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Biomedical subjects

M Silink

Publications and source records attributed to M Silink.

90 records · Page 5Linked to original sources
PubMed1979

Dicarboxylic aciduria: the response to fasting.

The urine of a child who presented with an episode of a disease resembling Reye's syndrome was found to contain large quantities of the dicarboxylic acids adipic and suberic acids, as well as the glycine conjugate of suberic acid, suberyl glycine. A variety of other dicarboxylic acids, both saturated and unsaturated, were also found in the urine at the time of the attack. It was found that the excretion of these unusual metabolites could be markedly increased by fasting for periods of greater than 10 h. These results indicate that the patient may have a defect in fatty acid oxidation which becomes clinically significant during periods of prolonged fasting.

Adipates↗
PubMed1978

Trisomy 18 in an 11 year old girl.

A case of trisomy 18, confirmed by G banded chromosome analysis, is reported in an eleven year old Australian girl. There is no cytogenetic evidence of mosaicism in the propositus or her parents. The patient's salient clinical features are severe mental and motor retardation with microcephaly, kyphoscoliosis and various congenital anomalies. She has very mild congenital heart disease. She has been totally institutionalised and has required constant medical care. Comparison of her condition with other long-term survivors with trisomy 18 reported in the literature, and also considered to be non-mosaic, reveals many similar features. However, no pattern emerges as to why these rare patients have survived.

Child↗
PubMed1975

Gamma-glutamyl hydrolase conjugase). Purification and properties of the bovine hepatic enzyme.

Bovine hepatic gamma-glutamyl hydrolase (conjugase) has been purified to homogeneity. A feature of the purification procedure was the use of high affinity macromolecular polyanion enzyme inhibitors which formed tight complexes with the enzyme altering its solubility, gel filtration, and ion exchange properties. The enzyme, which cleaves the gamma-glutamyl bonds of pteroylpolyglutamates, has a molecular weight of 108,000. It is a glycoprotein with an acid pH optimum, properties consistent with its lysosomal localization. Zinc is essential for enzyme stability. The presence of highly reactive sulfhydryl groups was evident from the extreme sensitivity to oxidizing agents and organomercurials. Very little thermal denaturation occurs below 65 degrees, but the enzyme is extremely sensitive to 0uffer anions, in keeping with the polyanionic nature of the substrate. In order to study the mechanism of action of the enzyme, a wide range of pteroylpolyglutamates, N-t-Boc polyglutamates and free polyglutamates were synthesized containing L-[U-14C]glutamic acid residues in different positions. Two pteroyltriglutamate derivatives were also synthesized in which an alpha bond replaced one of the two available gamma bonds. Time course studies of the products of the action of conjugase on these various substrates enabled us to draw the following conclusions about the enzyme: (a) peptide bond cleavage occurred only at gamma-glutamyl bonds and the presence of a COOH-terminal gamma bond was essential for enzyme action; (b) bond cleavage occurred with equal facility at internal points of the peptide chain and the enzyme should therefore be more appropriately classified as an acid hydrolase; (c) longer chain gamma-glutamyl peptides were preferentially attacked by the enzyme, the cleavage of diglutamyl peptides being extremely slow; and (d) cleavage of gamma bonds was independent of the NH2-terminal pteroyl moiety. Studies with polyanions such as the glycosaminoglycans and dextran sulfate supported the concept that the polyanion structure of the substrate was a major factor in substrate-active site interaction.

Animals↗
PubMedDate not supplied

Echocardiographic load-independent indices of contractility in children and adolescents with type I diabetes: effect of metabolic control and insulin on left ventricular performance.

A case-control study was carried out in a tertiary referral teaching hospital to evaluate left ventricular contractility in children and adolescents with type 1 diabetes and to study factors influencing left ventricular contractility. Thirty-four children and young adults with type 1 diabetes (age 10.8-21.8 years) were randomly selected from approximately 400 patients of the same age range in the outpatient department and compared with 16 non-diabetic controls (age 7.3-21.2 years). The relation of end-systolic wall stress to velocity of circumferential fiber shortening as a standard deviation score (SDS) from the normal range described by Colan et al. was used to assess left ventricular contractility. In the diabetic group the effect of age, duration of diabetes, metabolic control, insulin dose, and autonomic function on left ventricular contractility were studied. It was found that the end-systolic wall stress-velocity of circumferential fiber shortening relation was not different between diabetic subjects and controls [+0.52 (SEM 0.21) vs +0.90 (SEM 0.26) SDS, p = 0.3]. In the diabetic subjects, the end-systolic wall stress-velocity of circumferential fiber shortening relation was positively correlated with glycated hemoglobin (r = 0.37, p = 0.03) and insulin dose per kilogram of body weight (r = 0.36, p = 0.04). Those two variables together explained 24% of the variability in the end-systolic wall stress-velocity of circumferential fiber shortening relation. Twenty-eight of the diabetic subjects were also assessed for cardiac autonomic function. Disturbances of cardiac autonomic function were not associated with increased contractility.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Vascular responses by transcutaneous oximetry in adolescents with and without diabetes.

The vascular response of the skin was evaluated by transcutaneous oximetry (TcPO2) in the forearm in 119 adolescents with type I diabetes aged 10.4-19.8 (median 15.3) years, with a duration of diabetes 0.7 to 18.3 (median 7.8) years, and 49 nondiabetic adolescents aged 11.3-18.8 (median 15.5) years. Two different vascular stimuli were used: heating of the probe to 43 degrees C and 5 min of ischemia. Baseline TcPO2 after 13 min of equilibration at a probe temperature of 43 degrees C, postischemic maximum TcPO2, and the postischemic TcPO2 increase were significantly lower in the diabetic group compared to the control group (p = 0.0001, p < 0.0001, and p = 0.0001, respectively). In both the diabetic and the control groups, gender differences were found for baseline TcPO2 (p = 0.0001 and p = 0.0009, respectively) and postischemic maximum TcPO2 (p = 0.0001 and p = 0.005, respectively), the girls having consistently higher values. After controlling for gender by multiple linear regression analysis, duration of diabetes showed a significant effect on postischemic maximum TcPO2 (R2 = 22%, p = 0.02). The postischemic TcPO2 increase was not affected by gender. Lower values for the postischemic TcPO2 increase were related to higher GHb values (R2 = 4%, p = 0.03). Abnormal values for oximetry were associated only with some autonomic nerve function abnormalities. Differences in the vascular response to heat and ischemia as measured by transcutaneous oximetry can be demonstrated between adolescents with type I diabetes and nondiabetic controls, as well as between girls and boys. Lower values in diabetic subjects are weakly associated with diabetes duration and metabolic control, independent of gender.

Adolescent↗
PubMedDate not supplied

Glycosylated hemoglobin as an index of the prevalence and severity of diabetes in biethnic Fiji.

Glycosylated hemoglobin was compared with fasting blood glucose as a screening test for diabetes mellitus and as an index of the severity of diabetes in biethnic (Melanesian and Indian) Fiji. Age-adjusted diabetes prevalence in the test sample was higher in Indians by either criterion. According to the hemoglobin A1 criterion, Melanesians had prevalence rates of 8.2% (males) and 15.8% (females) compared to 17.0% (males) and 24.3% (females) in Indians. In contrast, fasting blood glucose criteria (WHO) gave higher rates in each group. Hemoglobin A1 levels were higher overall in Indians and females. The predictive value of an elevated fasting blood glucose test for an elevated hemoglobin A1 was 20.0% in Melanesians and 60.7% in Indians while that of a normal fasting blood glucose test for a normal hemoglobin A1 was 89.4% in Melanesians and 89.3% in Indians. The proportion of Indians with elevated hemoglobin A1 who were severely hyperglycemic was almost 7 times higher (40.9% vs. 5.8%) than that of Melanesians. The ethnic difference in the predictive value of fasting blood glucose levels for hemoglobin A1 levels appears to be related to the greater severity of hyperglycemia of diabetic Indians compared to diabetic Melanesians. Hemoglobin A1 levels provide information on both the qualitative as well as quantitative differences in diabetes between ethnic groups.

Adult↗
PubMedDate not supplied

Diabetes in the Melanesian and Indian peoples of Fiji: a study of risk factors.

Epidemiological risk factor patterns for diabetes mellitus determined by hemoglobin A1 and fasting blood glucose criteria were compared in the biethnic (Melanesian and Indian) nation of Fiji. The 2 diagnostic criteria elicited essentially similar risk factor patterns in Indians but ranking of predictors was altered in Melanesians. By either criterion age was a dominant risk factor for diabetes in both ethnic groups with age2 a predictor in Indians of elevated hemoglobin A1 (chi 2 = 7.8, P less than 0.005) and fasting blood glucose (chi 2 = 25.3, P less than 0.0001). Age- and sex-adjusted prevalence of diabetes was higher in Indians than in Melanesians [RR = 2.5 (1.9-3.3)]. A positive family history was associated with increased risk of diabetes in both ethnic groups by the hemoglobin A1 criterion [pooled RR = 2.3 (2.0-2.6)] but was not significant in Melanesians under the fasting blood glucose criterion. A positive family history was a strong predictor of severe hyperglycemia in both ethnic groups. The relative risk for diabetes was greater in females [1.5 (1.2-9.1)], with no ethnic difference. There was no urban-rural difference in either ethnic group. The similar risk factor patterns for diabetes diagnosed by hemoglobin A1 and severe hyperglycemia suggest that elevated hemoglobin A1 may constitute a useful screening test for 'high risk' diabetic subjects.

Adult↗
PubMedDate not supplied

Autonomic and peripheral nerve function in adolescents with and without diabetes.

In this study reference ranges were established for autonomic and peripheral nerve tests in 122 non-diabetic adolescents. Regression analysis was used to evaluate the effect of age and gender on neurological function. Increasing age was associated with: less heart rate variability during deep breathing (p = 0.03), higher thermal threshold for cold at the wrist (p = 0.009), and higher vibration threshold at the toe (p = 0.001) and medial malleolus (p = 0.01). Male gender was associated with higher Valsalva ratio (p = 0.0004), higher thermal threshold for hot at the foot (p = 0.002), and higher vibration threshold at the malleolus (p = 0.03). The REFVAL programme was used to determine parametric or non-parametric reference limits: the 5% limits for autonomic and 95% limits for peripheral tests. One hundred and eighty-one adolescents with diabetes were studied under identical conditions and similar effects of age and gender were found. Twenty-eight percent of the group with diabetes had at least one abnormal autonomic test result out of four (expected 18.5%); 24% had at least one abnormal peripheral test result out of six (expected 26.5%). Glycaemic control was associated with autonomic (p = 0.04) but not peripheral abnormalities. Using multiple regression analysis and adjusting for age and gender, there was no effect of diabetes duration or glycaemic control on neurological function.

Adolescent↗
PubMedDate not supplied

Diabetes microvascular complications in prepubertal children.

These are the baseline findings of a group of 68 prepubertal children enrolled in a longitudinal study of the development of early diabetes microvascular complications prior to gonadarche. The median age of the children was 9.8 years, the median diabetes duration 3.6 years and the mean HbA1c 8.4%. Mild nonproliferative retinopathy was present in 6 of 67 (9%) children, assessed by 7-field stereoscopic fundus photography. Those with retinopathy had higher total cholesterol (p < 0.05) and lower DHEAS (p < 0.01). Albumin excretion rate (AER) was calculated as the mean of three overnight consecutive urine collections. AER > 7.5 micrograms/min was present in 5 of 64 (8%), and one boy had a mean AER > 15 micrograms/min. Those with AER > 7.5 micrograms/min had higher diastolic blood pressure and diastolic blood pressure percentiles (p < 0.05). Longitudinal study of this cohort will establish which factors in the prepubertal years are important for the development of diabetes microvascular complications.

Albuminuria↗
PubMedDate not supplied

Large vessel dysfunction in diabetic adolescents and its relationship to small vessel complications.

Endothelial dysfunction is considered a key early event in atherosclerosis. Using a novel ultrasound method, brachial artery endothelial and smooth muscle physiology were studied in 20 adolescents with IDDM and compared to that in 20 nondiabetic subjects matched for age (13-22 years), gender and vessel size. Endothelium-dependent dilatation (EDD) was assessed in response to flow (EDD) and endothelium-independent vasodilatation after sublingual glyceryl trinitrate (GTN). Both EDD and GTN were reduced in those with IDDM compared with controls: 5% vs 9%, (p = 0.0002) and 14% vs 21% (p = 0.002). Abnormal EDD was found in 12 IDDM adolescents (diabetes duration 3.3-14.9 years). The maximum albumin excretion rate of the diabetic group was 17 micrograms/min. Four adolescents had retinopathy assessed by stereoscopic fundus photography. Three had at least one of four cardiovascular autonomic test abnormalities. There was no significant correlation observed between the test for early large vessel disease and those for diabetic microangiopathy. Large vessel dysfunction was the most common abnormality.

Adolescent↗
PubMedDate not supplied

Diabetes complication screening in 937 children and adolescents.

Results are presented of diabetes complication screening in children and adolescents aged 6-20 years. Their diabetes duration was 0.02-18.4 yr and median HbA1c over the preceding 36 months was 8.4% [IQR 7.8-9.3]. Gradable retinal photographs were obtained in 937: 110 less than 11 years (< 11 yr Gp). Albumin excretion rate (AER) was obtained from 3 timed overnight urine collections in 691: 100 in < 11 yr Gp. Early retinopathy was found in 27% (9% in < 11 yr Gp). Microalbuminuria (AER > or = 20 micrograms/min) was found in 4%. Significant individual risk factors for both complications were higher blood pressure, cholesterol, HbA1c, pubertal staging, older age and longer diabetes duration. Using multiple logistic regression, significant risk factors for retinopathy were longer duration and older age and in addition higher HbA1c. Diabetes complication screening detected early subclinical disease in children and adolescents who may benefit from lowering blood pressure and improving metabolic control. Screening should commence after five years of duration in young children, and after two years of duration in adolescents.

Adolescent↗