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Do histocompatibility antigens influence the risk of head and neck carcinoma?

Associations were sought between specific histocompatibility antigens (HLA) of the human major histocompatibility complex and the incidence of head and neck squamous cell carcinoma (SqCC). Seventy sequential patients with SqCC and 217 control subjects from the same geographic region were typed for HLA-A, HLA-B, and HLA-DR loci. These results were compared. Multivariate statistical analysis using stepwise logistic regression revealed significant associations between the incidence of SqCC and HLA-B14, HLA-DR3, and HLA-DR4 as well as smoking and the sex-smoking interaction. The authors concluded that certain host factors, including genetic constitution, and behavioral characteristics (i.e., smoking) as well as tumor biology, can influence the development of SqCC. The mechanism(s) of these associations may involve as yet undefined relationships between HLA region genes and the immune response.

Carcinoma, Squamous Cell↗

Lesions in donor kidneys: nature, incidence, and influence on graft function.

The aim of this study was to assess the influence of kidney-donor transmitted pathology on graft function. Light and immunofluorescent microscopic findings from a surgical biopsy taken prior to transplantation from 114 cadaveric kidney donors were analyzed. Moderate to severe mesangial IgA deposits were considered consistent with IgA nephropathy. Pathological abnormalities were correlated together with donor age, number of mismatches, and type of immunosuppression by multivariate statistical analysis with the serum creatinine values from patients who experienced no acute rejection at 1 year. Serum creatinine values (n = 52) were not correlated with either non-specific light microscopic lesions or immunofluorescent deposits found in the majority of kidney donors or with changes consistent with IgA nephropathy observed in 9% of the cases. There was, however, a correlation with donor age, which was also correlated with the extent of chronic lesions (P < 0.001).

Adolescent↗

FindEM--a fast, efficient program for automatic selection of particles from electron micrographs.

The FindEM particle picking program was tested on the publicly available keyhole limpet hemocyanin (KLH) dataset, and the results were submitted for the "bakeoff" contest at the recent particle picking workshop (Zhu et al., 2003b). Two alternative ways of using the program are demonstrated and the results are compared. The first of these approximates exhaustive projection matching with a full set of expected views, which need to be known. This could correspond to the task of extending a known structure to higher resolution, for which many 1000's of additional images are required. The second procedure illustrates use of multivariate statistical analysis (MSA) to filter a preliminary set of candidate particles containing a high proportion of false particles. This set was generated using the FindEM program to search with one template that crudely represents the expected views. Classification of the resultant set of candidate particles then allows the desired classes to be selected while the rest can be ignored. This approach requires no prior information of the structure and is suitable for the initial investigation of an unknown structure--the class averages indicate the symmetry and oligomeric state of the particles. Potential improvements in speed and accuracy are discussed.

Algorithms↗

Cardiac enzymes are irrelevant in the patient with suspected myocardial contusion.

BACKGROUND: Myocardial contusion is commonly diagnosed following blunt chest trauma, and has potentially lethal complications. Cost-effective case management in patients with suspected myocardial contusion is confounded by the low incidence of complications and the lack of a reliable test to predict them. The clinical usefulness of elevated cardiac enzyme levels is controversial. METHODS: We analyzed a 4-year experience of 359 patients with high-risk blunt chest trauma who were assessed using an established practice guideline. Our multivariate statistical model evaluated all of the early risk factors included in the guideline, specifically focusing on cardiac enzyme levels. RESULTS: Myocardial contusion was diagnosed in 30% of patients, and complications (dysrhythmias and cardiogenic shock) occurred in 5%. In no case was cardiac enzyme elevation the sole predictor of a complication. The cost of routine cardiac enzyme assay was substantial. CONCLUSION: Cardiac enzyme determinations have no useful role in the evaluation of patients with suspected myocardial contusion. They should be eliminated from current practice guidelines.

Adolescent↗

Current TNM classification of renal cell carcinoma evaluated: revising stage T3a.

PURPOSE: : Recent studies of rare cases of pT3a renal cell carcinoma extending directly into the adrenal gland showed worse survival than in other pT3a cases and recategorization as stage pT4 was suggested. We assessed the prognostic validity of a stage pT3a diagnosis based on perirenal fat infiltration. MATERIALS AND METHODS: : The records of 1,794 patients with renal cell carcinoma who underwent surgical resection between 1975 and 2000 at our institution were analyzed retrospectively. Focusing on pT3a tumors, as defined by perirenal fat infiltration, numerous clinical and histopathological parameters were investigated by univariate and multivariate statistical methods with cancer specific survival as the primary end point. RESULTS: : We identified 237 of 1,794 patients with perirenal fat infiltration, classified as having pT3a disease. In patients with pT3a tumors tumor size was a significant parameter predicting survival. The most significant cutoff value for tumor size in pT3a disease was 7 cm. Patients with distant metastasis had a worse prognosis independent of T classification. Therefore, to assess the prognostic value of the current T classification in regard to T3a tumors we excluded patients with tumor stage cM+ for further subgroup analysis. Survival comparison of pT1 pNall, cM0 (744 of 1,794 cases) and pT3a pNall, cM0 7 cm or less (100 of 237) as well as pT2 pNall, cM0 (265 of 1,794) and pT3a pNall, cM0 greater than 7 cm (93 of 237) yielded similar results. After splitting pT3a into a modified T1/T2 classification a significant difference in 5-year survival analysis for a modified T1/T2 stage was found (pT1 plus pT3a less than 7 cm 90% vs pT2 plus pT3a greater than 7 cm 73%, p <0.001). Subsequently multivariate analysis in all 1,794 patients showed that modified T stage was an independent significant predictor of cancer specific survival. CONCLUSIONS: : We suggest revising the current pT3a classification based on perirenal fat infiltration but rendering a modified pT1/pT2 classification, which resolves pT3a cases without the loss of prognostic validity. Perirenal fat infiltration should not be used to assign T category. Tumors directly infiltrating the adrenal gland should be reclassified as T4.

Carcinoma, Renal Cell↗

Safety, effectiveness, and patterns of use of olanzapine in acute schizophrenia: a multivariate analysis of a large naturalistic study in the hospital setting.

BACKGROUND AND OBJECTIVE: This study assessed the safety and effectiveness of the atypical antipsychotic olanzapine for the treatment of inpatients with acute schizophrenia. Furthermore, we evaluated patterns of use of olanzapine and their relationship to safety and effectiveness. PATIENTS AND METHOD: This was a prospective, comparative, nonrandomized, open-label, observational study of 848 patients with schizophrenia (International Classification of Diseases, 10th edition) hospitalized due to an acute psychotic episode. Data were collected during patients' entire hospital stay. Safety of antipsychotic therapy was assessed with an extrapyramidal symptoms questionnaire (based on the Udvalg for Kliniske Undersøgelser scale) and the report of spontaneous adverse events. Clinical status was assessed with the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impressions-Severity of Illness (CGI-S). A multivariate statistical approach was employed. RESULTS: Patients treated with olanzapine in monotherapy had the lowest risk of developing extrapyramidal symptoms (11.2%), whereas patients treated with conventional antipsychotics had a higher risk (39.0%; p < 0.001). Patients treated with olanzapine in monotherapy (even patients with prominent positive symptoms) displayed a higher rate of response compared with conventional antipsychotics-treated patients (p = .007). CONCLUSIONS: Olanzapine is a safe and effective treatment for patients with acute schizophrenia in the hospital setting, even for patients with prominent positive or agitation symptoms.

Acute Disease↗

Serum mannan-binding lectin-associated serine protease 2 levels in colorectal cancer: relation to recurrence and mortality.

PURPOSE: Mannan-binding lectin-associated serine protease 2 (MASP-2) is a plasma protein involved in inflammatory processes. MASP-2 circulates in complex with the protein mannan-binding lectin (MBL) or ficolins, and is activated to recruit the complement system when MBL binds to its targets. The level of MASP-2 is genetically determined, and the aim of the present study was to evaluate the effect of MASP-2 levels on postoperative infection, recurrence and survival. EXPERIMENTAL DESIGN: MASP-2 concentrations were determined in serum from 605 patients collected before elective resection for primary colorectal cancer. The primary end points were postoperative infection, time to any recurrence, and time to death. The median time of follow-up was 7.9 years. RESULTS: MASP-2 levels were not correlated to postoperative infections (P = 0.49). High MASP-2 levels significantly correlated with recurrent cancer disease [P = 0.03; hazard ratio (HR) = 1.4; 95% confidence interval (CI), 1.0-2.0] and with poor survival (P = 0.0005; HR = 1.4; 95% CI, 1.2-1.7). Multivariate statistical analysis, including age, gender, Dukes' stage of disease, tumor localization, and postoperative pneumonia, showed that the MASP-2 level had an independent prognostic value in the patients (P = 0.0001; HR = 1.5; 95% CI, 1.2-1.8). CONCLUSION: In the cohort of patients with colorectal cancer investigated, MASP-2 concentration in serum proved to be an independent prognostic marker with high MASP-2 levels predicting recurrence and poor survival. Postoperative infection could not be shown to be associated with MASP-2 levels.

Adult↗

[Prognostic factors in severe acute pancreatitis. Univariate and multivariate study].

OBJECTIVES: The aim of this study was to analyze the prediction of mortality in patients with severe acute pancreatitis. PATIENTS AND METHODS: In a retrospective study 43 patients with severe acute pancreatitis were included. All patients required ICU admittance and surgical treatment. We evaluated severity according to Ranson's criteria, APACHE II score, CT scan classification (Hill), intraoperative findings (Vankemmel's classification) and number of organs failure. We performed a univariant and multivariant statistic study with lineal discriminant analysis. RESULTS: The overall mortality was 46.5%. Ranson's score and APACHE II did not correlate with mortality. Hill's classification did not reach significance either. However, only the Vankemmel's classification and the number of organs failure had statistic value (p < 0.01). After lineal discriminant analysis, the association of more than 4 Ranson's criteria, APACHE II up to 9 points, grades IV and V in Hill's classification and 4 organs failure had a predictive value for mortality. CONCLUSIONS: In our limited experience the Vankemmel's classification and the number of organs failure had a predictive value for mortality in patients with acute pancreatitis. The association of more than 4 Ranson's criteria. APACHE II up to 8 points, grades IV-V in Hill's classification and 4 organs failure disclosed poor prognosis.

APACHE↗

Surgical revascularization after acute myocardial infarction. Does timing make a difference?

At present no consensus exists regarding the timing of surgical revascularization after acute myocardial infarction. Patients admitted with acute myocardial infarction between January 1990 and April 1993 underwent early cardiac catheterization if they had postinfarction ischemia or positive results on a low-level exercise stress test. If indications for surgical intervention were found at the time of catheterization, patients were operated on within 1 or 2 days or were discharged and returned for the operation within 2 to 3 weeks. During this period, we performed 2175 isolated coronary artery bypass graft procedures; 23 patients were operated on within 24 hours of acute myocardial infarction with an operative mortality of 4.4%, 30 patients underwent surgery between 24 and 72 hours after infarction with no deaths, 193 patients were operated on between 3 and 7 days after infarction with an operative mortality of 2.1%, 284 patients underwent revascularization between 1 week and 1 month after infarction with an operative mortality of 1.4%, and the 1645 patients without a recent infarction had a mortality rate of 1.9%. Multivariate statistical analysis was performed to evaluate mortality with these independent variables: reoperative surgery, sex, age, diabetes, timing of infarction, location of infarction, and type (transmural versus subendocardial). Myocardial infarction at any time interval less than 1 month before the operation was not associated with mortality when adjusted by these other risk factors. In addition, no differences were noted in length of stay, stroke rate, or prevalence of renal failure or pulmonary insufficiency. We conclude that nonemergency surgical revascularization can be done safely at any time interval after acute myocardial infarction, certainly after 72 hours, with no increase in operative mortality and acceptable morbidity.

Aged↗

Multivariate analysis of quantitative chemical and enzymic characterization data in classification of Actinobacillus, Haemophilus and Pasteurella spp.

Chemotaxonomic data for strains of Actinobacillus, Haemophilus and Pasteurella spp. were analysed using three multivariate statistical strategies: principal components, partial least squares discriminant, and soft independent modelling of class analogy. The species comprised Actinobacillus actinomycetemcomitans. Haemophilus aphrophilus, H. paraphrophilus, H. influenzae, Pasteurella multocida, P. haemolytica and P. ureae. Strains were characterized by cell sugar and fatty acid composition, lysis kinetics during EDTA and EDTA plus lysozyme treatment, and methylene blue reduction. In total 23 quantitative variables were compiled from chemotaxonomic analyses of 25 strains. A. actinomycetemcomitans and H. aphrophilus formed distinct classes which differed from those of H. paraphrophilus, H. influenzae and Pasteurella spp. All characterization variables, except those describing fatty acid content, contributed significantly to inter-species discrimination.

Actinobacillus↗

Factors influencing the rupture of abdominal aortic aneurysms.

The gross findings of 49,144 autopsies performed at two major hospitals in Rome were reviewed. There were 297 patients who were found to have atherosclerotic abdominal aortic aneurysm (AAA). The aneurysm was intact in 220 (74 per cent) and ruptured in 77 (26 per cent). The occurrence of aneurysm rupture was correlated to 17 variables by univariate and multivariate statistical analysis. Covariates found to be independently predictive of the rupture of AAA were the size of the aneurysm (p less than 0.001), arterial hypertension (p less than 0.001) and the presence of bronchiectasis (p less than 0.025.). Over-all, bronchiectasis was more common among patients with AAA than in the age-adjusted and sex-adjusted control population. The simultaneous presence of bronchiectasis and AAA suggests the presence of some inherited or acquired tendency to have ectasia of the connective tissue, aneurysm formation and rupture development.

Adult↗

Identification of sperm morphometric subpopulations in two different portions of the boar ejaculate and its relation to postthaw quality.

A statistical approach using sequentially principal component analysis (PCA), clustering, and discriminant analyses was developed to identify sperm morphometric subpopulations in well-defined portions of the fresh boar ejaculate. Semen was obtained as 2 portions (the first 10 mL of the sperm-rich fraction and the rest of the ejaculate, respectively) and frozen using a conventional protocol. Before freezing, an aliquot was used for computer-assisted sperm morphometry analysis (ASMA). Postthaw quality was evaluated using computer-assisted sperm analysis (CASA), and an annexin-V/PI assay evaluated sperm membranes. The PCA revealed that 3 variables represented more than 78% of the cumulative variance in sperm subpopulations. The clustering and discriminant analyses, based on 5780 individual spermatozoa, revealed the existence of 4 sperm subpopulations. The relative percentage of these subpopulations varied between boar and ejaculate portions. Linear regression models based on measured morphometric characteristics could account for up to 36% of the percentage of intact sperm membranes postthaw. The ASMA protocol used in our study was useful to detect subtle morphometric differences between spermatozoa, and the combination of this analysis with a multivariate statistical procedure gave new information on the biological characteristics of boar ejaculates that is not given by conventional sperm analysis.

Animals↗

mRNA expression, functional profiling and multivariate classification of colon biopsy specimen by cDNA overall glass microarray.

AIM: To understand the local pathophysiological alterations and gene ontology-based functional classification of colonic biopsies into inflammatory and neoplastic diseases. METHODS: Total RNA was extracted from frozen biopsies and amplified by T7-method. Expression profile was evaluated by Atlas Glass 1K microarrays. After microarray quality control, applicable data were available from 10 adenomas, 6 colorectal adenocarcinomas (CRCs), and 6 inflammatory bowel diseases (IBDs). Multivariate statistical and cell functional analyses were performed. Real-time RT-PCR and immunohistochemistry were used for validation. RESULTS: Discriminant analysis of selected genes, could correctly reclassify all 22 samples using 4 parameters (heat shock transcription factor-1, bystin-like, calgranulin-A, TRAIL receptor 3). IBD samples were characterized by overregulated chemokine (C-X-C motif) ligand 13, replication protein A1, E74-like factor 2 and downregulated TNF receptor-associated factor 6, BCL2-interacting killer genes. In adenomas upregulation of TNF receptor-associated factor 6, replication protein A1, E74-like factor 2 and underexpression of BCL2-associated X protein, calgranulin-A genes were found. CRC cases had significantly increased epidermal growth factor receptor, topoisomerase-1, v-jun, TNF receptor-associated factor 6 and TRAIL receptor 3, and decreased RAD51 and RAD52 DNA repair gene, protein phosphatase-2A and BCL2-interacting killer mRNA levels. Epidermal growth factor receptor RT-PCR and immunohistochemistry, topoisomerase-1 RT-PCR confirmed the chip results. CONCLUSION: Different histological alterations can be reclassified by functional, multivariate analysis using cDNA microarrays. Further studies with expanded sample number are needed for subclassification of pathological alterations.

Adenocarcinoma↗

Which patients need referral for anal sphincter electromyography?

Needle electromyography (EMG) of lower sacral myotomes is useful in certain patients with urinary, bowel, or sexual dysfunction. The aim of the study was to identify the clinical profile of patients who require such testing. Medical records were retrospectively reviewed, and findings evaluated using bivariate and multivariate statistics. A neuropathic condition affecting the lower sacral segments was diagnosed by quantitative concentric needle EMG of the external anal sphincter (EAS) muscle. Neuropathic changes in the EAS were found in 85 (44%) of 193 patients studied. On ordinal logistic regression analysis, bladder-emptying difficulties and perineal sensory loss were significantly related to the presence of a neuropathic EMG. No guidelines for referral for anal sphincter EMG could be defined that would include all patients with neuropathic abnormalities in the lower sacral segments. However, patients with bladder-emptying difficulties and perineal sensory loss seem to be the most suitable candidates for testing.

Adolescent↗

Studying phenotypic evolution using multivariate quantitative genetics.

Quantitative genetics provides a powerful framework for studying phenotypic evolution and the evolution of adaptive genetic variation. Central to the approach is G, the matrix of additive genetic variances and covariances. G summarizes the genetic basis of the traits and can be used to predict the phenotypic response to multivariate selection or to drift. Recent analytical and computational advances have improved both the power and the accessibility of the necessary multivariate statistics. It is now possible to study the relationships between G and other evolutionary parameters, such as those describing the mutational input, the shape and orientation of the adaptive landscape, and the phenotypic divergence among populations. At the same time, we are moving towards a greater understanding of how the genetic variation summarized by G evolves. Computer simulations of the evolution of G, innovations in matrix comparison methods, and rapid development of powerful molecular genetic tools have all opened the way for dissecting the interaction between allelic variation and evolutionary process. Here I discuss some current uses of G, problems with the application of these approaches, and identify avenues for future research.

Biological Evolution↗

Grading of transitional cell bladder carcinoma by image analysis of histological sections.

Image analysis of histological sections was used to achieve a more objective malignancy grading of transitional cell carcinoma of the bladder. Images from Feulgen-stained sections from a clinical material of 197 tumours were analyzed. Features at various levels of analysis, e.g. mainly related to individual objects, neighbouring objects and the entire image, were analyzed. The features used were based on relational rather than individual nuclear features. With this technique, typical tissue architecture and degree of order/disorder can be described. These characteristics were compared by means of multivariate statistical methods with the subjective grading of the pathologists at our institution. This comparison provided the best subset of features and the agreement between the subjective and computer-based classification was 73%. The size, orientation and variation of the grey scale of the nuclei were particularly powerful. On a continuous scale, from grade 1 to 2A and 2B to 3, the four grades formed two distinct classes, low and high grade. In this distribution, the intermediate grade 2A was identified as a displaced grade 1 and the other intermediate grade 2B as a displaced grade 3.

Carcinoma, Transitional Cell↗

Characterization of normal and abnormal canine superficial lymph nodes using gray-scale B-mode, color flow mapping, power, and spectral Doppler ultrasonography: a multivariate study.

The objective of this study was to characterize the ultrasonographic patterns of normal superficial lymph nodes and to evaluate whether ultrasonography can help discriminate between different lymphadenopathies (reactive, lymphoma, and metastases) in dogs. Three hundred and eighteen superficial lymph nodes in 142 dogs were studied by B-mode, color flow mapping, power, and spectral Doppler ultrasonography. Size, echogenicity, nodal border definition, presence of a nodal hilus, acoustic enhancement and distribution of vascular flow, as well as perfusion indices were measured. Multivariate statistics using discriminant analysis was used to determine which parameters can be used to predict the diagnosis of the lymph node. The size of the lymph node, distribution of vascular flow within the lymph node, and pulsatility index (PI) in combination gave a classification error of 23% for the four groups of lymph nodes. This was improved to 11% if the nodes were divided into two groups: benign and malignant. There was a significant difference in resistive index (RI) and PI between benign and malignant nodes. Cut-off values were determined using receiver operator curves, 0.68 RI and 1.49 PI.

Animals↗

[Personal support and mortality: a cohort analysis of the National Questionnaire Survey 1984-86].

OBJECTIVES: The aim of the study is to investigate the association between personal support and mortality experience in Germany. METHODS: Data source is the Life Expectancy Survey of the Federal Institute for Population Research (Wiesbaden). This study comprises the National Questionnaire Survey of the German Cardiovascular Prevention Study (1984-86) and a mortality follow-up (1998). Included are 7240 persons with German nationality aged 31-69 years at baseline. 957 persons (13.2%) died during the observation period from 1984-1998. An additive index combining familiy status and number of persons available in emergency situations was administered as indicator for social support. The multivariate statistical analysis was performed with the cox-regression method. RESULTS: Persons with low or very low personal support yielded in both sexes significantly higher relative risks for mortality during the 14 years of follow-up. The relative risks in the regression models including confounding factors for low personal support were 1.49 (p < 0.01) in males and 1.67 (p < 0.01) in females, and for very low personal support 1.81 (p < 0.05) in males and 2.31 (p < 0.01) in females. CONCLUSIONS: These results are indicating an increasing importance of personal support for the mortality experience in the general population.

Adult↗