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The association of hyperlipidemia with retinopathy in diabetic patients aged 15-50 years in the county of Umeå.

PURPOSE: To study possible associations between serum lipid levels and degree of retinopathy in a population-based study on a specific age-group of patients with diabetes mellitus in the county of Umeå, Sweden. METHODS: All patients with diabetes mellitus aged 15-50 years living in the county of Umeå were invited to the study. The participating subjects had a standard clinical examination and an eye examination performed. Seven-field stereoscopic photographs were taken of each eye, and the photos were sent to Grading Center, Hammersmith Hospital, London, U.K. for grading of the retinopathy. Blood samples were drawn for analysis of lipoprotein(a), high density lipoprotein (HDL) cholesterol, cholesterol and triglycerides. Univariate and multivariate statistical analyses were performed. RESULTS: In the present study only patients with type 1 diabetes mellitus were included, and 285 of the invited 308 diabetic subjects (93%) took part. When univariate analysis was applied we found statistically significant associations between higher lipoprotein(a) levels, higher triglyceride levels, higher cholesterol levels, lower HDL cholesterol/total cholesterol ratios and increasing severeness of retinopathy. However, in the multivariate analysis triglyceride levels lost their importance while all other significant associations were still present. CONCLUSION: Associations were found between higher levels of serum total cholesterol, declining ratios of high density lipoprotein (HDL) cholesterol/total cholesterol, higher levels of serum lipoprotein(a) and more severe retinopathy in diabetes mellitus type 1. No such association was found between serum triglycerides and degree of retinopathy.

Adolescent↗

Critical reappraisal of referrals to electromyography and nerve conduction studies.

A large number of examinees referred to electromyographic (EMG) laboratories do not have symptoms or signs suggestive of a peripheral nervous system disorder, and the aim of the present study was to check this. All examinees evaluated by the author in a "general" EMG laboratory in the first 4 months of 2002 were included. Data on examinees, referral physicians and diagnoses, clinical symptoms and signs, and electrodiagnostic findings were statistically evaluated. Three hundred examinees, 42% men, were included. A neurological diagnosis was provided in 55% of referrals. Electrodiagnostic abnormalities were found in 45% of examinees. Using multivariate statistics, a positive effect of neurological referral diagnosis, history of paraesthesias and of weakness and sensory loss on examination, and a negative effect of history of pain on pathological electrodiagnostic findings were found. Except 20 patients with carpal tunnel syndrome, no patient with normal clinical examination had abnormal electrodiagnostic findings. Our study confirmed the inappropriateness of referrals to electrodiagnostic examination to screen patients for peripheral nervous disorders. We propose electrodiagnostic examination mainly of patients with unequivocal clinical signs of a peripheral nervous system lesion and of patients with typical symptoms of the carpal tunnel syndrome.

Electromyography↗

Prognostic factors of gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GIST) are rare neoplasms of unknown etiology and pathogenesis. Their clinical behavior is very unpredictable and a reliable prognostic factor is lacking. The aim of this study was to analyze some prognostic factors and estimate which one is the most reliable. Thirty-eight biopsy specimens of GIST were immunolabeled for PCNA, CD34, vimentin, NSE and actin. The greatest diameter, histological grading, mitotic count, DNA-index and S-phase were estimated for each case. All patients were followed-up for at least 24 months or to death. The data were analysed by univariate and multivariate statistical analysis using a computer program. The results showed that greatest diameter, tumor grade, mitotic count and PCNA-index are prognostic factors in univariate analysis. In multivariate analysis only the greatest diameter is a useful prognostic factor for planning further therapy.

Adult↗

Statistical methods towards more efficient infiltration measurements.

A comprehensive knowledge about the infiltration situation in a catchment is required for operation and maintenance. Due to the high expenditures, an optimisation of necessary measurement campaigns is essential. Methods based on multivariate statistics were developed to improve the information yield of measurements by identifying appropriate gauge locations. The methods have a high degree of freedom against data needs. They were successfully tested on real and artificial data. For suitable catchments, it is estimated that the optimisation potential amounts up to 30% accuracy improvement compared to nonoptimised gauge distributions. Beside this, a correlation between independent reach parameters and dependent infiltration rates could be identified, which is not dominated by the groundwater head.

Analysis of Variance↗

Permutation-validated principal components analysis of microarray data.

BACKGROUND: In microarray data analysis, the comparison of gene-expression profiles with respect to different conditions and the selection of biologically interesting genes are crucial tasks. Multivariate statistical methods have been applied to analyze these large datasets. Less work has been published concerning the assessment of the reliability of gene-selection procedures. Here we describe a method to assess reliability in multivariate microarray data analysis using permutation-validated principal components analysis (PCA). The approach is designed for microarray data with a group structure. RESULTS: We used PCA to detect the major sources of variance underlying the hybridization conditions followed by gene selection based on PCA-derived and permutation-based test statistics. We validated our method by applying it to well characterized yeast cell-cycle data and to two datasets from our laboratory. We could describe the major sources of variance, select informative genes and visualize the relationship of genes and arrays. We observed differences in the level of the explained variance and the interpretability of the selected genes. CONCLUSIONS: Combining data visualization and permutation-based gene selection, permutation-validated PCA enables one to illustrate gene-expression variance between several conditions and to select genes by taking into account the relationship of between-group to within-group variance of genes. The method can be used to extract the leading sources of variance from microarray data, to visualize relationships between genes and hybridizations and to select informative genes in a statistically reliable manner. This selection accounts for the level of reproducibility of replicates or group structure as well as gene-specific scatter. Visualization of the data can support a straightforward biological interpretation.

Animals↗

Statistical analysis of compositional data in anatomy.

BACKGROUND: Variables which describe the composition, or relative size of components, of an organism need to be analysed in an appropriate manner. METHODS: A few of the appropriate descriptive and inferential techniques have been described and applied to a number of anatomical data sets. RESULTS: When applied to data on the composition of the vastus medialis in adults, a small but significant difference in average muscle fibre type distribution was demonstrated between males and females. There was little evidence for a relationship between fibre type distribution and age over the range considered. CONCLUSIONS: Graphical displays via ternary diagrams are a simple way of illustrating compositional data simultaneously between and within groups. Numerical analysis is likely to involve transformation of original variables before standard univariate or multivariate statistical techniques can be used.

Adult↗

Nuclear DNA content and pathology in radically treated pancreatic carcinoma. The prognostic significance of DNA ploidy, histology and nuclear grade.

BACKGROUND: Nuclear DNA content and pathology are considered to be prognostically relevant in several solid tumors, but controversial findings have emerged in pancreatic carcinoma (PC). Histopathology and DNA ploidy were each correlated with survival in radically treated PC to ascertain the hierarchy of their prognostic significance. METHODS: DNA ploidy was assessed by flow cytometry (FC) in neoplastic tissue samples from 60 patients with PC who were followed until death. Representative neoplastic areas were obtained by microdissection from archival paraffin embedded material (excluding any carcinoma with a coefficient of variation of the G0/G1 peak higher than 8%). Histologic data and FC patterns were related to prognostic behavior using univariate multivariate statistical analysis. RESULTS: Aneuploid cancers were detected in 39 of 60 patients. Univariate analysis showed that histologic grade, nuclear grade, and ploidy were significantly related to prognosis. On multivariate analysis, only histologic grade and DNA ploidy (diploid vs. aneuploid) were significant with significant interaction. CONCLUSIONS: The prognostic value of pathology and ploidy was demonstrated in patients treated radically for PC. As in other tumors characterized by a short survival, the clinical usefulness of any prognostic parameters is somewhat limited. However, the significant relationship between prognosis and DNA ploidy might be of interest in a cost-benefit analysis for selecting patients in whom an attempt at radical surgical treatment or adjunctive chemotherapy may be justified.

Adult↗

Micrometeorologic factors affecting field host-seeking activity of adult Dermacentor variabilis (Acari: Ixodidae).

Fifteen micrometeorologic or microenvironmental parameters, including temperature, moisture, wind, and solar radiation, were repeatedly measured at 1 m and 2.5 cm aboveground, in the litter layer, and in the soil concurrently with drag samples of questing American dog tick, Dermacentor variabilis (Say), in five plots (1 by 10 m) in Delaware County, Ohio. Multivariate statistical analyses of the resultant data showed that ambient temperature was the best general predictor of adult tick host seeking under the observed ranges of the observed parameters. Multivariate procedures included forward stepwise multiple regressions and principal components analyses. Solar radiation was covariant with ambient temperature but was much less predictive. A suppression of questing activity with increased ambient temperature was evident at the highest observed temperatures, implying an upper temperature limit for this activity.

Analysis of Variance↗

[Rate of liver fibrosis progression among patients with chronic hepatitis C in Poland].

AIM: To assess the rate of liver fibrosis (RLF) among previously untreated patients with chronic hepatitis C (CHC) and to identify predictors of rapid progression to cirrhosis in this group. PATIENTS AND METHODS: Medical records of 337 consecutive patients with biopsy proven CHC (anti-HCV and HCVRNA positive; F/M: 153/184; mean age at biopsy: 43 +/- 14 years) and with known probable age at infection have been analysed. There were no intravenous drug users among the patients. HBsAg--and HIV-positive subjects as well as those with other concomitant liver disease were excluded from the analysis. The RLF was defined as the ratio between fibrosis stage (scored 0-6 units [U] according to Ishak's criteria, with 6 representing established cirrhosis) and the duration of HCV infection (in years). The RLF was analysed in relation to the age at infection, sex, route of transmission, alcohol abuse, past HBV infection, acute hepatitis history, HCV genotype and hepatic steatosis. Based on published data, a patient with RLF > or = 0.3 U/yr (cirrhosis up to 20 years after HCV infection) was arbitrarily defined as a rapid progressor. Both uni- and multivariate statistical analyses were performed. RESULTS: The mean RLF was 0.14 +/- 0.17 U/yr (range 0-0.83) and the expected mean duration from infection to cirrhosis was 43 years. In multivariate analysis the only independent factors associated with an increase in RLF were the older age at infection and alcohol abuse (both with p < 0.0001). 58 [17.2%] patients were rapid progressors and the same factors as mentioned above have been independent predictors of cirrhosis up to 20 years after infection. There were as much as 55.5% of rapid progressors among alcohol abusers infected in the age over 30 and only 1.9% among non-alcoholic patients infected in the age up to 30 years. CONCLUSIONS: Our study showed that natural course of CHC in Poland is similar to other regions of the world. HCV-related liver disease progression is accelerated among alcohol abusers and infected in older age. In contrast, risk of cirrhosis seems to be minimal among non-alcoholic patients infected before the age of 30.

Adult↗

Cathepsin D and epidermal growth factor receptor immunohistochemistry does not predict recurrence of prostate cancer in patients undergoing radical prostatectomy.

PURPOSE: We determined if immunohistochemical expression of the epidermal growth factor receptor and cathepsin D in the primary tumor was of prognostic value in clinically localized prostate cancer after radical prostatectomy. MATERIALS AND METHODS: Immunohistochemical staining for epidermal growth factor receptor and cathepsin D was performed on 105 radical prostatectomy specimens from 2 academic centers. The epidermal growth factor receptor and cathepsin D expressions were graded using H scoring by an experienced pathologist blinded to other patient data, and compared with age, grade, stage, race and initial serologic (prostate specific antigen) recurrence. Univariate and multivariate statistical testing was performed. RESULTS: Immunohistochemically detectable epidermal growth factor receptor and cathepsin D expression was not correlated to age, race, stage or Gleason grade. In univariate and multivariate testing epidermal growth factor receptor and cathepsin D were not prognostic markers for disease progression following radical prostatectomy. CONCLUSIONS: Immunohistochemical analysis of the biomarkers cathepsin D and epidermal growth factor receptor in radical prostatectomy specimens does not predict disease recurrence. Further biological marker study is needed in clinically localized prostate cancer.

Aged↗

Open biliary tract surgery: multivariate analysis of factors affecting mortality.

BACKGROUND/AIM: The overall mortality rate in patients undergoing supraduodenal choledochotomy for benign biliary tract disease is around 3%. The aim of this study is to identify and quantify factors affecting the mortality in a group of patients undergoing open common bile duct exploration for benign biliary disease. METHODS: Patients (n = 158) who underwent common bile duct exploration during a 5-year period in a teaching hospital were retrospectively reviewed. RESULTS: Univariate and multivariate statistical analyses were performed. The former identified four statistically significant variables: age (p < 0.001), acute cholangitis on admission (p < 0. 001), heart disease (p < 0.05), and a dilated common bile duct on preoperative ultrasound scan (p < 0.05). Multivariate analysis identified three variables which independently increased operative mortality: age (p = 0.05), heart disease (p = 0.03), and cholangitis (p = 0.008). The latter was associated with the greatest operative mortality, since it increased almost eight times the risk to die after surgical intervention. CONCLUSION: We conclude that an adequate perioperative cardiovascular management may be important in order to improve surgical outcome. Appropriate antibiotic prophylaxis and subsequent treatment after routine operative bile cultures may reduce septic complications and mortality. Finally, an alternative procedure, such as endoscopic sphincterotomy, may be indicated in high-risk patients in order to drain the common bile duct preoperatively and to decrease the risk of unresponsive biliary sepsis.

Acute Disease↗

von Willebrand factor and factor VIII in renal transplant recipients under immunosuppression with cyclosporine and steroids. Sequential measurements over 4 months in 17 patients.

In 17 consecutive cadaver kidney transplant recipients treated with cyclosporine (CsA) and steroids, the median of antigenic and functional levels of von Willebrand factor (vWF) and factor VIII (FVIII) before transplantation were elevated (vWF:Ag: 206%, vWF:RCof: 202%; FVIII:Ag: 248%, FVIII:C: 224%; normal values 50-150%). Sequential measurements after transplantation and during CsA treatment revealed a transient significant increase of median values with highest amounts of vWF:Ag of 362% (2 p less than 0.0001), FVIII:Ag of 398% (2 p less than 0.001) and FVIII:C of 360% (2 p less than 0.0001) (Friedman test). vWF:RCof did not show statistically significant changes. After 4 months, levels of vWF and FVIII comparable to those obtained before transplantation were observed. In univariate statistical analysis no correlation was found between vWF of FVIII on the one hand and plasma creatinine levels, CsA dose or CsA whole blood through levels on the other hand. However, multivariate statistics revealed to some extent a positive influence of CsA blood levels on vWF:Ag levels. Patients with vascular rejection or chronic CsA nephrotoxicity showed significantly lower levels of vWF:Ag as compared with patients without endothelial cell damage in the kidney (2 p less than 0.05). However, the difference in vWF:Ag levels already existed before transplantation. In contrast to recent reports, plasma vWF levels were not indicative of vascular injury in kidney graft recipients nor was the marked elevation of vWF and FVIII associated with thromboembolic complications ascribed to CsA treatment.

Cadaver↗

P-cadherin expression in breast carcinoma indicates poor survival.

BACKGROUND: The cadherin family of cell-cell adhesion molecules and their associated proteins, the catenins, are essential to embryonic development and the maintenance of adult tissues. During development, the homotypic interaction of a particular cadherin with an identical cadherin expressed on a neighboring cell results in the sorting of cells to form distinctive tissues. Cadherins are believed to be tumor suppressors, and their altered expression and function have been associated with tumor development. METHODS: The authors examined the expression of P-cadherin, E-cadherin, and N-cadherin, and alpha-catenin and beta-catenin in 183 cases of invasive breast carcinoma by immunohistochemistry on paraffin sections using specific antibodies and a steam-based antigen retrieval method. RESULTS: P-cadherin was positive in 95 cases and negative in 88 cases of breast carcinoma. Positive P-cadherin expression in breast carcinoma showed a strong correlation with poor patient prognosis. Five years after surgery, 90% of the patients with P-cadherin negative tumors were alive in contrast to only 59% of patients with P-cadherin positive tumors. The difference in survival reached statistical significance (P = 0.0001) as early as 2 years after surgical treatment. Expression of N-cadherin, alpha-catenin, and beta-catenin did not correlate with patient survival. Multivariable statistical analyses of the data showed that expression of P-cadherin was independent of tumor size and lymph node metastases, but correlated inversely with estrogen/progesterone receptor status. In ductal carcinomas, positive P-cadherin expression correlated with a higher histologic grade. In contrast, expression of E-cadherin was low in high grade ductal carcinomas but negative tumors were uncommon. Negative or low E-cadherin expression did not correlate with poor survival. In lobular carcinomas, E-cadherin expression frequently was negative or low, and P-cadherin always was negative. CONCLUSIONS: Expression of P-cadherin in breast carcinoma is associated strongly with poor survival and constitutes an independent prognostic predictor. P-cadherin expression is a better indicator of clinical outcome than alterations in the expression of E-cadherin, N-cadherin, alpha-catenin, or beta-catenin.

Adult↗

MADE4: an R package for multivariate analysis of gene expression data.

SUMMARY: MADE4, microarray ade4, is a software package that facilitates multivariate analysis of microarray gene-expression data. MADE4 accepts a wide variety of gene-expression data formats. MADE4 takes advantage of the extensive multivariate statistical and graphical functions in the R package ade4, extending these for application to microarray data. In addition, MADE4 provides new graphical and visualization tools that aid in interpretation of multivariate analysis of microarray data.

Algorithms↗

Incidence and duration of breast-feeding of ill newborns.

The many biological advantages of breast milk call for promoting breast-feeding. The extent to which separation of ill newborns from their mothers negatively influences breast-feeding is not known. By means of a written inquiry, we investigated the prevalence of exclusive, partial, and no breast-feeding of 536 newborns hospitalized at a tertiary care neonatal center with no inborn patients. Three hundred twenty-seven questionnaires were completed correctly. Fifty percent of the mothers eventually succeeded in exclusive breast-feeding, 25% in partial breast-feeding, and 25% never breast-fed. The frequency of breast-feeding was similar to the Swiss average for the first 4 months of life in healthy newborns and declined more rapidly thereafter. Univariate and multivariate statistical analyses have shown that the following conditions influence breast-feeding negatively: gestational age < or = 33 weeks, maternal age > 25 years, and lower professional status of the father. Additionally, multivariate analysis revealed a promoting effect of previous breast-feeding. Exclusive breast-feeding has eventually been possible in half of the newborns who had initially been separated from their mothers due to illness. Knowledge of the conditions influencing breast-feeding in such populations should help to promote breast-feeding more specifically in tertiary neonatal centers.

Adult↗

Variables affecting treatment in benign paroxysmal positional vertigo.

OBJECTIVE: To identify variables affecting outcome in patients with benign paroxysmal positional vertigo (BPPV) treated with canalith repositioning maneuvers. STUDY DESIGN: Retrospective review of patients at a tertiary vestibular rehabilitation center. METHODS: Variables identified for statistical analysis included method of diagnosis, age, sex, onset association with trauma, semicircular canal involvement, presence of bilateral disease, treatment visits, and cycles of canalith repositioning maneuvers per treatment visit. Multivariate statistical analysis using Pearson chi2, likelihood ratio, linear-by-linear association, and cross-tabulation tests were performed. RESULTS: Two hundred fifty-nine patients with BPPV who received treatment were identified from 1996 to 1998. Average follow-up time was 16.9 months. 74.8% required one treatment visit, 19.0% required a second treatment visit, and 98.4% were successfully treated after three treatment visits. The remainder required up to seven treatment visits for relief of symptoms. Variables affecting the number of treatment visits included bilateral disease or location of disease other than in the posterior semicircular canal. Patient age, sex, method of diagnosis, and onset association with trauma had no statistically significant impact. CONCLUSION: Patients with benign paroxysmal positional vertigo not located in a single posterior semicircular canal are more likely to require multiple visits for canalith repositioning.

Adult↗

Prognostic significance of DNA cytometry in carcinoma of the uterine cervix FIGO stage IB and II.

OBJECTIVE: To assess the prognostic value of DNA-image cytometry in cervical carcinoma of the uterus and its relation to other established prognostic factors. STUDY DESIGN: The study included 116 cases of cervical carcinoma FIGO stages IB and II which were treated with radical abdominal hysterectomy. The median follow-up was 55 months (range 1-162 months). DNA image cytometry was performed on cytologic specimens prepared by enzymatic cell separation from formalin-fixed, paraffin-embedded tissues. DNA stemline ploidy, DNA stemline aneuploidy, 5c exceeding rate, 9c exceeding rate, 2c deviation index, and DNA malignancy grade were computed. DNA-variables as well as various clinical and histological variables were related to survival rates. RESULTS: In multivariate statistical analysis DNA stemline ploidy using 2.2c as a cut-off value and FIGO stage showed to be statistically significant available presurgery predictors of survival, whereas the postsurgical parameters lymphonodal status, tumor size and parametrial involvement were significantly correlated with survival. The synopsis of all parameters in a multivariate Cox model indicated that - with declining relevance - the number of positive pelvic lymph nodes, DNA stemline ploidy using a cut-off level at a modal value of 2.2c, largest pelvic lymph node, 5c exceeding rate, and ratio of carcinoma area to cervix area, were of predictive value for survival. CONCLUSIONS: Our results suggest that prognostic information deducted from classical staging parameters is successfully complemented by DNA image cytometry which can be applied pretherapeutically.

Adult↗

Prognostic value of E-cadherin, beta-catenin, P120ctn in patients with transitional cell bladder cancer.

BACKGROUND: Loss of E-cadherin-catenin mediated adhesion is known to play a major role in tumour progression in many human carcinomas. MATERIALS AND METHODS: By means of immunohistochemistry, we have investigated the expression of E-cadherin, beta-catenin and p120ctn in 102 transitional cell bladder carcinomas (TCCs) and statistically analysed these expressions with known clinicopathological parameters and patient survival. RESULTS: Abnormal expression of E-cadherin, beta-catenin and p120ctn was associated with high grade and high stage of TCCs (p < 0.001). Abnormal beta-catenin expression demonstrated a statistically significant correlation with poor patient survival (p = 0.03) while abnormal E-cadherin expression was associated with poor survival in patients with muscle invasive TCCs (p = 0.025). However, in multivariate statistical analysis a suggestive association with poor survival was observed only for E-cadherin (p = 0.06). Simultaneous abnormal expression of all the molecules demonstrated an association of suggestive significance with poor patient survival (p = 0.07). CONCLUSION: E-cadherin expression may be a useful prognostic marker in patients with invasive TCCs.

Adult↗