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The clinical predictors of sleepiness correlated with the multiple sleep latency test in an Asian Singapore population.

STUDY OBJECTIVES: To explore the clinical predictors of sleepiness as objectively determined by the Multiple Sleep Latency Test with the Epworth Sleepiness Scale, age, body mass index, and overnight polysomnographic parameters at a tertiary referral center Sleep Disorders Unit. DESIGN: Retrospective, consecutive case series review. SETTING: A multidisciplinary sleep disorders unit in Singapore General Hospital, a tertiary-care university-affiliated hospital. PATIENTS: 72 consecutive patients evaluated for sleep disorders with overnight polysomnograms and Multiple Sleep Latency Tests between March 2002 and September 2002. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Mean sleep latency on the Multiple Sleep Latency Test was 9.0 +/- 4.4 minutes, and mean Epworth Sleepiness Scale score was 10.8 +/- 5.8. On univariate analysis, mean sleep latency on the Multiple Sleep Latency Test showed a significant negative correlation with the Epworth Sleepiness Scale score, apnea-hypopnea index, body mass index, arousal index, and time spent below 90% oxygen saturation during overnight polysomnography. After performing multiple linear regression, only Epworth Sleepiness Scale score and apnea-hypopnea index remained significantly correlated (P = .039 and P = .008, respectively). An Epworth Sleepiness Scale score of 8 or above predicted a mean sleep latency on the Multiple Sleep Latency Test of less than 10 minutes with a sensitivity of 73.9% and specificity of 50.0%. CONCLUSIONS: The Epworth Sleepiness Scale and apnea-hypopnea index are useful predictors of sleepiness in our Asian Singapore population.

Adult↗

Value of some laboratory and clinical measurements in the treatment plan for advanced periodontitis.

In our previous study, we reported that only 13 of 46 adult patients with advanced periodontitis responded well to initial non-surgical periodontal therapy. In the present follow-up study, the remaining 33 patients were randomly treated further using either modified Widman flap surgery or systemic metronidazole. The patients responding unsatisfactorily to this 2nd treatment phase, received supplementary systemic chemotherapy or surgery, respectively. By using this study design, we determined which baseline clinical variables and/or laboratory findings predicted the treatment outcome in these study patients. Clinical variables included the assessment of bleeding, suppuration, probing pocket depth, furcation lesions, relative attachment level and radiographic infrabony defects. Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were cultured from subgingival plaque samples. The specific IgG and IgA antibody levels against 5 serotypes of A. actinomycetemcomitans were determined in serum and saliva. Elastase-like, trypsin-like and general protease activities were assessed from saliva. The bivariate statistical analyses showed that the most pronounced difference between the patients responding well to initial non-surgical therapy (group MC, n = 13), to either supplementary surgery or chemotherapy (group FT1, n = 11), or those responding to the complex therapy (group FT2, n = 17), was the prior extent of periodontal destruction expressed as the proportion of > or = 6 mm deep periodontal pockets. When multiple linear regression was used to investigate the influence of clinical and laboratory findings on the variation of treatment response between the 3 groups, the most significant explanatory factor was the simultaneous presence of subgingival A. actinomycetemcomitans and multiple deep periodontal pockets. None of the immunological or biochemical variables used had any further influence in the model. Pretreatment microbiological examination, especially for the detection of A. actinomycetemcomitans, seems to be a valuable laboratory screening method for identifying complex treatment need in adult patients with advanced periodontitis. However, the evaluation of the extent and pattern of periodontal breakdown remains crucial for choosing the treatment strategy including surgery and/or chemotherapy in A. actinomycetemcomitans-infected adult periodontitis patients.

Adult↗

The relationship between cognitive characteristics and decision making.

Team handball players (N = 118) underwent a number of cognitive tests to examine how much of their decision making (DM) ability, as measured through responses to game slides projected to them for 2 seconds under low and high exertion levels (i.e., walking and running), was accounted for by cognitive components. A stepwise multiple linear regression indicated that experience was the most pronounced predictor of DM capacity in both exertion conditions. In the walking condition, concentrational consistency, avoidance of concentrational mistakes, and short-term memory, together with experience, produced a multiple R of 0.48 with decision making. In the running condition, choice reaction time (CRT), intelligence, and short-term memory, together with experience, correlated 0.46 with DM. These differences in cognitive abilities, as predictors of DM under walking and running conditions, are discussed in terms of information processing models and other cognitive processes.

Attention↗

A multivariate prediction model for microarray cross-hybridization.

BACKGROUND: Expression microarray analysis is one of the most popular molecular diagnostic techniques in the post-genomic era. However, this technique faces the fundamental problem of potential cross-hybridization. This is a pervasive problem for both oligonucleotide and cDNA microarrays; it is considered particularly problematic for the latter. No comprehensive multivariate predictive modeling has been performed to understand how multiple variables contribute to (cross-) hybridization. RESULTS: We propose a systematic search strategy using multiple multivariate models [multiple linear regressions, regression trees, and artificial neural network analyses (ANNs)] to select an effective set of predictors for hybridization. We validate this approach on a set of DNA microarrays with cytochrome p450 family genes. The performance of our multiple multivariate models is compared with that of a recently proposed third-order polynomial regression method that uses percent identity as the sole predictor. All multivariate models agree that the 'most contiguous base pairs between probe and target sequences,' rather than percent identity, is the best univariate predictor. The predictive power is improved by inclusion of additional nonlinear effects, in particular target GC content, when regression trees or ANNs are used. CONCLUSION: A systematic multivariate approach is provided to assess the importance of multiple sequence features for hybridization and of relationships among these features. This approach can easily be applied to larger datasets. This will allow future developments of generalized hybridization models that will be able to correct for false-positive cross-hybridization signals in expression experiments.

Algorithms↗

Impact of arterial blood pressure and albuminuria on the progression of diabetic nephropathy in IDDM patients.

To evaluate the impact of systemic blood pressure and albuminuria on the progression of diabetic nephropathy, we followed 41 IDDM patients with persistent albuminuria (> 300 mg/24 h) by measuring glomerular filtration rate (51Cr-EDTA technique), blood pressure, and albuminuria. None of the patients were taking drugs other than insulin. Arterial blood pressure, albuminuria, and blood glucose were measured four to eight times/yr, whereas glomerular filtration rate was determined twice yearly. During the median investigation period of 36 (15-66) mo, glomerular filtration rate decreased from 102 +/- 23 to 83 +/- 27 ml.min-1 x 1.73 m-2 (P < 0.001), albuminuria increased from 633 to 1435 micrograms/min (P < 0.001), and blood pressure rose from 133/85 +/- 10/9 to 149/93 +/- 8/11 mmHg (P < 0.001). Univariate analysis revealed a significant correlation between the rates of decline in glomerular filtration rate and diastolic blood pressure (r = 0.52, P < 0.01) and glomerular filtration rate and albuminuria (r = 0.34, P < 0.02). But stepwise multiple linear regression analysis only showed a significant correlation between the rate of decline in glomerular filtration rate and diastolic blood pressure (P < 0.01). In patients with diastolic blood pressure below the mean value of 89 mmHg, stepwise multiple regression analysis showed that albuminuria and not blood pressure was correlated significantly with rate of decline in glomerular filtration rate. Patients were stratified by average value of diastolic blood pressure measured during the investigation period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Bioavailability of zinc from inorganic and organic sources for pigs fed corn-soybean meal diets.

Two experiments were conducted with pigs 1) to determine the effect of supplemental Zn on growth performance, bone Zn, and plasma Zn in pigs fed Zn-unsupplemented, corn-soybean meal diets and 2) to assess bioavailability of Zn from inorganic and organic Zn sources. In both experiments, weanling pigs were fed a diet with no supplemental Zn for 5 wk to deplete their Zn stores. In Exp. 1, 192 pigs were fed a corn-soybean meal diet (growing diet, 32 mg/kg of Zn; finishing diet, 27 mg/kg of Zn) supplemented with feed-grade ZnSO4.H2O to provide 0, 5, 10, 20, 40, and 80 mg/kg of supplemental Zn. Supplemental Zn did not affect weight gain, feed intake, or gain/feed during either the growing or the finishing period (P > .05). However, bone and plasma Zn concentrations increased linearly (P < .01) in response to supplemental Zn at dietary Zn levels between 27 mg/kg (basal) and 47 mg/kg (breakpoint). In Exp. 2, three levels of supplemental Zn from ZnSO4.H2O (0, 7.5, and 15 mg/kg of supplemental Zn) were used to construct a standard curve (metacarpal, coccygeal vertebrae, and plasma Zn concentrations regressed on supplemental Zn intake; R2 = .93, .89, and .82, respectively). From the standard curve, the bone and plasma Zn concentrations obtained from pigs fed 15 mg/kg of supplemental Zn from ZnO and 7.5 mg/kg of supplemental Zn from Zn-methionine (ZnMET) and Zn-lysine (ZnLYS) were used to calculate bioavailable Zn via multiple linear regression, slope-ratio analysis. The estimates of Zn bioavailability differed depending on which variable was used. Overall trends indicated the following rankings: ZnSO4.H2O > ZnMet > ZnO > ZnLys.

Animal Feed↗

Relationships between transcriptional and translational control of gene expression in Saccharomyces cerevisiae: a multiple regression analysis.

Natural selection for an increased translation efficiency has been proposed as the main determinant for the bias in codon usage observed in many genes of Saccharomyces cerevisiae. Recently, the efficiency of transcription of a large number of yeast genes has been determined, based on the cellular content of the respective mRNAs: this provides an additional dimension to the study of the multisep process of gene expression. Using a representative set of yeast genes with a known level of transcription, the relationship between transcriptional and translational steps was evaluated by a multiple linear regression model. This analysis demonstrated a positive correlation between the amount of transcript, given as the number of mRNA copies per cell for each individual gene, and indices evaluating the effects of translational selection on the corresponding codon usage pattern. This finding suggests a close association of the cellular mRNA content, regulated also at the transcriptional level, to its efficiency of translation, mediated by a fine-tuning of codon usage strategy. Moreover, multiple regression analysis demonstrated that the transcription level of a gene can be approximately predicted using indices of bias deriving from its nucleotide sequence. This allowed for an extensive investigation of uncharacterized regions of the complete genome sequence of S. cerevisiae, to detect new potential short protein coding genes that were not considered by previous searching procedures. Several small open reading frames exhibiting a statistically significant coding potential were thus identified as good candidates for functional analysis.

Amino Acid Sequence↗

Physical fitness of 9 year olds in England: related factors.

STUDY OBJECTIVE: To examine the influence of social factors, passive smoking, and other parental health related factors, as well as anthropometric and other measurements on children's cardiorespiratory fitness. DESIGN: This was a cross sectional study. SETTING: The analysis was based on 22 health areas in England. PARTICIPANTS: The subjects were 299 boys and 282 girls aged 8 to 9 years. Parents did not give positive consent for 15% of the eligible sample. A further 25% of the eligible sample did not participate because the cycle-ergometer broke down, study time was insufficient, or they were excluded from the analysis because they were from ethnic minority groups or had missing data on one continuous variable. MEASUREMENTS AND MAIN RESULTS: Cardiorespiratory fitness was determined using the cycle-ergometer test. It was measured in terms of PWC85%-that is, power output per body weight (watt/kg) assessed at 85% of maximum heart rate. The association between children's fitness and biological and social factors was analysed in two stages. Firstly, multiple logistic analysis was used to examine the factors associated with the children's ability to complete the test for at least four minutes. Secondly, multiple linear regression analysis was used to examine the independent association of the factors with PWC85%. In the logistic analysis, shorter children, children with higher blood pressure, and boys with a larger sibship size had poorer fitness. In the multiple regression analysis, only height (p < 0.001) was positively associated, and the sum of skinfold thicknesses at four sites (p = 0.001) was negatively associated with fitness in both sexes. In girls, a positive association was found with pre-exercise peak expiratory flow rate (p < 0.05), and there were negative associations with systolic blood pressure (p < 0.05) and family history of heart attack (p < 0.05). In boys an association was found with skinfold distribution and fitness (p < 0.05), so that children with relatively less body fat were fitter. Social and health behaviour factors such as father's social class, father's employment status, or parents' smoking habits were unrelated to child's fitness. CONCLUSION: Height and obesity are strongly associated, and systolic blood pressure to a small extent, with children's fitness, but social factors are unrelated.

Blood Pressure↗

Physiological determinants of nocturnal arterial oxygenation in patients with obstructive sleep apnea.

Among patients with similar degrees of obstructive sleep apnea (OSA) there is considerable variability in the degree of associated nocturnal hypoxemia. The factors responsible for this variability have not been clearly defined. Therefore we studied 44 patients with OSA to identify the physiological determinants of nocturnal arterial O2 saturation (SaO2). All patients underwent pulmonary function testing, arterial blood gas analysis, and overnight polysomnography. Mean nocturnal SaO2 ranged from 96 to 66% and apnea-hypopnea index from 11 to 128 per hour of sleep. Several anthropometric, respiratory physiological, and polysomnographic variables that could be expected to influence nocturnal SaO2 were entered into a stepwise multiple linear regression analysis, with mean nocturnal SaO2 as the dependent variable. Three variables [awake supine arterial PO2 (PaO2), expiratory reserve volume, and percentage of sleep time spent in apnea] were found to correlate strongly with mean nocturnal SaO2 (multiple R, 0.854; P less than 0.0001) and accounted for 73% of its variability among patients. Body weight, other lung volumes, and airflow rates influenced awake PaO2 and expiratory reserve volume but had no independent influence on nocturnal SaO2. In a further group of 15 patients with OSA a high correlation was obtained between measured nocturnal SaO2 and that predicted by the model (r = 0.87; P less than 0.001). We conclude that derangements of pulmonary mechanics and awake PaO2 (generally attributable to obesity and diffuse airway obstruction) are of major importance in establishing the severity of nocturnal hypoxemia in patients with OSA.

Adult↗

Arm span-height relationships in patients referred for spirometry.

Arm span has been proposed as a surrogate for standing height in the prediction of lung volumes in patients with thoracic deformities or who are unable to stand. The relationship between arm span and height has previously been reported as either a fixed ratio unaffected by age or as a regression equation in which the ratio varies as a function of age. We studied the relationship between standing height, arm span, race, sex, and age in 202 patients (ages 20 to 88 yrs) referred for screening spirometry. Multiple linear regression analysis found arm span, race, sex, and age to be predictive of standing height (r2 = 0.8659, p < 0.0001). Subgroup analysis revealed that age was a significant factor among males of either race, but not among females of either race. Fixed arm span to height ratios were also calculated for each group and may be used to estimate standing height with reasonable accuracy except at extremes of stature.

Adult↗

Early posttransplant serum osteoprotegerin levels predict long-term (8-year) patient survival and cardiovascular death in renal transplant patients.

The primary objectives of this analysis were to examine the effects of early posttransplantation (10 wk) serum levels of osteoprotegerin (OPG), mannose-binding lectin (MBL), and MBL-associated serine proteases (MASP; MASP-2 and MASP-3) on long-term (8-yr) patient survival, graft survival, and cardiovascular (CV) death. During a period of 16 mo (1995 to 1996), a total of 173 consecutive renal transplant recipients without diabetes before transplantation were included in a prospective study that was designed to address the impact of metabolic CV risk factors on survival and CV end points. Baseline sera from 172 patients were available for analysis. Follow-up data until January 1, 2004, were obtained from a national renal registry. Patients with high (fourth quartile) serum levels of OPG had significantly higher all-cause mortality (hazard ratio [HR] 6.3; 95% confidence interval [CI] 3.3 to 11.8; P<0.001) and CV death (HR 10.8; 95% CI 3.8 to 30.4; P<0.001) than patients with lower OPG concentrations. After multiple Cox regression analysis, high serum levels of OPG remained an independent predictor of all-cause mortality (HR 6.0; 95% CI 3.1 to 11.6, P<0.001) and CV death (HR 8.2; 95% CI 2.5 to 26.4; P<0.001). Multiple linear regression analysis revealed that age, creatinine clearance, and high-sensitivity C-reactive protein all were independently associated with OPG (R2=0.42). No significant association between OPG and death-censored graft loss was revealed. Serum levels of MBL, MASP-2, and MASP-3 were not significantly associated with patient survival, CV death, or graft loss. Early measured posttransplantation serum OPG is a highly significant independent predictor of death from any cause or CV death in white renal transplant recipients.

Adult↗

Ewing's sarcoma: value of tumor necrosis as a predictive factor.

Forty cases of Ewing's sarcoma filed at the Uruguayan Committee for the Study of Bone Tumors, in the 1956-1979 period, were reviewed in order to determine the prognostic importance of several clinical and histological factors. Necrosis showed a strong association with survival (regression coefficient of -0.59). In fact, those cases with slight necrosis presented an actuarial survival of 48 per cent at a five-year period, contrasting with no survivors in the group with marked necrosis. Multivariate techniques (Multiple Linear Regression and Analysis of Variance) were employed to identify possible subsets of Ewing's sarcoma. In particular, the combination of longer delay (time between the appearance of the first symptom and histologic diagnosis) and slight necrosis as well as treatment with multidrug chemotherapy and slight necrosis resulted in rather prolonged survivals. This suggests interactions between necrosis and delay, and necrosis and treatment. The strong predictive value of tumor necrosis is probably related with rapidly growing Ewing's sarcoma.

Adolescent↗

Intermediate density lipoprotein levels are strong predictors of the extent of aortic atherosclerosis in the St. Thomas's Hospital rabbit strain.

This study assessed nonfasting cholesterol and triglyceride in plasma and in lipoproteins as predictors of the extent of aortic atherosclerosis in 2 similar groups of rabbits from the St. Thomas's Hospital strain; the lipoprotein classes studied in the 2 groups were very low (VLDL), intermediate (IDL), low (LDL), and high density lipoprotein (HDL), and Sf greater than 60 lipoprotein, Sf 12-60 lipoprotein, LDL and HDL, respectively. These rabbits exhibit elevated plasma levels of VLDL, IDL, and LDL, with plasma cholesterol and triglyceride of up to 23 mmol/l and 7 mmol/l, respectively, and with up to 100% of the aortic intima bearing atherosclerosis-like lesions. In group 1 rabbits (n = 25), univariate linear regression showed that cholesterol in plasma, LDL, IDL and in VLDL each were positively associated with the extent of aortic atherosclerosis. In group 2 rabbits (n = 20), cholesterol in plasma, LDL and Sf 12-60, but not in Sf greater than 60 lipoprotein, was consistently positively associated with the extent of aortic atherosclerosis. Neither plasma triglyceride, triglyceride in lipoprotein fractions nor HDL cholesterol was associated consistently with the extent of atherosclerosis. Using step-up multiple linear regression among lipoprotein lipids, IDL and Sf 12-60 lipoprotein cholesterol were the most powerful independent predictors of the extent of aortic atherosclerosis in the 2 groups of rabbits. LDL cholesterol was the only other independent predictor. The results suggest that remnant lipoproteins, whether defined as IDL or Sf 12-60 lipoprotein, play an important causal role in atherosclerosis under conditions where plasma levels of these lipoproteins are elevated.

Animals↗

Factor of risk for hip fracture in normal Chinese men and women in Taiwan.

We have investigated the age-related change in factor of risk (Phi) for the proximal femoral load during free fall in 548 females and 240 males aged 21-79 years. These individuals were divided into either young (age <50 years) or old group (age >/=50 years). Another 26 females with hip fractures were included for comparison. The bone mineral density (BMD) of proximal femoral neck was measured by a Norland XR-26 dual-energy X-ray absorptiometer (DXA). The estimated fracture load (L) of femoral neck was calculated from the BMD with the regression equation derived by Courtney et al. [2,3] and estimated fall force (F) by body weight and height according to the regression equation derived by Nakamura et al. [6] respectively. Phi was defined as the quotient of F/L. The results showed an age-related decrease of BMD (P < 0.001) in both genders corrected for weight and height. By multiple linear regression analysis, the F decreased significantly with aging corrected for BMD in old males (partial r = -0.255, P < 0.01) and increased with aging in all females (young, partial r=0.287, p < 0.001; old, partial r = 0.252, P < 0.001). L decreased significantly with aging corrected for height and weight in males (young, partial r = -0.401, P < 0.01; old, partial r = -0.178, P < 0.05) and females (young, partial r = -0. 168, P < 0.05; old, partial r = -0.459, P < 0.001). However Phi decreased with aging in young males (P < 0.01) and females (young: P < 0.001, old: P < 0.001). Phi increased in old women but not in old men, and was higher in old women compared with old men. The 26 patients with hip fractures had a significantly higher Phi value than 85 age-matched women. In conclusion, Phi may provide a comprehensive comparison of the risk of hip fracture in the elderly population.

Absorptiometry, Photon↗

Nutrient intake and progression of coronary artery disease.

The relation between nutrient intake and progression of coronary artery disease was examined in 50 men receiving a lipid-lowering diet or usual care in the St. Thomas' Atherosclerosis Regression Study. Nutrient intake was assessed by diet history. Changes in coronary angiograms were measured by quantitative image analysis. In univariate linear regression analysis progression of disease over 39 months, as measured by decrease in minimum absolute width of coronary segments, was directly related to dietary energy (p < 0.001) and to the absolute intakes of total fat (p < 0.001), saturated fat (p < 0.001), monounsaturated fat (p = 0.016) and cholesterol (p = 0.06). No significant associations were seen with polyunsaturated fat, carbohydrate, protein, fiber, alcohol or with the ratio of intakes of polyunsaturated fatty acids to saturated fatty acids. In multiple linear regression analysis the associations of change in minimum absolute width of coronary segments with total or saturated fat persisted when adjusted for plasma low-density lipoprotein cholesterol concentration, age, weight, blood pressure, smoking or treatment group assignment. The findings suggest that in middle-aged men, progression of CAD is strongly influenced by intake of saturated fatty acids, an effect mediated in part by mechanisms other than the influence of this nutrient on plasma cholesterol and low-density lipoprotein cholesterol.

Basal Metabolism↗

Alternative QSAR models for selected estradiol and cytochrome P450 ligands: comparison between classical, spectroscopic, CoMFA and GRID/GOLPE methods.

The performance of the spectroscopic EVA (eigenvalue) and EEVA (electronic eigenvalue) methods was tested with data sets applying coumarin 7-hydroxylation inhibitors (28 compounds) for cytochrome P450 mouse CYP2A5 and human CYP2A6 enzymes and 11ss-, 16a-, and 17a-substituted estradiol derivatives (30 compounds) for the lamb uterine estrogen receptor, and compared with the performance of the classical Hansch-type, CoMFA and GRID/GOLPE methods. Besides the internal predictability, the external predictability of the models was tested with several randomized training and test sets to ensure the validity and reliability of the models. Partial least squares (PLS) regression was employed as a general statistical tool with the EVA and EEVA methods. Some supplementary models were also built using only one PLS component with McGowan's volumes (MgVol and MgVol(2)) as additional descriptors and employing multiple linear regression (MLR) as the modelling tool. In general, both the internal and external performance of the EVA model, and more especially the EEVA model, with one PLS component and MgVol parameters was satisfactory, being either as good as or clearly better than that of the Hansch-type, CoMFA and GRID/GOLPE models.

Cytochrome P-450 Enzyme System↗

Risk factors for multiple organ system failure and death in critically injured patients.

BACKGROUND: This study was undertaken to evaluate the relative importance of factors related to the extent of multiple organ system failure (MOSF) and outcome in critical trauma. METHODS: We performed a retrospective case series analysis of 206 consecutive patients with trauma admitted to a surgical intensive care unit during a 5-year period. Multivariate methods were used to select independent factors related to the MOSF score and subsequent death. RESULTS: Multiple linear regression selected advancing age, prior chronic conditions, malnutrition, injury severity score (ISS), coma on admission, use of H2-receptor antagonists or antacids, number of blood transfusions, and intraabdominal infection as independent factors related to the MOSF score. Multiple logistic regression selected advancing age, chronic disease, ISS, and MOSF score as major predictors of death. CONCLUSIONS: Advancing age, prior chronic disease, malnutrition, coma on admission, and use of H2-receptor antagonists or antacids may impair host defenses of the gastrointestinal tract and predispose to invasive infection, thereby aggravating the severity of existing MOSF. These findings, together with the predominance of Enterobacteriaceae in patients with infection, suggest that bacterial translocation may be important in the late MOSF septic state. Although infection, particularly intraabdominal infection, is a major risk factor for MOSF, a nonspecific host response to critical trauma, as expressed by the ISS and transfusion requirement, and intestinal endotoxin may contribute to the development of the syndrome.

Adolescent↗

Progression of diabetic nephropathy: role of plasma homocysteine and plasminogen activator inhibitor-1.

Among patients with diabetic nephropathy, the decline in glomerular filtration rate (GFR) varies substantially, ranging from 2 to 20 mL/min per year. Identification of predictors of progression in diabetic nephropathy is important. Plasma total homocysteine (tHcy) rises with urinary albumin excretion rate in diabetes, and plasminogen activator inhibitor-1 (PAI-1) has been correlated with increased matrix accumulation in various glomerulopathies. In this prospective observational cohort study, we evaluated the importance of baseline tHcy and PAI-1 as predictors of the rate of decline in GFR. Baseline tHcy and PAI-1 were measured in 157 type 1 diabetic patients with diabetic nephropathy (92 men; mean age, 41 +/- 10 years; mean diabetes duration, 27 +/- 8 years; median GFR, 80 mL/min/1.73 m(2) [range, 23 to 143 mL/min/1.73 m(2)]). Hereafter, GFR was measured yearly with a plasma clearance technique for at least 3 years (median, 7 years [range, 3.0 to 8.3 years]). The mean rate of decline in GFR was 3.7 +/- 0.3 mL/min per year. A linear regression analysis revealed a borderline significant relationship between rate of decline in GFR and tHcy (P = 0.069) and PAI-1 (P = 0.087). Analysis of the rate of decline in GFR and tertiles of tHcy and PAI-1 revealed that increasing levels of tHcy were correlated with a significantly faster decline in GFR (P = 0.025), whereas increasing levels of PAI-1 were not. After adjustment for other well-established risk factors for progression of nephropathy in a multiple linear regression analysis, however, neither tHcy levels nor PAI-1 levels were independent predictors of rate of decline in GFR.

Adult↗