the operation and on 5 postoperative days. RESULTS: In the unreamed group, the only significant difference between contralateral and nailed legs was in raised leg skin temperature (p = 0.0001). In the reamed group, tibialis posterior distal arterial peak pulses and transcutaneous oxygen tension remained at a significantly lower level and leg skin temperature at a significantly higher level, respectively, in the nailed legs after the operation when compared with contralateral legs (p = 0.0026, p = 0.0001, and p = 0.0001, respectively). There were no statistical differences between preoperative and postoperative values in the measured parameters in both groups. Additionally, there were no intergroup changes in the measured parameters in the injured legs. CONCLUSION: The present study suggests that altered distal arterial pulsations, decreased transcutaneous oxymetry values, and thermal reaction are not due to differences in nailing method but caused by a manifestation of the trauma mechanism of the tibial shaft fracture. The potentially negative effects of reaming to soft tissue perfusion parameters could not be established.

Adult↗

The insulin-like growth factor system in vascular smooth muscle: interaction with insulin and growth factors.

Vascular smooth muscle cells (SMCs) occur throughout the vascular tree and have important physiological functions. They are also involved in pathological processes such as development and progression of atherosclerotic lesions, restenosis following angioplasty, and in hypertension. This review is focused on the role of the insulin-like growth factor (IGF) system in proliferation, migration, and hypertrophy of vascular SMCs and its interaction with insulin and other growth factors. The IGF-I receptor is highly expressed in SMCs in intact arteries and in cultured SMCs and is activated by binding of IGF-I to the two alpha-subunits. Insulin and IGF-II from the circulation can interact with the IGF-I receptor at higher concentrations. Insulin receptors are few or absent in SMCs and circulating insulin concentrations in vivo are probably too low for a direct action of insulin on the IGF-I receptor in SMCs. Receptor activation initiates a number of signal transduction pathways. Increased phosphatidylinositol turnover and calcium mobilization correlates with actin filament reorganization and stimulation of directed migration of the SMC in a gradient of IGF-I. The effects of IGF-I receptor activation on signal transduction pathways (eg, the MAP kinase cascade) implicated in DNA synthesis and proliferation are weak and this correlates with the meager mitogenic activity of IGF-I in SMC. Several components of the IGF-system in SMC are regulated by growth factors such as platelet-derived growth factor (PDGF)-BB and basic fibroblast growth factor (bFGF).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Insulin treatment improves microalbuminuria and other cardiovascular risk factors in patients with type 2 diabetes mellitus.

OBJECTIVES: Insulin treatment of patients with type 2 diabetes causes hyperinsulinaemia and improves glycaemic control. We have studied how this affects risk factors for cardiovascular disease. DESIGN: Patients with secondary failure to oral hypoglycaemic agents were studied whilst still taking oral agents and after insulin treatment for 8 weeks in an open study. SETTING: Department of Internal Medicine, University Hospital, Linköping. SUBJECTS: Ten consecutive patients with type 2 diabetes and secondary failure to oral hypoglycaemic agents. INTERVENTIONS: Switching oral treatment to insulin treatment. MAIN OUTCOME MEASURES: Effect on several cardiovascular risk factors. RESULTS: Fasting and postprandial plasma insulin concentrations were increased by insulin treatment whereas C-peptide concentrations were lowered. HbA1c was reduced from 8.9 +/- 0.3% (mean +/- SEM) to 6.3 +/- 0.2% after 8 weeks. There was a weight gain of 2.8 +/- 0.7 kg. Plasma concentrations of total- and very-low-density-lipoprotein (VLDL) cholesterol, VLDL-, low density lipoprotein and high-density-lipoprotein triglycerides were all reduced. The plasma concentration of apolipoprotein B was also lowered. Tissue plasminogen activator antigen measured after venous occlusion showed a significant reduction whilst plasminogen activator inhibitor 1 activity was 26.0 +/- 9.8 IU ml-1 on oral treatment and 18.2 +/- 4.7 IU ml-1 on insulin treatment (NS). Albumin excretion in the urine was reduced and the percentage reduction correlated with the percentage lowering of the tissue plasminogen activator antigen concentration after venous occlusion but not with the percentage change of basal tissue plasminogen activator antigen concentration. CONCLUSIONS: Insulin treatment of patients with type 2 diabetes and secondary failure to oral hypoglycaemic agents causes hyperinsulinaemia and improves or has no unfavourable effect on several cardiovascular risk factors.

Adult↗

Long-term improvement of glycemic control by insulin treatment in NIDDM patients with secondary failure.

OBJECTIVE: To evaluate the long-term efficacy of insulin treatment of patients with non-insulin-dependent diabetes mellitus (NIDDM) and secondary failure to oral hypoglycemic agents. RESEARCH DESIGN AND METHODS: Twenty-one NIDDM patients with secondary failure were studied while they were still on oral agents. Then they were switched to insulin treatment, and after a median of 27 months, a long-term evaluation was conducted. RESULTS: At the long-term evaluation, metabolic control was still markedly improved by insulin treatment, with reduction of HbA1c from 8.8 +/- 0.2 (mean +/- SE) to 6.9 +/- 0.3% (P < 0.0001), lowering of very-low-density lipoprotein (VLDL) cholesterol concentration from 0.97 +/- 0.3 to 0.69 +/- 0.1 mM (P < 0.03), and lowering of total triglycerides from 2.8 +/- 0.6 to 1.8 +/- 0.3 mM (P < 0.005), mainly due to reduction of VLDL triglycerides. Body weight increased during the first year, but not thereafter (71.3 +/- 2.5 kg during oral treatment, 78.9 +/- 2.9 and 79.8 +/- 3.2 kg after 12 and 36 months of insulin treatment, respectively). Blood pressure did not change. Fasting and postprandial insulin concentrations increased, and C-peptide concentrations were lowered. CONCLUSIONS: Improvements of glycemic control and lipoprotein concentrations in patients with NIDDM and secondary failure persist also after insulin treatment for 2-3 years in spite of weight gain and hyperinsulinemia.

Adult↗

Hypoglycaemia and cardiac arrhythmias in patients with type 2 diabetes mellitus.

Improved blood glucose control by insulin treatment in patients with Type 2 (non-insulin dependent) diabetes mellitus increases the risk for hypoglycaemic episodes. Our objective was to investigate if hypoglycaemia causes electrocardiographic changes and cardiac arrhythmias in patients with Type 2 diabetes. Six insulin-treated patients with Type 2 diabetes and no known cardiac disease took part in the study. Hypoglycaemia was induced by insulin infusion aiming at a plasma glucose less than or equal to 2.0 mmol l-1 or hypoglycaemic symptoms. All patients experienced hypoglycaemic symptoms. The median lowest arterial plasma glucose was 2.0 mmol l-1. Arterial plasma adrenaline concentration increased from 0.4 +/- 0.1 (mean +/- SE) to 6.9 +/- 0.3 nmol l-1 (p less than 0.001) while serum potassium was lowered from 4.1 +/- 0.3 mmol l-1 to 3.5 +/- 0.2 mmol l-1 (p less than 0.001). The heart rate increased significantly during hypoglycaemia except in one patient who developed hypoglycaemic symptoms and a severe bradyarrhythmia at a plasma glucose of 4.4 mmol l-1. One patient developed frequent ventricular ectopic beats during hypoglycaemia while four patients showed no arrhythmia. ST-depression in ECG leads V2 and V6 was observed during hypoglycaemia in five patients (p less than 0.05) and four patients developed flattening of the T-wave. In conclusion, the study supports the hypothesis that hypoglycaemia in patients with Type 2 diabetes may be hazardous by causing cardiac arrhythmias.

Arrhythmias, Cardiac↗

C-peptide profiles in patients with non-insulin-dependent diabetes mellitus before and during insulin treatment.

The objective of the study was to evaluate the effect of insulin treatment on insulin secretion in patients with non-insulin-dependent diabetes mellitus (NIDDM). Ten patients with NIDDM were first investigated while still taking oral hypoglycemic agents, and then randomized to a crossover study with two eight-week periods of insulin treatment (oral treatment having been stopped) given either as mainly intermediate-acting insulin twice daily (2-dose) or as preprandial regular insulin and intermediate-acting insulin at bedtime (4-dose). In the patients treated with oral agents the 24-h C-peptide area under the curve was similar to that in the controls, but the profile was different with a rise at breakfast but with almost absent meal peaks during the rest of the day. Insulin treatment improved glycemic control markedly, lowered urinary C-peptide excretion and the serum C-peptide concentrations being reduced by more than 50%. The shape of the C-peptide profiles was unaltered and there were no significant differences between the two insulin regimens. The decrease in serum C-peptide concentration during insulin treatment correlated with the change in blood glucose. Fasting serum C-peptide concentrations correlated closely with the 24-h C-peptide area under the curve. In conclusion, insulin treatment of NIDDM patients with secondary failure to oral agents greatly reduces the insulin secretion, probably owing to the reduction in blood glucose.

Aged↗

Effect of different insulin regimens on plasma lipoprotein and apolipoprotein concentrations in patients with non-insulin-dependent diabetes mellitus.

The effect of insulin treatment with 2 different insulin regimens on the plasma concentrations of lipoproteins and apolipoproteins A1 and B was studied in 10 patients with non-insulin-dependent diabetes mellitus (NIDDM) and secondary failure to oral hypoglycaemic agents. The investigation was performed as a randomized crossover study with treatment periods of 8 weeks. Insulin was given either as mainly intermediate acting insulin before breakfast and dinner (2-dose insulin) or as regular insulin preprandially with intermediate acting insulin at bedtime (4-dose insulin). A similar improvement in glycaemic control was obtained with both insulin regimens. On treatment with oral agents the patients were found to have higher total plasma triglycerides and lower plasma high density lipoprotein (HDL) cholesterol than a matched non-diabetic control group. Insulin treatment almost completely normalized these lipid disturbances by reducing mean total plasma triglycerides with 36% and increasing plasma HDL cholesterol with 20% on 2-dose and 17% on 4-dose. The triglyceride concentration in the very low density lipoprotein (VLDL) fraction was reduced. Mean plasma low density lipoprotein (LDL)-cholesterol was not affected by any treatment. There was an increase of similar magnitude in both HDL2 and HDL3 concentrations but only the change in the HDL3 subfraction was statistically significant. Mean plasma apolipoprotein A1 concentration increased with 9% (P less than 0.05) while there was no significant change in the plasma apolipoprotein B concentration. The changes in the plasma concentrations of lipoproteins and apolipoproteins A1 and B were almost identical on 2- and 4-dose insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Efficacy, tolerance and hormonal effects of a new oral angiotensin converting enzyme inhibitor, ramipril (HOE 498), in mild to moderate primary hypertension.

The immediate (0 to 24 hours) and long-term (4 weeks) hypotensive effects of a new long-acting angiotensin converting enzyme inhibitor, ramipril (HOE 498), as well as adverse effects and tolerance, were evaluated in 34 patients with primary hypertension. Further, effects on serum and urinary aldosterone and circulating angiotensin II concentrations were measured. After short- and long-term administration of 5 or 10 mg of ramipril, the mean blood pressure was significantly lowered compared with placebo. The mean maximum decrease in blood pressure was noted 4 to 8 hours after administration of ramipril once daily. Sustained blood pressure reduction was achieved after 4 weeks of treatment. Serum concentrations of aldosterone and plasma levels of circulating angiotensin II were reduced for up to 12 hours after drug intake, and tended to return to pretreatment levels at 24 hours. Serum angiotensin converting enzyme activity was markedly suppressed for more than 24 hours after a single dose of 5 or 10 mg ramipril. No subjective or objective adverse effects were noted, and the tolerance to the drug was very good.

Administration, Oral↗