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Biomedical subjects

G M Berger

Publications and source records attributed to G M Berger.

At least 37 records · Page 2Linked to original sources
PubMed1989

Multiple mutations underlying familial hypercholesterolemia in the South African population.

Ten restriction fragment length polymorphisms of the LDL receptor gene were used for haplotype analysis in 12 unrelated patients with homozygous familial hypercholesterolemia. These patients were drawn from the Black, Coloured, and White population groups and collectively represent 24 mutant alleles underlying the FH phenotype. Five distinct haplotypes were detected. Hybridization analysis using DNA codigested with EcoRI and PstI revealed that haplotype IV was associated with two distinct mutations. When coupled to the recent demonstration by other workers of two receptor defects in South African Afrikaners homozygous for FH and haplotype I, these data are suggestive of at least seven distinct LDL receptor mutations in the FH patients examined and thus in the general South African population.

Ethnicity↗
PubMed1989

Treatment of hypercholesterolemia with the HMG CoA reductase inhibitor, simvastatin.

We report the results of a two center study on the use of the HMG Co A reductase inhibitor, simvastatin, in 44 patients suffering from familial hypercholesterolemia or from primary hypercholesterolemia of unknown etiology. The study included two separate phases: Phase I was part of a multicenter, 4-week, placebo-controlled trial; phase II was a 6-month, open extension trial, the object of which was to reduce low density lipoprotein (LDL) cholesterol levels to below the 50th percentile by increasing the dose of simvastatin, by the use of additional lipid-lowering medication, or both. Our phase I results were commensurate with those reported for the entire international cohort of 272 patients, indicating a clear dose-response relationship, with approximately 75% of the maximum reduction in LDL-C levels being achieved with 20 mg/day and over 90% of the maximum being achieved with 40 mg of simvastatin per day. In the open extension trial, the results from the 2 centers were essentially similar. Total cholesterol fell by 29% on the 20 mg/day dose and by 34% on the full dose of 40 mg/day. LDL-C levels were reduced by 40% on the 40 mg/day schedule, and triglycerides also fell to between 20% and 40% below baseline values. HDL-C concentration rose by 14% and 17.6%. The effects of simvastatin were uniform, both within and between the two cohorts. The addition of cholestyramine caused a further substantial reduction in LDL-cholesterol to below 55% of the initial value in four patients, whereas bezafibrate further enhanced the fall in triglycerides and the increase in high-density lipoprotein cholesterol, but had only a slight effect on LDL-C levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Accuracy and reproducibility of cholesterol assay in the western Cape.

The accuracy and precision of cholesterol assay in the western Cape region is reported. The survey was carried out over 15 weeks utilising three human EDTA plasma pools with normal, borderline high and high cholesterol levels respectively. All 11 laboratories in the region providing a service to academic, provincial or military hospitals or to the private medical sector were included in the study. Ten of the 11 laboratories utilised automated enzymatic methods of cholesterol assay whereas 1 used a manual procedure based on the Liebermann-Burchard reaction. Methods were standardised by means of a variety of commercial calibrator material in all except 1 laboratory which used reference sera from the Centers for Disease Control, Atlanta. The performance of the 4 best laboratories met the standard of precision recommended for cholesterol assay, viz. total coefficient of variation of less than or equal to 2.5%. However, only 2 of the 11 laboratories achieved the optimum objective of an overall bias of less than 2.0% together with precision of less than or equal to 2.5%. Rational use of cholesterol assay for diagnosis and management will therefore require standardisation of cholesterol assay on a common reference material and greater attention to analytical factors influencing the reproducibility of results. Intrinsic biological variation also contributes uncertainty to the interpretation of a single value. Thus important clinical decisions must be based on two or more assays carried out using appropriate methodology.

Cholesterol↗
PubMed1988

Action limits for serum total cholesterol. A statement for the medical profession by an ad hoc committee of the Heart Foundation of Southern Africa.

Hypercholesterolaemia is common in many segments of the South African population, both by virtue of high mean population serum total cholesterol (TC) values and of a high prevalence of familial hypercholesterolaemia (FH). Age-specific action limits for TC are proposed in order to remove the variation in 'normal values' used by different laboratories. The action limits are derived from epidemiological studies rather than purely statistical norms. They are used to designate individuals as falling into high, moderate and ideal TC ranges. The high-risk action limit has also proved to be useful for screening for FH. After an initial screening TC estimation, the further management of a patient will depend on the TC risk category and the presence or absence of other risk factors. Risk factors such as hypertension, a smoking habit, a low high-density lipoprotein cholesterol value, diabetes, evidence of existing coronary heart disease (CHD) or a family history of premature CHD multiply the risk conferred by elevated TC, and change the moderate-risk status of an individual with moderately elevated TC to a high-risk status. Intensity of investigation, treatment and follow-up depend on the overall risk status of an individual patient. Drug therapy is reserved for high-risk patients who have not responded to a reasonable trial of non-drug measures. Other reversible risk factors are treated in their own right. The guidelines embodied in this report are intended to facilitate and justify the clinical approach to individual patients with hypercholesterolaemia. They do not replace the need for a population strategy to reduce risk factors in the general population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Nutritional status, dietary intake and disease patterns in rural Hereros, Kavangos and Bushmen in South West Africa/Namibia.

A survey of Hereros, Kavangos and Bushmen living in the rural districts of South West Africa/Namibia was undertaken in order to assess their dietary intakes, nutritional status and disease patterns. The results showed that Hereros were taller and heavier, with the highest incidence of obesity (15-30%) and hypertension. Their diet consisted chiefly of refined maize meal supplemented with sour milk, and their blood lipid levels were generally lower than Western standards. The diet of Kavangos, based on homeground millet supplemented with fish and fresh vegetables, was better balanced. However, malnutrition was more common particularly in hospital patients where 40% had infective disease. Finally, the diet of Bushmen was extremely poor consisting of whatever was available (generally maize meal) and excessive use of home-brewed alcohol. The majority were malnourished and 73% of those hospitalised had tuberculosis. The blood lipid levels of Bushmen and Kavangos were exceptionally 'favourable' by Western standards but associated with chronic malnutrition. The survival of Bushmen in modern society is a matter of grave concern.

Black or African American↗
PubMed1988

A new LDL receptor gene deletion mutation in the South African population.

A previous study of the low density lipoprotein (LDL) receptor gene haplotype distribution in 12 unrelated South African patients with homozygous familial hypercholesterolaemia indicated the existence of several different receptor gene mutations in this patient pool. We have now screened these subjects for large insertion or deletion mutations at their receptor gene loci by restriction fragment size analysis using the Southern blot hybridization technique. We have detected a hitherto undescribed 2.5-kb deletion, which mapped to the central region of the gene, and most likely includes all of exons 7 and 8. The deletion was confined to two of the three so-called coloured individuals in this racially divided sample. Both probands were homozygous for the deletion with a strong possibility of consanguinity in one of the families. Mendelian inheritance was shown in both families and all carriers detected manifested elevated plasma LDL cholesterol levels. The origin of the deletion is unclear but may have been present in the indigenous Khoisan population or have been brought to South Africa by early European or Indonesian settlers.

Blotting, Southern↗
PubMed1988

Familial lipoprotein lipase deficiency: abnormal lipoproteins and defective metabolism of low density lipoproteins in cultured human skin fibroblasts.

Lipoproteins (chylomicrons + VLDL, VLDL, IDL, LDL and HDL) were separated from the plasma of 2 patients with primary, familial lipoprotein lipase deficiency. Chylomicrons were excessively enriched with cholesteryl esters. VLDL and IDL were of almost normal composition. LDL separated into 2 fractions LDL1 and LDL2, both triglyceride- and protein-rich and cholesteryl ester-poor. LDL2, the main LDL fraction, was denser and smaller than normal LDL. HDL3 was the only HDL population identified and was also triglyceride- and protein-rich and cholesteryl ester-poor. These observations indicate excessive triglyceride and cholesteryl ester transfer between chylomicrons and LDL and HDL. VLDL and its immediate catabolic product, IDL, seem to be spared the effects of the lipid transfer reaction. The biological reactivity of LDL1 and LDL2 was investigated in upregulated cultured human skin fibroblasts. Both exhibited defective specific binding to the LDL receptor and ineffective capacity to down-regulate sterol synthesis. These abnormalities were more pronounced with LDL3. The ineffective downregulation of sterol synthesis is most probably due to both the cholesterol content of the LDLs and their reduced binding to the LDL receptor. The defective binding of the LDLs to the receptor can be attributed to the abnormal composition of the lipoproteins and, to a lesser degree, reduced diameters (only LDL2). It is concluded that abnormal composition of LDL, in particular of lipid moieties, may change the affinity of the moiety of the lipoprotein towards the LDL receptor.

Adult↗
PubMed1988

Hyperlipidemia, pregnancy and pancreatitis.

Hypertriglyceridemia is a recognized complication of pregnancy. In patients with familial hypertriglyceridemia, the biochemical changes are greatly enhanced during pregnancy and may be associated with acute pancreatitis, a potentially fatal triad. Three patients were studied, in one of whom previously undiagnosed hyperlipidemia resulted in a fatal attack of fulminant acute pancreatitis. In the other two patients, this complication was avoided by close monitoring and restriction of dietary facts. A history of episodic abdominal cramps, often beginning in early childhood, or the presence of lipemic fasting plasma should alert the clinician to the presence of severe familial hypertriglyceridemia. Early diagnosis allows for the institution of relatively simple management strategies, which diminish the risk of pancreatitis.

Acute Disease↗
PubMed1987

Low-density lipoprotein-receptor gene haplotypes in Afrikaans-speaking patients with homozygous familial hypercholesterolaemia. Further evidence in support of a founder gene.

Pvu II and Stu I restriction fragment length polymorphisms of the low-density lipoprotein-receptor gene were used for receptor allele haplotype analysis in 6 unrelated white Afrikaans-speaking subjects with homozygous familial hypercholesterolaemia (FH). Five patients were homozygous for P-S+, one of four possible haplotypes, and 1 patient showed compound heterozygosity for P-S+ and P+S-. The haplotype distribution in these patients differed from the calculated distribution in the general Afrikaner population at the 5-10% level of significance. These data support the founder gene hypothesis advanced to account for the high frequency of FH in the Afrikaans population. Four non-Afrikaner homozygous FH patients, also investigated in this study, manifested a variety of haplotypes in conformity with the heterogeneity underlying FH reported by others.

Adolescent↗
PubMed1987

Association of a DNA polymorphism in the apolipoprotein C-III gene with diverse hyperlipidaemic phenotypes.

We found an increased prevalence of an Sst-1 restriction fragment length polymorphism (RFLP), localized to the apolipoprotein C-III gene, in lipid clinic patients with diverse hyperlipidaemic phenotypes. Studies on a normolipidaemic control population confirmed previous reports of differing frequencies of the RFLP in different racial groups. Reexamination of the patient data, taking into account racial composition, provided further support for an association of the Sst-1 RFLP with primary hypercholesterolaemia, type III hyperlipoproteinaemia, as well as with hypertriglyceridaemia as had previously been observed. These results suggest that the Sst-1 site is linked to a gene defect with a minor or subtle phenotypic effect which enhances the expression of a co-existent major monogenic defect of lipoprotein transport.

Apolipoprotein C-III↗
PubMed1987

Acute effects of moderate exercise on plasma lipoprotein parameters.

The acute, transient effects of moderate exercise on plasma lipoprotein parameters were assessed in 12 healthy, normolipidemic male volunteers subjected to a 5.5-km run at a comfortable pace. The course was completed in 31.5 min (range 23-43 min) and elicited a significant increase in pulse rate and plasma lactate levels and a fall in diastolic blood pressure. Of the plasma lipid parameters, total phospholipid, apo B-associated phospholipid, plasma triglyceride, and free fatty acid levels increased substantially immediately after the run and, except for triglyceride, were still raised 2 h later. Lesser but also significant increases were also noted in high-density lipoprotein-cholesterol (HDL-C), HDL3-C, and HDL-phospholipid concentrations after the run. The increase in HDL-phospholipid persisted for 2 h but the others returned to basal levels. Apolipoprotein Al, lecithin: cholesterol acyltransferase activity, total cholesterol, low-density lipoprotein-cholesterol, and the free cholesterol:cholesterol ester ratio remained essentially unaltered by exercise. The results were compatible with an increased secretion of triglyceride and phospholipid-rich VLDL, followed by the rapid clearance of the triglyceride moiety from the plasma and some redistribution of surface components to the HDL fraction.

Adult↗
PubMed1987

An incomplete form of familial lipoprotein lipase deficiency presenting with type I hyperlipoproteinemia.

The author reports the case of a patient with an incomplete form of familial lipoprotein lipase deficiency associated with type I hyperlipoproteinemia manifesting an autosomal recessive pattern of inheritance. The patient presented with hepatosplenomegaly, abdominal pain, and fasting chylomicronemia. A Western diet elicited a steep increase in plasma triglyceride concentration and the appearance of floating chylomicrons over a clear infranatant in fasting plasma. Postheparin lipoprotein lipase activity was moderately reduced to 38% of control values. Adipose tissue lipoprotein lipase activity was 10% of normal, whereas his muscle enzyme activity was within the reference range. Two-dimensional electrophoresis of plasma apolipoproteins revealed the presence of normal activator (apolipoprotein C-II). These results confirm the importance of the adipose tissue enzyme for the clearance of diet-derived plasma triglycerides.

Adipose Tissue↗
PubMed1986

A diversity of genetic hyperlipoproteinaemias in black patients. Experience at the Lipid Clinics at Groote Schuur Hospital and Red Cross War Memorial Children's Hospital, Cape Town.

The clinical and laboratory features of genetic hyperlipoproteinaemia (HLP) in 10 black patients attending the Lipid Clinics at Groote Schuur Hospital and Red Cross War Memorial Children's Hospital are reported. Five had type III HLP characterized by severe cutaneous xanthomas, which facilitated initial detection. Three adult patients suffered from heterozygous primary hypercholesterolaemia compatible with the diagnosis of familial hypercholesterolaemia (FH) caused by a low density lipoprotein receptor defect. They differed, however, from the typical presentation in lacking the Achilles tendon xanthomas characteristic of this condition. One patient presented in childhood with an unusual form of homozygous FH; the remaining patient had type V HLP. Seven of the 10 patients were male and most had risk factors for atherosclerosis in addition to the HLP. Despite the fact that the average age of the 9 adult patients is at present 52 years, only 1 has manifested overt atherosclerotic vascular disease. Compliance with therapy was variable but a generally satisfactory response was obtained in about half the patients, the reduction of plasma lipids in the type IIa subjects being disappointing. These data point to an important area for future study.

Black People↗
PubMed1986

Clearance defects in primary chylomicronemia: a study of tissue lipoprotein lipase activities.

Tissue and postheparin lipoprotein lipase (LPL) activities were assayed in a heterogeneous group of eight chylomicronemic subjects ranging in age from 15 years to 55 years. Three patients, presenting with the classical genetic and clinical features of type I hyperlipoproteinemia, had virtually absent adipose tissue LPL activity and markedly reduced muscle LPL activity (between 5% and 20% of normal). A fourth patient, with a similar but more benign lipoprotein and clinical phenotype, showed reduced adipose tissue LPL activity (10% of control) but retained essentially normal muscle enzyme. This patient represents a variant form of familial LPL deficiency. Two of the four remaining patients presented with typical features of adult type V hyperlipoproteinemia associated with familial hypertriglyceridemia (type IV and V phenotypes) in first-degree relatives. Adipose tissue LPL activities were 25% to 35% of the control mean in these patients, but muscle activities were normal or elevated. A third patient had suggestively similar tissue enzyme levels, but a family study could not be carried out. The eighth patient presented with a brittle type V phenotype, normolipidemia in the two first-degree relatives available for study and normal lipolytic activity in adipose tissue, muscle, and postheparin plasma assayed against a 14C-triolein substrate. An oral fat load in this patient, however, led to a marked but transient increase in light scattering suggesting defective clearance. Mixing experiments in vitro using a chylomicron substrate strongly suggested an extrinsic defect of lipolysis due to the inhibitory effect of excess very low density lipoprotein peptides, presumably apo C-III.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1985

Analbuminaemia. Clinical and laboratory features in a South African patient.

A 10-year-old white boy suffering from primary analbuminaemia presented with a 6-month history of ankle oedema. From infancy he had suffered from asthma and respiratory tract infections. His somatic growth was retarded but his mental and motor development was normal. The plasma albumin level was markedly reduced (81 mg/l) but a number of other plasma protein levels showed compensatory increases above the normal range. A study of the binding of unconjugated bilirubin added to the patient's plasma in vitro revealed an accumulation within the high-density lipoprotein fraction. It is suggested that the relative absence of severe illness in analbuminaemia reflects similar compensatory mechanisms afforded by the increase in non-albumin plasma protein levels and by other metabolic adjustments.

Ankle↗
PubMed1984

High-density lipoproteins, reverse cholesterol transport and atherosclerosis--recent developments.

High-density lipoproteins (HDLs) carry about 33% of the plasma cholesterol, while most of the remainder is carried by the low-density lipoprotein (LDL) fraction. The former appears to be associated with the efflux and redistribution of cholesterol present in non-hepatic tissues. In consequence, HDL is thought to play a prominent role in reverse cholesterol transport, which may be the basis for the negative association between plasma HDL levels and the prevalence of atherosclerosis within populations. Recent advances in the biochemistry of HDL and reverse cholesterol transport offer new hope of providing more powerful prognostic indices of the likelihood of premature coronary artery atherosclerosis in the individual. Currently, however, these new approaches are limited to research centres. An accurate HDL cholesterol assay, interpreted in the light of total cholesterol and particularly the atherogenic LDL fraction, is nevertheless capable of assisting in the recognition of the at-risk patient.

Adolescent↗
PubMed1984

Studies on cultured fibroblasts in a case of methylmalonic aciduria.

A case of methylmalonic aciduria is described. The clinical course was unusually mild, the child surviving to the age of 8 years. Studies on cultured fibroblasts confirmed a defect in propionate metabolism which was non-responsive to hydroxycobalamin in vitro. Polyethylene-glycol-induced cell fusion with a known methylmalonyl co-enzyme apomutase-deficient cell line showed genetic complementation indicating that in this patient the defect was in one of the enzymes required for 5-deoxyadenosyl cobalamin synthesis.

Apoenzymes↗