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Biomedical subjects

H Lithell

Publications and source records attributed to H Lithell.

At least 217 records · Page 12Linked to original sources

Plasma fat elimination tissue lipoprotein lipase activity and plasma fatty acid composition during sequential treatment with etretinate and isotretinoin.

In an attempt to elucidate the mechanisms underlying retinoid-induced hyperlipidemia, the effects of etretinate (Tigason) and isotretinoin (Roaccutane) on two different plasma fat elimination variables and on the plasma fatty acid composition were studied. Twelve patients with various hyperkeratotic disorders participated in a double-blind cross-over study of etretinate and isotretinoin. Each drug was given for 8 weeks with an 8-week intermission. On five occasions an intravenous fat tolerance test (IVFTT) was performed and the lipoprotein lipase activity (LPLA) in adipose tissue and skeletal muscle was measured. Isotretinoin significantly reduced the fat elimination rate as measured by IVFTT (p less than 0.001) and also decreased the muscle LPLA (p less than 0.05). The etretinate-induced depression of these variables was not statistically significant. The LPLA of adipose tissue and the plasma fatty acid composition were not markedly altered by any of the drugs. The observed changes are probably not sufficient to entirely explain retinoid-induced hyperlipidemia but the results strengthen the opinion that plasma lipid metabolism is more unfavourably affected by isotretinoin than etretinate.

Adipose Tissue↗

Metabolic profile in obese women with the polycystic ovary syndrome.

Nine obese women with oligo- or ameno-rrhoea, all with clinical and endocrinological signs of polycystic ovary syndrome (PCO) were submitted to metabolic studies. Their mean weight was 96 kg and their mean plasma testosterone concentration was 3.5 nmol/l. A group of nine obese, regularly menstruating women of similar age and degree of obesity (mean body weight 102 kg) served as controls. Their mean testosterone concentration was 1.9 nmol/l. The high-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I concentrations in plasma were significantly lower in women with PCO than in control women. Furthermore, in the whole group the testosterone level showed significant inverse relationships to HDL-cholesterol (r = -0.64; P less than 0.01) and apo A-I (r = -0.59; P less than 0.01). The lipoprotein lipase activity (LPLA) in adipose tissue was lower in the women with PCO than in the control group with levels similar to those found in adipose tissue in men. There was an inverse relationship between the testosterone concentration in plasma and LPLA in adipose tissue (r = -0.51; P less than 0.05). The fat cells were of similar size at different regions in the women with PCO but showed marked differences in the control subjects who had much larger cells at the femoral than the abdominal site. The results show that the hyperandrogenism in PCO affects adipose tissue LPLA which could explain the lower HDL cholesterol values in women with PCO.

Adipose Tissue↗

Hypertriglyceridemia--acute pancreatitis--ischemic heart disease. A case study in a pair of monozygotic twins.

Hyperlipoproteinemia type V, with serum triglyceride concentrations of about 20 mmol/l, was detected in a pair of monozygotic, 40-year-old twin brothers. One of them had had recurrent attacks of pancreatitis, the other not. The endocrine and exocrine pancreatic functions were apparently normal, supporting that the pancreatitis was secondary to the hypertriglyceridemia. After successful lipid-lowering therapy the attacks of abdominal pain disappeared and remained absent during a 13-year follow-up period. The other twin died of ischemic heart disease nine years after the discovery of his lipid abnormality. The reduction of his lipid levels had been much less successful. His average "atherogenic index" (the ratio of cholesterol in low density to that in high density lipoproteins) was normal but increased to a very high value if cholesterol in very low density lipoproteins was also included together with the low density ones in the numerator. Lipoprotein particles modified in composition may have contributed to an increased uptake through a scavenger pathway and promoted atherosclerosis.

Acute Disease↗

Lipoprotein composition of human suction-blister interstitial fluid.

Interstitial fluid (IF) was obtained in 27 apparently healthy subjects (12 males, 15 females) by applying mild suction (200-250 mm Hg) on the skin either on the midvolar forearm or on the paraumbilical region of the abdomen. The IF concentrations of lipids and apolipoproteins (apo) were studied and compared with those of serum (S). The mean ratio between interstitial fluid and serum (IF/S ratio) varied from 0.14 for forearm apoE to 0.29 for apoA-II on the abdomen. This ratio was consistently lower for apoE, C-II, C-III, and B than for apoA-I and A-II, and significantly lower on the arm than on the abdomen for all apolipoproteins studied. The IF/S ratios showed marked variations among individuals. However, interstitial fluid apolipoprotein concentrations at different blister sites were highly correlated within each individual. Studies with agarose gel electrophoresis and density gradient ultracentrifugation revealed that large triglyceride-rich particles were virtually lacking in interstitial fluid and that the relation between the low density lipoproteins (LDL) and high density lipoproteins (HDL) was shifted towards a greater proportion of HDL. The lipoprotein distribution in the HDL range of interstitial fluid differed from that of serum showing one maximum at a density of about 1.070 g/ml (serum HDL2 about 1.090 g/ml) and one at a density of 1.130-1.140 g/ml (serum HDL3, 1.110-1.120 g/ml). The former subfraction contained most of the lipoprotein-bound apoE while the latter contained the major part of apoA-I and apoA-II. Studies of the lipoproteins of interstitial fluid may add to our understanding of the development of atherosclerosis and xanthomatosis and may also provide valuable information on the permeability of the capillary membrane in normo- and pathophysiological states.

Adult↗

Effects of leguminous seeds in a mixed diet in non-insulin-dependent diabetic patients.

The effects of moderate addition of leguminous seeds to a mixed diabetic diet were evaluated in 15 inadequately controlled patients with non-insulin-dependent diabetes mellitus. A control diet and a diet with an increased content of peas and beans (leguminous diet) were given consecutively for a 3-week period each on a metabolic ward. Seven of the patients started with the control diet and 8 with the leguminous diet. On an energy basis the diets comprised 20% protein and 33-34% fat, the ratio between polyunsaturated and saturated fatty acids was 1.4. The analysed dietary fibre contents of the control and leguminous diets were 24 and 37 g/day per 6.7 MJ (1,600 kcal) respectively. The content of digestible carbohydrates was similar in the 2 diets. The mean body weight did not differ after the 2 dietary treatment periods. All patients showed improved glucose control during treatment irrespective of the type of diet given. The fasting blood glucose concentration on admission was 14.3 +/- 0.9 mmol/l (mean +/- SEM). This value had decreased to 9.9 +/- 0.8 during the last week of the control period and to 9.7 +/- 0.6 during the last week of the leguminous diet period. The mean postprandial glucose concentration at 3 pm was significantly lower during the leguminous diet period. The mean urine glucose excretion was significantly lower during the leguminous diet period. The fasting serum lipid concentrations decreased during treatment with each diet, but there were no significant differences between these values at the end of the 2 diet treatment periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 2↗

Serum lipoprotein in active rheumatoid arthritis and other chronic inflammatory arthritides. I. Relativity to inflammatory activity.

Lipoprotein metabolism was investigated in 69 patients with untreated active rheumatoid arthritis (n = 48) and in seronegative spondylarthropathies (n = 21). The patients had high inflammatory activity as measured by erythrocyte sedimentation rate and C-reactive protein (CRP). Serum cholesterol and cholesterol levels in the very-low-density lipoprotein (VLDL), low-density lipoprotein, and high-density lipoprotein fractions were reduced by 20% to 30% compared with healthy controls; and triglyceride levels in VLDL and high-density lipoprotein were reduced by 10% to 30%. There were significant correlations between the inflammatory activity and certain lipoprotein lipids, ie, between CRP and VLDL triglycerides, VLDL cholesterol, and serum triglycerides. The fractional elimination rate (K2) measured by an intravenous fat tolerance test was 30% higher in the patients than in the controls despite reduced tissue lipoprotein lipase activities. There was correlation between CRP and the K2 value. These findings suggest that it is the degree of inflammatory activity that governs the altered lipoprotein metabolism in untreated active chronic inflammatory arthritides. The relationships between CRP and VLDL and between CRP and K2 suggest that the VLDL particles may be altered by inflammatory process, and that the increased elimination may take place through the "scavenger pathway."

Adipose Tissue↗

Serum lipoprotein in active rheumatoid arthritis and other chronic inflammatory arthritides. II. Effects of anti-inflammatory and disease-modifying drug treatment.

Serum lipids and lipoprotein patterns were prospectively analyzed in 33 previously untreated patients with active chronic inflammatory arthritides during different anti-inflammatory and disease-modifying drug regimens. Before treatment the lipoprotein pattern was characterized by low cholesterol concentrations in all lipoprotein fractions and low triglyceride concentrations in the very-low-density lipoprotein fraction as well as in the high-density lipoprotein fraction. During treatment with prednisolone combined with azathioprine or cyclophosphamide (n = 10), a reduction of the disease activity was achieved and the lipoprotein pattern was normalized; similar results were noted in a small group of patients (n = 4) treated with prednisolone alone while nonsteroidal anti-inflammatory drug therapy (n = 9) neither significantly affected the lipoprotein pattern nor the inflammatory activity measured by the acute-phase reactants. The long-term treatment with penicillamine (n = 4) and chloroquine (n = 6) induced both a clinical remission of the disease and a reduction of the inflammatory activity. The lipoprotein concentrations started to reverse to the normal values during penicillamine treatment. In contrast, in the chloroquine-treated group the alterations in lipoprotein lipid concentrations were further pronounced, ie, the cholesterol and triglyceride concentrations in serum and the very-low-density lipoprotein fraction decreased.

Adolescent↗

Metabolic effects of a change in antihypertensive treatment.

Twenty hypertensive men, aged 58 to 62 years, who had been treated with a combination of different drugs for many years, had their therapy changed in a stepwise manner to a combination of 50 mg of atenolol per day and 2 to 15 mg of prazosin per day. The effects of each change of treatment were assessed separately five to six months after the change. Serum lipids and high-density lipoprotein concentrations were determined, and an intravenous glucose tolerance test was performed at the start of the study and after each change. In the group in which therapy was changed from a diuretic to prazosin, serum cholesterol and triglyceride concentrations decreased significantly by 11 and 42 percent, respectively, but in the group in which therapy was changed from hydralazine to prazosin, there were no alterations in serum lipids or lipoproteins. The changes in therapy had no overall effects on glucose or insulin parameters evaluated with an intravenous glucose tolerance test. However, prazosin was associated with an increase in the fasting blood glucose level and a decrease in the peak insulin value after glucose injection, both of which were dose-related effects. The data indicate that the glucose turnover was at least as good after a switch from diuretic to prazosin treatment as before at lower insulin values. In those patients in whom therapy was switched from propranolol to 50 mg of atenolol per day, the serum triglyceride concentration decreased by about 10 percent, whereas in the group in which therapy was changed from 100 to 50 mg of atenolol per day, there were no serum lipid or lipoprotein alterations. The results show that a combination of 50 mg of atenolol per day and prazosin has metabolic advantages over combined diuretic and propranolol treatment. Such advantages may be of importance in the long-term treatment of hypertensive patients.

Animals↗

A comparison of the effects of bisoprolol and atenolol on lipoprotein concentrations and blood pressure.

Forty-two patients (28 men, 14 women, age range 27-65 years) with newly discovered mild to moderate hypertension were randomly allocated to treatment with either bisoprolol or atenolol for a double-blind comparison of these two beta 1-adrenoceptor blocking drugs. Two doses of each drug (10 and 20 mg/d for bisoprolol and 50 and 100 mg/d for atenolol) were given, each dose for a 3-month period, the dose to be given first being decided by random allocation of the patients. During the second 3-month period, the patient received the alternative dose. After treatment for 6 and 12 weeks with each dose, the blood pressure, heart rate, and lipoprotein concentrations were checked. Bisoprolol treatment (both 10 and 20 mg) resulted in a decrease in blood pressure in the supine position from 154/100 to 138/89 mm Hg; and atenolol treatment resulted in decreases from 161/102 to 145/90 mm Hg (50 mg/d) and 146/91 mm Hg (100 mg/d). The drugs and doses did not differ in their effect. The triglyceride content in very low density lipoproteins (VLDL) increased during treatment with bisoprolol (10 mg/d) from 1.04 to 1.31 mmol/l (p less than 0.05); during treatment with atenolol (100 mg/d) it increased from 0.90 to 1.14 mmol/l (p less than 0.05). The cholesterol content in low density lipoproteins did not change, but that in high density lipoproteins (HDL) decreased during treatment with both drugs (from 1.22 to 1.10 mmol/l with bisoprolol 20 mg/d, p less than 0.01: and from 1.21 to 1.13 mmol/l with atenolol 100 mg/d, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Alcohol intemperance and social disability as risk factors for different causes of death.

At a follow-up 7-10 years after a health screening of 50-year-old men in Uppsala, 101 of the 2322 participants and 51 of the 446 non-participants had died. The incidence was thus almost three times as high among non-participants as among participants. Registration at the Temperance Board and/or the Bureau of Social Services was 2-3 times more common among the deceased subjects than among the living irrespective of participation in the health screening. A multiple logistic analysis revealed that non-participation and both types of registration were associated with an increased risk of death. For death from neoplasm only registration at the Bureau of Social Services, and not that at the Temperance Board, was a risk factor. For ischaemic heart disease (IHD), on the other hand, registration at the Temperance Board was the strongest risk factor, the other type of registration being secondary, and non-participation in the screening was a non-significant risk factor. The importance of alcohol intemperance as a risk factor for IHD was reflected in the fact that every second subject dying a sudden death (classified as IHD death) was registered at the Temperance Board. These results indicate that alcohol intemperance entails an increased risk of developing fatal complications to IHD, and social disability may carry with it a risk of both neoplasm and, to a lesser extent, death from IHD.

Alcohol Drinking↗

Muscle adaptations and glucose control after physical training in insulin-dependent diabetes mellitus.

Six men and three women with insulin-dependent diabetes (without complications) participated in physical training three times a week for 20 weeks. Physical training did not change the concentration of fasting blood-glucose, glucose excretion in urine or glucosylated haemoglobin (HbA1). However, the glucose disposal rate during euglycaemic clamp increased after training. In two patients a minor reduction of insulin dosage was necessary to alleviate slight hypoglycaemic episodes. The training resulted in significant increases in quadriceps isometric and dynamic strength and endurance. Maximal oxygen uptake increased by 8%, the activity of glycolytic enzymes in vastus lateralis muscle by 47% for hexokinase, and 30% for tri-osephosphate dehydrogenase and 25% for lactic dehydrogenase, the activity of oxidative enzymes by 42% for citrate synthase and 46% for 3-hydroxy-acyl-CoA-dehydrogenase. The glycogen concentration in the vastus lateralis muscle did not change significantly. Lipoprotein lipase activity did not change in muscle, nor in adipose tissue. The mean muscle fibre area increased by 25% and the area of FTa fibres by 30%. The new formation of capillaries around different muscle fibres was significant for FTb fibres (26%). The proliferation of capillaries, however, appeared to be insufficient to cope with the increased area of muscle fibres. As a result, the mean area of muscle fibre supplied by one capillary (a measure of diffusion distance) significantly increased after training for FTa fibres. It is concluded that with the exception of deficient proliferation of capillaries, patients with insulin-dependent diabetes mellitus show a normal central and peripheral adaptation to physical training. Physical training does not apparently improve blood glucose control in most cases, despite an increased insulin sensitivity.

Adaptation, Physiological↗

Effects of obesity, hyperinsulinemia, and glucose intolerance on insulin action in adipose tissue of sixty-year-old men.

The relative effects of obesity alone, and in combination with fasting hyperinsulinemia and glucose intolerance, on the peripheral action of insulin in adipose tissue were investigated in twenty-four 60-yr-old men, who had been followed for 10 yr. They were divided into four groups of six subjects each on the basis of the following criteria: (1) normal body weight, normal fasting insulin level, and normal glucose tolerance; (2) moderate obesity, normal fasting insulin level, and normal glucose tolerance; (3) moderate obesity, fasting hyperinsulinemia, and normal glucose tolerance; and (4) moderate obesity, fasting hyperinsulinemia, and newly developed, moderate, untreated fasting hyperglycemia and/or glucose intolerance (i.e., mild type II diabetes mellitus). Specific adipocyte insulin binding and the effects of the hormone on adipose tissue lipolysis and glucose oxidation were determined. Insulin receptor binding per cell and per cell surface area were similar in all four groups. Regarding antilipolysis, the insulin sensitivity was the same in all groups and the maximum effect was significantly increased in the three obese groups, as compared with the normal-weight control group. In groups 1-3, insulin stimulated adipose tissue glucose oxidation in a dose-dependent way, and the sensitivity and responsiveness to insulin were comparable. In contrast, in the obese glucose-intolerant subjects (4) there was no significant effect of insulin on glucose oxidation when the hormone was added in increasing concentrations of less than or equal to 35 nmol/L. The basal glucose oxidation was similar in all four study groups. The in vivo insulin tolerance was gradually reduced in groups 2-4, as compared with the normal-weight control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

A comparison of the hypotensive and metabolic effects of 50 and 100 mg atenolol per day.

Nine patients who had been treated for hypertension for many years with atenolol in a dose of 100 mg/day took part in this 18-month study, during which the dosage alternated between 50 and 100 mg/day for two-month periods. Blood pressure, heart rate, serum triglycerides and cholesterol and high density lipoprotein (HDL) lipids were checked at the end of each period. Altogether 27 and 32 measurements were made at the 50 and 100 mg dose levels respectively. Heart rate was lower by three beats/min (p less than 0.05) at the higher dose, but blood pressure and serum lipids and HDL cholesterol were not significantly different at the two dose levels.

Atenolol↗

Effects of long-term ketoconazole therapy on serum lipid levels.

Serum cholesterol and triglycerides were determined in 36 patients receiving an 8-month course of oral ketoconazole 200 mg/day in order to study its effect on lipid metabolism. The mean serum cholesterol concentration had decreased by 15% (p less than 0.001) after 1 month, but on continued medication it returned to the pretreatment state; after discontinuation of therapy it increased transiently by 13% (p less than 0.001). Triglycerides increased during ketoconazole administration and at the end of the trial the mean triglyceride concentration was 48% higher than the baseline value (p less than 0.02). Although most lipid values during therapy lay within the normal ranges, 6 patients developed transient hypertriglyceridaemia. There was no correlation between the changes in lipids and peak serum ketoconazole levels. In one subject studied in more detail the concentration of very low density lipoprotein triglycerides rose during therapy, whereas high density lipoprotein cholesterol decreased slightly. The lipoprotein lipase activity in muscle and, in particular, in adipose tissue was significantly suppressed during ketoconazole treatment. Serum lipids and, if possible, serum lipoproteins should be carefully monitored in patients receiving long-term oral ketoconazole therapy.

Adipose Tissue↗

Serum triglycerides are a risk factor for myocardial infarction but not for angina pectoris. Results from a 10-year follow-up of Uppsala primary preventive study.

At a follow-up 7-10 years after a health survey of men born in 1920-1924 in the municipality of Uppsala, 31 of the participants (n = 2322) had died from ischaemic heart disease (IHD). In response to a letter to all men alive in 1980, 106 men declared that they had had a myocardial infarction (MI) (verified or suspected). In 58 cases MI was verified from the hospital records. 28 other men had had typical central chest pain (angina pectoris) only. In another 20 men other diagnoses explained the chest pain for which they were treated in hospital. The health screening values for S-cholesterol and S-triglycerides, blood pressure and smoking habits were analysed in relation to the occurrence of IHD. In this prospective study, smoking, hypertension, S-cholesterol and S-triglycerides were identified as risk factors for fatal and non-fatal MI. The risk factor values were similar in subjects suffering from angina pectoris only to those in subjects who also developed ECG and/or transferase changes, with the exception of S-triglyceride concentration, which was normal in the group with angina pectoris. The subjects who had a fatal MI had a significantly higher blood pressure than those with non-fatal MIs, but otherwise these two groups did not differ. The results emphasize the importance of scrutinizing questionnaire data with regard to chest pain and of selection of end-points when risk factor patterns are described for cardiovascular diseases.

Aged↗

Effects on the serum lipoprotein concentrations by lipid-lowering diets with different fatty acid compositions.

It has been reported that lipid-lowering diets may reduce high density lipoprotein as well as low density lipoprotein cholesterol but that the reduction of the high density lipoproteins is less pronounced with diets of lower P/S ratios. The aim of the present study was therefore to investigate whether the effects on the low density lipoproteins could be maintained, but those on the high density lipoproteins diminished, by reducing the P/S ratio from 1.3 to 0.7. Fourteen hyperlipoproteinaemic patients in a metabolic ward were given two fat-modified diets during two consecutive 3-week periods in a randomized order. The diets were identical with regard to nutrient composition but differed with regard to the P/S ratios, which were 1.3 and 0.7, respectively. The average serum lipoprotein lipid composition and the apolipoprotein concentrations were similar at the end of the two periods. However, in the group of patients (n = 7) who started on the diet with P/S ratio 1.3 the low density lipoprotein cholesterol increased significantly (p less than 0.05) by 7% and the apolipoprotein B concentration by 10% (p less than 0.001) when shifting to the diet with P/S ratio 0.7. No changes of the high density lipoprotein concentrations were seen. The relative content of saturated fatty acids, of oleic acid, and of arachidonic acid in the plasma lipid esters decreased, but the content of linoleic acid increased, when shifting from the diet with a P/S ratio of 0.7 to that of 1.3.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗