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Biomedical subjects

D J van Schalkwyk

Publications and source records attributed to D J van Schalkwyk.

At least 19 recordsLinked to original sources

The effect of repeated gavage doses of fumonisin B1 on the sphinganine and sphingosine levels in vervet monkeys.

Fumonisins occur widely around the world in maize products intended for human and animal consumption posing a health hazard. Direct measurement of fumonisins in physiological fluids as a biomarker of exposure is not practicable, however fumonisins disrupt sphingoid metabolism by inhibition of sphinganine N-acyltransferase. In this study the disruption in sphinganine (Sa) and sphingosine (So) levels in plasma and urine was measured in vervet monkeys (Cercopithecus aethiops) dosed with repeated gavages of 1mg fumonisin B1 (FB1)/kg body weight three times/week continuously over a 51-day period. The plasma Sa/So ratio reached a maximum (mean of 4.3) after 30 days in the dosed monkeys with a three-fold increase above the ratio of the control monkeys and then declined slowly to double the value in controls after 51 days. The lack of a clear elevation in urinary Sa/So ratios after 51 days of multiple exposure in the dosed monkeys indicates that the plasma ratio is more sensitive than urinary changes in monkeys. This is confirmed by the plasma levels of liver function enzymes of which aspartate transaminase, glutamyl-transferase and lactate dehydrogenase were increased in the dosed monkeys, while the plasma indicators of renal function were not increased above the levels in the control monkeys. Thus repeated low doses of FB1 can cause sustained disruption of sphingoid metabolism.

Animals↗

The effect of a single gavage dose of fumonisin B(2) on the sphinganine and sphingosine concentrations in vervet monkeys.

The disruption in sphinganine (Sa) and sphingosine (So) concentrations in plasma and urine of vervet monkeys (Cercopithecus aethiops) was measured following a single gavage dose of either 1 (low dose) or 10 mg (high dose) fumonisin B(2) (FB(2))/kg body weight. Blood and urine were collected over a 51-day period. In the low-dose monkeys, none of the parameters measured increased significantly above the control values. In the high-dose monkeys the plasma Sa/So ratios were significantly increased (P< 0.05) above the corresponding control ratios after 3 days and continued to be significantly raised for another 27 days, whereafter the ratios declined to control values after 51 days. The plasma aspartate transaminase (AST) activities increased significantly above their control values from day 5 to day 23 and the gamma-glutamyl transferase (GGT) activities from day 7 until the end of the study period. The plasma cholesterol concentration and alanine transaminase (ALT) and lactate dehydrogenase (LDH) activities increased transiently, but not significantly, and returned to control values within the study period. The urinary Sa/So ratio, plasma creatinine and urea values in both groups of monkeys did not increase above the control values. This study demonstrated that a single large dose of FB(2) can cause transient disruption of sphingoid metabolism in vervet monkeys.

Animals↗

Disruption of sphingolipid metabolism in non-human primates consuming diets of fumonisin-containing Fusarium moniliforme culture material.

The fumonisin mycotoxins are produced by Fusarium moniliforme Sheldon, a contaminant of corn worldwide. The two most abundant analogues (fumonisins B1 and B2) are known to be potent inhibitors of sphingosine N-acyltransferase (ceramide synthase) and hence to disrupt de novo sphingolipid biosynthesis. The sphingoid bases, sphingosine and sphinganine (and hence their ratio), were measured at varying intervals over a period of 60 weeks in the serum of non-human primates (vervet monkeys; Cercopithecus aethiops) which were consuming diets containing 'low' and 'high' amounts of F. moniliforme culture material, such that their total daily fumonisin intake was approximately 0.3 and 0.8 mg/kg body weight/day, respectively. Although no significant differences were found in the serum levels of sphingosine compared to controls, serum sphinganine levels in the experimental groups (mean of 219 nM and 325 nM, respectively) were significantly (P = 0.02) elevated above the levels in controls (mean 46 nM). As a consequence, the ratio sphinganine:sphingosine was significantly (P = 0.003) elevated from a mean of 0.43 in the control group to 1.72 and 2.57 in the experimental groups, respectively. Similar changes in sphingolipid profiles were also measured in urine with an increase of the ratio from 0.87 in controls to 1.58 and 2.17 in the experimental groups, although the differences were not statistically significant. Hence, the disruption of sphingolipid biosynthesis in vervet monkeys by fumonisins in culture material added to their diet can effectively be monitored in the serum as an elevation of the sphinganine:sphingosine ratio.

Animals↗

Cancer promoting potential of different strains of Fusarium moniliforme in a short-term cancer initiation/promotion assay.

A short-term cancer initiation/promotion bioassay was established to screen 10 toxic strains of Fusarium moniliforme for their cancer promoting activity in rats. The assay consisted of a four week 'promoting' treatment, effected by incorporating culture material (5%) of each strain into the diet, commencing one week after an initiation treatment with diethylnitrosamine (DEN, 200 mg/kg). The appearance of gamma-glutamyltranspeptidase-positive (GGT+) foci was used as an indication of promoting activity. Three out of 10 strains of F. moniliforme obtained from corn from a high risk area for esophageal cancer in Transkei, southern Africa, had significant cancer promoting activity. A highly significant correlation was found between toxicity expressed as reduction in body weight gain and cancer promoting activity. This finding suggests that the compounds responsible for the hepatotoxicity and hepatocarcinogenicity of F. moniliforme could be identical.

Animals↗

Serum ferritin and mean corpuscular volume as predictors of bone marrow iron stores.

The prognostic value of serum ferritin (SF) as a predictor of bone marrow iron stores (BMS) was evaluated in an attempt to use SF and other readily available clinical and laboratory parameters in the more accurate prediction of BMS without bone marrow aspiration. The results of routine haematological studies of 1000 patients referred for a bone marrow examination as part of their diagnostic evaluation at Tygerberg Hospital were statistically analysed. Significant associations were found. The CHAID programme of automatic interaction detection as developed by Kass was used to determine the optimum classification. A statistical model in the form of a dendrogram has been computed for this hospital population and this laboratory for future predictions of BMS using only the values for SF and mean corpuscular volume. The predictions were statistically very highly significant, especially in patients with iron deficiencies.

Anemia↗

[Small-for-age babies: etiological factors in the Cape colored population].

One hundred and thirty-one small-for-dates Cape Coloured newborns and their mothers were compared with 81 appropriately grown Cape Coloured newborns and their mothers in order to determine aetiological factors in intra-uterine growth retardation. The mothers of the small-for-dates babies differed from the control mothers in the following respects: their postpartum weight and weight for height were less, their placentas were lighter, their incomes were lower, they smoked more heavily, attended antenatal clinics less frequently, and their social conditions, educational status, dietary intake, weight gain during pregnancy and attitude towards pregnancy were inferior. Their previous babies weighed less than the previous babies of control mothers. The study mothers, however, had higher total serum protein, serum albumin and haematocrit levels, which can probably be explained by a smaller plasma volume expansion. The VDRL test on cord blood was more often positive in study babies, but the mean cord blood IgM level did not differ in study and control babies. It is concluded that socio-economic factors play a major role in the aetiology of small-for-dates babies in the Cape Coloured population. Controlled trials of dietary supplementation seem to be indicated in high-risk mothers in this population group.

Black or African American↗

Maternal nutrition and the duration of pregnancy.

Maternal weight assessed at the start of the last trimester was found to be a determinant of the duration of pregnancy in 1022 women. It is suggested that maternal nutrition influences birth weight by altering both the rate of intra-uterine growth and the gestational period.

Body Weight↗

The site of placental insertion and fetal growth.

A simple method of examining the placenta and its attached membranes after vaginal delivery was used to assess the site of placental insertion in utero. The placental site was determined in 187 term infants. Birth weight and length were not influenced by the position of the placenta, but infants with placentas situated at the fundus had significantly larger heads. Infants with low-lying placentas were at no growth disadvantage.

Birth Weight↗

Ascaris lumbricoides and the human immunogenic response: enhanced IgE-mediated reactivity to common inhaled allergens.

The relationship between the IgE-mediated immunogenic response to Ascaris and similar responses to common inhaled allergens was determined. Sixty-six of 170 allergic asthmatics from an area in which Ascaris infestation was endemic had positive skin-prick reactions to Ascaris antigen. The number and size of skin-prick reactions to common inhaled allergens were greater in this group than in the 104 Ascaris-negative allergic asthmatics. Specific serum IgE antibodies were determined by the radio-allergosorbent test. The serum IgE levels for Ascaris and three common inhaled allergens correlated well with the skin reactions induced by the same antigens. Total IgE and serum IgE antibody levels for the three inhaled allergens were higher in patients who had positive results on skin testing with Ascaris antigen than in those with negative results. There was no similar association between Dermatophagoides pteronyssinus and six common inhaled allergens. An Ascaris-induced immune response was associated with enhanced IgE-mediated reactivity to common inhaled allergens in both allergic and clinically non-allergic subjects.

Adolescent↗

Cholecystojejunocholecystostomy: a new method of biliary drainage in auxiliary liver allotransplantation.

A subhepatic, whole auxiliary liver allotransplant technique, previously developed in the pig, was assessed for technical feasibility in 26 human cadaver transplants. All technical aspects of the subhepatic technique were feasible, with the exception of donor to recipient gallbladder-to-gallbladder anastomosis, which could only be performed in 50% of subjects due to excessive separation of the two gallbladders. To oversome the problem, an original technique was developed--namely, the use of an isolated, vascularized, isoperistaltic loop of jejunum to act as a conduit between donor and recipient gallbladders (cholecystojejunocholecystostomy). Cholecystojejunocholecystostomy was subsequently developed and studied in a series of live porcine auxiliary allografts. The local, reginal, and general effects seen in 14 allografted pigs with cholecystojejunocholecystostomy were compared with those seen in a parallel and identical series of 14 allografts with cholecystocholecystostomy. The subhepatic transplantation technique is described in detail for the first time. Liver biopsies, blood samples, and clinical data were obtained at weekly intervals and at 28 days all survivors were killed. Cholecystojejunocholecystostomy proved to be a successful method of biliary drainage in the pig. Thirteen of the 14 interposed jejunal loops were viable and essentially normal at autopsy, leaks and naked eye stasis were infrequent, and the histological incidence of intrahepatic cholangitis and cholestasis minimal. The local, regional, and general effects were comparable in every way with those obtained with cholecystocholecystostomy.

Animals↗

[An epidemiological study of peripheral blood studies].

A statistical random sample of 600 patients from the population referred to Tygerberg Hospital for peripheral blood investigations was analysed statistically with an IBM 370/158 computer. Suitable transformations were used for normalization of the data. The results of Coulter Model S investigations, platelet counts (coulter F), erythrocyte sedimentation rates, differential counts (with regard to neutrophil, lymphocyte, monocyte and eosinophil counts), age, race and sex of the patients, as well as possible associations between the day of the week and the haematological tests were investigated independently for each of the four race and sex groups, i.e. White men, White women, non-White men and non-White women. Machine sorting was used to obtain graphs representing the mean values of 12 haematological variables versus age in the four race and sex groups. Regression analysis between the different variables was done, and mean values are reported. Normal haematological limits (+/- 2 standard deviations) for the different age groups were used, and with machine processing the results were evaluated as low, normal or high in order to obtain a table for the visualization of a normal or abnormal distribution, skewness to the right or left, and percentages of abnormal values for each variable for each of the different age groups in the four race and sex groups. In this study we investigated a selected group of patients. No conclusions with regard to 'normal' values can be made, but, with the use of statistical computing of routine numerical data, an approach to epidemiology is demonstrated.

Adolescent↗

Heterozygote advantage in cystic fibrosis: mosquito tests.

Tests to demonstrate a preference by mosquitoes for stinging controls as opposed to obligate heterozygotes for Cystic Fibrosis proved negative. If a heterozygote advantage caused a lower malarial incidence in carriers in South West Africa, it must have worked through the malarial parasite being adversely affected by a serum factor. This remains to be tested.

Culicidae↗

Stature and weight of Coloured primigravidas in Cape Town.

The stature and weight of Coloured primigravidas delivering at term in Cape Town were investigated. When compared with White mothers they were found to be significantly shorter, lighter and thinner. It is postulated that both childhood undernutrition and an inadequate diet during pregnancy are responsible for these findings.

Black or African American↗

Placental size at birth.

The placentas of 1,081 infants born to Coloured primigravidas in Cape Town were examined. The values for gross and trimmed placental weight, chorionic surface area and thickness are given for each week of gestation from 32 to 41 weeks. These results indicate the pattern of placental growth and provide a basis for further studies to evaluate deviations of intra-uterine growth in this population.

Anthropometry↗

After court.

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Asthma↗

Comparative contraceptive experience with three-month and six-month medroxyprogesterone acetate regimens.

Three-month (150 mg) and six-month (450 mg) contraceptive regimens of medroxyprogesterone acetate (DMPA) as an intramuscular depot injection are compared in this paper. A total of 19,875 women participated in the study, accounting for 220,530 woman-months of use. A Pearl index of 0.1069 for the three-month regimen was significantly lower than for the six-month group, where the index was 0.4943 (p less than 0.01). Side effects were limited insofar as personal reasons and loss to follow-up were the most important single category for discontinuation of this contraceptive method. No thrombotic incidents occurred. It is concluded that both contraceptive regimens of DMPA appear to be acceptable with regard to use-effectiveness, patient acceptance and prevalence of side effects.

Adolescent↗