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Biomedical subjects

G Bos

Publications and source records attributed to G Bos.

At least 19 recordsLinked to original sources

Dietary polyunsaturated fat intake is associated with low-density lipoprotein size, but not with susceptibility to oxidation in subjects with impaired glucose metabolism and type II diabetes: the Hoorn study.

OBJECTIVE: A high monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) intake is associated with lower plasma low-density lipoprotein (LDL)-cholesterol. However, PUFA may increase the susceptibility of LDL to undergo oxidative modifications. The aim of this study was to analyze the association of habitual dietary fat intake with LDL size and oxidizability. DESIGN: Cross-sectional. SETTING: Cohort study. SUBJECTS: Seven hundred and fifty-eight subjects with normal, impaired glucose metabolism and type II diabetes. INTERVENTIONS: Mean LDL size was measured by high-performance gel-filtration chromatography. In vitro oxidizability of LDL was determined by measuring lag time, reflecting the resistance of LDL to copper-induced oxidation. Information about dietary fat intake was obtained by a validated food frequency questionnaire. RESULTS: PUFA intake (energy percent) was significantly and negatively associated with LDL size in subjects with type II diabetes (standardized beta (95% confidence interval) -0.17 (-0.28;-0.06)) and impaired glucose metabolism - although not statistically significant - (-0.09 (-0.24;0.05)), but not in subjects with normal glucose metabolism (0.01 (-0.10;0.12)) (P-value for interaction=0.02). No significant associations were observed for total, saturated fat and MUFA intake with LDL size. Intake of fat was associated with lag time; however, the small magnitude of the associations suggested that the composition of dietary fat is not a major factor affecting lag time. The same association with lag time was observed in all three glucose metabolism categories. CONCLUSIONS: In individuals with abnormal glucose metabolism, higher PUFA intake is associated with smaller LDL particle size, but does not alter the susceptibility of LDL to in vitro oxidation. SPONSORSHIP: Dutch Diabetes Research Foundation, and the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO).

Aged↗

Heart and muscle involvement by extra-medullary myeloid leukemia: a case report and review of the literature.

Extra-medullary myeloid tumours (EMT) have been described after curative treatment for acute myeloid leukaemia (AML) in increasing numbers after allogeneic stem cell transplantation. The sites of manifestations are ubiquitous and the discovery is most frequently guided by symptoms reported by the patient or by findings on clinical examination. This study reports a case of EMT in muscles and the heart 1.5 years after allogeneic transplantation for an AML with t(8;21)(q22;23) who achieved a complete remission by use of an idarubicine-based combination chemotherapy. Pathological and imaging findings are presented and treatment options are discussed.

Adult↗

A combination of high concentrations of serum triglyceride and non-high-density-lipoprotein-cholesterol is a risk factor for cardiovascular disease in subjects with abnormal glucose metabolism--The Hoorn Study.

AIMS/HYPOTHESIS: Type 2 diabetes is not only associated with hyperglycaemia, but also with disorders of lipid metabolism. The aim of this study was to investigate the association of triglyceride and non-HDL-cholesterol concentrations with cardiovascular disease in subjects with normal and abnormal glucose metabolism. METHODS: Subjects were 869 men and 948 women aged 50 to 75 who participated in the Hoorn Study, a population-based cohort study that started in 1989. Glucose metabolism was determined by a 75 g OGTT. High fasting triglyceride and non-HDL-cholesterol concentrations were defined as above the median of the study population. RESULTS: After 10 years of follow-up, the age- and sex-adjusted hazard ratios for cardiovascular disease were 1.35 (1.11-1.64) and 1.71 (1.40-2.08) for high triglycerides and high non-HDL-cholesterol, respectively, after mutual adjustment. After stratification for glucose metabolism status, the hazard ratios for cardiovascular disease for non-HDL-cholesterol were 1.70 (1.31-2.21) in normal glucose metabolism and 1.56 (1.12-2.18) in abnormal glucose metabolism. Triglycerides were not a risk factor in subjects with normal glucose metabolism, with a hazard ratio of 0.94 (0.73-1.22), but in subjects with abnormal glucose metabolism, the hazard ratio for cardiovascular disease was 1.54 (1.07-2.22). In subjects with abnormal glucose metabolism, the hazard ratio for the combined presence of high triglycerides and non-HDL-cholesterol was 2.12 (1.35-3.34). CONCLUSION: Our data suggest that in people with abnormal glucose metabolism, but not in those with normal glucose metabolism, high triglyceride concentration could be associated with the risk of cardiovascular disease, particularly in people with high non-HDL-cholesterol.

Blood Glucose↗

Hyperhomocysteinaemia is associated with coronary events in type 2 diabetes.

OBJECTIVES: Amongst nondiabetic individuals, a high serum homocysteine concentration is an independent but relatively weak risk factor for coronary events. However, it is not known whether homocysteine increases risk of coronary events in type 2 diabetes. Therefore, we examined the combined effect of homocysteine and type 2 diabetes on risk of fatal and nonfatal coronary events. SUBJECTS: We assessed the 10-year risk of coronary events associated with homocysteine amongst diabetic (n = 140) and nondiabetic (n = 361) individuals. DESIGN: We did this in the Hoorn Study, a population-based study of glucose tolerance and related complications in Caucasian men and women aged 50-75 years. RESULTS: The incidence rate for coronary events was 2.63 (29 of 140) per 100 person-years amongst diabetic and 1.29 (42 of 361) amongst nondiabetic individuals. Amongst diabetic individuals, risk of coronary events increased 28% for each 5-micromol L(-1) increment of homocysteine (hazard ratio, 1.28; 95% CI, 1.02-1.58). This risk was independent of age, sex, hypertension, total cholesterol, HDL-cholesterol, cigarette smoking, body mass index and glomerular filtration rate. In nondiabetic participants, homocysteine was not associated with an increased risk of coronary events (hazard ratio for each 5-micromol L(-1) increment of homocysteine, 0.86; 0.52-1.41). CONCLUSIONS: These data suggest that homocysteine is significantly associated with coronary events in individuals with type 2 diabetes, independent of traditional cardiovascular risk factors. Investigation of the effect of treatment with vitamin B on prognosis of individuals with type 2 diabetes is warranted.

Aged↗

Associations of LDL size with in vitro oxidizability and plasma levels of in vivo oxidized LDL in Type 2 diabetic patients.

AIMS: Oxidative modification of low-density lipoprotein (LDL) is believed to be a key step in the genesis of atherosclerotic lesions. The presence of small, dense LDL is associated with accelerated atherosclerosis and is common in diabetic patients. The aim of this study was to investigate the relationship of in vitro LDL oxidizability and circulating in vivo oxidized LDL with LDL particle size in Type 2 diabetic patients and healthy control subjects. SUBJECTS AND METHODS: The study group consisted of 58 elderly well controlled Type 2 diabetic patients and 58 control subjects with normal glucose metabolism. LDL particle size was measured by high-performance gel-filtration chromatography. In vitro oxidizability of LDL was measured by monitoring conjugated diene formation and plasma levels of circulating oxidized LDL were determined by ELISA. RESULTS: In vitro susceptibility of LDL to oxidation was not related to plasma levels of in vivo oxidized LDL, nor to LDL particle size. In the diabetic patients, but not in the control group, an inverse relation between LDL size and in vivo oxidized LDL was observed (r=-0.35, P=0.007). This relation was strengthened after controlling for LDL-cholesterol concentration (r=-0.52, P<0.001). CONCLUSIONS: In agreement with the view that small, dense LDL accelerates atherosclerosis, an inverse relationship was observed between LDL size and circulating in vivo oxidized LDL in Type 2 diabetic patients. Our results also suggest that in vitro susceptibility to oxidation is not a suitable surrogate measure for in vivo LDL oxidation.

Aged↗

Bisphosphonates in multiple myeloma.

BACKGROUND: Multiple myeloma is a disease characterized by the neoplastic proliferation of a clone of plasma cells that can lead to bone destruction. Bisphosphonates are specific inhibitors of osteoclastic activity. Therefore, there is a pharmacological basis for their use in multiple myeloma. However, the exact clinical role of bisphosphonates in multiple myeloma remains unclear. OBJECTIVES: Primary: to determine whether adding bisphosphonates to standard therapy in multiple myeloma decreases skeletal-related morbidity (pathological fractures), skeletal-related mortality and overall mortality. Secondary: to determine the effects of bisphosphonates on pain, quality of life and incidence of hypercalcemia. SEARCH STRATEGY: We searched MEDLINE (1966 - June 2001), LILACS (1982 - June 2001), EMBASE (1974 - December 2000) and the Cochrane Controlled Trials Register (all years, latest Issue 03/2001) to identify all randomized trials in multiple myeloma. All of these references were accessed in order to identify trials related to the use of bisphosphonates in myeloma. All relevant references in each article were also scanned. We also performed a handsearch of relevant meeting proceedings from 1993 to 2000. Additionally, manufacturers of bisphosphonates and researchers in the field were contacted. SELECTION CRITERIA: Randomised trials with a parallel design on the use of bisphosphonate in myeloma compared with placebo or no treatment as a control group. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility, methodological quality and abstracted data. A third reviewer checked all data after the extraction was completed. Statistical heterogeneity was tested using random and fixed effect models. All pooled data are reported using Peto odds ratios and, when appropriate, as absolute risk reduction and the number needed to treat to prevent or to cause a pathological event. MAIN RESULTS: Eleven trials were included with 1113 patients analysed in bisphosphonates groups, and 1070 analysed in control groups. There was no significant statistical heterogeneity among trials for the endpoints selected for comparison in this review. The pooled analysis of the published evidence demonstrated the beneficial effect of bisphosphonates on prevention of pathological vertebral fractures [OR=0.59 (95% confidence interval (CI) 0.45-0.78); P=0.0001] and on amelioration of pain [OR = 0.59 (95%CI 0.46-0.76); P=0.00005]. However, the analysis of the effect of bisphosphonates on pain was based on clinically heterogeneous data and must be interpreted with caution. Although there was no statistical heterogeneity between groups, the benefit was most apparent with clodronate and pamidronate. In absolute terms, the result may be interpreted to mean that 10 (95%CI 7-20) patients with multiple myeloma should be treated to prevent one vertebral fracture, and 11 (95%CI 7-28) to prevent one patient experiencing pain. We found no significant effect of bisphosphonates on mortality, on the reduction of non-vertebral fractures or on the incidence of hypercalcemia. There were no significant adverse effects associated with the administration of bisphosphonates. Our results are based on the extraction of published data, which were sometimes poorly reported, and thus the results should be understood as the best possible summation of available evidence. REVIEWER'S CONCLUSIONS: Adding bisphosphonates to the treatment of myeloma reduces pathological vertebral fractures and pain but - from the published evidence - not mortality. On current evidence, clodronate or pamidronate may be the preferred agents.

Bone Diseases↗

In vivo demonstration of microvascular pathology by intravital microscopy in experimental chronic graft-versus-host disease: analogy with scleroderma.

Experimental models of chronic graft-versus-host disease have been advocated for studying the pathogenesis of scleroderma. However, microvascular abnormalities have not been documented in these models, whereas in man, cutaneous microvascular pathology (demonstrable by intravital microscopy) is a common feature of scleroderma. In our study scleroderma-like skin disease was evoked by allogeneic bone marrow transplantation in rats. Intravital microscopy of the skin of these animals showed strongly dilated capillaries, resembling the dilated loops in patients. This finding demonstrates that chronic graft-versus-host (scleroderma-like) disease may be pertinent to study the pathogenesis of microvascular injury in scleroderma.

Animals↗

Cellular and humoral immunity in patients with hyperthyroid Graves' disease before, during and after antithyroid drug treatment.

Many reports of thyroid stimulating immunoglobulins (TSI) in relation to treatment of Graves' disease have been published and with variable results concerning prediction of permanent remission or relapse after therapy. A range of methods has been used and little has been published measuring TSI by using their ability to stimulate cyclic AMP production in human thyroid cells in monolayer culture. We therefore conducted a prospective study of the predictive value of such an assay in patients with hyperthyroid Graves' disease before, during and after treatment of one year with methimazole and thyroid hormone substitution. Furthermore, the possible relationship between activated suppressor T lymphocytes and TSI in patients followed before, during and after medical therapy has been studied. Patients were divided into two groups; group I, 15 patients, who stayed in remission and group II, 14, who relapsed during the first year after discontinuation of therapy. Mean TSI activity did not differ between the two groups before and during the first half year of medication. In the second half year of treatment, however, mean TSI activity was significantly lower in group I. TSI activity at the end of treatment appeared to have no value in predicting final outcome. Increased TSI activity in group II during treatment was reflected in an increased pertechnetate thyroidal uptake as compared to that in group I. There was no relationship between changes in TSI activity and T cell subsets (Leu 1, 2a, 3a). We found no difference in T lymphocytes between the two groups at any time during observation. Subsets of T lymphocytes in both patient groups did not differ from normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Prosthetic replacement of the proximal humerus.

Eighteen patients had prosthetic proximal humeral replacement with either a metal or ceramic prosthesis. Three replacements were performed for fracture nonunions, five for benign neoplasms, six for low-grade malignancies, and four for high-grade malignancies. Retention of elbow and hand function was good. In five of the 11 ceramic prostheses, failure occurred at the humeral-prosthetic junction even though it was designed for biologic fixation. Ten of 18 prostheses subluxated or dislocated. Twelve of 18 patients have had revision operations. While the revision rate in this initial series was high, valuable experience was gained for further investigations of shoulder arthroplasty.

Adolescent↗

Evidence that the uptake of tri-iodo-L-thyronine by human erythrocytes is carrier-mediated but not energy-dependent.

We investigated 3,3',5-tri-iodo-l-thyronine transport by human erythrocytes and by ;ghosts' prepared from these cells. Uptake of tri-iodothyronine by erythrocytes at 37 degrees C was time-dependent with a maximum reached after 60min. Tracer analysis after incubation for 1min revealed only one saturable binding site, with K(m) 128+/-19nm (mean+/-s.e.m.; n=7) and V(max.) 4.6+/-0.7pmol of tri-iodothyronine/min per 6x10(7) cells. After 10min incubation K(m) 100+/-16nm (n=10) was found with V(max.) 7.7+/-1.2pmol of tri-iodothyronine/10min per 6x10(7) cells. At 0 degrees C the uptake system is still active, with K(m) 132+/-26nm and V(max.) 1.8+/-0.3pmol of tri-iodothyronine/10min per 6x10(7) cells. The V(max.) with intact cells is 5-fold greater than the V(max.) with membranes derived from the same amount of cells when uptake studies are performed in media with similar free tri-iodothyronine concentrations. This indicates that at least 80% of tri-iodothyronine taken up by the intact erythrocytes enters the cell. This saturable uptake system can be inhibited by X-ray-contrast agents in a dose-dependent fashion. (+/-)-Propranolol, but not atenolol, has the same effect, indicating that the membrane-stabilizing properties of (+/-)-propranolol are involved. Furthermore, there is no inhibition by ouabain or vanadate, which indicates that tri-iodothyronine uptake is not dependent on the activity of Na(+)+K(+)-dependent adenosine triphosphatase. We have prepared erythrocyte ;ghosts', resealed after 2.5min with 0mm-, 2mm- or 4mm-ATP inside. Inclusion of ATP and integrity of the membrane of the erythrocyte ;ghosts' were verified on the basis of an ATP-concentration-dependent functioning of the Ca(2+) pump. No difference was found in the uptake of tri-iodothyronine by erythrocyte ;ghosts' with or without ATP included, indicating that uptake of tri-iodothyronine is not ATP-dependent. The following conclusions are drawn. (1) Tri-iodothyronine enters human erythrocytes. (2) There is only one saturable uptake system present for tri-iodothyronine, which is neither energy (i.e. ATP)-dependent nor influenced by the absence of an Na(+) gradient across the plasma membrane. This mode of uptake of tri-iodothyronine by human erythrocytes is in sharp contrast with that of rat hepatocytes, which uptake system is energy-dependent and ouabain-sensitive [Krenning, Docter, Bernard, Visser & Hennemann (1978) FEBS Lett.91, 113-116; Krenning, Docter, Bernard, Visser & Hennemann (1980) FEBS Lett.119, 279-282]. (3) X-ray-contrast agents inhibit tri-iodothyronine uptake by erythrocytes in a similar fashion to that by which they inhibit the uptake of tri-iodothyronine by rat hepatocytes [Krenning, Docter, Bernard, Visser & Hennemann (1982) FEBS Lett.140, 229-233].

Adenosine Triphosphate↗

Inherited thyroxine excess: a serum abnormality due to an increased affinity for modified albumin.

Further analysis of sera from euthyroid subjects with dominantly-inherited, elevated serum total thyroxine (T4) and free T4 index but with normal free T4 levels was performed as an extension of a previous study (Hennemann et al., 1979a). Scatchard analysis and isoelectric focusing of whole sera and purified serum fractions suggest that this T4 excess is due to increased T4 binding by modified serum albumin. Recognition of this syndrome and appreciation that the free T4 index does not reflect the free T4 levels is important to protect patients from the consequences of an incorrect diagnosis of thyrotoxicosis.

Humans↗

Thyrotrophin binding inhibiting immunoglobulins in Graves' disease before, during and after antithyroid therapy, and its relation to long-acting thyroid stimulator.

Thyrotrophin binding inhibiting immunoglublins (TBII) were measured in twenty-five patients with unequivocal hyperthyroid Graves' disease with a radioreceptor assay for TSH before, during and the end of treatment with antihyroid drugs and triiodothyronine. To assess the outcome of this therapy patients were followed for 10--90 months (mean 63 months). Before treatment there was significant correlation between TBII activity and serum thyroxine (r = -0.48, P less 0.05) and between TBII activated and 24 hour 131I thyroid uptake (r = -0.57, P less than 0.01). No relationship was found between TBII activated and 20 min, 4 hour and 48 hour 131I thyroid uptakes before institution of therapy. During treatment a significant correlation between TBII index and 20 min 131I thyroid uptake was found (r = -0.55, P less than 0.001). Both before and during treatment there was a significant correlation between TBII and LATS activity (r = -0.65, P less than 0.001). From the magnitude of this correlation coefficient it can be concluded that related, although not the same immunoglobulins, are measured with the two assay techniques. It is not possible to predict the occurrence of a relapse from the presence or absence of TBII activity at the end of treatment in this group of patients. The relapse rate was four out of eight for patients without TBII activity in their serum at the end of treatment and five out of nine for patients with TBII activity. From the data presented it can be concluded that although there is a significant relation between TBII activity and some indices of thyroid function before and during treatment, the correlation coefficients are too small to conclude that TBII alone is responsible for the hyperfunction of the thyroid. The same conclusion can be drawn from the fact that TBII activity has no prognostic value in relation to a possible relapse.

Adult↗