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PubMed2004

UGT1A1 gene variations and irinotecan treatment in patients with metastatic colorectal cancer.

SN-38 is the active metabolite of irinotecan and it is metabolised through conjugation by uridine diphosphate glucuronosyl transferase (UGT1A1). The major toxicity of irinotecan therapy is diarrhoea, which has been related to the enzymatic activity of UGT1A1. We examined the influence of the UGT1A1 gene promoter polymorphism in the toxicity profile, in the response rate and in the overall survival (OS) in 95 patients with metastatic colorectal cancer treated with an irinotecan-containing chemotherapy. Genotypes were determined by analysing the sequence of TATA box of UGT1A1 of genomic DNA from the patients. Clinical parameters and genotypes were compared by univariate and multivariate statistical methods. The more frequent adverse effects were asthenia (34 patients), diarrhoea (29 patients) and neutropenia (20 patients). Severe diarrhoea was observed in 7/10 homozygous (70%) and 15/45 heterozygous (33%) in comparison to 7/40 (17%) wild-type patients (P=0.005). These results maintained the statistical significance in logistic regression analysis (P=0.01) after adjustment for other clinical relevant variables. The presence of severe haematological toxicity increased from wild-type patients to UGT1A1(*)28 homozygotes, but without achieving statistical significance. No relationship was found between the UGT1A1(*)28 genotypes and infection, nausea or mucositis. In univariate studies, patients with the UGT1A1(*)28 polymorphism showed a trend to a poorer OS (P=0.09). In the multivariate analysis, the genotype was not related to clinical response or to OS. The role of the UGT1A1 genotype as a predictor of toxicity in cancer patients receiving irinotecan demands the performance of a randomized trial to ascertain whether genotype-adjusted dosages of the drug can help to establish safe and effective doses not only for patients with the UGT1A1(*)28 homozygous genotype but also for those with the most common UGT1A1 6/6 or 6/7 genotype.

Adult↗
PubMed1994

Echographic classification of intraocular tumours. A 15-year retrospective analysis.

The data on echographic routine diagnosis of intraocular tumours (prominence equal to, or larger than 2 mm) during the years 1976-1990 in the authors' department, were analyzed by multivariate statistical methods, using the final diagnosis either from pathology after enucleation or from the confirmed clinical diagnosis. The material consisted of melanomas (n = 325), metastases (n = 44), haemangiomas (n = 19) and other intraocular tumours (n = 16). The best set of echographic parameters in descending order of significance was: reflectivity (A-mode), choroidal excavation (B-mode), shape (B-mode), and regularity (A/B mode). Echographic differentiation by computer analysis of data on the three main kinds of tumours (melanoma/metastasis/haemangioma) separate from all the remaining tumours was expressed by the correct fraction: melanoma 89%, metastasis 80% and haemangioma 97%. The clinical echographic classification for these cases was 89%, 93% and 99.5%, respectively. The simultaneous differentiation between the three classes was found to yield a correct fraction of 85% by computer statistics and 95% by routine echography. The results of the present study might be used for prospective classification through the use of the parameter 'knowledge base' contained in the statistical classification procedure.

Choroid Neoplasms↗
PubMed1991

[Multivariate analysis of prognostic factors in patients with prostatic cancer].

A multivariate statistical analysis of 9 potential prognostic factors was made, using data gathered on 107 patients admitted between 1975 and 1987. After each variable was assessed separately for its prognostic importance by means of univariate analysis, a multivariate analysis using Cox's proportional hazards regression model and multivariate logistic model was done. These tests identified Gleason's score as the most important factor for all patients followed by M category and alkaline phosphatase (ALP), while Gleason's score alkaline phosphatase and age at diagnosis were most important for stage D patients. For short-term survival, the significant prognostic factors were Gleason's score and M category while for long term survival they were Gleason's score and age. T. category, stage, acid phosphatase, prostatic acid phosphatase, and treatment were found to be significantly related to survival time when examined individually; they were not found to be significant in the multivariate analysis.

Age Factors↗
PubMed2005

Invasive squamous cell carcinoma of vulva: prognostic significance of clinicopathologic parameters.

AIM: To investigate the prognostic significance of several clinicopathologic parameters in patients with invasive squamous cell carcinoma of the vulva. METHODS: We retrospectively studied 43 patients with invasive squamous cell carcinoma of the vulva treated with radical vulvectomy at the Department of Gynecology and Obstetrics at Zagreb University School of Medicine, Croatia, in the period from 1978-1996. At the time of analysis, follow-up information was obtained for all patients, 18 (41.9%) of whom have died and 25 (58.1%) who were alive at the time of the last contact. The mean follow-up time of surviving patients was 121 months (range, 6-216 months). Cox proportional hazard analysis was performed to examine the prognostic significance of age, menstrual status, clinical stage, diameter and localization of the tumor, histological grade, nuclear grade, depth of tumor invasion, presence of vascular space invasion, tumor growth pattern, presence of lymph node metastasis, DNA ploidy, proliferative activity, and mode of therapy. RESULTS: The overall 5-year survival for this group of patients was 62.3%. The results of univariate statistical analysis confirmed that statistically significant prognostic parameters included the age of patients (P=0.038), clinical stage (P=0.001), nuclear grade (P=0.002), the depth of tumor invasion (P<0.001), and presence of lymph node metastasis (P=0.001). On the other hand, the results of multivariate statistical analysis showed that only the depth of tumor invasion (P<0.001) can be considered independent, statistically significant prognostic parameter. CONCLUSION: Our data suggest that the depth of tumor invasion represents the most important prognostic parameter in the group of patients with invasive squamous vulvar carcinoma. Clinical significance of DNA ploidy and proliferative activity was not found.

Adult↗
PubMed1986

Can the results of contemporary aortic valve replacement be improved?

Although the results of contemporary aortic valve replacement are excellent, cardiac surgeons must identify the factors that predict postoperative morbidity and mortality to develop alternative strategies for high-risk patients. Two hundred seventy-seven consecutive patients undergoing isolated aortic valve replacement between 1982 and 1984 were evaluated. Thirty-seven clinical and 13 preoperative hemodynamic variables were analyzed by univariate and multivariate statistics to determine the risk factors for postoperative morbidity and mortality. The operative mortality was 3%, the incidence of a postoperative low output syndrome was 12%, and the incidence of a perioperative myocardial infarction was 5%. A multivariate, logistic regression analysis found that age was the only the only independent predictor of mortality. Three factors independently predicted postoperative low output syndrome: age, the presence of coronary artery disease, and the peak systolic gradient in patients with aortic stenosis. Patients with aortic stenosis had a higher incidence of postoperative ventricular dysfunction (17%) than those with mixed valvular disease (9%) or aortic regurgitation (5%). Perioperative myocardial infarction was predicted by the extent of coronary artery disease. The incidence of perioperative myocardial infarction was higher in patients with triple-vessel coronary artery disease (13%) and those with left main stenosis (18%) than in patients with single- or double-vessel disease (4%) or those without coronary artery disease (4%). Because of the higher risk of aortic valve replacement in older patients, the risk-benefit ratio of the operation must be carefully assessed in the elderly. Improved methods of myocardial protection may reduce the risks for patients with aortic stenosis and symptomatic triple-vessel coronary artery disease.

Adult↗
PubMed2003

Metabolic syndrome best defines the multivariate distribution of blood variables in postinfarction patients.

The hypothesis was tested that metabolic syndrome (MS) plays a leading role in approximating the multivariate distribution of thrombogenic and metabolic blood variables in a population of postinfarction patients. The multivariate statistical technique of factor analysis was used to determine blood variable clustering 2 months after myocardial infarction. Five clusters resulted in two separate independent factors, dyslipidemia and metabolic, reflecting MS and the remaining interpreted as cholesterol-lipoprotein, vascular-inflammatory, and coagulation. All five factors accounted for 55% of total variance with MS-associated factors accounting for 20% and individual factor contributions as follows: 11.6, 8.6, 12.9, 11.9, and 9.6%, respectively. There were no interactions of metabolic variables with thrombogenic variables or CRP in any factor. Results of subgroup analysis in males and females and in patients on and not on statins were all similar to the total group. We conclude there is no interaction of variables of MS or cholesterol-lipoprotein factors with those of thrombogenic factors. This independence yields the potential for use of factors in evaluating CVD risk. Further, the importance of MS in this group of postinfarction patients is emphasized, as the largest contribution to total variance was from MS factors, meaning that these variables best approximate the original multivariate distribution.

Aged↗
PubMed2003

Pure ductal carcinoma in situ and in situ component of ductal invasive carcinoma of the breast. A preliminary morphometric study.

Nuclear pleomorphism is a fundamental feature in evaluating the aggressiveness of ductal carcinoma in situ (DCIS) of the breast. In this study, pure DCIS and the in situ component (IS-comp) of invasive duct carcinoma (IDC) are compared in order to verify if these are two different entities or the same process observed at different times during its evolution. Five cases of pure DCIS and nine of IDC with extensive in situ component were selected. They were moderately and poorly differentiated. 30 nuclei for each DCIS, and 30 nuclei for both the in situ and invasive component of each IDC were studied; thus, a total of 720 nuclei were submitted to the SAM (Shape Analytical Morphometry) analysis, which enables a numerical expression not only of dimensions (area, perimeter, diameter) but also of nuclear contour irregularities and nuclear shape distortions. Univariate statistical comparisons were carried out between the nuclei of: (1) DCIS and in situ component of invasive duct carcinoma, (2) DCIS and the invasive component of infiltrating carcinoma and (3) between the in situ and invasive component of infiltrating carcinoma. Multivariate analysis was utilized to compare nuclei of DCIS with the in situ component of IDC. The in situ features of each tumor were also evaluated with the mitotic index (MI). Nuclei of pure DCIS resulted significantly larger (p < 0.001) and with a more regular shape (p < 0.001) than those of the in situ component of IDC. No differences were observed between the nuclei of the in situ and the invasive component of infiltrating carcinomas. Multivariate statistical analysis discriminated 77% of nuclei of in situ proliferation when both G2 and G3 tumors were considered, and 80% when only G3 tumors were considered. In conclusions morphological differences exist between pure DCIS and the in situ component of IDC, which may be an expression of their biological behavior; moreover, these morphological differences seem to have a better discriminating power within the same histological grade.

Adult↗
PubMed2000

Influence of atrial fibrillation on the morbido-mortality of patients on hemodialysis.

BACKGROUND: The consequences of atrial fibrillation (AF) on morbido-mortality of patients on hemodialysis have not been fully explored. The objective of this study was to determine the prevalence of AF in patients on hemodialysis and to evaluate its influence on the development of thromboembolic phenomena (TEP). METHODS: The incidence of AF in 190 patients in our hemodialysis program was assessed, and the patients were followed up for 1 year. Pertinent demographic and biochemical parameters were entered into univariate and multivariate statistical analyses to evaluate associations with overall mortality and TEP such as cerebrovascular accident, transitory ischemic accident, or peripheral embolism. RESULTS: In 13.6% of patients, AF was found; 9.4% of these were of the permanent type. In the multivariate analysis, only increased age was associated with a higher probability of having arrhythmia (odds ratio, 1.10; 95% confidence interval, 1.03-1.17; P =.003). During follow-up, 23% of the patients with AF died compared with 6% of those in sinus rhythm (P <.05), although AF did not appear to be an independent predictive factor for death. Thirty-five percent of the patients with AF and 4% with sinus rhythm had TEP (P <.01). In the multivariate analysis, AF was identified as the only independent predictor for TEP (odds ratio, 8; 95% CI, 2.3-27; P =.0008). CONCLUSIONS: AF is a frequent arrhythmia in patients on hemodialysis, and approximately 1 in 3 hemodialysis patients with AF had thromboembolic complications within 1 year of follow-up. These findings suggest that the consensus contraindication of prophylactic anticoagulation therapy for this group of patients may need to be redefined.

Adult↗
PubMed2005

Risk factors in predicting a poor response to sildenafil citrate in elderly men with erectile dysfunction.

OBJECTIVE: To assess the clinical efficacy of sildenafil and the potential predictors of poor response to sildenafil in elderly patients with erectile dysfunction (ED). PATIENTS AND METHODS: The study included 162 patients (aged > or = 60 years) treated with sildenafil for at least 8 weeks; all patients were evaluated with a history, physical examination, measurement of total testosterone and a pharmacological erection test. Sexual function before and 8 weeks after treatment was assessed using the self-administered International Index of Erectile Function (IIEF). Treatment was considered successful when the patient attained a higher grade on the erectile function (EF) domain score, and an affirmative response to the overall assessment question. Factors influencing treatment outcome were evaluated by univariate and multivariate statistical analysis. RESULTS: The overall efficacy with sildenafil was 47% (76/162). On univariate analysis, uncontrolled diabetes, current smoking, hypogonadism (<3 microg/L testosterone) and low pretreatment EF domain score (<17) were selected as predictors of a poor response. On multivariate logistic regression, a low pretreatment EF domain score was the strongest independent prognostic factor for a poor response (odds ratio 2.25, 95% confidence interval, 1.45-7.33), and this was followed by hypogonadism (1.89, 1.12-3.16) and current smoking (1.34, 1.04-3.52). CONCLUSION: In a real clinical setting, sildenafil was effective for about half of the elderly men. The baseline EF domain score, hypogonadism and current smoking were significantly associated with failure of sildenafil. These results suggest that modifying reversible risk factors, e.g. stopping smoking and replacing testosterone, would be beneficial in augmenting the efficacy of sildenafil in elderly men.

Aged↗
PubMed2002

Extracting information from two-dimensional electrophoresis gels by partial least squares regression.

Two-dimensional gel electrophoresis (2-DE) produces large amounts of data and extraction of relevant information from these data demands a cautious and time consuming process of spot pattern matching between gels. The classical approach of data analysis is to detect protein markers that appear or disappear depending on the experimental conditions. Such biomarkers are found by comparing the relative volumes of individual spots in the individual gels. Multivariate statistical analysis and modelling of 2-DE data for comparison and classification is an alternative approach utilising the combination of all proteins/spots in the gels. In the present study it is demonstrated how information can be extracted by multivariate data analysis. The strategy is based on partial least squares regression followed by variable selection to find proteins that individually or in combination with other proteins vary informatively in relation to the experimental conditions. Finding of such coherent protein patterns leads to identification of potential relations between the involved proteins, and will be useful for focusing further investigation of proteins that relate to the chosen experimental conditions.

Electrophoresis, Gel, Two-Dimensional↗
PubMed2003

Automated analysis of morphometric parameters for accurate definition of erythrocyte cell shape.

BACKGROUND: Modification of erythrocyte morphology is clinically important in hematology and medicine. Its detection is routinely performed by subjective microscopic evaluation, which is difficult and strongly dependent on the operator's expertise. We developed an original automated methodology to analyze erythrocyte cell shape modification to support and improve the operator's capability and expedite measurements. METHODS: We used morphometric parameters derived from optical microscope images elaborated with an image processing software (NIH Scion Image) to construct a new application for statistical multivariate discriminant analysis. RESULTS: For each cell type the elaboration of the morphometric parameters allowed us to develop a chromogenic index, a dimension index, a biconcavity index, and a density profile. The measurements of these indexes were used to construct a statistical methodology that could discriminate among erythrocyte morphologies according to Bessis. When applied casewise, the model effectively differentiated between discocytes, target cells, ovalocytes, macrocytes, and microcytes, with an agreement of 70% between actual and predicted classifications. CONCLUSIONS: The results clearly demonstrated that a set of opportunely selected morphometric parameters derived from optical microscope images and statistically analyzed can effectively discriminate with a high degree of certainty among different shape modifications that red blood cells can undergo in various in vitro and in vivo conditions. This method represents the first attempt to automate the definition of erythrocyte morphology and may have important applications in cases in which the detection of erythrocyte cell shape changes is crucial.

Automation↗
PubMed2001

[Quantitative analysis of tear protein profile for soft contact lenses--a clinical study].

PURPOSE: Approximately 3% of the patients with refractive errors wear contact lenses. Recent studies revealed contradictory results regarding the changes of the tear film in contact lens wearers. The aim of this study was to analyze the influence of wearing contact lenses on the tear protein patterns. The study was performed using a new method to analyze quantitatively the tear proteins based on digital image analysis of electrophoretical separations followed by multivariate statistical calculations. METHODS: Two groups were examined: 121 healthy volunteers (KO) and 66 wearers of soft contact lenses (KL). The tear proteins were separated by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE). For each electrophoretic lane, a densitograph was built by digital image analysis. Subsequently a multivariate analysis of discriminance was performed. RESULTS: The concentration of the tear proteins lactoferrin, sIgA, lysozyme and albumin was slightly reduced. In contrast, the concentration of lipocalin was increased in the tears of contact lens wearers (p < 0.07). However, including all peaks found in each electrophoretic lane, the analysis of discriminance found a statistical significant difference between KO and KL (Wilks' Lambda = 0.88; p < 0.0001). CONCLUSIONS: Wearing contact lenses leads to significant changes in the composition of tear-film proteins. However, the pathomechanism of this alteration of the tear film is still unclear. Because of the large number of contact lens wearers, these alterations should be examined further.

Albumins↗
PubMed1992

Testing hypotheses on dioptric power.

Transformation of dioptric power from the conventional clinical representation as sphere, cylinder, and axis to the vectorial representation known as the vector h makes it possible to apply formal multivariate statistical methods to dioptric power. Methods are described for testing hypotheses on mean dioptric power and on variance-covariance of dioptric power for one and more than one population. A number of numerical examples are presented. Attention is drawn to the underlying assumption of multivariate normality, to other limitations of the methods, and to pitfalls in the use of the methods. Three-dimensional scatter plots, shown by means of stereo-pair drawings, are useful for detecting departures from normality.

Humans↗
PubMedDate not supplied

Deterioration of patellofemoral articular surfaces after anterior cruciate ligament reconstruction.

One hundred eighty-seven patients who had undergone intraarticular anterior cruciate ligament reconstruction using either a fresh-frozen allogeneic tendon or central third autogenous pateller tendon 3 to 89 months previously were arthroscopically evaluated. The focus was on secondary changes of the patellofemoral joint at the time of second-look arthroscopy. Overall, 93 knees deteriorated, 74 knees remained unchanged, and 14 improved. The deteriorative changes were predominantly located around the central ridge of the patellae, although all but two knees remained free from anterior knee pain. Statistical multivariate analysis showed surgical approach by conventional medial parapatellar incision and use of the central one-third of the autogenous patellar tendon graft as possible risk factors for the deterioration, although chi-square analysis failed to demonstrate statistical significance for the latter.

Adolescent↗
PubMed2006

Association between rmpA and magA genes and clinical syndromes caused by Klebsiella pneumoniae in Taiwan.

BACKGROUND: The association of the magA gene with the hypermucoviscosity phenotype relevant to the pathogenesis of Klebsiella pneumoniae liver abscess has been reported in Taiwan. Similarly, the rmpA gene, known as a positive regulator of extracapsular polysaccharide synthesis that confers a mucoid phenotype, may be another candidate gene causing hypermucoviscosity. However, the association of rmpA with K. pneumoniae clinical syndromes is unreported. We aimed to investigate the clinical correlation between rmpA and primary Klebsiella abscess, focusing on sites other than the liver. METHODS: From July 2003 through December 2004, a total of 151 K. pneumoniae isolates recovered from 151 patients with bacteremia were collected from 2 large medical centers in southern Taiwan. Clinical data were collected from medical records. The genes rmpA and magA were amplified by polymerase chain reaction using specific primers. RESULTS: The prevalences of hypermucoviscosity, rmpA, and magA were 38%, 48%, and 17%, respectively. As determined by statistical multivariate analysis, strains carrying rmpA were significantly associated with the hypermucoviscosity phenotype, and there was a significant correlation with purulent tissue infections, such as liver abscess and lung, neck, psoas muscle, or other focal abscess. CONCLUSION: Our data support a statistical correlation between the rmpA gene and virulence in terms of abscess formation for these hypermucoviscous K. pneumoniae strains. Hypermucoviscosity associated with rmpA, together with a thorough physical examination, may be helpful as a guide to carry out appropriate diagnostic tests on patients with an initially unknown source of K. pneumoniae bacteremia, particularly when looking for the occurrence of an underlying abscess.

Bacteremia↗
PubMed1990

Estimating dose response in chronic toxicity studies: 24-month administration of acrylonitrile in drinking water of Fischer 344 rats.

It is shown that low-dose extrapolation based on observed numbers of animals with tumors cannot be used within the standard frameworks of either toxicological or statistical methods since the conclusions cannot be examined critically with additional experiments. The traditional methods of examining dose response in toxicology are considered, and it is shown that they cannot be used as long as the studies are carried out to the animals' old age and the controls have senile lesions. Traditional multivariate statistical methods are proposed to examine the effect of dose on the shift in senile lesions that is induced by treatment. One method (using standard software for the computation of linear discriminant functions) is then applied to the tumorous and non-tumorous lesions found in this study. It is shown that doses as low as 3 ppm have a statistically significant effect, and 1 ppm is proposed as the "no mean effect level".

Acrylonitrile↗
PubMed1988

Self rated depression in relation to DSM-III classification: a statistical isolinear multiple components analysis.

The Zung Self-Rating Depression Scale (SDS) was presented to 99 depressed inpatients. The patients were categorized according to DSM-III as suffering from minor depression, major depression without melancholia and major depression with melancholia and/or with psychotic features. Differences in self-reported symptoms between these categories were studied with multivariate statistical techniques including linear discriminant analysis (LDA) and statistical isolinear multiple components analysis (SIMCA). Patients with minor depression rate themselves significantly less depressed than those with major depression. Patients with major depression without melancholia are less depressed than those with melancholia and/or psychotic features. The three DSM-III depressive categories can be regarded as belonging to a clinical continuum in which they form relevant levels with quantitative differences in self-reported symptoms. These differences are not only defined by gradual shiftings in the overall severity of illness, but also by quantitative differences in the severity of some target symptoms, i.e. agitation, retardation, diurnal variation, loss of libido, fatiguability, insomnia, anorexia, sadness and anhedonia.

Adjustment Disorders↗
PubMed1994

Prognostic factors in gliomas. A multivariate analysis of clinical, pathologic, flow cytometric, cytogenetic, and molecular markers.

BACKGROUND: The ability to divide subsets of patients with glial neoplasms into prognostic groups currently is limited because only a few clinical and pathologic variables are available. The goal of this investigation was to identify biologic factors of potential prognostic value in patients with cerebral gliomas. METHODS: This prospective investigation used clinical, pathologic, flow cytometric, cytogenetic, and molecular genetic variables as potential prognostic factors in 207 patients with newly diagnosed gliomas (153 astrocytic tumors of the fibrillary type, 31 oligodendrogliomas, and 23 pilocytic astrocytomas). Classification and regression tree (CART) analysis was performed as part of the multivariate statistical analysis. RESULTS: The age of the patient and the grade of the tumor were confirmed as strong prognostic factors. Cytogenetic or molecular genetic abnormalities of chromosomes 7 and 10 were associated with poor survival in univariate analysis (P < 0.0001). CART multivariate analysis identified several subsets of patients with different prognoses. In the subset of patients younger than 66.5 years with Grade 4 tumors, the survival time was longer for those with aneuploid tumors than for those with nonaneuploid tumors. In the subset of patients with Grades 1-3 tumors, the survival time was longer for those whose tumors had a %G2M of less than 6.9 than for those whose tumors had a %G2M of 6.9 or greater. CONCLUSION: This investigation provides further evidence that flow cytometry, cytogenetic, and molecular genetic factors that may have prognostic value in patients with gliomas can be identified.

Adult↗