PubMed Health⌕ Search

Biomedical subjects

G J Tevaarwerk

Publications and source records attributed to G J Tevaarwerk.

At least 19 recordsLinked to original sources

Outcome of thyrotoxicosis treatment with 3 different modalities.

OBJECTIVE: To assess the efficacy of 3 different treatment modalities for thyrotoxicosis and a comparison of their cost effectiveness. METHODS: The case records of 100 patients treated for thyrotoxicosis at King Khalid National Guard Hospital in Jeddah were reviewed, during the period January 1992 through to January 2000. Their various treatments and responses were recorded as well as their thyriometabolic status, one year following the last treatment. The treatment consisted of an average of 9 months of antithyroid medication, thyroidectomy or treatment with radioactive iodide. Cure was defined as a patient being euthyroid or hypothyroid for a minimum period of at least one year. Cost-effectiveness was calculated as the total cost of treating the patient in a specific treatment modality, divided by those who were considered to be cured. RESULTS: For the remainder, the cost could not be definitively determined. The mean age was 41+/- 15.7 years, with female to male ratio of 6:1. Grave's disease was the underlying cause in 76% of cases, toxic multinodular goiter in 13% and toxic nodule in 1%. Ninety-one patients, who were treated with anti-thyroid medication for an average of 9 months, had a success rate of 11%. The success rate with surgery was 54.5%, while of 68 patients treated with radioactive iodide 65 (96%) were cured. Radioactive iodide was the most cost effective modality of treatment costing 1700 Saudi Riyals, followed by surgery at 40,000 Saudi Riyals. Medical treatment was the most expensive at 135,000 Saudi Riyals per cure. CONCLUSION: A treatment of thyrotoxicosis with radioactive iodine is much more efficacious than medical or surgical modalities. Furthermore, it is by far the most cost effective and has no harmful effects.

Antithyroid Agents↗

Fibroblast growth factor-2 (FGF-2) is present in maternal and cord serum, and in the mother is associated with a binding protein immunologically related to the FGF receptor-1.

Fibroblast growth factor-2 (FGF-2) is expressed in human fetal tissues and placenta. We, therefore, determined whether FGF-2 appeared in either fetal or maternal circulations during normal pregnancies [fetuses appropriate for gestational age (AGA)] or those complicated by fetal growth restriction (small for gestational age). Cordocentesis was performed, and matched maternal blood was collected between 19-39 weeks gestation, whereas maternal and cord blood and amniotic fluid (AF) were collected at term. FGF-2 was extracted from maternal serum (MS), cord serum (CS), and AF by heparin-Sepharose affinity chromatography and subjected to Western blot analysis or quantified by specific RIA. Western blot analysis of MS, CS, and AF revealed, in each case, a single immunoreactive FGF-2 species of 18 kilodaltons (kDa), although this was not present in nonpregnant serum. In AGA pregnancies, immunoreactive FGF-2 was present in MS from at least 18 weeks gestation and rose to maximum values at the end of second trimester (weeks 28-31; mean +/- SEM, 342 +/- 62 pmol/L), but by term had declined (weeks 40-42; 104 +/- 24 pmol/L). In CS, FGF-2 immunoreactivity was highest at weeks 18-20 of gestation (662 +/- 144 pmol/L), but thereafter, slowly declined to term (weeks 40-42; 119 +/- 28 pmol/L). Immunoreactive FGF-2 levels in MS and CS of small for gestational age pregnancies in the second trimester tended to be lower than those in AGA pregnancies, but differences were not statistically significant. AF also contained immunoreactive FGF-2 at term (91 +/- 35 pmol/L). Neutral gel chromatography on Sephadex G-200 revealed that FGF-2 immunoreactivity eluted as a broad peak with an apparent molecular size of 55-160 kDa. These same fractions contained peptides of 55-60, 90-95, and 120-130 kDa, which were recognized by antisera against the extracellular domain of the high affinity FGF receptor, FGFR1, after Western blot. Ligand blot analysis of the same nitrocellulose filters using 125I-labeled FGF-2 revealed that the 55- to 60-kDa species specifically bound FGF-2. This binding species was not recognized during Western blot analysis using an antiserum raised against the intracellular tyrosine kinase domain of FGFR1, suggesting that it represents a truncated receptor form. Similar FGFR1 immunoreactive species were present in nonpregnant female and male sera, but were barely detectable in term CS or AF.(ABSTRACT TRUNCATED AT 400 WORDS)

Amniotic Fluid↗

Fibroblast growth factor 2 is elevated in term maternal and cord serum and amniotic fluid in pregnancies complicated by diabetes: relationship to fetal and placental size.

We previously detected immunoreactive fibroblast growth factor 2 (FGF-2) in maternal and fetal circulations. Here, we determined whether the amounts of FGF-2 in term maternal serum, cord serum, and amniotic fluid were altered in pregnancies complicated by diabetes, as these are associated with a higher incidence of fetal macrosomia and increased placental size. Serum and amniotic fluid were collected at term from normal pregnancies (n = 17), women with pregestational insulin-dependent diabetes (n = 37; group A), patients with previously undiagnosed diabetes (n = 32; group B), women with gestational diabetes (n = 85; group C), and women with a milder form of glucose intolerance in pregnancy (n = 16; group D). Mean newborn weight and length, and placental weight did not significantly differ between normal and diabetic pregnancies, although the placental weight tended to be higher in the latter. However, 24% of the infants in group A and 19% in group B had a birth weight in excess of the 90th percentile. Levels of insulin in cord serum and amniotic fluid in groups A and B were significantly elevated compared to control values. FGF-2 was extracted from serum and amniotic fluid by heparin-Sepharose affinity chromatography and subjected to Western blot analysis or quantified by specific RIA. Western blot analysis of maternal serum, cord serum, and amniotic fluid from diabetic pregnant patients revealed, in each case, a single immunoreactive FGF-2 species of 18 kilodaltons; this was absent from nonpregnancy serum. In normal term pregnancies, the mean immunoreactive FGF-2 level in cord serum was 119 +/- 28 pmol/L, and that in amniotic fluid was 91 +/- 35 pmol/L. Values were significantly increased (2- to 4-fold) in both cord serum and amniotic fluid for all groups of diabetic patients. The mean FGF-2 level in normal term maternal serum was 104 +/- 24 pmol/L, and this was significantly increased in diabetic patients in groups B and C. The amount of FGF-2 in maternal serum showed a positive correlation with newborn weight and length, and placental weight (P < 0.05 or better, by Spearman rank correlation), and significant positive correlations also existed between the amounts of FGF-2 in cord serum and newborn or placental weight. The results suggest that the FGF-2 levels in maternal serum, cord serum, and amniotic fluid at term are elevated in pregnancies complicated by diabetes, and that the amounts of FGF-2 in maternal serum and cord serum are correlated with fetal and placental size.

Adult↗

An ocular dynamic study supporting the hypothesis that hypothyroidism is a treatable cause of secondary open-angle glaucoma.

To examine the hypothesis that glaucoma may be a manifestation of unrecognized hypothyroidism, we studied 25 consecutive patients with newly diagnosed hypothyroidism who presented to an endocrinology clinic. Using tonography and tonometry, we demonstrated a reduction in facility of outflow in the hypothyroid state. With treatment of the hypothyroidism alone there was a statistically significant improvement in facility of outflow, intraocular pressure and Po/C (p < 0.002). Our results support the hypothesis that secondary open-angle glaucoma may be a manifestation of hypothyroidism and that the glaucoma will resolve on treatment of the primary disease.

Adolescent↗

Reversal of poorly controlled glaucoma on diagnosis and treatment of hypothyroidism.

Hypothyroidism was diagnosed in a 62-year-old woman with poorly controlled primary open-angle glaucoma, including a disc hemorrhage and a documented arcuate scotoma. After 1 year of thyroxine therapy the glaucoma was easily controlled, pilocarpine treatment was stopped and the visual fields were completely normal. To our knowledge this is the first report in the modern literature of reversal of open-angle glaucoma with treatment of hypothyroidism.

Female↗

Calcium and the Fc receptor on human platelets.

We have described the calcium dependence of the IgG Fc receptor (Fc-R) on human platelets by analyzing the direct binding of radiolabelled Fc fragments, monomers and dimers of IgG. Specific binding to platelets was undetectable at 37 degrees C in a calcium-free preparation but readily detected when calcium was restored. Scatchard analysis of the binding data for the calcium-restored platelets permitted calculation of the available Fc-R and the Ka of binding for the different IgG ligands. The mean Ka of binding for 12 normal subjects varied from 10(7) to 10(8) L/M, with an equal receptor number measured by Fc fragments and dimers of IgG, but a lesser amount for monomeric IgG. There was no apparent difference in Fc-R number for platelets from 6 normal male versus 6 normal female subjects. At 4 degrees C binding was detectable for dimers and polymers of IgG in a calcium-free preparation and this was markedly increased with recalcification. Thus, our data are consistent with an Fc receptor population on human platelets whose avidity for binding is significantly enhanced in a calcium-restored medium.

Blood Platelets↗

An ultrasensitive radioligand assay for IgG using the protein A on Staphylococcus aureus bacteria.

The purpose of this study was to develop a simple and sensitive assay to measure IgG. Human IgG was radiolabelled with 125Iodine and 7.5 ng was incubated with heat-killed Staphylococcus aureus bacteria (Cowan 1 strain). To replicate sets of tubes, increasing amounts of a standard IgG preparation were added. The samples were incubated at room temperature for two hours and separated by centrifugation. Using this assay it was found that the IgG concentration could readily be determined in one nanoliter or less of human serum. There was no significant cross-reactivity with IgA, IgE and IgM or the F(ab')2 fragment of IgG. Serial dilutions of normal human or SLE sera, rabbit or guinea pig sera, the Fc fragment of human IgG and a mouse monoclonal anti-human DNA antibody parallelled the dose response curve obtained with standard human IgG. The method correlated well (r=0.89) with a routinely used nephelometric method. The mean (+/- SD) IgG concentration in 20 normal subjects measured by this assay was 10 +/- 3.6 g/L.

Humans↗

Quantification of nonenzymically glycated albumin and total serum protein by affinity chromatography.

We have evaluated an affinity-chromatographic procedure for determination of glycated albumin (GA) and glycated total serum protein (GSP). Recovery of these analytes was inversely related to free glucose concentration, thus necessitating removal of free glucose. For this we used molecular-exclusion chromatography on G-25 Sephadex, or dialysis, the latter procedure resulting in significantly (p less than 0.05) lower concentrations of GSP and GA. Total protein concentration and percent glycation are also inversely related, and so protein concentrations must be standardized before the assay. Within- and between-run CVs for both GSP and GA were less than 6.5 and 18%, respectively, the determination of GA being generally the more precise of the two. Labile glycated fractions, lipemia, icterus, hemolysis, and type of anticoagulant did not affect the results, but assay temperature did. Diabetic subjects showed substantially higher concentrations of GA and GSP than did normal subjects. Because of the life span of these analytes in circulation, their measurement may provide a short-term index of glycemic control.

Blood Glucose↗

Insulin binding to myotonic dystrophy fibroblasts.

Insulin receptor binding was examined in cultured skin fibroblasts from 10 myotonic dystrophy patients and 10 age- and sex-matched control subjects. The conditions for insulin binding to fibroblasts were optimal and employed HEPES binding buffer, pH 8.0 at 15 degrees C for 5 h. These conditions correspond to those previously employed with monocytes from MyD subjects. The normalized initial insulin binding capacity showed a decrease of 62% from 5.04 +/- 0.28% of the total labeled insulin added/mg protein in the control to 1.93 +/- 0.13% in the myotonic dystrophy group (P less than 0.01) due mainly to a marked reduction in high affinity receptors or in receptor affinity. The addition of 1.0 ng/ml of unlabeled insulin produced significant decreases to 3.80 +/- 0.25% in the control group and 1.24 +/- 0.09% in the MyD group. The results are similar to previously reported findings with monocytes from myotonic dystrophy patients and suggest that a surface membrane defect exists in this disease. However, the conditions that have been employed in the binding procedures in all of the studies, while optimal, are performed at a high pH and low temperature and could have an important bearing on the interpretation of a membrane disorder.

Adolescent↗

Evaluation of an affinity chromatographic procedure for the determination of glycosylated hemoglobin (HbA1).

An affinity chromatographic method for the determination of glycosylated hemoglobin (HbA1) was evaluated. The procedure was shown to be precise, the within- and between-assay coefficients of variation being less than 5%. It was also shown to correlate well with electrophoresis (r = 0.968) and ion-exchange chromatography (r = 0.916). An inverse relationship was shown to exist between increasing temperature and HbA1 levels measured by affinity chromatography. A statistically significant difference was found for samples run at 20 degrees C and 25 degrees C respectively, suggesting that the method should be run in a temperature-controlled environment. The affinity procedure was also shown not to be affected by the type of anticoagulant, the concentration of hemoglobin in the hemolysate, and acetylation.

Acetylation↗

Interference of fetal hemoglobin and labile glycosylated hemoglobin with measurements of glycosylated hemoglobin.

We examined the effect of fetal hemoglobin and labile glycosylated hemoglobin on a number of diverse methods used to measure glycosylated hemoglobin. Samples were supplemented with various amounts of cord blood to give proportions of fetal hemoglobin ranging from 1 to 20% of total hemoglobin concentration. Procedures in which the separation of hemoglobin A1 from the major hemoglobin A fraction is based on differences in ionic properties (cation-exchange chromatography and electrophoresis) are subject to interference by fetal hemoglobin, whereas procedures that base the quantitation on other properties (colorimetry and affinity column chromatography) are not. The same procedures that are affected by the presence of fetal hemoglobin are also subject to interference by labile glycosylated hemoglobin. We conclude that the affinity chromatographic and colorimetric methods may give a more nearly accurate determination of glycosylated hemoglobin.

Chromatography, Affinity↗

A method for maintaining normoglycemia during labour and delivery in insulin-dependent diabetic women.

The effectiveness of combining the subcutaneous administration of short- and intermediate-acting insulin with the intravenous infusion of glucose in maintaining normoglycemia during labour and delivery in insulin-dependent diabetic women was tested. Fifty women were given intermediate-acting insulin twice daily in doses that were fractions of their usual dose, based on the projected duration of labour. In addition, they were given regular (i.e., short-acting) insulin every 6 hours, the dose being 1% of their total daily insulin dose for every increase of 10 mg/dl above 100 mg/dl (5.6 mmol/l) in the plasma glucose level 1 hour previously; the levels were measured every 3 hours. All the patients were fasting and received a basal intravenous infusion of 6 g/h of glucose; the rate of infusion was increased by 1 g/h for every decrease of 10 mg/dl in the plasma glucose level below 100 mg/dl. The mean plasma glucose levels (+/- standard deviation) were 90 +/- 46 mg/dl after 3 hours of labour, 92 +/- 35 mg/dl after 6 hours, 97 +/- 49 mg/dl after 9 hours and 107 +/- 65 mg/dl after 12 hours. With only one exception, in a premature infant, the 5-minute Apgar scores were identical to those of the infants of nondiabetic women.

Apgar Score↗

Charcoal as a phase separating agent in ligand assays: mechanism of action and the effect of dextran and various proteins on the adsorption of of small molecules.

In ligand assays, charcoal mixed with dextran is sometimes used to separate free from bound ligand. This is done with the view that dextran "coats" the charcoal and produces a sieve effect on its surface. To further elucidate the mechanism of differential adsorption of small molecules to charcoal, studies were made on the interaction between a number of commonly measured ligands and charcoal, either unmixed or mixed with dextran, albumin, immunoglobulin (IgG) or insulin. "Coating" with dextran was shown not to have any effect on subsequent adsorption of the various ligands. However, coating charcoal with albumin, IgG or insulin did have an effect and even augmented subsequent adsorption of small molecules under certain conditions. It is concluded that the use of "dextran coating" of charcoal to give a sieve effect for the separation of small molecules from large ones is unnecessary and has no basis in fact. This is not the case for coating charcoal with proteins.

Animals↗

Human platelet-immune complex interaction in plasma.

The plasmas of four patients with SLE were found to contain two anti-DNA antibody populations of widely varying affinity. The addition of double-stranded DNA to the anti-DNA plasmas resulted in formation of precipitating (insoluble) and soluble immune complexes. Human platelets suspended at physiologic concentrations in the anti-DNA plasmas during the immune complex formation underwent aggregation and release that correlated positively with precipitating (insoluble) immune complex formation but not with soluble complex formation. Preformed insoluble immune complexes induced platelet aggregation and release in a significant linear fashion, and release was inhibited by increasing concentrations of soluble immune complexes or Fc-fragments. The release reaction was completely inhibited by blocking the Fc-pieces of the preformed insoluble DNA-anti-DNA immune complexes. Soluble complexes of DNA-anti-DNA and A-anti-A at equimolar IgG concentrations produced similar degrees of inhibition, which were much greater than equimolar concentrations of Fc-fragments. The ability of increasing concentrations of soluble immune complex formed at fixed antibody concentration to cause greater inhibition of platelet release suggests that occupancy of the antigen binding sites of the antibody increases its ability to block the platelet Fc-receptor. The inhibition is similar for soluble complexes of varying antigen molecular size. This is compatible with the concept that a conformational change in the antibody occurs after antigen binding and results in an increase in binding strength at the platelet Fc-receptor site. We conclude that insoluble DNA-anti-DNA immune complexes induce aggregation and release of human platelets at physiologic concentrations in plasma via the platelet Fc-receptor.

Antibodies, Antinuclear↗

Pregnancy in diabetic women: outcome with a program aimed at normoglycemia before meals.

A program designed to achieve normal plasma glucose concentrations before meals was tested in 83 insulin-dependent diabetic women during 110 pregnancies. The women rigidly controlled their carbohydrate intake but not their total energy intake, and twice daily they injected a combination of short-acting (Toronto) and intermediate-acting (NPH or Lente) insulin. Obstetric care was highly individualized and was aimed at avoiding or minimizing the impact of complications, such as hypertension, on the fetus and ensuring fetal lung maturity before delivery. The mean plasma glucose levels before meals (+/- standard error of the mean) were 136 +/- 9, 117 +/- 5 and 101 +/- 2 mg/dl during the first, second and third trimesters respectively. Obstetric complications included hypertensive disease of pregnancy (in 30.0%) and hydramnios (in 16.4%). The mean gestational age (+/- standard deviation [SD]) was 38.1 +/- 1.8 weeks, the cesarean section rate 45.4% and the mean stay in hospital for diabetes control before delivery (+/- SD) 15.7 +/- 9.6 days. The perinatal mortality rate was 0.9%. Neonatal problems included congenital anomalies in 3.6%, somatomegaly in 24.6%, hypoglycemia in 26.5%, hypocalcemia in 17.3% and hyperbilirubinemia in 39.4%. There were nine cases (8.2%) of the respiratory distress syndrome, four (3.6%) of which were severe. These findings lend support to the importance of a policy aimed at achieving normoglycemia and fetal lung maturity before delivery, goals that are attainable without lengthy antenatal hospitalization.

Adolescent↗