Experience with a provocative test of calcitonin release as a prospective screening for preclinical medullary thyroid carcinoma in MEN type 2A family members.

We report our experience with a provocative test of calcitonin (CT) release using a combined stimulus of intravenous 10% CaCl2 solution and pentagastrin on 34 normal adults (15 females: age 41 +/- 12.3 years and range 22-65 years; and 19 males: age 43 +/- 9.1 years and range 23-60 years) and in 44 family members of three proven multiple endocrine neoplasia type 2A syndrome (MEN 2A) patients. A commercial radioimmunoassay was used to determine the serum CT levels. Peak CT levels were reached within 2 to 5 minutes after administration of the stimulus in all subjects tested. In the group of normal subjects there was no significant difference in the mean basal CT levels between males (54.8 +/- 21.7 pg/ml) and females (56.5 +/- 34.8 pg/ml), whilst the mean peak response values for males was 146.3 +/- 120.6 pg/ml, which was significantly different from the mean value of females, namely 71.6 +/- 39.0 pg/ml. We did not find significant correlations between the basal CT level, peak CT response, and age. Of the 44 family members tested, 9 showed an exaggerated CT response to the combined stimulus and subsequently had a total thyroidectomy. Histological examination confirmed C-cell hyperplasia (CCH) in one and medullary thyroid carcinoma (MTC) in the other 8. Three of the 9 had high basal plasma CT levels. The 9 patients were retested postoperatively and all showed a flat response to the combined stimulus. Those family members with histological proof of MTC or CCH were screened for genetic linkage to the disease gene for MEN 2A using probe MCK2, and showed correlation in each instance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Altered vitamin B6 homeostasis during aminophylline infusion in the beagle dog

The effect of intravenous infusion of aminophylline, a strong inhibitor of pyridoxal kinase, on intra- and extracellular vitamin B6 homeostasis was investigated in four beagle dogs. Plasma and erythrocyte pyridoxal levels increased by 118% and 117% respectively after 3 hours of aminophylline infusion, (4 mg/kg body weight/hour), however, infusion of beta-hydroxyethyltheophylline, which does not inhibit pyridoxal kinase, had no effect on either intra- or extracellular vitamin B6 aldehyde derivative levels. It is suggested that theophylline induced pyridoxal kinase inhibition resulted in a disturbed equilibrium between pyridoxal and pyridoxal 5'-phosphate.     

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)     

Towards standardisation of pre- and post-analytical variables in the assessment of lipid risk factors for ischaemic heart disease

A wide disparity exists between statistical and optimal reference ranges for total cholesterol (TC) levels in South Africa. The haphazard downward adjustments by some laboratories over the years have resulted in highly variable and confusing 'normal cholesterol' values. Using essentially the same enzymatic method and equipment the TC upper limits varied by almost 50% (5.7-8.5 mmol/l) in 24 private laboratories, while it ranged from 5.7 mmol/l to 6.7 mmol/l in 6 academic hospital laboratories. The greatest disparity occurred in the lower limits of 'normal' for high-density lipoprotein cholesterol (HDLC), which ranged from 0.45 mmol/l to 1.43 mmol/l. Although triglycerides may not be an independent risk factor for ischaemic heart disease, the upper limit ranged from 1.69 mmol/l to 2.5 mmol/l despite comparable methods and equipment used. Lipid data obtained on approximately 5,000 healthy adults from the Transvaal, Natal and the Orange Free State revealed remarkable similarities to those obtained in the CORIS study. It therefore confirms the applicability of the CORIS epidemiological findings to other westernized groups in different regions of South Africa. This congruency in blood lipid values and methodologies used in different laboratories should also enable all state and private laboratories to use the same age-specific limits for desirable TC and HDLC levels.     

Evaluation of a family at risk for the multiple endocrine neoplasia type 2A (MEN 2A) syndrome.

A multidisciplinary group was formed to advise on strategy and to co-ordinate the management of a family at risk for the multiple endocrine neoplasia type 2A (MEN 2A) syndrome. A proposed strategy is outlined in which DNA analysis and provocative calcitonin testing is central.     

Biochemical reference values in elderly black subjects

Biochemical reference values for the black age group of greater than or equal to 65 years were determined from the black urban population of the Orange Free State. Biochemical investigations performed were those included in the Sequential Multiple Analyser Computer profile because it includes the 20 most requested clinical chemistry investigations. Most of the reference values corresponded to values for the same age groups in the Western world. There was no age-related rise in the alkaline phosphatase values, which suggested absence of occult Paget's disease. Reference values for serum total protein and globulin were found to be higher than values derived from elderly white groups.     

Possible mechanisms through which dietary pectin influences fibrin network architecture in hypercholesterolaemic subjects

It is suspected that not only fibrinogen concentration but also the quality of fibrin networks may contribute to cardiovascular risk. Evidence is accumulating that a “prudent” diet may protect against diseases associated with raised clotting factors. The effect of diet on fibrinogen is, however, still controversial. In a previous study performed in our laboratory, it was shown that dietary pectin influences fibrin network architecture in hypercholesterolaemic men without causing any changes in fibrinogen concentration. To elucidate the possible mechanisms, it was necessary to study the possibility that pectin may itself have indirect effects on fibrin network architecture. Pectin is fermented in the gastrointestinal tract to acetate, propionate, and butyrate. In humans, only acetate reaches the circulation beyond the liver. This investigation primarily examined the possibility that pectin may, through acetate, influence fibrin network architecture in vivo. The effects of pectin and acetate supplementation in hypercholesterolaemic subjects were compared. Furthermore, this study also aimed at describing the possible in vitro effects of acetate on fibrin network architecture. Two groups of 10 male hyperlipidaemic volunteers each received a pectin (15 g/day) or acetate (6.8 g/day) supplement for 4 weeks. Acetate supplementation did not cause a significant change in plasma fibrinogen levels. As in the pectin group, significant differences were found in the characteristics of fibrin networks developed in plasma after 4 weeks of acetate supplementation. Fibrin networks were more permeable (from 213±76 to 307±81×10¹¹ cm²), had lower tensile strength (from 23±3 to 32± 9% compaction), and were more lyseable (from 252±11 to 130±15 minutes). These results strongly suggest that the effect of pectin on network architecture could partially be mediated by acetate. Progressive amounts of acetate were used in vitro to investigate the possibility that acetate may be directly responsible for changes that occurred in fibrin network architecture in the plasma medium. Results indicated that acetate influenced fibrin network architecture directly. From the results, it seems highly possible that acetate may be responsible in part for the beneficial effects of pectin supplementation in vivo. It is evident that pectin or acetate supplementation can be useful during the treatment or prevention of some clinical manifestations, especially those associated with raised total cholesterol and possibly also plasma fibrinogen.     

Hoodia gordonii: an up-to-date review of a commercially important anti-obesity plant

Hoodia gordonii is a spiny succulent plant popularly consumed for its purported anti-obesity effect. Traditionally used by the Khoi-San of South Africa and Namibia as a hunger and thirst suppressant while on long hunting trips, the commercialisation of this plant has been highly controversial due to intellectual property rights and benefit sharing issues, as well as the fact that several prominent pharmaceutical companies involved in its development have withdrawn their interest. Quality control has been the main focus of scientific studies as the supply of H. gordonii plant material is limited due to its sparse geographical distribution, slow maturation rate, need for a permit to cultivate or export material as well as high public demand, contributing to adulteration of a large amount of products. Despite the isolation of numerous steroidal glycosides from H. gordonii, the main focus has been on the pregnane glycoside P57, considered to be the active ingredient and marker molecule to determine quality of raw material and products. Publications based on scientific studies of key aspects such as in vivo biopharmaceutics, the biological activity of all chemical constituents, clinical efficacy, and especially safety are insufficient or completely absent causing great concern as H. gordonii is one of the most widely consumed anti-obesity products of natural origin. This review offers an up-to-date overview of all the current available knowledge pertaining to H. gordonii achieved by systematic analysis of the available literature.