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T Stijnen

Publications and source records attributed to T Stijnen.

At least 19 recordsLinked to original sources
PubMed2001

Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease.

BACKGROUND: Previous studies have suggested that the use of nonsteroidal antiinflammatory drugs (NSAIDs) may help to prevent Alzheimer's disease. The results, however, are inconsistent. METHODS: We studied the association between the use of NSAIDs and Alzheimer's disease and vascular dementia in a prospective, population-based cohort study of 6989 subjects 55 years of age or older who were free of dementia at base line, in 1991. To detect new cases of dementia, follow-up screening was performed in 1993 and 1994 and again in 1997 through 1999. The risk of Alzheimer's disease was estimated in relation to the use of NSAIDs as documented in pharmacy records. We defined four mutually exclusive categories of use: nonuse, short-term use (1 month or less of cumulative use), intermediate-term use (more than 1 but less than 24 months of cumulative use), and long-term use (24 months or more of cumulative use). Adjustments were made by Cox regression analysis for age, sex, education, smoking status, and the use or nonuse of salicylates, histamine Hz-receptor antagonists, antihypertensive agents, and hypoglycemic agents. RESULTS: During an average follow-up period of 6.8 years, dementia developed in 394 subjects, of whom 293 had Alzheimer's disease, 56 vascular dementia, and 45 other types of dementia. The relative risk of Alzheimer's disease was 0.95 (95 percent confidence interval, 0.70 to 1.29) in subjects with short-term use of NSAIDs, 0.83 (95 percent confidence interval, 0.62 to 1.11) in those with intermediate-term use, and 0.20 (95 percent confidence interval, 0.05 to 0.83) in those with long-term use. The risk did not vary according to age. The use of NSAIDs was not associated with a reduction in the risk of vascular dementia. CONCLUSIONS: The long-term use of NSAIDs may protect against Alzheimer's disease but not against vascular dementia.

Aged↗
PubMed2001

Balloon dilation and stent implantation for treatment of femoropopliteal arterial disease: meta-analysis.

PURPOSE: To perform a meta-analysis of long-term results of balloon dilation and stent implantation in the treatment of femoropopliteal arterial disease. MATERIALS AND METHODS: The English-language literature was searched for studies published between 1993 and 2000. Inclusion criteria for articles were presentation of long-term primary patency rates, standard errors (explicitly reported or derivable), and baseline characteristics of the study population. Two reviewers independently extracted data, and discrepancies were resolved by consensus. Primary patency rates were combined by using a technique that allows adjustment for differences across study populations. Analyses were adjusted for lesion type and clinical indication. RESULTS: Nineteen studies met the inclusion criteria, representing 923 balloon dilations and 473 stent implantations. Combined 3-year patency rates after balloon dilation were 61% (standard error, 2.2%) for stenoses and claudication, 48% (standard error, 3.3%) for occlusions and claudication, 43% (standard error, 4.1%) for stenoses and critical ischemia, and 30% (standard error, 3.7%) for occlusions and critical ischemia. The 3-year patency rates after stent implantation were 63%-66% (standard error, 4.1%) and were independent of clinical indication and lesion type. Funnel plots demonstrated an asymmetric distribution of the data points associated with stent studies. CONCLUSION: Balloon dilation and stent implantation for claudication and stenosis yield similar long-term patency rates. For more severe femoropopliteal disease, the results of stent implantation seem more favorable. Publication bias could not be ruled out.

Arterial Occlusive Diseases↗
PubMed2001

Bone mineral density assessed by phalangeal radiographic absorptiometry before and during long-term growth hormone treatment in girls with Turner's syndrome participating in a randomized dose-response study.

To assess bone mineral density (BMD) in girls with Turner's syndrome before and during long-term treatment with GH, longitudinal measurements using phalangeal radiographic absorptiometry were performed in 68 girls with Turner's syndrome. These previously untreated girls, age 2-11 y, participating in a randomized, dose-response trial, were randomly assigned to one of three GH dosage groups: group A, 4 IU/m(2)/d ( approximately 0.045 mg/kg/d); group B, first year 4 IU/m(2)/d, thereafter 6 IU/m(2)/d ( approximately 0.0675 mg/kg/d); or group C, first year 4 IU/m(2)/d, second year 6 IU/m(2)/d, thereafter 8 IU/m(2)/d ( approximately 0.090 mg/kg/d). In the first 4 y of GH treatment, no estrogens for pubertal induction were prescribed to the girls. Thereafter, girls started with 17beta-estradiol (5 microg/kg body weight/d, orally) when they had reached the age of 12 y. BMD results were adjusted for bone age and sex, and expressed as SD scores using reference values of healthy Dutch girls. At baseline, almost every individual BMD value of bone consisting predominantly of cortical bone, as well as that of bone consisting predominantly of trabecular bone, was within the normal range of healthy girls and the SD scores were not significantly different from zero [mean (SE) 0.38 (0.22) and -0.04 (0.13)]. During 7 y of GH treatment, BMD SD scores showed a significant increase to values significantly higher than zero [mean (SE) 0.87 (0.15) and 0.95 (0.14)]. The increment in BMD SD score of bone consisting predominantly of cortical bone was significantly higher in group C compared with that of the other two GH dosage groups. The pretreatment bone age was significantly negatively related to the increment in BMD SD score. We found no significant influence of spontaneous puberty or the use of low-dose estrogens in the last 3 y of the study period on the increment in BMD SD score during 7 y of GH treatment. In conclusion, most untreated young girls with Turner's syndrome have a normal volumetric BMD. During 7 y of GH treatment with 4, 6, or 8 IU/m(2)/d, the BMD SD score increased significantly.

Absorptiometry, Photon↗
PubMed2001

[(123)I]metaiodobenzylguanidine and [(111)In]octreotide uptake in begnign and malignant pheochromocytomas.

Selecting the appropriate approach for resection and follow-up of pheochromocytomas (PCCs) is highly dependent upon reliable localization and exclusion of multifocal, bilateral, or metastatic disease. Metaiodobenzylguanidine (MIBG) scintigraphy was developed for functional localization of catecholamine-secreting tissues. Somatostatin receptor imaging (SRI) has a high sensitivity for localizing head and neck paragangliomas, but studies of intraabdominal PCCs are rare. In this study we review our experience of [(123)I]MIBG and SRI, performed since 1983 and 1989, respectively, in the work-up of primary and recurrent PCCs. Scintigraphic results were correlated with catecholamine secretion, size and site, malignancy, associated tumor syndromes, and morphological features. [(123)I]MIBG scans were performed in a total of 75 patients, in 70 cases before resection of primary PCCs and in 5 cases because of recurrent disease. Ninety-one PCCs were resected. The overall detection rates were 83.3% and 89.8% for PCCs larger than 1.0 cm. Multifocal disease was detected in 4 patients with [(123)I]MIBG. [(123)I]MIBG uptake correlated with greater size of PCC (r = 0.33; P = 0.008) and greater concentration of plasma epinephrine (r = 0.32; P = 0.006). [(123)I]MIBG-negative PCCs (n = 14) had significantly (P = 0.01) smaller diameters than [(123I)]MIBG-positive tumors. Furthermore, [(123)I]MIBG uptake was significantly higher in unilateral (P = 0.02), benign (P = 0.02), sporadic (P = 0.02), intraadrenal (P = 0.02), and capsular invasive (P = 0.03) PCCs than in bilateral, malignant, MEN2A/2B-related, extraadrenal, and noninvasive PCCs, respectively. The detection rate of SRI was only 25% (8 of 32) for primary benign PCCs. In 14 patients metastases occurred, which were effectively visualized with [(123)I]MIBG in 8 of 14 cases. SRI was able to detect metastases in 7 of 8 cases, including 3 [(123)I]MIBG-negative metastatic cases. In addition, [(123)I]MIBG and SRI detected 2 recurrences. In conclusion, [(123)I]MIBG uptake is correlated with the size, epinephrine production, and site of PCCs. Its role in bilateral and MEN2A/2B-related PCCs seems limited. In cases of recurrent elevation of catecholamines, localization of metastases and/or recurrence should be attempted with [(123)I]MIBG scintigraphy. In suspicious metastatic PCCs, SRI might be considered to supplement [(123)I]MIBG scintigraphy.

3-Iodobenzylguanidine↗
PubMed2001

Incidence and progression rates of age-related maculopathy: the Rotterdam Study.

PURPOSE: To describe the incidence rate of age-related macular degeneration (AMD) and the progression rates of early stages of age-related maculopathy (ARM), and to study the hierarchy of fundus features that determine progression. METHODS: A group of 4953 subjects aged 55 years and older living in Rotterdam, The Netherlands, was studied at baseline and at 2-year follow-up to determine the incidence of neovascular and atrophic AMD. A subgroup of 1244 subjects was studied for progression of early stages of ARM. Fundus transparencies were graded for features of ARM using the International Classification System. ARM was stratified in four exclusive stages, according to type of drusen and presence of pigmentary irregularities. RESULTS: The overall 2-year cumulative incidence of AMD was 0.2%, increasing to 1.8% in subjects of 85 years and older. Of those in the early stages, one fourth showed progression to a more severe stage. The most important predictors for progression were more than 10% of macular area covered by drusen (odds ratio [OR] 5.7, 95% confidence interval [CI] 2.9-11.3), presence of depigmentation (OR 4.0, 95% CI 2.5-6.4), and hyperpigmentation (OR 3.4, 95% CI 2.1-5.4). CONCLUSIONS: The incidence of AMD appears to be lower in The Netherlands than in the United States. Progression of early ARM stages occurs in a distinct pattern at a stable rate, with a large area of drusen and presence of pigmentary changes as the most important predictors.

Age Distribution↗
PubMed2000

Baseline risk as predictor of treatment benefit: three clinical meta-re-analyses.

A relationship between baseline risk and treatment effect is increasingly investigated as a possible explanation of between-study heterogeneity in clinical trial meta-analysis. An approach that is still often applied in the medical literature is to plot the estimated treatment effects against the estimated measures of risk in the control groups (as a measure of baseline risk), and to compute the ordinary weighted least squares regression line. However, it has been pointed out by several authors that this approach can be seriously flawed. The main problem is that the observed treatment effect and baseline risk measures should be viewed as estimates rather than the true values. In recent years several methods have been proposed in the statistical literature to potentially deal with the measurement errors in the estimates. In this article we propose a vague priors Bayesian solution to the problem which can be carried out using the 'Bayesian inference using Gibbs sampling' (BUGS) implementation of Markov chain Monte Carlo numerical integration techniques. Different from other proposed methods, it uses the exact rather than an approximate likelihood, while it can handle many different treatment effect measures and baseline risk measures. The method differs from a recently proposed Bayesian method in that it explicitly models the distribution of the underlying baseline risks. We apply the method to three meta-analyses published in the medical literature and compare the results with the outcomes of the other recently proposed methods. In particular we compare our approach to McIntosh's method, for which we show how it can be carried out using standard statistical software. We conclude that our proposed method offers a very general and flexible solution to the problem, which can be carried out relatively easily with existing Bayesian analysis software. A confidence band for the underlying relationship between true effect measure and baseline risk and a confidence interval for the value of the baseline risk measure for which there is no treatment effect are easily obtained by-products of our approach.

Bayes Theorem↗
PubMed2000

Education and the risk for Alzheimer's disease: sex makes a difference. EURODEM pooled analyses. EURODEM Incidence Research Group.

The hypothesis that a low educational level increases the risk for Alzheimer's disease remains controversial. The authors studied the association of years of schooling with the risk for incident dementia and Alzheimer's disease by using pooled data from four European population-based follow-up studies. Dementia cases were identified in a two-stage procedure that included a detailed diagnostic assessment of screen-positive subjects. Dementia and Alzheimer's disease were diagnosed by using international research criteria. Educational level was categorized by years of schooling as low (< or =7), middle (8-11), or high (> or =12). Relative risks (95% confidence intervals) were estimated by using Poisson regression, adjusting for age, sex, study center, smoking status, and self-reported myocardial infarction and stroke. There were 493 (328) incident cases of dementia (Alzheimer's disease) and 28,061 (27,839) person-years of follow-up. Compared with women with a high level of education, those with low and middle levels of education had 4.3 (95% confidence interval: 1.5, 11.9) and 2.6 (95% confidence interval: 1.0, 7.1) times increased risks, respectively, for Alzheimer's disease. The risk estimates for men were close to 1.0. Finding an association of education with Alzheimer's disease for women only raises the possibility that unmeasured confounding explains the previously reported increased risk for Alzheimer's disease for persons with low levels of education.

Age Distribution↗
PubMed2000

Randomized clinical trial of adenosine 5'-triphosphate in patients with advanced non-small-cell lung cancer.

BACKGROUND: Extracellular adenosine 5'-triphosphate (ATP) is involved in the regulation of a variety of biologic processes, including neurotransmission, muscle contraction, and liver glucose metabolism, via purinergic receptors. In nonrandomized studies involving patients with different tumor types including non-small-cell lung cancer (NSCLC), ATP infusion appeared to inhibit loss of weight and deterioration of quality of life (QOL) and performance status. We conducted a randomized clinical trial to evaluate the effects of ATP in patients with advanced NSCLC (stage IIIB or IV). METHODS: Fifty-eight patients were randomly assigned to receive either 10 intravenous 30-hour ATP infusions, with the infusions given at 2- to 4-week intervals, or no ATP. Outcome parameters were assessed every 4 weeks until 28 weeks. Between-group differences were tested for statistical significance by use of repeated-measures analysis, and reported P values are two-sided. RESULTS: Twenty-eight patients were allocated to receive ATP treatment and 30 received no ATP. Mean weight changes per 4-week period were -1.0 kg (95% confidence interval [CI] = -1.5 to -0.5) in the control group and 0.2 kg (95% CI = -0.2 to +0.6) in the ATP group (P =.002). Serum albumin concentration declined by -1.2 g/L (95% CI= -2.0 to -0.4) per 4 weeks in the control group but remained stable (0.0 g/L; 95% CI = -0.3 to +0.3) in the ATP group (P =.006). Elbow flexor muscle strength declined by -5.5% (95% CI = -9.6% to -1. 4%) per 4 weeks in the control group but remained stable (0.0%; 95% CI= -1.4% to +1.4%) in the ATP group (P =.01). A similar pattern was observed for knee extensor muscles (P =.02). The effects of ATP on body weight, muscle strength, and albumin concentration were especially marked in cachectic patients (P =.0002, P =.0001, and P =. 0001, respectively, for ATP versus no ATP). QOL score changes per 4-week period in the ATP group showed overall less deterioration than in the control group-physical scores (-0.2% versus -2.4%; P =. 0002); functional scores (+0.4% versus -5.5%; P =.02); psychologic scores (-0.7% versus -2.4%; P =.11); overall QOL score (+0.1% versus -3.5%; P =.0001). CONCLUSIONS: This randomized trial demonstrates that ATP has beneficial effects on weight, muscle strength, and QOL in patients with advanced NSCLC.

Adenosine Triphosphate↗
PubMed2000

Proliferative index in phaeochromocytomas: does it predict the occurrence of metastases?

Evaluation of the malignant potential of phaeochromocytomas in the absence of metastases presents a formidable challenge to both clinicians and pathologists. Until now, no widely accepted clinical, histological, immunohistochemical or molecular method has become available to discriminate malignant from benign phaeochromocytomas. In other endocrine tumours, estimation of proliferative activity by MIB-1 immunostaining has emerged as a promising approach for the determination of metastatic potential. In this study, the utility of MIB-1 immunostaining as a predictive marker for the occurrence of metastases in phaeochromocytomas was evaluated. In addition, the density of S100-positive sustentacular cells was studied, since their depletion has been identified as a negative predictive marker in smaller series. Furthermore, several clinicopathological parameters were evaluated. One hundred and ten patients operated on for a total of 99 benign and 37 malignant phaeochromocytomas were studied. All malignant tumours had documented metastases. The histopathological diagnosis of primary tumours and metastases was reviewed and graded for angioinvasion, capsular extension, and intra-tumoural necrosis. The proliferative index (percentage of MIB-1-positive cells) and the density of S100-positive cells were assessed. In addition, age at resection, associated familial tumour syndromes, tumour size, and tumour location were recorded. Univariate analysis revealed statistically significant correlations between malignancy and proliferative index (p<0.0005) and depletion of S100-positive sustentacular cells (p<0.0005). Fifty per cent of the malignant, but none of the benign phaeochromocytomas had a proliferative index greater than 2.5%. Higher age at resection (p=0. 03), sporadic occurrence (p<0.0005), extra-adrenal location (p<0. 0005), tumour size (p<0.0005), and necrosis (p=0.03) were also significantly associated with malignancy. Logistic regression showed that proliferative index (p=0.0072), size (p=0.0022), and extra-adrenal location (p=0.0012) of the primary tumour were independently predictive for malignancy. In conclusion, this study indicates that assessing the proliferative activity of phaeochromocytomas by MIB-1 immunohistochemistry can predict the occurrence of metastases. The predictive value of S100 immunostaining, tumour size, and extra-adrenal location of the tumour was also confirmed.

Adolescent↗
PubMed2000

Incidence trends for colorectal cancer in California: implications for current screening practices.

PURPOSE: The sensitivities of different screening methods for precancerous adenomas may affect the anatomical distribution of colorectal cancers. We used statewide data from California to describe time trends in the distribution of colorectal carcinoma. SUBJECTS AND METHODS: Between 1988 and 1996, 110,378 cases of colorectal cancer were recorded in the California Cancer Registry database. Tumors proximal to, but not including, the sigmoid colon were termed "right-sided." The remaining tumors, excluding the anus, were termed "left-sided." Multivariable analyses were used to determine the effects of age, sex, and race on changes in tumor location over time. RESULTS: During the study period, the annual incidence of colorectal cancer decreased steadily, from 200 to 162 cases per 100,000 residents. The decrease in left-sided tumors was about twice that observed on the right (-24.3% vs -11.6%). This disparity remained significant when adjusted for age, sex, and race (P = 0.0001). CONCLUSION: The incidence of colorectal cancer in California is decreasing, particularly for left-sided (distal) tumors. Current screening recommendations, which emphasize examination of the distal colon, may need to be expanded to include the entire colon.

Age Distribution↗
PubMed2000

Pediatric renal transplantation in the Netherlands.

In the Netherlands, pediatric kidney transplantation programs are available in four centers. We retrospectively analyzed the results obtained over the past decade. Between 1985 and 1995, 231 patients (139 boys) received 269 transplants, including 61 repeat. The recipients were aged 1.9-21.8 yrs (mean 10.9), the donors 0.3-63.3 yrs (median 11.4, mean 19.7). Immunosuppression consisted of corticosteroids, cyclosporin A and azathioprine, in various combinations and dosages. The patient survival during follow-up was 97%. The overall graft survival was 73% at 1 yr and 60% at 5 yrs after transplantation. Major causes of graft loss were acute rejection (21%), thrombosis (12%) and chronic rejection (28%). Acute rejection episodes were noted in 74% of all grafts. First acute rejection episodes had a moderate predictive value for graft loss (relative risk (RR), compared to rejection-free grafts, 5.9). First rejection episodes occurring later than 3 months after transplantation were considerably more predictive (RR 18.3) than early ones. Grafts from living related donors (n = 35) yielded a superior 5-yr graft survival (77%) and remained free of rejection more often than grafts from adult cadaveric donors(43% vs. 25%). The results of pre-emptive transplants were excellent (n = 13, 5-yr survival 100%). Repeat transplants had the same results as primary transplants. Recipients younger than 4 yrs showed a poor 5-yr graft survival of 38% (n = 13). Single kidney grafts from donors younger than 4 yrs (n = 35) had a 5-yr graft survival of 44%. In contrast, kidneys from these young donors did well if transplanted en bloc (n = 10, 5-yr graft survival 89%). These overall results are in line with those of others. The results may be improved by expansion of immunosuppressive therapy in the first year and by thrombosis prophylaxis in high-risk patient-donor combinations. Better results may be expected from more extensive use of living related donations, pre-emptive transplantation and en bloc transplantation instead of single kidneys of young donors.

Adolescent↗
PubMed2000

A longitudinal study on bone mineral density until adulthood in girls with Turner's syndrome participating in a growth hormone injection frequency-response trial.

OBJECTIVE: The aim of this study was to assess the volumetric bone mineral density (BMD) in girls with Turner's syndrome (TS) before and during growth hormone (GH) treatment in combination with low dose oestrogens as well as three years after discontinuation of GH treatment. DESIGN: In a prospective, randomized injection frequency-response study, the effect of GH treatment in combination with low dose ethinyl oestradiol (starting with 0.05 microgram/kg/day), on BMD was evaluated, comparing twice daily (BID) with once daily (OD) injections of a total GH dose of 6 IU/m2/day until adult height was reached. After discontinuation of GH treatment, the dosage of oestrogens was further increased to adult supplementation levels. PATIENTS: Nineteen untreated girls with TS, mean (SD) baseline pretreatment age 13.3 (1.7) (range 11.0-17.6) year. MEASUREMENTS: Before and during GH treatment, measurements of volumetric BMD were performed using phalangeal radiographic absorptiometry. In addition, the BMD measurements were repeated three years after discontinuation of GH treatment. BMD results were adjusted for bone age and sex, and expressed as SD-scores (SDS) using reference values of healthy Dutch girls. RESULTS: At baseline, most individual BMD values of cortical bone as well as those of trabecular bone were within the normal range of healthy girls. However, the mean BMD SDS of the trabecular bone was significantly lower than zero. During treatment, the BMD SDS showed a significant increment to values equal or higher than zero after mean (SD) GH treatment period of 36.6 (7.5) months. The increase in BMD of the cortical bone was significantly higher in the OD group than in the BID group. The BMD SDS in the last year of GH treatment was not significant different between the two injection frequency groups. Three years after discontinuation of GH treatment, the BMD values had increased further similar as in healthy girls, resulting in BMD values all within normal range or even higher. CONCLUSIONS: Most untreated girls with Turner syndrome, age >/= 11 years, have a normal volumetric BMD of the cortical, as well as of the trabecular bone compared to healthy girls. During GH treatment with 6 IU/m2/day in combination with low dose oestrogens, the BMD SDS increases significantly. After discontinuation of GH treatment and the use of oestrogens in an adult dosage, the BMD was as high as in young healthy women.

Adolescent↗
PubMed2000

Carbohydrate metabolism during growth hormone treatment and after discontinuation of growth hormone treatment in girls with Turner syndrome treated with once or twice daily growth hormone injections.

OBJECTIVE: To assess possible side-effects of treatment with supraphysiological GH dosages on carbohydrate (CH) metabolism in girls with Turner syndrome (TS) during GH treatment until adult height is reached as well as after discontinuation of GH treatment. DESIGN: In a prospective, randomized injection frequency-response study, the effect of GH treatment in combination with low dose ethinyl oestradiol on CH metabolism was evaluated, comparing twice daily (BID) with once daily (OD) injections of a total GH dose of 6 U/m2/day until adult height was reached. PATIENTS: Nineteen untreated girls with TS, mean (SD) pretreatment age 13.3 (1.7) (range 11.0-17.6) year. MEASUREMENTS: Glucose and insulin concentrations during oral glucose tolerance tests (OGTT) were measured before and during GH treatment, as well as at 6 months after discontinuation of GH treatment. RESULTS: GH treatment was discontinued after a mean of 43 (range 27-57) months. In one of the 19 girls, a different girl at each time point before, during and after discontinuation of GH treatment, the glucose response to OGTT after 120 minutes was above 7.8 mmol/l but below 11.1 mmol/l, indicating impaired glucose tolerance. None of the girls developed diabetes mellitus. Fasting glucose levels did not significantly change during, or after discontinuation of GH treatment. The 3 h area under the curve for time-concentration adjusted for fasting levels during the OGTT for glucose showed a significant decrease during GH treatment. In contrast to the glucose levels, GH treatment induced considerably higher insulin levels compared to pretreatment values. After discontinuation of GH insulin levels decreased to values comparable with pretreatment levels. None of these observed changes were different between the GH injection frequency groups. The changes in CH variables during and after discontinuation of GH were not related to changes in body mass index. CONCLUSIONS: GH treatment with 6 U/m2/day in combination with low dose ethinyl oestradiol in girls with Turner syndrome aged > or =11 years did not negatively influence glucose levels, but induced higher levels of insulin indicating relative insulin resistance. These changes in insulin levels were independent of the frequency of the GH injections (once vs. twice daily). After discontinuation of GH treatment, insulin values decreased to baseline levels.

Adolescent↗
PubMed2000

Role of macrophages in nephrolithiasis in rats: an analysis of the renal interstitium.

Interstitial calcium oxalate (CaOx) crystals can be found in primary oxalosis and in secondary hyperoxaluria. In a rat model for nephrolithiasis, we investigated whether such crystals can be removed by the surrounding interstitial cells. CaOx crystals were induced by a crystal-inducing diet based on ethylene glycol (EG) and ammonium chloride (CID). Both lithogenic compounds were added to the drinking water. After 9 days, the animals received normal drinking water for 2 days. Using this CID, only the interstitial crystals are retained. Subsequently, half of the population remained on normal drinking water (normo-oxaluria), whereas the other half received a low dose of EG alone (chronic hyperoxaluria). The rats were killed at regular times thereafter. The results showed that the kidney-associated oxalate significantly declined during normo-oxaluria, but remained high during chronic hyperoxaluria. Interstitial cells positive for the leukocyte common antigen (CD45; which identifies all types of leukocytes), the ED1 antigen (which is specific for monocytes and macrophages), and the major histocompatibility class II antigen (MCHII), respectively, had increased in number, with minor differences between both rat populations. The cells around the interstitial crystals were mostly positive for ED1. Multinucleate giant cells were regularly observed. These cells were positive for CD45 and ED1 and sometimes also for MCHII. The crystals in these cells were moderately positive for acid phosphatase and carbonic anhydrase II. It is concluded that interstitial CaOx crystals can be removed under normo-oxaluric conditions and that, in all likelihood, macrophages and multinucleate giant cells are involved in that process.

Ammonium Chloride↗
PubMed2000

Carbohydrate metabolism during long-term growth hormone (GH) treatment and after discontinuation of GH treatment in girls with Turner syndrome participating in a randomized dose-response study. Dutch Advisory Group on Growth Hormone.

To assess possible side-effects of GH treatment with supraphysiological doses on carbohydrate (CH) metabolism in girls with Turner syndrome (TS) during long term GH treatment and after discontinuation of GH treatment, the results of oral glucose tolerance tests and hemoglobin A1c measurements were analyzed in 68 girls with TS participating in a randomized dose-response trial. These previously untreated girls, aged 2-11 yr, were randomly assigned to 1 of 3 GH dosage groups: group A, 4 IU/m2 x day (-0.045 mg/kg x day); group B, first year ,4 IU/m2 day; thereafter, 6 IU/m2 x day (approximately 0.0675 mg/kg x day); group C, first year, 4 IU/m2 x day; second year, 6 IU/m2 x day; thereafter, 8 IU/m2 x day (approximately 0.090 mg/kg x day). After the first 4 yr, girls 12 yr of age or older started with 5 microg/kg BW-day 17beta-estradiol for induction of puberty. To assess the effects of long term high dose GH treatment on CH metabolism, the 7-yr data from the oral glucose tolerance tests in 9 girls of group C were evaluated (group C1). To determine whether the changes in CH metabolism during GH treatment would persist after discontinuation of GH treatment, the data for 28 girls who had reached adult height (group A, n = 9; group B, n = 10; group C, n = 9) were evaluated at baseline, after 4 yr of GH treatment, and 6 months after discontinuation of GH. Seven-year data for group C1 showed that glucose levels did not significantly change during GH treatment, whereas fasting insulin levels as well as glucose-induced insulin levels increased significantly. The data for the 28 girls who were treated with GH for a mean (SD) period of 85.3 (13.3) months demonstrated that the GH-induced higher insulin levels decreased to values close to or equal to pretreatment values after discontinuation of GH treatment. Changes in CH variables were not significantly related to the GH dose. Hemoglobin A1c levels never showed an abnormal value. The prevalence of impaired glucose tolerance was low, and none of the girls developed diabetes mellitus. In conclusion, long term GH treatment with dosages up to 8 IU/m2 x day in girls with TS has no adverse effects on glucose levels, but induced higher levels of insulin, indicating relative insulin resistance. The increased insulin levels during long term GH treatment decreased after discontinuation of GH treatment to values close to or equal to pretreatment values. Although the reversibility of the effects of long term GH is reassuring, the consequence of long term hyperinsulinism is still unknown.

Carbohydrate Metabolism↗
PubMed1999

Gender differences in the incidence of AD and vascular dementia: The EURODEM Studies. EURODEM Incidence Research Group.

OBJECTIVE: To study the difference in risk for dementing diseases between men and women. BACKGROUND: Previous studies suggest women have a higher risk for dementia than men. However, these studies include small sample sizes, particularly in the older age groups, when the incidence of dementia is highest. METHODS: Pooled analysis of four population-based prospective cohort studies was performed. The sample included persons 65 years and older, 528 incident cases of dementia, and 28,768 person-years of follow-up. Incident cases were identified in a two-stage procedure in which the total cohort was screened for cognitive impairment, and screen positives underwent detailed diagnostic assessment. Dementia and main subtypes of AD and vascular dementia were diagnosed according to internationally accepted guidelines. Sex- and age-specific incidence rates, and relative and cumulative risks for total dementia, AD, and vascular dementia were calculated using log linear analysis and Poisson regression. RESULTS: There were significant gender differences in the incidence of AD after age 85 years. At 90 years of age, the rate was 81.7 (95% CI, 63.8 to 104.7) in women and 24.0 (95% CI, 10.3 to 55.6) in men. There were no gender differences in rates or risk for vascular dementia. The cumulative risk for 65-year-old women to develop AD at the age of 95 years was 0.22 compared with 0.09 for men. The cumulative risk for developing vascular dementia at the age of 95 years was similar for men and women (0.04). CONCLUSION: Compared with men, women have an increased risk for AD. There are no gender differences in risk for vascular dementia.

Aged↗
PubMed1999

[Roaming through methodology. XVI. What to do about missing data].

Medical scientific research involving multiple measurements in patients is usually complicated by missing values. In case of missing values the choice is to limit the analysis to the complete cases or to analyse all available data. Both methods may suffer from substantial bias and may only be applied in a valid way if the rather strong assumption of 'missing completely at random' holds for the missing values, i.e. the missing value is not related to the other measured data nor to unmeasured data. Two other statistical methods may be applied to deal with missing values: the likelihood approach and the multiple imputation method. These methods make efficient use of all available data and take into account information implied by the available data. These methods are valid under the less stringent assumption of 'missing at random', i.e. the missing value is related to the other measured data, but not to unmeasured data. The best approach is to ensure that no data are missing.

Clinical Trials as Topic↗