PubMed Health⌕ Search

Biomedical subjects

A H Zwinderman

Publications and source records attributed to A H Zwinderman.

At least 145 records · Page 8Linked to original sources

Correlation of heart rate variability with cardiac functional and metabolic variables in cyclists with training induced left ventricular hypertrophy.

OBJECTIVE: To examine the correlation between heart rate variability and left ventricular mass in cyclists with an athlete's heart. METHODS: Left ventricular mass and diastolic function were determined at rest and myocardial high energy phosphates were quantified at rest and during atropine-dobutamine stress in 12 male cyclists and 10 control subjects, using magnetic resonance techniques. Ambulatory 24 hour ECG recordings were obtained, and time and frequency domain heart rate variability indices were computed. RESULTS: In the cyclists, the mean of all RR intervals between normal beats (meanNN), the SD of the RR intervals, and their coefficient of variation were significantly greater than in control subjects (p < 0.01, p < 0.01, and p < 0.05, respectively). For cyclists and control subjects, only meanNN correlated with left ventricular mass (r = 0.48, p = 0.038). The heart rate variability indices that correlated with functional or metabolic variables were: meanNN v E/A peak (the ratio of peak early and peak atrial filling rate) (r = 0.48, p = 0.039); the root mean square of successive differences in RR intervals among successive normal beats v E/A area (ratio of peak early and peak atrial filling volume) (r = 0.48, p = 0.040); percentage of successive RR intervals differing by more than 50 ms v the phosphocreatine to ATP ratio at rest (r = 0.54, p = 0. 017); and the SD of the average RR intervals during all five minute periods v the phosphocreatine to ATP ratio during stress (r = 0.60, p = 0.007). CONCLUSIONS: Highly trained cyclists have increased heart rate variability indices, reflecting increased cardiac vagal control compared with control subjects. Left ventricular mass has no major influence on heart rate variability, but heart rate variability is significantly correlated with high energy phosphate metabolism and diastolic function.

Adult↗

Effect of inhaled steroids on airway hyperresponsiveness, sputum eosinophils, and exhaled nitric oxide levels in patients with asthma.

BACKGROUND: Airway hyperresponsiveness, induced sputum eosinophils, and exhaled nitric oxide (NO) levels have all been proposed as non-invasive markers for monitoring airway inflammation in patients with asthma. The aim of this study was to compare the changes in each of these markers following treatment with inhaled glucocorticosteroids in a single study. METHODS: In a randomised, double blind, placebo controlled, parallel study 25 patients with mild asthma (19-34 years, forced expiratory volume in one second (FEV1) >75% predicted, concentration of histamine provoking a fall in FEV1 of 20% or more (PC20) <4 mg/ml) inhaled fluticasone propionate (500 microg twice daily) for four weeks. PC20 to histamine, sputum eosinophil numbers, and exhaled NO levels were determined at weeks 0, 2, and 4, and two weeks after completing treatment. Sputum was induced by inhalation of hypertonic (4.5%) saline and eosinophil counts were expressed as percentage non-squamous cells. Exhaled NO levels (ppb) were measured by chemiluminescence. RESULTS: In the steroid treated group there was a significant increase in PC20, decrease in sputum eosinophils, and decrease in exhaled NO levels compared with baseline at weeks 2 and 4 of treatment. Subsequently, each of these variables showed significant worsening during the two week washout period compared with week 4. These changes were significantly different from those in the placebo group, except for the changes in sputum eosinophils and exhaled NO levels during the washout period. There were no significant correlations between the changes in the three markers in either group at any time. CONCLUSIONS: Treatment of asthmatic subjects with inhaled steroids for four weeks leads to improvements in airway hyperresponsiveness to histamine, eosinophil counts in induced sputum, and exhaled nitric oxide levels. The results suggest that these markers may provide different information when monitoring anti-inflammatory treatment in asthma.

Administration, Inhalation↗

Daytime-selective antihypertensive activity of celiprolol.

Day-activity rhythms of heart rate and blood pressure are thought to be mediated mainly through the sympathetic nervous system and may have greater amplitudes in patients with hypertension owing to increased daytime and largely normal nighttime values. Drug-induced nighttime hypotension in patients with chronic hypertension has been associated with the precipitation of cardiac failure and a fall in cerebral flow. The authors examined the effects of a single dose and of a 4-week treatment with different classes of antihypertensive drugs on ambulatory blood pressure (ABP) in 10 patients with mild hypertension. Data were assessed by polynomial analysis (Harvard Graphics 3). A single oral dose of enalapril 10 mg, amlodipine 5 mg, carvedilol 25 mg, and celiprolol 200 mg produced a mean reduction of 24-hour ABP compared to placebo of, respectively, 24/11, 11/5, 13/6, and 12/5 mm Hg (p values between <0.02 and <0.001). With enalapril, amlodipine, and carvedilol, between-subject variability contributed significantly to the overall variability in the measurements (p values between 0.05 and 0.01 versus zero), whereas with celiprolol this was not so. Although the beta blockers reduced daytime blood pressures similarly to the ACE inhibitor or the calcium channel blocker, they did not reduce nighttime blood pressures. These results were confirmed by an 8-week crossover trial comparing enalapril 10 mg daily with celiprolol 200 mg daily in the same group of patients. The authors conclude (1) that beta blockers produce a more stable reduction of blood pressure in patients with mild hypertension less affected by pressor effects through the sympathetic nervous system; (2) that beta blockers, unlike ACE inhibitors and calcium channel blockers, do not give rise to nighttime hypotension in this category of patients; and (3) that the selective beta blocker celiprolol may even perform better in these respects than the nonselective beta blocker carvedilol.

Administration, Oral↗

Comparison of 50-mg and 100-mg sustained-release isosorbide mononitrate in the treatment of stable angina pectoris: effects on quality-of-life indices. Dutch Mononitrate Quality of Life (DUMQOL) Study Group.

High-dosage nitrates are more effective for the management of anginal symptoms but produce more adverse effects, including development of tolerance and the zero-hour effect (rebound angina at the end of the dosing interval). Such effects may reduce the beneficial effect of treatment on quality of life. In a self-controlled, 6-month study, the effects on symptoms and quality of life of 50 mg and 100 mg sustained-release isosorbide mononitrate (SR ISMN), administered once daily, on anginal symptoms and quality of life (QOL) were assessed in 453 patients with stable angina pectoris. QOL was assessed by means of a test battery based on the Medical Outcomes Short-Form 36 Health Survey and the Angina Pectoris Quality of Life Questionnaire. The internal consistency and reliability of the multiitem scales were estimated by use of Cronbach's alpha coefficient. Based on their improvements in New York Heart Association (NYHA) angina classification, patients who received 100 mg daily showed greater improvement than those who received 50 mgdaily; the mean difference between treatments was consistent with a significantly greater improvement of mobility and angina indices. Adverse effects, as estimated by side-effect index, including rebound angina at times of rest, and by patient compliance rating, differed slightly between the two treatment regimens and were even less problematic with the higher dosage than with the lower dosage. Psychological distress index and life satisfaction scores also were significantly higher with 100 mg than with 50 mg daily. The results of this study suggest that SR ISMN 100 mg once daily provided a better NYHA angina classification than SR ISMN 50 mg did and did not produce further adverse effects. In addition SR ISMN 100 mg improved various QOL indices more than SR ISMN 50 mg did, particularly the mobility index and certain life satisfaction scores, which are the most important indicators of QOL in this category of patients.

Aged↗

Combination of calcium channel blockers and beta-blockers for patients with exercise-induced angina pectoris: beneficial effect of calcium channel blockers largely determined by their effect on heart rate.

The combination of calcium channel blockers and beta-blockers is more effective for the treatment of exercise-induced angina pectoris than beta-blocker monotherapy. As ischemia in exercise-induced angina is essentially preceded by an increase in heart rate, calcium channel blockers with a negative chronotropic property may perform better for this purpose than nonchronotropic compounds. A 335-patient, 10-week, double-blind, parallel-group comparison of amlodipine 5 mg and 10 mg, diltiazem 200 mg and 300 mg, and mibefradil 50 mg and 100 mg treatment added to baseline beta-blocker treatment was performed. Exercise testing (ETT) was performed by bicycle ergometry. All of the calcium channels blockers significantly delayed the onset of 1 mm ST-segment depression on ETT (p < 0.001 for any treatment vs. baseline). In addition, mibefradil, in both low- and high-dose treatments, produced the largest delays (low dose: different from diltiazem and amlodipine by 24.1 and 29.8 seconds, respectively, p < 0.003 and < 0.001; high dose: different from diltiazem and amlodipine by 33.7 and 37.0 seconds, respectively, p < 0.001 and < 0.001). A stepwise logistic regression analysis revealed that this beneficial effect of calcium channel blockers was largely dependent on their effect on heart rate. Serious symptoms of dizziness likewise occurred significantly more frequently on mibefradil (p < 0.05 vs. diltiazem) and urged no fewer than 19 patients on mibefradil to withdraw from the trial. The authors conclude that calcium channel blockers with a negative chronotropic property provide a better delay of ischemia in patients with exercise-induced angina, but the concomitant risk of intolerable dizziness may reduce this benefit.

Adolescent↗

Lipoprotein lipase activity is decreased in a large cohort of patients with coronary artery disease and is associated with changes in lipids and lipoproteins.

Lipoprotein lipase (LPL) is crucial in the hydrolysis of triglycerides (TG) in TG-rich lipoproteins in the formation of HDL particles. As both these lipoproteins play an important role in the pathogenesis of atherosclerotic vascular disease, we sought to assess the relationship between post-heparin LPL (PH-LPL) activity and lipids and lipoproteins in a large, well-defined cohort of Dutch males with coronary artery disease (CAD). These subjects were drawn from the REGRESS study, totaled 730 in number and were evaluated against 75 healthy, normolipidemic male controls. Fasting mean PH-LPL activity in the CAD subjects was 108 46 mU/ml, compared to 138 44 mU/ml in controls (P < 0.0001). When these patients were divided into activity quartiles, those in the lowest versus the highest quartile had higher levels of TG (P < 0.001), VLDLc and VLDL-TG (P = 0.001). Conversely, levels of TC, LDL, and HDLc were lower in these patients (P = 0.001, P = 0.02, and P = 0.001, respectively). Also, in this cohort PH-LPL relationships with lipids and lipoproteins were not altered by apoE genotypes. The frequency of common mutations in the LPL gene associated with partial LPL deficiency (N291S and D9N carriers) in the lowest quartile for LPL activity was more than double the frequency in the highest quartile (12.0% vs. 5.0%; P = 0.006). By contrast, the frequency of the S447X LPL variant rose from 11.5% in the lowest to 18.3% (P = 0.006) in the highest quartile. This study, in a large cohort of CAD patients, has shown that PH-LPL activity is decreased (22%; P = 0.001) when compared to controls; that the D9N and N291S, and S447X LPL variants are genetic determinants, respectively, in CAD patients of low and high LPL PH-LPL activities; and that PH-LPL activity is strongly associated with changes in lipids and lipoproteins.

Adult↗

Measurements of blood pressure with various techniques in daily practice: uncertainty in diagnosing office hypertension with short-term in-hospital registration of blood pressure.

OBJECTIVE: To predict blood pressure outside the clinic from a short-term in-hospital registration for patients referred for ambulatory blood pressure monitoring (ABPM) with special attention to office hypertension. PATIENTS AND METHODS: A series of measurements of blood pressure was performed by the same technician for 187 patients, 82% of whom were being administered antihypertensive therapy. She performed three mercury measurements of blood pressure (Hg stress 1) and then three manually started measurements with a semi-automatic device (Dinamap 1846SX; Dinamap stress) alternated with three manually started readings with a SpaceLabs 90207 monitor (SpaceLabs stress) on the contralateral non-dominant arm. The in-hospital session was continued with 15 automatic Dinamap registrations at 2 min intervals without the technician being present (Dinamap unstressed, five periods of three measurements averaged) before the patient left the hospital for 24h ABPM. RESULTS: The percentages of patients with hypertension in the office (systolic blood pressure >/= 140 mmHg or diastolic blood pressure >/= 90 mmHg, or both) were 80% with Hg stress 1, 76% with Dinamap stress and 85.0% with SpaceLabs stress. Average diastolic SpaceLabs stress was 6.0+/-5.6 mmHg (significantly) higher than diastolic Dinamap stress, whereas the difference between systolic blood pressures was 0.2+/-10.0 mmHg. No further change in blood pressure occurred after the fourth period of Dinamap unstressed measurements. Office hypertension defined as SpaceLabs stress systolic blood pressure >/= 140 mmHg or diastolic blood pressure >/= 90 mmHg, or both, and SpaceLabs daytime systolic blood pressure < 135 mmHg and diastolic blood pressure < 85 mmHg was found in 21 individuals. Office hypertension defined with similar cut-off points in the comparison of Dinamap stress versus Dinamap unstressed period 5 was found in 29 cases, 10 of which overlapped with the definition SpaceLabs stress versus SpaceLabs daytime. The differences between Dinamap stress and Dinamap unstressed period 5 were significantly correlated to the changes of SpaceLabs stress and SpaceLabs daytime both for systolic (r =0.41) and for diastolic (r =0.32) blood pressures. CONCLUSIONS: Measurements of blood pressure in the office with various techniques (mercury, Dinamap and SpaceLabs) are not equivalent. Office hypertension cannot be reliably predicted from a short-term semi-automatic in-hospital registration of blood pressure with a Dinamap device.

Adolescent↗

Clinical findings with implications for genetic testing in families with clustering of colorectal cancer.

BACKGROUND: Germ-line mutations in DNA mismatch-repair genes (MSH2, MLH1, PMS1, PMS2, and MSH6) cause susceptibility to hereditary nonpolyposis colorectal cancer. We assessed the prevalence of MSH2 and MLH1 mutations in families suspected of having hereditary nonpolyposis colorectal cancer and evaluated whether clinical findings can predict the outcome of genetic testing. METHODS: We used denaturing gradient gel electrophoresis to identify MSH2 and MLH1 mutations in 184 kindreds with familial clustering of colorectal cancer or other cancers associated with hereditary nonpolyposis colorectal cancer. Information on the site of cancer, the age at diagnosis, and the number of affected family members was obtained from all families. RESULTS: Mutations of MSH2 or MLH1 were found in 47 of the 184 kindreds (26 percent). Clinical factors associated with these mutations were early age at diagnosis of colorectal cancer, the occurrence in the kindred of endometrial cancer or tumors of the small intestine, a higher number of family members with colorectal or endometrial cancer, the presence of multiple colorectal cancers or both colorectal and endometrial cancers in a single family member, and fulfillment of the Amsterdam criteria for the diagnosis of hereditary nonpolyposis colorectal cancer (at least three family members in two or more successive generations must have colorectal cancer, one of whom is a first-degree relative of the other two; cancer must be diagnosed before the age of 50 in at least one family member; and familial adenomatous polyposis must be ruled out). Multivariate analysis showed that a younger age at diagnosis of colorectal cancer, fulfillment of the Amsterdam criteria, and the presence of endometrial cancer in the kindred were independent predictors of germ-line mutations of MSH2 or MLH1. These results were used to devise a logistic model for estimating the likelihood of a mutation in MSH2 and MLH1. CONCLUSIONS: Assessment of clinical findings can improve the rate of detection of mutations of DNA mismatch-repair genes in families suspected of having hereditary nonpolyposis colorectal cancer.

Adaptor Proteins, Signal Transducing↗

Functional and metabolic evaluation of the athlete's heart by magnetic resonance imaging and dobutamine stress magnetic resonance spectroscopy.

BACKGROUND: The question of whether training-induced left ventricular hypertrophy in athletes is a physiological rather than a pathophysiological phenomenon remains unresolved. The purpose of the present study was to detect any abnormalities in cardiac function in hypertrophic hearts of elite cyclists and to examine the response of myocardial high-energy phosphate metabolism to high workloads induced by atropine-dobutamine stress. METHODS AND RESULTS: We studied 21 elite cyclists and 12 healthy control subjects. Left ventricular mass, volume, and function were determined by cine MRI. Myocardial high-energy phosphates were examined by 31P magnetic resonance spectroscopy. There were no significant differences between cyclists and control subjects for left ventricular ejection fraction (59+/-5% versus 61+/-4%), left ventricular cardiac index (3.4+/-0.4 versus 3.4+/-0.4 L x min(-1) x m[-2]), peak early filling rate (562+/-93 versus 535+/-81 mL/s), peak atrial filling rate (315+/-93 versus 333+/-65 mL/s), ratio of early and atrial filling volumes (3.0+/-1.0 versus 2.6+/-0.6), mean acceleration gradient of early filling (5.2+/-1.4 versus 5.8+/-1.9 L/s2), mean deceleration gradient of early filling(-3.1 +/- 0.9 versus -3.2 +/- 0.7 L/s2), mean acceleration gradient of atrial filling (3.6+/-1.8 versus 4.5+/-1.7 L/s2), and atrial filling fraction (0.23+/-0.06 versus 0.26+/-0.04, respectively). Cyclists and control subjects showed similar decreases in the ratio of myocardial phosphocreatine to ATP measured with 31P magnetic resonance spectroscopy during atropine-dobutamine stress (1.41+/-0.20 versus 1.41+/-0.18 at rest to 1.21+/-0.20 versus 1.16+/-0.13 during stress, both P=NS). CONCLUSIONS: Left ventricular hypertrophy in cyclists is not associated with significant abnormalities of cardiac function or metabolism as assessed by MRI and spectroscopy. These observations suggest that training-induced left ventricular hypertrophy in cyclists is predominantly a physiological phenomenon.

Adaptation, Physiological↗

Comparison of induction of hprt mutations by 1,3-butadiene and/or its metabolites 1,2-epoxybutene and 1,2,3,4-diepoxybutane in lymphocytes from spleen of adult male mice and rats in vivo.

Induction of hprt mutations by 1,3-butadiene (BD) and its metabolites 1,2-epoxybutene (EB) and 1,2,3,4-diepoxybutane (DEB) was studied in lymphocytes from spleens of 6- to 14-week-old mice and 10- to 11-week-old rats. For unknown reasons, results from experiments with mice that received inhalation exposure to BD were quite variable. In the first experiment, mice were exposed for 5 days to 200, 500 or 1300 ppm and this resulted in a statistically significant, dose-dependent, induction of mutations. When the experiment was repeated and an extra expression time for mutations was included, it was not possible to detect induction of mutations. In a third experiment, a 6-day exposure to 500 ppm was mutagenic when mice with zero mutants were not excluded from the statistical analysis of the data. The monofunctional metabolite EB appeared to be mutagenic in mice (3 x 33 and 3 x 100 mg/kg), but not in rats (3 x 33 and 100 mg/kg or 30 days drinking water with 0.1, 0.3, or 1.0 mM EB). Contrary to expectations, there was no induction of mutations in mice and rats exposed to the bifunctional metabolite DEB (mice, 3 x 7, 21, 3 x 14, or 42 mg/kg; rats, 20 or 40 mg/kg or 30 days drinking water with 0.3 or 1 mM DEB), although in our earlier studies with mice and rats, DEB treatment significantly enhanced frequencies of micronuclei in splenocytes and in early spermatids of mice and rats. Some of these results differ from findings reported by other investigators. It is now becoming evident that these differences are, to a large extent, due to differences in age of the animals at the time of treatment. For example, the mutagenic potency of BD, EB and DEB was stronger in preweanling mice or 4-week-old mice than in 8- to 12-week-old adult mice.

Age Factors↗

The role of a common variant of the cholesteryl ester transfer protein gene in the progression of coronary atherosclerosis. The Regression Growth Evaluation Statin Study Group.

BACKGROUND: The high-density lipoprotein (HDL) cholesterol concentration is inversely related to the risk of coronary artery disease. The cholesteryl ester transfer protein (CETP) has a central role in the metabolism of this lipoprotein and may therefore alter the susceptibility to atherosclerosis. METHODS: The DNA of 807 men with angiographically documented coronary atherosclerosis was analyzed for the presence of a polymorphism in the gene coding for CETP. The presence of this DNA variation was referred to as B1, and its absence as B2. All patients participated in a cholesterol-lowering trial designed to induce the regression of coronary atherosclerosis and were randomly assigned to treatment with either pravastatin or placebo for two years. RESULTS: The B1 variant of the CETP gene was associated with both higher plasma CETP concentrations (mean [+/-SD], 2.29+/-0.62 microg per milliliter for the B1B1 genotype vs. 1.76+/-0.51 microg per milliliter for the B2B2 genotype) and lower HDL cholesterol concentrations (34+/-8 vs. 39+/-10 mg per deciliter). In addition, we observed a significant dose-dependent association between this marker and the progression of coronary atherosclerosis in the placebo group (decrease in mean luminal diameter: 0.14+/-0.21 mm for the B1B1 genotype, 0.10+/-0.20 mm for the B1B2 genotype, and 0.05+/-0.22 mm for the B2B2 genotype). This association was abolished by pravastatin. Pravastatin therapy slowed the progression of coronary atherosclerosis in B1B1 carriers but not in B2B2 carriers (representing 16 percent of the patients taking pravastatin). CONCLUSIONS: There is a significant relation between variation at the CETP gene locus and the progression of coronary atherosclerosis that is independent of plasma HDL cholesterol levels and the activities of lipolytic plasma enzymes. This common DNA variant appears to predict whether men with coronary artery disease will benefit from treatment with pravastatin to delay the progression of coronary atherosclerosis.

Anticholesteremic Agents↗

Sulfasalazine in the treatment of juvenile chronic arthritis: a randomized, double-blind, placebo-controlled, multicenter study. Dutch Juvenile Chronic Arthritis Study Group.

OBJECTIVE: To assess the efficacy, tolerability, and safety of sulfasalazine (SSZ) in the treatment of juvenile chronic arthritis (JCA). METHODS: We conducted a 24-week randomized, placebo-controlled, double-blind, multicenter study of patients with active JCA of both oligoarticular and polyarticular onset. Patients were treated with a dosage of 50 mg/kg/day of SSZ (maximum 2,000 mg/day) or placebo. The efficacy variables were joint scores, physician's, parents', and patient's overall assessments, and laboratory parameters of inflammation. RESULTS: Of the 69 patients enrolled, 52 (75%) completed the trial. Six patients (18%) withdrew from the placebo group, and 11 (31%) withdrew from the SSZ group (P = 0.18). In the intention-to-treat analysis of end point efficacy, between-group differences were significant for the overall articular severity score (P = 0.02), all global assessments (P = 0.01), and the laboratory parameters (P < 0.001). Adverse events occurred more frequently in the SSZ group and were the main reason for withdrawal (P < 0.001), but in all instances, these events were transient or reversible upon cessation of treatment. CONCLUSION: The results of this first placebo-controlled study show that SSZ is effective and safe in the treatment of children with oligoarticular- and polyarticular-onset JCA, although it was not well tolerated in one-third of the patients.

Adolescent↗

No increased risk of malignancies and mortality in cyclosporin A-treated patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the cyclosporin A (CSA)-attributed risk of developing malignancies in general and malignant lymphoproliferative diseases (LPDs) and skin cancers in particular, as well as the CSA-attributed incidence of mortality in patients with rheumatoid arthritis (RA). METHODS: In a retrospective, controlled cohort study, the incidence of malignancies and mortality was evaluated in 208 CSA-treated patients with RA compared with 415 matched control patients with RA between 1984 and 1995. Patients were followed up for a median of 5.0 years (range 1.4-12.0). RESULTS: Forty-eight cases of malignancy (8 in the CSA group and 40 in the control group; relative risk [RR] 0.40, 95% confidence interval [95% CI] 0.19-0.84) were identified, of which 8 were malignant LPDs (2 CSA versus 6 control; RR 0.67, 95% CI 0.14-3.27) and 14 were skin cancers (2 CSA versus 12 control; RR 0.33, 95% CI 0.08-1.47). Seventy-three patients died (16 CSA versus 57 control; RR 0.56, 95% CI 0.33-0.95) due primarily to cardiovascular diseases (4 CSA versus 22 control; RR 0.36, 95% CI 0.13-1.04) or a malignancy (3 CSA versus 8 control; RR 0.67, 95% CI 0.18-2.43). Proportional hazards regression analysis with correction for potential confounding factors did not significantly change the results. CONCLUSION: The study findings suggest that CSA treatment in RA patients does not increase the risk of malignancies in general or the risk of malignant LPDs or skin cancers in particular. Moreover, the incidence of mortality in CSA-treated RA patients was comparable to that in matched control RA patients.

Adult↗

A comparison of the Futuro wrist orthosis with a synthetic ThermoLyn orthosis: utility and clinical effectiveness.

OBJECTIVE: To compare the short-term utility and clinical effectiveness of the commercial-made Futuro wrist orthosis with a newly developed, custom-made ThermoLyn wrist orthosis. METHODS: Using a randomized cross-over trial, 10 patients with rheumatoid arthritis used each of the two orthoses for two weeks. Outcome measures were patients' judgments with respect to different statements about utility and clinical assessments including pain and swelling of the wrist and finger joints, range of motion of the wrist, and grip strength. At the end of the study the patients were asked which of the two orthoses they preferred and why. RESULTS: Patients tended to favor the Futuro wrist orthosis with respect to pain relief and to handling the orthosis. The visual analog scale score of the appearance of the ThermoLyn wrist orthosis was a little higher than that of the Futuro wrist orthosis, but the difference was not statistically significant. Clinical parameters such as pain in the wrist, swelling of the wrist and finger joints, and movements of the wrist showed that the Futuro orthosis tended to be more effective than the ThermoLyn orthosis. None of the differences reached statistical significance. At the end of the study, 5 patients preferred the Futuro and 5 patients the ThermoLyn wrist orthosis. Arguments in favor of the ThermoLyn orthosis were better hygiene, stability, and no need to remove the orthosis during dirty and wet conditions. Arguments in favor of the Futuro orthosis were greater suppleness and freedom of movement. CONCLUSIONS: The ready-made fabric Futuro wrist orthosis appears to be as good as the more expensive individually made synthetic ThermoLyn wrist orthosis with respect to short-term utility and clinical effectiveness. The conditions under which the orthosis will be worn will help to decide which orthosis is the best for the patient. In the event that the patient wants to use the orthosis in wet and dirty conditions, the ThermoLyn wrist orthosis is a good alternative to the Futuro wrist orthosis.

Adult↗

Extracellular matrix in human diabetic nephropathy: reduced expression of heparan sulphate in skin basement membrane.

In diabetic nephropathy, expression of glycosaminoglycan side chains of heparan sulphate proteoglycan in the glomerular basement membrane is reduced proportionally to the degree of proteinuria. We performed a cross-sectional study to evaluate whether non-vascular basement membranes also show a decrease in heparan sulphate side chain staining in patients with diabetic nephropathy. We evaluated the skin basement membrane for extracellular matrix components in the following groups: control subjects (n = 16); patients with Type 1 diabetes and normoalbuminuria (n = 17), microalbuminuria (n = 7), and macroalbuminuria (n = 16); patients with Type 1 diabetes and diabetic nephropathy undergoing renal replacement therapy (n = 13); and non-diabetic patients undergoing renal replacement therapy (n = 21). The following antibodies were used for this immunohistochemical study: monoclonal antibodies against the heparan sulphate side chain (JM403) and core protein (JM72) of the glomerular heparan sulphate proteoglycan; polyclonal antibodies against the core protein (B31); polyclonal antibodies against collagen types I, III, and IV, fibronectin, and laminin; and monoclonal antibodies against the noncollagenous domain of alpha1(collagen IV) and alpha3(collagen IV), against transforming growth factor beta(2G7), and against advanced glycosylation end products (4G9). Expression of heparan sulphate side chains was reduced in the skin basement membrane of patients with overt diabetic nephropathy, of those with Type 1 diabetes undergoing renal replacement therapy, and those with non-diabetic renal failure. Increased intensity of staining was found for collagen type I and advanced glycosylation end products in patients with diabetic nephropathy. Changes in the extracellular matrix of the skin basement membrane seem to be similar to those in the glomerular basement membrane. These findings support the suggestion that patients with diabetic nephropathy also have altered heparan sulphate and collagen staining in extrarenal basement membranes. However, patients with non-diabetic renal failure also had reduced expression of heparan sulphate in the skin basement membrane, suggesting that this finding is not specific for diabetic nephropathy.

Adult↗

The prevalence of low bone mineral density in Dutch perimenopausal women: the Eindhoven perimenopausal osteoporosis study.

The aim of this study was to estimate the prevalence of osteopenia and osteoporosis in perimenopausal women, and to assess determinants of low bone mineral density (BMD). All women born between 1941 and 1947 (aged between 46 and 54 years) living in the city of Eindhoven were invited to participate in the study: 5896 white Dutch women, representing 73% of the total number of Dutch women in this age group, were studied. Of these, 24% were using estrogen preparations and 19% had undergone hysterectomy, with or without oophorectomy. All women were interviewed and bone mineral density (BMD) of the lumbar spine was measured by dual-energy X-ray absorptiometry (DXA). Osteopenia and osteoporosis were defined according to the criteria proposed by a WHO working group. In the population studied the prevalence of osteopenia and osteoporosis was 27.3% and 4.1%, respectively. With progression from premenopause to menopause, the prevalence of osteoporosis increased from 0.4% to 12.7%, and that of osteopenia from 14.5% to 42.8%. An increased risk for low BMD (osteopenia and osteoporosis) was associated with age, menopausal status and smoking, while alcohol consumption, high body mass index (BMI) and use of estrogens had a protective effect. This study of a large population-based cohort of perimenopausal women revealed a high prevalence of low bone mass and, therefore, a higher risk for osteoporotic fractures. The data further suggest that, when issues on the long-term efficacy and safety of preventive treatments are resolved, it may be possible to identify women at higher risk who are most likely to benefit from screening strategies.

Absorptiometry, Photon↗

Renographic indices for evaluation of changes in graft function.

Radionuclide renal diagnostic studies play an important role in assessing renal allograft function, especially in the early post-transplant period. In the past two decades various quantitative parameters have been derived from the radionuclide renogram to evaluate changes in perfusion and/or function of the kidney allograft. In this review article we discuss the quantitative parameters that have been used to assess graft condition, with emphasis on the early postoperative period. These quantitative methods are divided into parameters used for assessing renal graft perfusion and parameters used for evaluating parenchymal function. The blood flow in renal transplants can be quantified (a) by measuring the rate of activity appearance in the kidney graft, (b) by calculating the ratio of the integral activity under the transplanted kidney and arterial curves and (c) by calculating the renal vascular transit time. In this article we review a number of parenchymal uptake and excretion indices, such as the accumulation index, the graft uptake capacity at 2 and 10 min, the excretion index and the elimination index. The literature on these parameters shows that they have some practical disadvantages. In addition, values suffer from significant overlap when various graft pathologies coexist. A retrospective study was designed in our institution to evaluate the clinical usefulness of some of the frequently used previously published methods in which the graft function is quantitatively assessed in the early post-transplant period. The quantitative parameters studied which were reasonably reproducible in our hands included: global perfusion index (GPI), cortical perfusion index (CPI), vascular transit time, and the parenchymal parameters uptake capacity at 2 min (UC2) and elimination index (K3/20). The patient population in this study consisted of 43 patients with 157 technetium-99m mercaptylacetyltriglycine renograms. The perfusion indices GPI and CPI did not allow differentiation of the acute tubular necrosis (ATN) group from the acute rejection (AR) group; however, they were of value in monitoring the improvement in the condition of the graft dysfunction in both the AR and ATN groups. As for the parenchymal parameters, both UC2 and K3/20 were able to differentiate stable graft function (SGF) versus AR and ATN groups but were unable to separate AR from ATN dysfunction. The ability of these parenchymal parameters to detect improvement in the graft function was poor and statistically non-significant. From the literature data and our own findings it is concluded that radionuclide scintigraphy of renal transplants has assumed an important role, especially if performed serially, in monitoring graft function in the post-transplant period. Many quantitative parameters have been derived from the radionuclide renogram to evaluate changes in perfusion and/or function of the kidney allograft. It appears that these quantitative numerical values are unable to differentiate unequivocally between grafts with ATN and AR cases. The real value of these parameters lies in the follow-up of the dysfunction processes, which helps the clinician to determine the appropriate therapeutic regimen.

Humans↗