A pilot scheme for improving the accuracy of serum cholesterol measurement in Scotland and Northern Ireland.

The measurement of plasma cholesterol is subject to particularly stringent requirements of bias and imprecision because clinically important action limits lie within the bulk of the population distribution. A pilot scheme was conducted with the aim of improving the accuracy of the assay of cholesterol in 26 laboratories in Scotland and Northern Ireland. This involved the distribution of three sets of authentic human sera with varying cholesterol concentrations assigned by the reference Abell-Kendall method which was established and validated in a central laboratory. The precision (coefficient of variation) of cholesterol testing was 1.71% across all laboratories at the first distribution and this did not alter subsequently. Mean bias was initially 4.07% (median 4.14%) relative to the Abell-Kendall assigned values and this figure had fallen to 1.12% (median 0.92%) by the third distribution. We conclude that through a standardization scheme it is possible in a relatively short time to improve bias significantly and meet the criterion of < 2-3% bias required for optimum cholesterol measurement.

Plasma triglyceride and low density lipoprotein metabolism.

This study examines the relationship between plasma triglyceride and low density lipoprotein (LDL) levels by measuring the turnover of the native and 1,2 cyclohexanedione-treated lipoprotein in 25 healthy adults. Plasma triglyceride showed a strong positive correlation with circulating LDL apoprotein (apo LDL) mass. In order to achieve a satisfactory fit to the kinetic data it was necessary to postulate the existence of two plasma apo LDL pools (A and B). When subjects were grouped in quintiles on the basis of circulating apo LDL mass, pool A predominated in those in the lowest quintile. The fractional catabolic rate (FCR) of apo LDL from this pool was high (FCR = 0.57 +/- 0.06 pools day-1). As plasma triglyceride and apo LDL mass rose, apoprotein accumulated in the more slowly metabolized pool B as a result of an increase in the rate of input of apo LDL into the latter. The fractional clearance rate of protein from this pool remained unchanged at 0.26 +/- 0.04 pools day-1. Synthesis of apo LDL into pool B correlated with plasma triglyceride (r = 0.553, P less than 0.01), suggesting that the protein in this pool was derived from large, triglyceride-rich very low density lipoprotein.

Short-term changes in lipoproteins and apoproteins during cyclical oestrogen-progestogen replacement therapy.

Lipoproteins and apoproteins were measured weekly in a group of 18 post-menopausal women treated with a cyclical hormone replacement regimen comprising 28 days on conjugated equine oestrogens (0.625 mg/day) with the addition of norgestrel (0.15 mg/day) for the last 12 days of the cycle. There were no significant changes in total triglyceride, very low-density-lipoprotein (VLDL) cholesterol or high-density-lipoprotein (HDL) cholesterol levels. Low-density lipoprotein (LDL) and total cholesterol levels fell, the differences being significant after two weeks. The LDL/HDL cholesterol ratio also fell significantly over 1 week of treatment. There were no significant changes in either HDL2 or HDL3 cholesterol. The HDL2/HDL3 cholesterol ratio did, however, alter significantly, increasing during the oestrogen-only phase. Apart from this ratio, none of the parameters measured showed any significant differences as between the oestrogen-only phases and the oestrogen/norgestrel phases. There were no significant changes from baseline values in the levels of apoproteins AI, AII or B. The apoprotein AI/AII ratio was significantly increased, the levels being higher during the oestrogen phase of the cycle. There was no significant change in the apoprotein B/AI ratio. The apoprotein B/LDL cholesterol ratio showed a statistically significant increase after 4 weeks. There was no evidence of any cyclical changes. We conclude that the results of this study are generally favourable with regard to coronary heart disease risk but that the change in the apoprotein B/LDL ratio merits further investigation.

A comparison of commercial kits for the measurement of lipoprotein(a).

Five commercial kits for the assay of lipoprotein(a) were investigated and two of these, the Immuno Enzyquick and Biopool TintElize, both enzyme-linked immunoassays, were studied in detail. Whilst there was a strong correlation between the results obtained using the two methods there was a significant difference between the absolute values. In view of its higher precision at low levels and robust performance, the Enzyquick kit (Immuno Ltd) was selected for use in this laboratory.

Low-density lipoprotein metabolism in the nephrotic syndrome.

Hyperlipidemia is a consistent feature of the nephrotic syndrome. In this study, low-density lipoprotein (LDL) metabolism has been investigated in nine patients with nephrotic syndrome and varying degrees of proteinuria. In subjects with moderate proteinuria (less than 10 g/d), total plasma cholesterol values were elevated to approximately 160% of normal due mainly to an increase in circulating LDL cholesterol. Metabolic studies showed that a defect in LDL clearance via the receptor pathway was responsible for its accumulation. The total amount of LDL apolipoprotein catabolized by this mechanism was only 55% of the value seen in controls; 60% more LDL was channelled into alternative, receptor-independent, catabolic pathways. Heavier proteinuria was associated with substantial increases in plasma triglyceride and very-low-density lipoprotein (VLDL) levels. The defect in LDL catabolism was aggravated by oversynthesis of the lipoprotein, which expanded the plasma LDL pool to 250% of normal. These observations indicate that the hyperlipidemia of the nephrotic syndrome is multifactorial in origin. The altered catabolism of LDL may be important in predisposing these subjects to premature atherosclerosis.

Lipoprotein and apolipoprotein levels in postmenopausal women on continuous oestrogen/progestogen therapy.

Levels of serum lipoproteins and apolipoproteins were monitored for 48 weeks in two groups of women taking part in a double-blind trial of continuous oestrogen/progestogen with and without oestriol. There were no differences between the effects of the two treatments on the substances measured. Triglycerides did not change and there was a transient fall in very low density lipoprotein cholesterol. Low density lipoprotein cholesterol fell over the first 24 weeks but rose thereafter to pretreatment levels. There was a decrease in high density lipoprotein (HDL) cholesterol due to a transient fall in HDL2 cholesterol and a gradual decrease in HDL3 cholesterol. Consequently, the only change in lipid levels present after 48 weeks was a decrease in HDL3 cholesterol, the clinical significance of which is uncertain. There was, however, an increase in apoprotein B levels and decreases in apoprotein AI and AII levels. These alterations in apoprotein levels may be unfavourable, since apoprotein B levels have been positively correlated and apoprotein AI and AII levels negatively correlated with coronary heart disease.

Effects of conjugated equine oestrogens with and without the addition of cyclical norgestrel on serum and urine electrolytes, and the biochemical indices of bone metabolism and liver function.

Serum and urine electrolytes, and biochemical indices of bone metabolism and liver function were measured in 51 post-menopausal women treated with two hormone replacement therapy regimens for 24 wk. Twenty-six of the women were treated continuously with conjugated equine oestrogens (0.625 mg/day) and the remainder were treated as above with the addition of norgestrel (0.15 mg/day) during the last 12 days of each 28-day cycle. Both treatment regimens affected electrolytes in a similar manner. The most consistent effect was a reduction in serum sodium levels and a reduction in urinary sodium/creatinine ratios. The combined regimen appeared to have a greater effect on sodium reabsorption. Both regimens decreased all the biochemical indices of bone metabolism measured, viz serum calcium (corrected for albumin), phosphate and alkaline phosphatase and urinary calcium/creatinine and hydroxyproline/creatinine ratios. The preparations used decreased the parameters by similar amounts over the 24 wk indicating that both were equally effective in reducing bone turnover. The data suggested, however, that the combined regimen had a more profound effect on bone metabolism during the early phase of treatment. The two treatment regimens had broadly the same effects on the biochemical indices of liver function, reducing albumin levels and all the liver enzymes. Judging by these indices neither regimen had a deleterious effect on liver function. We conclude that the two hormone replacement regimens have similar effects on the biochemical indices measured, but there are subtle differences between the two treatments which merit further research.

The effects of conjugated equine estrogens plus cyclical dydrogesterone on serum lipoproteins and apoproteins in postmenopausal women.

Serum lipoprotein and apoprotein concentrations were monitored for 24 weeks in 26 postmenopausal women treated with conjugated equine estrogens (0.625 mg/day) with the addition of dydrogesterone (10 mg/day) for the last 12 days of each 28 day cycle. The women had had no previous hormone replacement therapy. The estrogen plus dydrogesterone regimen caused significant (P less than 0.05) increases in triacylglycerol and HDL cholesterol concentrations. Both HDL2 and HDL3 cholesterol were increased. There were no other significant changes in lipoprotein concentrations. Both apoprotein AI and apoprotein AII concentrations increased significantly (P less than 0.05) over the study period. The ratios of apoprotein AI to apoprotein AII, apoprotein AI to HDL cholesterol and apoprotein AII to HDL cholesterol did not change. At the doses employed in this study, the use of dydrogesterone as a progestogen alters the effects of conjugated equine estrogens on lipoproteins and reinforces the view that the effects of a combined HRT regimen cannot be predicted from a consideration of the effects of the individual components.

Changes in the bone and liver isoenzymes of alkaline phosphatase in postmenopausal women being treated with norethisterone.

The effects of norethisterone therapy on alkaline phosphatase isoenzyme activities were studied in a group of postmenopausal women. There was a significant fall in total alkaline phosphatase activity after 8 wk which was still in evidence after 24 wk. Both bone and liver alkaline phosphatase isoenzyme activities were decreased during the first 16 wk on treatment, but after 24 wk only the bone phosphatase activity was significantly lower than the pretreatment level. The other biochemical indices of bone metabolism and liver function were also measured during the study. The results indicate that bone specific alkaline phosphatase activity is a more sensitive index of bone activity than total alkaline phosphatase and that monitoring of total activity may in some instances be misleading.

A comparison of the effects of lipoproteins of two progestogens used during cyclical hormone replacement therapy.

Lipoprotein levels were measured in 11 women who had been treated with 0.625 mg/day conjugated equine oestrogens with the addition of 0.15 mg/day DL-norgestrel for the last 12 days of each 28 day cycle for 48 wk. Treatment was then changed to an identical oestrogen regimen with dydrogesterone, 10 mg/day, as progestogen and monitoring continued for a further 24 wk. The oestrogen plus norgestrel regimen caused a significant reduction in low density lipoprotein (LDL) cholesterol levels. During the 24 wk after the change of therapy, levels of high density lipoprotein (HDL) increased significantly due to an increase in the HDL2 fraction and there was an upward trend in LDL cholesterol which did not attain statistical significance. We conclude that, when used in combination with conjugated equine oestrogens, changing from norgestrel, 0.15 mg/day, to dydrogesterone, 10 mg/day, does not lead to any significant improvement in lipoprotein profile.

Lipoprotein and apoprotein levels in postmenopausal women during treatment with norethisterone.

Lipoprotein and apolipoprotein levels were monitored in 21 postmenopausal women during 6 months' treatment with norethisterone. There was no significant change in low density lipoprotein (LDL) cholesterol but apoprotein B levels rose significantly (p less than 0.001) thus increasing the apoprotein:cholesterol ratio in LDL. High density lipoprotein (HDL) cholesterol levels decreased significantly (p less than 0.001) in the first two months and did not change significantly thereafter. The HDL2 subfraction was reduced to a greater extent than the HDL3 subfraction. Apoprotein AI and AII levels were both reduced as was the apoprotein AI:AII ratio. The ratios of apoproteins AI and AII to HDL cholesterol were increased. We conclude that norethisterone has an adverse effect on the important risk factors for cardiovascular disease.

Estudio etiológico de enfermedades en vias respiratorias de niños / Etiologic study of respiratory tract diseases in children

"De Diciembre de 1982 a Marzo de 1983 fueron estudiados 401 niños menores de 6 años en la ciudad de La Ceiba, Honduras: 226 niños con síntomas de vías respiratorias y un grupo control (asintomático) de 175 niños. Se determinó la incidencia y prevalencia de diferentes tipos de virus y bacterias en la población estudiada, mediante aislamiento de antígenos y/o detección de anticuerpos séricos. Se obtuvo una incidencia de un 6l,06

de los pacientes estudiados con enfermedad respiratoria de etiología viral, ocupando el primer lugar el Virus Sincitial Respiratorio (RSV) con un 27,13

y en segundo lugar el Parainfuenza Virus (Para Flu) con un 22,19

. Otros virus fueron identificados en menor porcentaje. Se obtuvo una prevalencia de un 91,27

de pacientes con enfermedad respiratoria de etiología viral en la población estudiada. Tambiém aquí el virus más frecuentemente diagnosticado fue el RSV (70,07

). No se encontró gran diferencia en la distribución viral según nivel socio-económico ni sexo. También se detectaron anticuerpos séricos para el Mycoplasma pneumoniae en un 5,48

de los pacientes estudiados, para el Haemophilus Influenzae tipo b (H. flu b) en un 0,99

, para Chlamydiae en un 3,99

y para el Streptococcus pneumoniae 93 (Sp 93) en 1,99

de los pacientes, mostrando relativamente una mayor incidencia entre el grupo de niños en edad pre-escolar (2 a 6 años) (AU)

Estudio etiológico de enfermedades en vias respiratorias de niños / Etiologic study of respiratory tract diseases in children

"De Diciembre de 1982 a Marzo de 1983 fueron estudiados 401 niños menores de 6 años en la ciudad de La Ceiba, Honduras: 226 niños con síntomas de vías respiratorias y un grupo control (asintomático) de 175 niños. Se determinó la incidencia y prevalencia de diferentes tipos de virus y bacterias en la población estudiada, mediante aislamiento de antígenos y/o detección de anticuerpos séricos. Se obtuvo una incidencia de un 6l,06% de los pacientes estudiados con enfermedad respiratoria de etiología viral, ocupando el primer lugar el Virus Sincitial Respiratorio (RSV) con un 27,13% y en segundo lugar el Parainfuenza Virus (Para Flu) con un 22,19%. Otros virus fueron identificados en menor porcentaje. Se obtuvo una prevalencia de un 91,27% de pacientes con enfermedad respiratoria de etiología viral en la población estudiada. Tambiém aquí el virus más frecuentemente diagnosticado fue el RSV (70,07%). No se encontró gran diferencia en la distribución viral según nivel socio-económico ni sexo. También se detectaron anticuerpos séricos para el Mycoplasma pneumoniae en un 5,48% de los pacientes estudiados, para el Haemophilus Influenzae tipo b (H. flu b) en un 0,99%, para Chlamydiae en un 3,99% y para el Streptococcus pneumoniae 93 (Sp 93) en 1,99% de los pacientes, mostrando relativamente una mayor incidencia entre el grupo de niños en edad pre-escolar (2 a 6 años)