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Biomedical subjects

Aeilko H Zwinderman

Publications and source records attributed to Aeilko H Zwinderman.

At least 37 records · Page 2Linked to original sources
PubMed2005

Genetic inflammatory factors predict restenosis after percutaneous coronary interventions.

BACKGROUND: Restenosis is a negative effect of percutaneous coronary intervention (PCI). No clinical factors are available that allow good risk stratification. However, evidence exists that genetic factors are important in the restenotic process as well as in the process of inflammation, a pivotal factor in restenosis. Association studies have identified genes that may predispose to restenosis, but confirmation by large prospective studies is lacking. Our aim was to identify polymorphisms and haplotypes in genes involved in inflammatory pathways that predispose to restenosis. METHODS AND RESULTS: The GENetic DEterminants of Restenosis (GENDER) project is a multicenter prospective study, including 3104 consecutive patients after successful PCI. Forty-eight polymorphisms in 34 genes in pathways possibly involved in the inflammatory process were analyzed. The 16Gly variant of the beta2-adrenergic receptor gave an increased risk of target vessel revascularization (TVR). The rare alleles of the CD14 gene (-260T/T), colony-stimulating factor 2 gene (117Thr/Thr), and eotaxin gene (-1328A/A) were associated with decreased risk of TVR. However, through the use of multiple testing corrections with permutation analysis, the probability of finding 4 significant markers by chance was 12%. CONCLUSIONS: Polymorphisms in 4 genes considered involved in the inflammatory reaction showed an association with TVR after PCI. Our results may contribute to the unraveling of the restenotic process. Given the explorative nature of this analysis, our results need to be replicated in other studies.

Amino Acid Substitution↗
PubMed2005

Lipoprotein lipase gene polymorphisms and the risk of target vessel revascularization after percutaneous coronary intervention.

OBJECTIVES: We sought to identify polymorphisms in genes that predispose to restenosis. BACKGROUND: Variations in the lipoprotein lipase (LPL) gene have been implicated in a number of pathophysiologic conditions associated with coronary heart disease. The present study examines the impact of polymorphisms in the LPL gene on restenosis (defined by target vessel revascularization [TVR]) in a large patient population undergoing percutaneous coronary intervention (PCI). A mouse model for restenosis was used to further investigate LPL's role in restenosis. METHODS: The GENetic DEterminants of Restenosis (GENDER) project is a multicenter, prospective study design that enrolled 3,104 consecutive patients after successful PCI. These patients were genotyped for four different LPL gene polymorphisms. In apolipoprotein E (ApoE)*3-Leiden transgenic mice, arterial messenger ribonucleic acid (mRNA) was used to assess LPL expression during a cuff-induced restenotic process. RESULTS: Using multivariable analysis, carriers of the 447Ter allele of the LPL enzyme showed a lower risk of TVR compared with 447Ser homozygotes (p = 0.005). In the mouse model, LPL mRNA levels were increased 40-fold compared with control arteries at 6 h after cuff placement. CONCLUSIONS: The LPL C/G polymorphism (Ser447Ter), resulting in a truncation of the two C-terminal amino acids of the mature LPL protein, appears to be an important protective factor for TVR in humans. The role of LPL in this process was further established in a mouse model, where LPL expression was very strongly up-regulated in the target arterial wall, suggesting a contribution of this lipolytic enzyme to restenosis. Possibly, LPL Ser447Ter genotyping may lead to better risk stratification and tailored therapy in the prevention of restenosis after PCI.

Angioplasty, Balloon, Coronary↗
PubMed2005

Colorectal liver metastases: CT, MR imaging, and PET for diagnosis--meta-analysis.

PURPOSE: To perform a meta-analysis to obtain sensitivity estimates of computed tomography (CT), magnetic resonance (MR) imaging, and fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for detection of colorectal liver metastases on per-patient and per-lesion bases. MATERIALS AND METHODS: MEDLINE, EMBASE, Web of Science, and CANCERLIT databases and Cochrane Database of Systematic Reviews were searched for relevant original articles published from January 1990 to December 2003. Criteria for inclusion of articles were as follows: Articles were reported in the English, German, or French language; CT, MR imaging, or FDG PET was performed to identify and characterize colorectal liver metastases; histopathologic analysis (surgery, biopsy, or autopsy), intraoperative observation (manual palpatation, intraoperative ultrasonography [US]), and/or follow-up US was the reference standard; and data were sufficient for calculation of true-positive or false-negative values. A random-effects linear regression model was used to obtain sensitivity estimates in assessment of liver metastases. RESULTS: Of 165 identified relevant articles, 61 fulfilled all inclusion criteria. Sensitivity estimates on a per-patient basis for nonhelical CT, helical CT, 1.5-T MR imaging, and FDG PET were 60.2%, 64.7%, 75.8%, and 94.6%, respectively; FDG PET was the most accurate modality. On a per-lesion basis, sensitivity estimates for nonhelical CT, helical CT, 1.0-T MR imaging, 1.5-T MR imaging, and FDG PET were 52.3%, 63.8%, 66.1%, 64.4%, and 75.9%, respectively; nonhelical CT had lowest sensitivity. Estimates of gadolinium-enhanced MR imaging and superparamagnetic iron oxide (SPIO)-enhanced MR imaging were significantly better, compared with nonenhanced MR imaging (P = .019 and P < .001, respectively) and with helical CT with 45 g of iodine or less (P = .02 and P < .001, respectively). For lesions of 1 cm or larger, SPIO-enhanced MR imaging was the most accurate modality (P < .001). CONCLUSION: FDG PET had significantly higher sensitivity on a per-patient basis, compared with that of the other modalities, but not on a per-lesion basis. Sensitivity estimates for MR imaging with contrast agent were significantly superior to those for helical CT with 45 g of iodine or less.

Colorectal Neoplasms↗
PubMed2005

Compromised LCAT function is associated with increased atherosclerosis.

BACKGROUND: Prospective epidemiological studies have shown that low plasma levels of HDL cholesterol (HDL-C) are associated with an increased risk for cardiovascular disease (CVD). Despite nearly 40 years of research, however, it is unclear whether this also holds true for individuals with severely reduced levels of HDL-C due to mutations in the lecithin:cholesterol acyltransferase (LCAT) gene. Better insight into CVD risk in these individuals may provide clues toward the potential of LCAT as a pharmaceutical target to raise HDL-C levels. METHODS AND RESULTS: Lipids, lipoproteins, high-sensitivity C-reactive protein (CRP), and carotid artery intima-media thickness (IMT) were assessed in 47 heterozygotes for LCAT gene mutations and 58 family controls. Compared with controls, heterozygotes presented with a mean 36% decrease in HDL-C levels (P<0.0001), a 23% increase in triglyceride levels (P<0.0001), and a 2.1-fold increase in CRP levels (P<0.0001). Mean carotid IMT was significantly increased in heterozygotes compared with family controls (0.623+/-0.13 versus 0.591+/-0.08 mm). After adjustment for age, gender, and alcohol use, this difference proved statistically significant (P<0.0015). CONCLUSIONS: The data show that heterozygosity for LCAT gene defects is associated with low HDL-C levels and elevated concentration of triglycerides and CRP in plasma. This phenotype underlies increased IMT in carriers versus controls, which suggests that LCAT protects against atherosclerosis. This in turn indicates that targeting LCAT to raise HDL-C may reduce CVD risk.

Adult↗
PubMed2005

Effect of a high-intensity weight-bearing exercise program on radiologic damage progression of the large joints in subgroups of patients with rheumatoid arthritis.

OBJECTIVE: To investigate whether a high-intensity exercise program accelerates the rate of radiologic damage of the large joints in predefined subgroups of patients with rheumatoid arthritis. METHODS: The data of 277 participants in a 2-year randomized controlled trial, comparing the effects of high-intensity exercises with usual care, were used. Linear regression analysis was used to test which predefined variables at baseline (age, disease duration, disease activity, physical capacity, functional ability, joint damage) modified the effect of high-intensity exercise on the progression of radiologic damage of the large joints over 24 months. RESULTS: Baseline radiologic joint damage was the only variable associated with the effect of high-intensity exercise on joint damage progression in large joints. In a subgroup of 218 patients with no or little joint damage (defined as Larsen score < or = 5; 80% of our study population) the proportions of patients with an increase in joint damage were similar for the exercise and usual-care group (35% versus 36%, risk ratio [RR] 1.0 [0.7-1.4]; P = not significant), whereas, in a subgroup of 59 patients who already had extensive damage of large joints (defined as Larsen score >5) the proportion was significantly higher in the exercise group (85% versus 48%, RR 1.8 [1.2-2.6]; P < 0.05). CONCLUSION: High-intensity weight-bearing exercises appear to accelerate joint damage progression in patients with preexisting extensive damage. Patients with extensive large joint damage should, therefore, be advised to refrain from activities excessively loading the damaged joints.

Adult↗
PubMed2005

Reliability of computerized image analysis for the evaluation of serial synovial biopsies in randomized controlled trials in rheumatoid arthritis.

Analysis of biomarkers in synovial tissue is increasingly used in the evaluation of new targeted therapies for patients with rheumatoid arthritis (RA). This study determined the intrarater and inter-rater reliability of digital image analysis (DIA) of synovial biopsies from RA patients participating in clinical trials. Arthroscopic synovial biopsies were obtained before and after treatment from 19 RA patients participating in a randomized controlled trial with prednisolone. Immunohistochemistry was used to detect CD3+ T cells, CD38+ plasma cells and CD68+ macrophages. The mean change in positive cells per square millimetre for each marker was determined by different operators and at different times using DIA. Nonparametric tests were used to determine differences between observers and assessments, and to determine changes after treatment. The intraclass correlations (ICCs) were calculated to determine the intrarater and inter-rater reliability. Intrarater ICCs showed good reliability for measuring changes in T lymphocytes (R = 0.87), plasma cells (R = 0.62) and macrophages (R = 0.73). Analysis by Bland-Altman plots showed no systemic differences between measurements. The smallest detectable changes were calculated and their discriminatory power revealed good response in the prednisolone group compared with the placebo group. Similarly, inter-rater ICCs also revealed good reliability for measuring T lymphocytes (R = 0.68), plasma cells (R = 0.69) and macrophages (R = 0.72). All measurements identified the same cell types as changing significantly in the treated patients compared with the placebo group. The measurement of change in total positive cell numbers in synovial tissue can be determined reproducibly for various cell types by DIA in RA clinical trials.

Arthritis, Rheumatoid↗
PubMed2005

Responsiveness: a reinvention of the wheel?

BACKGROUND: Since the mid eighties, responsiveness is considered to be a separate property of health status questionnaires distinct from reliability and validity. The aim of the study was to assess the strength of the relationship between internal consistency reliability, referring to an instrument's sensitivity to differences in health status among subjects at one point in time, and responsiveness referring to sensitivity to health status changes over time. METHODS: We used three different datasets comprising the scores of patients on the Barthel, the SIP and the GO-QoL instruments at two points in time. The internal consistency was reduced stepwise by removing the item that contributed most to a scale's reliability. We calculated the responsiveness expressed by the Standardized Response Mean (SRM) on each set of remaining items. The strength of the relationship between the thus obtained internal consistency coefficients and SRMs was quantified by Spearman rank correlation coefficients. RESULTS: Strong to perfect correlations (0.90-1.00) was found between internal consistency coefficients and SRMs for all instruments indicating, that the two can be used interchangeably. CONCLUSION: The results contradict the conviction that responsiveness is a separate psychometric property. The internal consistency coefficient adequately reflects an instrument's potential sensitivity to changes over time.

Activities of Daily Living↗
PubMed2005

Modelling the correlation between the activities of adjacent genes in Drosophila.

BACKGROUND: Correlation between the expression levels of genes which are located close to each other on the genome has been found in various organisms, including yeast, drosophila and humans. Since such a correlation could be explained by several biochemical, evolutionary, genetic and technological factors, there is a need for statistical models that correspond to specific biological models for the correlation structure. RESULTS: We modelled the pairwise correlation between the expressions of the genes in a Drosophila microarray experiment as a normal mixture under Fisher's z-transform, and fitted the model to the correlations of expressions of adjacent as well as non-adjacent genes. We also analyzed simulated data for comparison. The model provided a good fit to the data. Further, correlation between the activities of two genes could, in most cases, be attributed to either of two factors: the two genes both being active in the same age group (adult or embryo), or the two genes being in proximity of each other on the chromosome. The interaction between these two factors was weak. CONCLUSIONS: Correlation between the activities of adjacent genes is higher than between non-adjacent genes. In the data we analyzed, this appeared, for the most part, to be a constant effect that applied to all pairs of adjacent genes.

Algorithms↗
PubMed2005

Development of a standardized method of assessment of radiographs and radiographic change in juvenile idiopathic arthritis: introduction of the Dijkstra composite score.

OBJECTIVE: To evaluate the sensitivity to change of a newly developed radiologic assessment tool, the Dijkstra score, and to develop a numeric composite score and progressor classification scheme to apply in juvenile idiopathic arthritis (JIA) trials. METHODS: A placebo-controlled trial of sulfasalazine (SSZ) in patients with oligoarticular- and polyarticular-onset JIA yielded the data for this study. Data were obtained from 418 sets of radiographs of the clinically involved and contralateral joints (at study entry and at 6 months' followup) from 66 JIA patients. The Dijkstra score assesses the presence or absence of swelling, osteopenia, joint space narrowing, growth abnormalities, subchondral bone cysts, erosions, and malalignment. These signs were combined in the Dijkstra composite score, to assess inflammation (DI), growth (DG), and damage (DD). Progression was defined as an increase in either the DG or the DD score. Scores were evaluated among all radiographs, a standard set of films (hand, foot, and knee), and per patient. All scores were used to explore differences between the 2 treatment groups. RESULTS: Over time, 58% of joints remained normal, 23% remained abnormal but stable, 14% showed an increase in signs, and 5% showed a decrease in signs. Of the 66 JIA patients, 12% had normal radiographic findings throughout followup, 27% showed abnormalities at some sites without change, and 61% showed change in at least 1 site. Changes in the DI, DG, and DD scores varied considerably per type of joint and occurred most frequently in joints of the standard set. DI and DG scores changed most often in the knees, while DD scores changed primarily in the hands and feet. The disease course in 8% of joints was classified as progressive. Films of SSZ-treated patients, versus the placebo group, showed less deterioration by the DD scores (P = 0.04), and the disease course was more often classified as nonprogressive in the SSZ group (P = 0.037). When progressors were defined as those who had at least one radiograph showing progression, significantly more placebo-treated patients were considered progressors (P = 0.046). CONCLUSION: In this trial data set, the Dijkstra composite score and the resulting progressor classification system are comprehensive and feasible tools that are sensitive to change and discriminate between clinical situations. They should now be tested by other investigators and in other data sets.

Antirheumatic Agents↗
PubMed2005

Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews.

BACKGROUND AND OBJECTIVES: Studies of diagnostic accuracy most often report pairs of sensitivity and specificity. We demonstrate the advantage of using bivariate meta-regression models to analyze such data. METHODS: We discuss the methodology of both the summary Receiver Operating Characteristic (sROC) and the bivariate approach by reanalyzing the data of a published meta-analysis. RESULTS: The sROC approach is the standard method for meta-analyzing diagnostic studies reporting pairs of sensitivity and specificity. This method uses the diagnostic odds ratio as the main outcome measure, which removes the effect of a possible threshold but at the same time loses relevant clinical information about test performance. The bivariate approach preserves the two-dimensional nature of the original data. Pairs of sensitivity and specificity are jointly analyzed, incorporating any correlation that might exist between these two measures using a random effects approach. Explanatory variables can be added to the bivariate model and lead to separate effects on sensitivity and specificity, rather than a net effect on the odds ratio scale as in the sROC approach. The statistical properties of the bivariate model are sound and flexible. CONCLUSION: The bivariate model can be seen as an improvement and extension of the traditional sROC approach.

Data Interpretation, Statistical↗
PubMed2005

Polymorphisms in APOA1 and LPL genes are statistically independently associated with fasting TG in men with CAD.

The objective of this paper was to identify the single nucleotide polymorphisms (SNPs) that show unshared effects on plasma triglyceride (TG) levels and to investigate whether these SNPs show statistically independent effects on plasma TG levels. In total, 59 polymorphisms in 20 genes involved in lipid metabolism were investigated. Polymorphisms were selected for a multivariate ANOVA model if they showed an univariate association with TG (after adjustment for HDL-C and LDL-C) in more than 50% of bootstrap samples that were made from the original data. The multivariate model included 512 men with coronary artery disease from the REGRESS study who were completely genotyped for eight polymorphisms selected in the univariate procedure (ie, APOA1 G(-75)A, ABCA1 C(-477)T, ABCA1 G1051A, APOC3 T3206G, APOE Arg158Cys, LIPC C(-514)T, LPL Asn291Ser and LPL Ser447Stop). The gene variants APOA1 G(-75)A (P=0.04) and LPL Asn291Ser (P=0.03) were significantly associated with plasma TG levels in this multivariate analysis. The eight polymorphisms explained 8.9% of the variation in plasma TG levels. In conclusion, this study showed statistically independent effects of gene variants in the APOA1 and LPL genes on fasting plasma levels of TG. Nevertheless, only a small part of variation in TG levels could be explained by the polymorphisms.

Apolipoprotein A-I↗
PubMed2005

Genetic variation in the rate-limiting enzyme in cholesterol catabolism (cholesterol 7alpha-hydroxylase) influences the progression of atherosclerosis and risk of new clinical events.

CHD (coronary heart disease) is a complex disorder which is, in part, related to serum cholesterol levels. The rate-limiting enzyme in the catabolism of cholesterol into bile acids is CYP7A1 (cholesterol 7alpha-hydroxylase). The effect of the CYP7A1 A-278C promoter polymorphism on the progression of atherosclerosis, risk of a new clinical event and the influence of this variant on cholesterol-lowering therapy was investigated in 715 male patients with coronary atherosclerosis participating in REGRESS (Regression Growth Evaluation Statin Study). Genotype distributions were as follows: 283 with AA; 330 with AC and 102 with CC. There were no significant differences in baseline characteristics and serum lipids between genotypes. After 2 years, CC carriers had more progression of diffuse and focal atherosclerosis compared with AA carriers, as indicated by a larger decrease in MSD (mean segment diameter; 0.09 mm compared with 0.06 mm respectively; P=0.009) and MOD (minimum obstruction diameter; 0.09 mm compared with 0.05 mm respectively; P=0.024). Inclusion of risk factors for CHD in the model showed the same trend, although not significant for MOD (P=0.01 for MSD, and P=0.06 for MOD). In addition, CC carriers had an almost 2-fold higher risk of a new clinical event compared with AA carriers [RR (95% CI) 1.93 (1.11-3.36); P=0.02; where RR is relative risk and CI is confidence interval]. Inclusion of risk factors for CHD in the model showed the same trend, although not significant [RR (95% CI), 1.74 (0.96-3.12); P=0.06]. In conclusion, we present evidence that the CC variant of the A-278C polymorphism in the rate-limiting enzyme in the catabolism of cholesterol, CYP7A1, increases the progression of atherosclerosis and possibly the risk of a new clinical event.

Analysis of Variance↗
PubMed2005

Evaluation of saphenous vein coronary artery bypass graft flow by cardiovascular magnetic resonance.

Cardiovascular magnetic resonance (CMR) with flow velocity mapping has emerged as a noninvasive method to measure flow in saphenous vein coronary artery bypass grafts. The aim of the current study was to retrospectively test two previously described analysis methods on a large CMR data set and to compare their diagnostic accuracy in detecting diseased vein grafts. In 125 vein grafts of 68 patients, volume flow parameters (volume flow, systolic and diastolic peak flow, diastolic-to-systolic flow ratio at rest and during adenosine stress, and flow reserve) were derived from the velocity maps. Method 1 implemented basal flow < 20 ml/min or flow reserve < 2, yielding a sensitivity and specificity of 70% and 38% in the detection of a diseased graft or recipient vessel. Method 2 used receiver operating characteristic (ROC) curve analysis and implemented all significant volume flow parameters in a logistic regression model, yielding a sensitivity of 74% with a specificity of 68% in the detection of a diseased graft or recipient vessel. Evaluating single and sequential grafts separately, this method yielded a sensitivity and specificity of 79% and 87% for single grafts, and 62% and 94% for sequential grafts in the detection of > or = 50% stenosis in grafts or recipient vessels. Cut-off values were formulated for the respective volume flow parameters, which maximally separate grafts with and without > or = 50% stenosis. Using ROC curve analysis with logistic regression the specificity of the analysis method improved considerably. For the current data set the best results were acquired when single and sequential grafts were separately analyzed.

Aged↗
PubMed2005

Tumor necrosis factor-alpha plays an important role in restenosis development.

Genetic factors appear to be important in the restenotic process after percutaneous coronary intervention (PCI), as well as in inflammation, a pivotal factor in restenosis. TNFalpha, a key regulator of inflammatory responses, may exert critical influence on the development of restenosis after PCI. The GENetic DEterminants of Restenosis (GENDER) project included 3104 patients who underwent a successful PCI. Systematic genotyping for six polymorphisms in the TNFalpha gene was performed. The role of TNFalpha in restenosis was also assessed in ApoE*3-Leiden mice, TNFalpha knockout mice, and by local delivery of a TNFalpha biosynthesis inhibitor, thalidomide. The -238G-1031T haplotype of the TNFalpha gene increased clinical and angiographic risk of restenosis (P=0.02 and P=0.002, respectively). In a mouse model of reactive stenosis, arterial TNFalpha mRNA was significantly time-dependently up-regulated. Mice lacking TNFalpha or treated locally with thalidomide showed a reduction in reactive stenosis (P=0.01 and P=0.005, respectively). Clinical and preclinical data indicate that TNFalpha plays an important role in restenosis. Therefore, TNFalpha genotype may be used as a risk marker for restenosis and may contribute to individual patient screening prior to PCI in clinical practice. Inhibition of TNFalpha may be an anti-restenotic target strategy.

Aged↗
PubMed2005

The use of a newly designed nonabsorbable polymeric stent in reconstructing the vas deferens: a feasibility study in New Zealand white rabbits.

OBJECTIVES: To investigate the use of a newly designed stent in the reconstruction of the vas deferens. MATERIALS AND METHODS: In 26 New Zealand White rabbits, 13 conventional one-layer microscopic reconstructions were compared with 13 stented reconstructions of the vas deferens. The newly designed nonabsorbable polymeric stent was shaped to facilitate the rejoining of the two loose ends of the vas deferens, using a central ridge to prevent migration. Semen was collected before and after surgery, using an artificial vaginal system (26 samples before and 115 after surgery). The individual and average total sperm count, motility and progressive motile sperm density (PMSD), were compared after surgery for both groups. After the final semen analysis, rabbits were killed and patency was assessed histologically at the site of the anastomosis. RESULTS: After an initial decline the mean total sperm count increased in both groups. The increase was significantly larger (P = 0.05) in the stented rabbits. The mean motility and PMSD showed no significant differences between both groups (P = 0.11 and 0.71, respectively). Histological examination of the anastomosed area showed partial obstruction (>50% narrowing of the original lumen) in five of the 13 conventionally treated rabbits, with no strictures in the stented group. Despite the narrowing in the conventional group the patency rates were not affected. The mean (range) operating time for the conventional and stented groups was 132 (99-168) and 98 (62-113) min, respectively (P < 0.001). CONCLUSIONS: The total sperm counts, motility and PMSD showed no or little difference after surgery between the conventional and stented rabbits. The stented reconstruction was easy, had no secondary stricturing and reduced the operating time.

Animals↗
PubMed2005

Proposal for a definition of lifelong premature ejaculation based on epidemiological stopwatch data.

INTRODUCTION: Consensus on a definition of premature ejaculation has not yet been reached because of debates based on subjective authority opinions and nonstandardized assessment methods to measure ejaculation time and ejaculation control. AIM: To provide a definition for lifelong premature ejaculation that is based on epidemiological evidence including the neurobiological and psychological approach. METHODS: We used the 0.5 and 2.5 percentiles as accepted standards of disease definition in a skewed distribution. We applied these percentiles in a stopwatch-determined intravaginal ejaculation latency time (IELT) distribution of 491 nonselected men from five different countries. The practical consequences of 0.5% and 2.5% cutoff points for disease definition were taken into consideration by reviewing current knowledge of feelings of control and satisfaction in relation to ejaculatory performance of the general male population. MAIN OUTCOME MEASURES: Literature arguments to be used in a proposed consensus on a definition of premature ejaculation. RESULTS: The stopwatch-determined IELT distribution is positively skewed. The 0.5 percentile equates to an IELT of 0.9 minute and the 2.5 percentile an IELT of 1.3 minutes. However, there are no available data in the literature on feelings of control or satisfaction in relation to ejaculatory latency time in the general male population. Random male cohort studies are needed to end all speculation on this subject. Exact stopwatch time assessment of IELT in a multinational study led us to propose that all men with an IELT of less than 1 minute (belonging to the 0.5 percentile) have "definite" premature ejaculation, while men with IELTs between 1 and 1.5 minutes (between 0.5 and 2.5 percentile) have "probable" premature ejaculation. Severity of premature ejaculation (nonsymptomatic, mild, moderate, severe) should be defined in terms of associated psychological problems. CONCLUSION: We define lifelong premature ejaculation as a neurobiological dysfunction with an unacceptable increase of risk to develop sexual and psychological problems anywhere in a lifetime. By defining premature ejaculation from an authority-defined disorder into a dysfunction based on epidemiological evidence it is possible to establish consensus based on epidemiological evidence. Additional epidemiological stopwatch studies are needed for a final decision of IELT values at both percentile cutoff points.

Age Factors↗
PubMed2005

Thyroid-stimulating hormone assessments in a Dutch cohort of 620 men with lifelong premature ejaculation without erectile dysfunction.

INTRODUCTION: Apart from the involvement of central serotonergic neurotransmission on lifelong premature ejaculation, interference of thyroid function has been speculated. AIM: To study thyroid function in a large group of men with lifelong premature ejaculation (LPE). METHODS: Lifelong premature ejaculation was defined as an intravaginal ejaculation latency time (IELT) of less than 1 minute. Any consecutive man with LPE and no erectile dysfunction assessed by medical history and the International Index of Erectile Function (IIEF-5) was eligible for the study. Apart from the assessment of thyroid-stimulating hormone (TSH) also free thyroxin (f T4) was determined in case of a TSH of <0.3 mU/L or TSH of >4.0 mU/L (being the lower and upper limits of normal values, respectively). Blood samples were drawn throughout the day within office hours. MAIN OUTCOME MEASURES: Thyroid-stimulating hormone and f T4. RESULTS: Included were 620 men; age (mean+/-SD) was 39.9+/-9.4 years (range 19-65). TSH concentrations from morning, early and late afternoon samples did not differ. The geometrical mean TSH concentration was 0.85 mU/L (95% confidence intervals: 0.82-0.90) with a coefficient of variation of 57.9%. Fourteen men had a TSH of <0.3 mU/L (2.2%), while five men (0.8%) of >4.0 mU/L. All men with an abnormal TSH had a normal f T4 (between 10 and 20 pmol/L). No relationship was found between age and TSH concentrations. CONCLUSION: Thyroid-stimulating hormone distribution was analyzed in a cohort of Dutch men with lifelong premature ejaculation and no erectile dysfunction. According to statistical analysis, there appeared to be no interaction between this ejaculatory complaint and the prevalence of thyroidal dysfunction. However, further studies are needed to gain more insight into the role of thyroid dysfunction and regulation of ejaculation time.

Adult↗