Biomedical subjects
Publications and source records attributed to G Sigurdsson.
A nationwide survey of the incidence of clinical thyrotoxicosis in Iceland was made during the three-year period 1980-1982. An annual incidence of 23.6 per 100 000 inhabitants was found, females outnumbering males by 4.2:1; 72% of all patients were aged 20-49. Graves' disease was considered the cause in 83.3% of the patients.
A kindred of four generations with inherited elevation of serum thyroxine binding globulin (TBG) is reported. To our knowledge this is the twelfth kindred reported with this disorder. Of the 35 family members studied, 10 females and 5 males had elevated serum TBG. The patients were clinically euthyroid. The pedigree data was consistent with an X-chromosome linked mode of inheritance.
In Iceland a problem oriented medical record system for primary health care has been developed. A contact-form is used to record data on all contacts between the inhabitants in a district and the health center. A minicomputer is used for retrieval and analysis. One rural health center using this system has been successful in recording a basic set of data on all contacts taking place since 1976 and linking these data to the national register data for the population in the district. Most health centers in Iceland are now adopting this system, because it seems to be: A valuable aid in the treatment of patients, which improves the quality of the treatment. A useful source of information of the health of the population, which among other things makes possible the identification of those at special risk. A good instrument for research and teaching. A useful source of statistics on the primary care services.
The human relationship between healer and patient constitutes the basis of medical practice. It has been customary for health professionals to make a written record of their observations on the interaction. The efforts to produce better records consist of structuring them more clearly and extracting certain items of information in order to be able to index them like books in a library. The electronic computer can solve some of these problems but general practitioners have to be aware of the limitations of the computer.
The participants in a community health survey in the Reykjavik area answered the question whether a first-degree relative had had myocardial infarction (MI), hypertension (HT) or cerebral stroke. The mean total serum cholesterol level was 5-10 mg/dl higher in the group with a positive history of MI than in the negative group. The frequency of hyperlipidaemia and the levels of other risk factors measured (blood pressure and body mass index) were similar in both groups. The group with a positive family history (FH) of HT had a mean systolic blood pressure 6-8 mmHg higher and diastolic hypertension (greater than 105 mmHg) on a single measurement twice as frequently as the negative group. The mean systolic blood pressure in the group with positive FH of stroke was 8-10 mmHg higher than in the negative group. The study thus suggests that positive FH of HT or stroke among first-degree relatives is a worthy indication for blood pressure measurements, at least after the age of 40.
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The endocrine response to stress, as reflected by the plasma concentrations of ACTH and cortisol, was investigated in 14 children receiving two different premedications during halothane anaesthesia for adenoidectomy. Seven children (group A) were premedicated with diazepam 5 mg rectally and atropine 0.3-0.4 mg sublingually and seven (group B) received a rectal combination of diazepam 0.5 mg kg-1, morphine 0.15 mg kg-1 and hyoscine 0.01 mg kg-1. Before and after surgery plasma concentrations of ACTH and cortisol were lower in group B than in group A. In group A mean values for ACTH increased from 40.7 ng line-1 before adenoidectomy to 352.9 ng litre-1 (P less than 0.001) after adenoidectomy. The corresponding increase in group B was from 12.1 ng litre-1 to 82.1 ng litre-1 (P less than 0.01). In group A mean cortisol concentrations increased from 235.7 nmol litre-1 to 655.7 nmol litre-1 after adenoidectomy (P less than 0.01) and in group B from 121.4 nmol litre-1 to 427.9 nmol litre-1 (P less than 0.01). End-tidal carbon dioxide tension was approximately the same in both groups. It was concluded that the combination of diazepam, morphine and hyoscine decreased the endocrine response to stress.
1. The mass of the extravascular pool of low-density lipoprotein (LDL) in liver was measured in rats injected intravenously with radioiodinated LDL by determining the radioactive iodine remaining in the extravascular tissues of liver and in plasma when the hepatic intravascular and extravascular radioactive iodine had equilibrated (equilibrium-time method). 2. The mass of the extravascular pool of LDL in the liver was about 6% of the total intravascular pool. Total extravascular pool of LDL in eight rats, obtained by multicompartmental analysis of the time-curve of disappearance of radioiodinated LDL from blood plasma, was 43 +/- 15% (mean +/- SD) of the intravascular pool. 3. Hence the hepatic extravascular pool comprises only about 14% of the total extravascular pool of LDL in the rat.
A number of 2203 middle-aged Icelandic men (aged 34-61 years) participated in a health survey in Reykjavik in 1967-68. Blood glucose in the fasting state and during an oral glucose tolerance test (OGTT) showed a unimodal distribution with a slight skewness towards higher values. A positive age gradient was established, which showed an increment of about 7 mg/dl per decade in capillary blood sugar values at 11/2 hours after a 50 g oral glucose load. The age gradient was mostly independent of age-related changes in body weight. A 71/2 year followup of the eligible participants (response rate 80%) showed an overall 1% incidence of metabolic deterioration to "overt diabetes" during this period. Those with positive screening tests (50 g OFTT) at baseline were at greater risk of developing diabetes, but the incidence of deterioration in this group was low, about 1% per year. The progression to diabetes was significantly related to body weight at baseline, suggesting that weight reduction might be beneficial in individuals showing impaired glucose tolerance at medical examination. This study, however, lends support to recent reports showing that mildly impaired glucose tolerance cannot be equated with early diabetes.
Isolated rat livers were perfused for four hours in a recirculating system containing washed rat erythrocytes. Biologically screened radioiodinated rat high density lipoproteins (1.090 < d < 1.21 g/ml) were added to the perfusate with different amounts of whole serum to supply unlabeled rat high density lipoproteins. The protein moiety of the lipoprotein contained more than 95% of the radioiodine. The fraction of apolipoprotein mass degraded during the perfusion was quantified by the linear increment of non-protein-bound radioiodine in the perfusate, corrected for the increment observed during recirculation of the perfusate in the absence of a liver. The small amount of (131)I secreted into bile was added to calculate the fractional catabolic rate. The fractional catabolic rate ranged from 0.22 to 0.63% per hour in 12 experiments and was inversely related to the size of the perfusate pool of high density apolipoprotein. The absolute catabolic rate of high density apolipoprotein (fractional catabolic rate x pool size) in three livers in which the concentration of rat HDL in the perfusate approximated that in intact rats was 69.5 +/- 10.4 micro g hr(-1) (mean +/- SD). The rate of disappearance of cholesteryl esters of rat high density lipoproteins (labeled biologically by injecting donor rats with [5-(3)H]mevalonic acid) from the liver perfusate did not exceed that of the apoprotein component. These rates were compared with catabolic rates for rat high density lipoproteins in intact rats. Fractional catabolic rate in vivo, obtained by multicompartmental analysis of the disappearance curve of (131)I-high density apolipoprotein from blood plasma, was 11.9 +/- 1.3% hr(-1) (mean +/- SD). Total catabolic rate in vivo (fractional catabolic rate x intravascular pool of high density apolipoprotein) was 986 +/- 145 micro g hr(-1) (mean +/- SD). The results suggest that only a small fraction of high density lipoproteins in blood plasma of rats is degraded directly by the liver.-Sigurdsson, G., S-P. Noel, and R. J. Havel. Quantification of the hepatic contribution to the catabolism of high density lipoproteins in rats.
Serum lipid and lipoprotein concentrations have been measured in 985 men and women sampled from communities in London, Naples, Uppsala and Geneva. This was done to define normal ranges, detect inter-population differences, and relate such differences to levels of lipids in the major lipoprotein classes of plasma. Cholesterol and triglyceride concentrations showed substantial differences between the four populations; levels of these lipids showed parallel trends, which were attributable to differences in low density lipoprotein and very low density lipoprotein concentrations. By contrast, high density lipoprotein cholesterol concentrations showed little or no interpopulation differences. Geographical differences in serum triglyceride and cholesterol levels were not correlated with variation in the prevalence of obesity.
Isolated rat livers were perfused for 4 hours in a recirculating system containing washed rat erythrocytes. Biologically screened, radioiodinated low density lipoproteins (1.030 < d < 1.055 g/ml) were added to the perfusate with different amounts of whole serum to supply unlabeled rat low density lipoproteins. Apolipoprotein B contained 90% of the bound (131)I, other apolipoproteins contained 4%, and lipids contained the remainder. The fraction of apolipoprotein mass degraded during the perfusion was quantified by the linear increment of non-protein-bound radioiodine in the perfusate, corrected for the increment observed during recirculation of the perfusate in the absence of a liver. The fractional catabolic rate ranged from 0.3 to 1.7%/hr in seven experiments and was inversely related to the size of perfusate pool of low density apolipoprotein. The catabolic rate of low density apolipoprotein (fractional catabolic rate x pool size) in four livers, in which the concentration of rat low density lipoproteins was 50-100% of that present in intact rats, was 5.3 +/- 2.7 micro g hr(-1) (mean +/- SD). Similar results were obtained with human low density lipoproteins. These rates were compared with catabolic rates for the apoprotein of rat low density lipoproteins in intact animals. Fractional catabolic rate in vivo, obtained by multi-compartmental analysis of the disappearance curve of (131)I-labeled low density apolipoprotein from blood plasma, was 15.2 +/- 3.1% hr(-1) (mean +/- SD). Total catabolic rate in vivo (fractional catabolic rate x intravascular pool of low density apolipoprotein) was 76 +/- 14 micro g hr(-1) (mean +/- SD). The results suggest that only a small fraction of low density apolipoprotein mass in rats is degraded by the liver.
The intravenous fat tolerance test (IVFTT) has been introduced as a measure of the fractional catabolic rate of the endogenous triglyceride of plasma. To assess the validity of this test we have compared this test in 21 normal and hyperlipidaemic subjects with direct measurement of the fractional catabolic rate of autologous radio-iodinated VLDL. There was a strong positive correlation between the rate constant K2 of the IVFTT and the fractional catabolic rate of VLDL-apolipoprotein B (r=+0.87). The two rates were considerably different in magnitude. The IVFTT appears to be a valid index of the fractional catabolic rate of VLDL. Its limitations and uses are discussed.
The metabolism of the apoprotein of low-density apoliporprotein-B was studied in a father and son with familial hypobetalipoproteinemia. The synthetic rate of apolipoprotein-B was below the normal range in both subjects, while the fractional removal rate was normal. It is concluded that the subnormal concentration of low-density lipoprotein (LDL) inthese two subjects is due to a low synthetic rate. The synthetic rate of apolipoprotein-B of very low-density lipoprotein (BLDL-apoB) measured in the father was subnormal. The fraction of the VLDL-apoB pool which was oncverted into LDL-apoB was within the normal range. It is suggested that a low synthetic rate of VLDL may underlie the disorder.
In studies of calcium metabolism in 13 unselected patients with untreated sarcoidosis all were normocalcaemic but five had hypercalcuria. All had normal renal function. Calcium absorption was indexed by a double isotope test. 45Ca hyperabsorption occurred in six patients. Ten kinetic studies were carried out with 47Ca and in six bone turnover was increased. 45Ca absorption correlated well with the calculated bone uptake rate of calcium, and with urine calcium excretion. These results suggest that in sarcoidosis abnormalities in calcium metabolism are fairly common although they rarely result in sustained hypercalcaemia.
The metabolism of low density lipoprotein (LDL) was studied in eighteen hypertriglyceridaemic patients by injecting autologous radioiodinated LDL. Over 95% of the label was bound to the protein moiety of LDL and therefore the metabolic data reflect the fate and distribution of LDL apoprotein (apo B). The hypertriglyceridaemic subjects included ten with Type V, five with Type IV, two with Type III and one with Type IIb hyperlipoproteinaemia. For comparison identical studies were carried out in seven normal subjects and five patients with heterozygous familial hyperbetalipoproteinaemia (Type IIa). The groups differed considerably in mean LDL-cholesterol concentration. The patients with Type V lipoprotein pattern had significantly lower LDL-cholesterol concentration (mean 0.754 g/1) than the normal group (mean 1.237 g/1). Raised LDL-cholesterol levels were observed in all patients with heterozygous familial hyperbetalipoproteinaemia. The synthetic rate of LDL-apoprotein was found to be similar in all three groups (hypertriglyceridaemic, normal and hypercholesterolaemic). The highest synthetic rate was observed in the patient with Type IIb pattern. However, the fractional catabolic rate (FCR) of LDL-apoprotein differed significantly. The highest mean FCR was found in the Type V group (0.65 +/- 0.17 day-1) compared with 0.41 +/- 0.09 day-1 in the normal group and 0.185 +/- 0.05 day-1 in the Type IIa group. A strong inverse correlation was found between FCR and LDL apoprotein concentration in the whole series (r = -0.90, p less than 0.001) as well as within the Type V group (r = -0.87, p less than 0.01). These data indicate that the low plasma levels of LDL frequently observed in patients with very high plasma triglyceride levels are due to a high removal rate of LDL in these patients rather than to abnormal LDL synthesis.
The metabolism of very low density lipoprotein-B (VLDL-B) peptide was studied in nineteen subjects with endogenous hypertriglyceridaemia (Types V, IV and IIb), three patients with heterozygous familial hyperbetalipoproteinaemia (Type IIa) and eight healthy subjects, by reinjecting autologous radioiodinated VLDL. The kinetics of VLDL-B peptide were followed. The mean turnover rate of VLDL-B peptide was significantly higher in the hypertriglyceridaemic group than in the control group but a considerable overlap in turnover rate was found between these groups. The patients with heterozygous familial hyperbetalipoproteinaemia had a normal turnover rate of VLDL-B peptide. A significant positive correlation was found between the turnover rate of VLDL-B peptide and VLDL-triglyceride concentration in the whole series. It is concluded that the underlying defect in endogenous hypertriglyceridaemia is heterogeneous. Overproduction of VLDL is a major determining factor in some patients whereas a reduced clearance is the determining factor in others.
1. The intravenous fat-tolerance test and serum lipid and lipoprotein measurements were carried out in ninety-three normal subjects, fifty-one patients with ischaemic heart disease and thirty patients with peripheral vascular disease. 2. The fractional turnover rate of exogenous triglyceride was significantly slower in patients with ischaemic heart disease and in patients with peripheral vascular disease than in normal men. The rate was also slower in normal men than normal women. 3. Serum triglyceride and cholesterol concentrations were higher in both vascular disease groups than in control subjects. 4. The proportion of both groups of patients who had a subnormal fractional turnover rate of exogenous triglyceride was 35%, and 32% of patients had hypertriglyceridaemia in the fasting state; 27% of patients were hypercholesterolaemic. 5. Although the intravenous fat-tolerance test did not provide significantly better discrimination between cardiovascular patients and control subjects than did measurement of serum triglyceride, the results suggest that hypertriglyceridaemia in such patients may be separable into a group in which impaired triglyceride clearance may be partly responsible, and a group in which overproduction of serum triglyceride may be the major mechanism of the hyperlipidaemia.