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PubMed1989

Hepatic resection of metastasis from colorectal carcinoma. Morbidity, mortality, and pattern of recurrence.

To identify the factors that determine the morbidity and mortality of liver resection of metastases from colorectal carcinoma and the variables that may influence the pattern of recurrence, the survival time and the disease-free rate, a univariate and-multivariate statistical analysis (30 variables using Student's t-test, Fischer's exact test, and chi square test) was performed. Intraoperative blood loss of greater than 3500 ml was found to be a significant risk factor to developing postoperative complications (p less than 0.05 by x2). After a mean follow-up of 25.8 months, 26 of the 35 patients studied (74%) had recurrent disease. In the univariate analysis, the following factors appear to be reliable predictors of early recurrence: poor degree of differentiation of the primary colorectal tumor, the presence of multiple liver metastases, the male gender, and the presence of tumor at the margin of the resected hepatic tissue (p less than 0.05). However, only the latter two factors appeared also to affect the survival time and the disease-free rates at 2 years after hepatic resection of metastases (p less than 0.05). In the multivariate analysis (factors tested simultaneously), presence of an advanced liver metastatic disease (Stage II or III) consistently indicated early recurrence and poor survival (p less than 0.005). The liver was the most common site of recurrence as the sole site of recurrence (54%) or in combination with other sites (88%)--followed by the lungs (31%) and the site of colonic resection (8%). Twenty-nine (83%), 14 (40%), and nine (26%) patients survived without recurrent disease at 1, 2, and 3 or more years, respectively, after hepatic resection of metastases. In six patients (17%), no significant palliation was noted, primarily because of early recurrence (less than 6 months). From this data, resection of hepatic metastases from colorectal cancer appears to offer a realistic therapeutic option to a selected group of patients, but only if the resective procedure can be performed with an operative mortality rate of less than 5%.

Adenocarcinoma↗
PubMed2001

The influence of cephalometric parameters on resonance of speech in cleft lip and palate patients. An interdisciplinary study.

There are only few studies concerning the correlation between craniofacial morphology and resonance of speech in cleft palate patients. Moreover, these investigations show a considerable inhomogeneity in material and method, their basic approach was predominantly retrospective, and the statistical methods were restricted to univariate procedures. Thus, the aim of the present study was twofold: firstly to clarify the extent to which correlations exist between craniofacial morphology and resonance of speech in cleft palate patients, subject to a sufficiently large number of patients being available to ensure differentiation with regard to age and cleft type, and secondly, within a prospective longitudinal study in juvenile cleft palate patients, to investigate whether pubertal craniofacial growth changes result in changes of resonance. The collective comprised 137 cleft palate patients. The following investigations were performed: lateral cephalometry, nasometry, and standardized speech recording. Additionally, these investigations were repeated in 51 juvenile patients after a minimum time interval of 2 years. In order to analyze the complex relations between craniofacial morphology and degree of hypernasality, multivariate statistical procedures were applied. The results of the present study indicate complex correlations between cephalometric parameters and resonance of speech, requiring age-specific differentiation. In this regard, the ratios between the length of the soft palate and the sagittal depth of the nasopharyngeal airway were of prime importance. Beyond this, significant correlations were found between craniofacial growth changes and changes of resonance during puberty which might be influenced both by dentofacial orthopedics and by maxillofacial surgery.

Adolescent↗
PubMed2002

A gene-expression signature as a predictor of survival in breast cancer.

BACKGROUND: A more accurate means of prognostication in breast cancer will improve the selection of patients for adjuvant systemic therapy. METHODS: Using microarray analysis to evaluate our previously established 70-gene prognosis profile, we classified a series of 295 consecutive patients with primary breast carcinomas as having a gene-expression signature associated with either a poor prognosis or a good prognosis. All patients had stage I or II breast cancer and were younger than 53 years old; 151 had lymph-node-negative disease, and 144 had lymph-node-positive disease. We evaluated the predictive power of the prognosis profile using univariable and multivariable statistical analyses. RESULTS: Among the 295 patients, 180 had a poor-prognosis signature and 115 had a good-prognosis signature, and the mean (+/-SE) overall 10-year survival rates were 54.6+/-4.4 percent and 94.5+/-2.6 percent, respectively. At 10 years, the probability of remaining free of distant metastases was 50.6+/-4.5 percent in the group with a poor-prognosis signature and 85.2+/-4.3 percent in the group with a good-prognosis signature. The estimated hazard ratio for distant metastases in the group with a poor-prognosis signature, as compared with the group with the good-prognosis signature, was 5.1 (95 percent confidence interval, 2.9 to 9.0; P<0.001). This ratio remained significant when the groups were analyzed according to lymph-node status. Multivariable Cox regression analysis showed that the prognosis profile was a strong independent factor in predicting disease outcome. CONCLUSIONS: The gene-expression profile we studied is a more powerful predictor of the outcome of disease in young patients with breast cancer than standard systems based on clinical and histologic criteria.

Adult↗
PubMed1994

Electron cryomicroscopy and digital image processing of lipoprotein(a).

Electron cryomicroscopy was used to study the structure of human lipoprotein(a) (Lp(a)), a plasma lipoprotein implicated in cardiovascular disease. An individual Lp(a) particle consists of a neutral lipid core within a shell of phospholipid, cholesterol and glycoprotein. In principle, electron cryomicroscopy images of single particles should contain structural detail attributable to the density differences among these components and the surrounding buffer. We observed such structural detail in images of frozen, hydrated Lp(a) particles. Lp(a) particles appeared to be roughly spherical in shape with an average diameter of 210 A. As is generally true for unstained samples in vitreous ice, imaged with a low electron dose, these images have low contrast with low signal-to-noise ratios. To increase the signal-to-noise ratio, we averaged classes of similar particles. We began with a set of 5813 randomly oriented Lp(a) particles and generated classes using a linear multivariate statistical method, followed by hierarchical ascendant classification. Our initial classification, based on only the first eight eigenvectors, separated particles on the basis of gross size and shape. After a rough reference-free alignment step, a second classification used the finer details in the images. This approach yielded class averages with structural detail only faintly visible in the raw, single images.

Freezing↗
PubMed1998

Electron crystallography of yeast RNA polymerase II preserved in vitreous ice.

Two-dimensional (2-D) crystals of yeast RNA polymerase preserved in vitreous ice were studied by electron crystallographic and single-particle techniques. An electron density projection map of the enzyme was calculated from the data, which extended to a resolution of about 12 A, but was unexpectedly weak at resolutions higher than about 20 A. Multivariate statistics analysis revealed a large amount of variability in unit-cell structure in the polymerase crystals, partially related to high mobility of certain polymerase domains. Those same domains were previously identified as being involved in a conformational transition in the enzyme that controls DNA processivity and access to the active center cleft. Electron microscopic studies of other large multiprotein complexes are likely to require similar approaches to those described here.

Crystallography↗
PubMed1990

Red cell enzyme polymorphisms in the Balearic Islands. II. A comparison based on multivariate analyses.

A sample of 2143 individuals from Mallorca, coming from six geographic regions of this island: "Es Raiguer", "La Muntanya", "Es Plà", "Mijgorn", "Llevant" and "Palma", as well as 390 individuals from Eivissa island have been studied for the following six red cell enzyme systems: Esterase-D (ESD), acid phosphatase-1 (ACP1), glyoxalase-I (GLO1) 6-phosphogluconate dehydrogenase (PGD), phosphoglucomutase-1 (PGM1) and adenylate-kinase (AK1). The data were processed by means of multivariate statistical procedures: principal components, factorial correspondence and cluster analyses. The results indicate that ACP1 and ESD were the most suitable systems for the characterization of these caucasian populations, while GLO1 was important when different ethnic groups were included in the analyses. The Balearic gene frequencies fell within the European standard. Slight genetic distances were detected among the different Balearic populations, notably with the exception of the high differentiation of "La Muntanya".

Cluster Analysis↗
PubMed1999

Loss of heterozygosity and protein expression of APC gene in renal cell carcinomas.

This study evaluated the potential contribution of the APC gene to malignant transformation in patients with renal cell carcinoma. We tested 36 human renal cell carcinoma samples and 18 adjacent normal kidney tissues for the expression of APC protein, both wild and truncated types, by western blot using antibodies that recognize either the carboxy or the amino epitope of the APC protein. The same tumor samples together with autologous peripheral blood were also analyzed at the DNA level. Using specific oligonucleotide primers for exons 11 and 15, gene instability was followed by polymerase chain reaction/loss of heterozygosity (LOH) (on the basis of restriction fragment length polymorphism). Molecular data were also compared to pathohistological diagnosis, TNM stage, and patient's age using multivariate statistical methods. All normal renal tissues revealed expression of the wild-type APC protein. Neither wild nor mutant type proteins were found in 36% (13/36) of tumor samples; the rest of tumor tissues expressed the wild-type protein (312 kDa). Mutated APC protein, with a molecular weight of 117 kDa, was found in only one tumor sample. From 36 tumor samples 16 (44.4%) were informative for RsaI exon 11 polymorphic site, while only half of these (8/16) demonstrated LOH. From 13 tumor samples that had no detectable protein product by western blot analysis eight were homozygous for the exon 11 polymorphism and were tested for another polymorphic site, MspI/exon 15. The overall proportion of LOH cases for both polymorphisms tested was 52.9% (9/17). Pathohistological diagnosis and molecular data showed no correlation. However, multivariate analysis determined a stage strong positive correlation of age and TNM with the presence of LOH and the absence of the wild-type APC protein. Out results suggest that the APC tumor suppressor gene plays a role in renal carcinogenesis. Alterations in this gene are responsible for tumor evolution and progression, but cannot be considered as a first event in tumor initiation.

Adenomatous Polyposis Coli Protein↗
PubMed1999

Risk factors for perinatal human immunodeficiency virus transmission in patients receiving zidovudine prophylaxis. Pediatric AIDS Clinical Trials Group protocol 076 Study Group.

OBJECTIVE: To identify modifiable obstetric factors associated with the failure of zidovudine chemoprophylaxis to prevent perinatal human immunodeficiency virus type 1 (HIV-1) transmission. METHODS: We analyzed data from Pediatric AIDS Clinical Trials Group protocol 076, a randomized, double-masked, placebo-controlled trial that demonstrated that a zidovudine regimen could prevent perinatal HIV-1 transmission. We estimated the zidovudine treatment effect using the relative reduction in transmission risk among women randomized to treatment with zidovudine compared with women randomized to receive placebo. Univariate and multivariate statistical analyses were used to assess whether the treatment effect differed in magnitude according to potential antepartum or intrapartum risk factors. RESULTS: In the univariate analysis, the zidovudine treatment effect was found to differ significantly in magnitude according to quartile of maternal weight at the time of study entry (interaction test, P = .03); among women in the heaviest-weight quartile (weight more than 82 kg), there was a 26% relative reduction in transmission risk, compared with a 79% relative reduction among the other three quartiles (interaction test, P = .05). In the zidovudine treatment group, women who transmitted HIV-1 were significantly more likely than nontransmitters to have had antepartum procedures or conditions associated with increased risk of fetal exposure to maternal blood or cervicovaginal secretions (43% compared with 19%, P = .04). In the multivariate analysis, adjustment for the plasma HIV-1 RNA level and CD4+ cell percentage did not eliminate the differential treatment effect according to these factors. CONCLUSION: High maternal weight and conditions associated with fetal exposure to maternal blood or cervicovaginal secretions may diminish the efficacy of zidovudine chemoprophylaxis.

Anti-HIV Agents↗
PubMed2004

Dental microwear in anubis and hybrid baboons (Papio hamadryas, sensu lato) living in Awash National Park, Ethiopia.

We describe dental microwear in baboons (Papio hamadryas sensu lato) from the anubis-hamadryas hybrid zone of Awash National Park, Ethiopia, outline its variation with sex and age, and attempt to relate the observed microwear pattern to environment and diet. Casts of the maxillary second molar of 52 adult and subadult individuals of both sexes were examined with a scanning electron microscope at x 500. Digitized micrographs were taken at a consistent location on facet 9, and microwear was recorded with an image analysis software package. Univariate and multivariate statistics were used to investigate the shape, size, and density of microwear features. The overall pattern of microwear exhibits an unusual combination of high feature density, with numerous small pits and relatively wide striations, and a high correlation between width of pits and striations across individuals. We interpret this pattern as predominantly the consequence of abrasion by relatively small-caliber environmental grit when accidentally ingested with tough foods such as dried seeds and fruits, as expected in a terrestrial omnivore living in a dusty habitat. Statistical analysis revealed no significant differences between groups defined by sex, age, or troop membership, a result consistent with qualitative observations of feeding habits in this population, and which lends no support to the hypothesis that the longer jaws of adult males should result in longer striations. A trend towards greater feature density in females, however, might be due to limited sexual dinichism, and merits further investigation.

Analysis of Variance↗
PubMed1992

Multivariate quantitative structure-toxicity relationships in a series of dopamine mimetics.

The techniques of principal components analysis and non-linear mapping are routinely used by computer chemists at SmithKline Beecham Pharmaceuticals in the process of drug development by relating the structure of a compound to its chemical activity. To our knowledge these techniques had not previously been applied to the association between the structure of a compound and its toxicological properties. Using a series of 12 structurally related compounds (11 were active dopamine mimetics and one was inactive), of which five were known to be teratogenic and seven were non-teratogenic, it was possible to demonstrate that molecular modelling techniques could be applied to differentiate toxicological data. The structure/property relationships of these compounds were investigated using calculated physicochemical properties, molecular modelling and multivariate statistical techniques. A data set of 56 molecular descriptors was used to represent this series of compounds. Analysis of the data set using principal components analysis and non-linear mapping suggested that teratogenicity was associated with four molecular properties. Moreover, the electronic nature of the 4-phenyl group appeared to be an important determinant of the teratogenesis.

Abnormalities, Drug-Induced↗
PubMed1996

Rational choice of molecular dynamics simulation parameters through the use of the three-dimensional autocorrelation method: application to calmodulin flexibility study.

We examined the effects of several adjustable parameters for use in molecular dynamics simulations of proteins using both standard criteria (radius of gyration, root mean square deviation from starting coordinates, molecular mechanics energy) and a new description of protein conformations by 3-D autocorrelation vectors (3-D ACV). We chose calmodulin (CaM) as a protein model and analysed 23 simulations using different combinations of the four molecular dynamics parameters studied, such as the dielectric constant (epsilon), the heating phase time (H), the thermal bath coupling time (zeta T) and the time step size (delta t). The correctness of the various trajectories generated with different parameter sets was evaluated through geometric analysis and use of a knowledge-based profile method. It is shown that 3-D ACV combined with multivariate statistical analysis provides a convenient way to describe and compare molecular dynamics simulations and constitutes a valuable complementary tool to standard methods. Using these methods, comparison of the various simulations performed on CaM indicated that the best in vacuo parameter set was epsilon = 1 x r, H = 15 ps, zeta T = 0.1 ps and delta t = 1 fs in fairly good agreement with previous less extensive comparisons of molecular dynamics trajectories.

Binding Sites↗
PubMed2003

Risk factors for sports injuries--a methodological approach.

The methodology for studies designed to investigate potential risk factors for sports injury is reviewed, using the case of hamstring strains as an example. Injuries result from a complex interaction of multiple risk factors and events. Therefore, a multivariate statistical approach should be used. In addition, the sample size of the study needs to be considered carefully. Sample size mainly depends on the expected effect of the risk factor on injury risk, and to detect moderate to strong associations 20-50 injury cases are needed, whereas small to moderate associations would need about 200 injured subjects. Studies published to date on the risk factors for hamstring strains have methodological limitations, and are too small to detect small to moderate associations.

Athletic Injuries↗
PubMed2004

Extracorporeal lithotripsy for salivary calculi: a long-term clinical experience.

OBJECTIVES/HYPOTHESIS: The objective was to assess in a large series of patients with a long-term clinical follow-up the validity of extracorporeal electromagnetic shock wave lithotripsy as a minimally invasive therapy for sialolithiasis. STUDY DESIGN: Consecutive patient series. METHODS: Three hundred twenty-two consecutive symptomatic outpatients with single or multiple calculi in the submandibular (234 patients) or parotid (88 patients) gland underwent a complete extracorporeal electromagnetic shock wave lithotripsy treatment. Treatment results were classified into three groups: successful result with complete ultrasonographic elimination of the stone after lithotripsy, successful result with residual ultrasonographic fragments that were less than 2 mm in diameter, and unsuccessful result with residual ultrasonographic fragments that were greater than 2 mm in diameter. Univariate and multivariate statistical analyses were performed. RESULTS: Complete elimination of the stone was achieved in 45% of patients. On ultrasonography, residual fragments (<2 mm in diameter) were detected in 27.3% of patients, and persisting fragments greater than 2 mm in diameter were assessed in 27.7% of patients. In 3.1% of patients, all with submandibular gland stones, sialoadenectomy was performed. Recurrence of calculi in the treated gland was observed during a median follow-up period of 57 months in four patients with complete ultrasonographic clearance of the stone occurring 10 to 58 months after lithotripsy. Univariate analysis showed that a favorable treatment result was significantly associated with the younger age of the patients (< or = 46 y), parotid and intraductal localization of the stone, diameter of the stone (< or = 7 mm), and number of therapeutic sessions (< or = 6). On multivariate analysis, the age of the patient, parotid site of the stone, stone diameter, number of therapeutic sessions, and number of shock waves were associated with favorable outcome. CONCLUSION: Extracorporeal electromagnetic shock wave lithotripsy is to be considered an efficient, minimally invasive treatment modality for salivary calculi.

Adolescent↗
PubMed1990

Review of the two sample t tests.

The t test is a valuable statistical manipulation of moderate strength to determine whether a significant difference exists between the means of two groups, either paired or unpaired. Generally, the larger the t value, the greater chance of its statistical significance. Sample size also will influence the point at which t becomes significant, that is, the larger the size of n, the smaller the t required to become significant. As the number of degrees of freedom becomes larger, a smaller t value is sufficient to reject the null hypothesis, and as variability increases, the true chance for significant difference decreases. It should be noted that a common error in the use of the t test occurs with excessive repetition of the test on the same dataset. A resultant type 1 error will be introduced that incorrectly concludes that significant differences have been demonstrated when, in fact, they have resulted not from significance but from repeated statistical application. In other words, if a .05 level of significance is used repeatedly on a dataset, the investigator is assuming that there is a 1 in 20 chance of finding a significant difference when there is no true difference between variables. It becomes obvious that if 20 repeated applications of the t test were performed, one would expect to find one significant difference by chance alone when no true difference exists. If more than 10 applications of the t test are being conducted on the same dataset, the investigator should lower the level of significance (.01) on each individual t test of the entire set so fewer null hypotheses are rejected. t Tests numbering 40 to 50 should have an alpha level of .005. An alternative approach would be to consult a statistician and use multivariate statistical procedures.

Analysis of Variance↗
PubMed1998

Specific association of photosystem II and light-harvesting complex II in partially solubilized photosystem II membranes.

In this study, we report the structural characterization of photosystem II complexes obtained from partially solubilized photosystem II membranes. Direct observation by electron microscopy, within a few minutes after a mild disruption of the membranes with the detergent n-dodecyl-alpha,D-maltoside, revealed the presence of several large supramolecular complexes. Images of these complexes were subjected to multivariate statistical analysis and classification procedures, resolving a new complex consisting of the previously characterized dimeric supercomplex of photosystem II and light-harvesting complex II [Boekema et al., Proc. Natl. Acad. Sci. USA 92 (1995) 175-179] and two additional, symmetrically organized protein masses each containing a second type of trimeric light-harvesting II complex. We conclude that large and labile integral membrane proteins, such as photosystem II, can be quickly structurally characterized without extensive purification.

Membrane Proteins↗
PubMed1997

Symmetric GroEL-GroES complexes can contain substrate simultaneously in both GroEL rings.

Incubation of rhodanese with hche aperonins GroEL and GroES (1:2 GroEL14:GroES7 molar ratio) under functional and steady state conditions for ATP leads to the formation of a high proportion of rhodanese-bound symmetric complexes (GroEL14(GroES7)2), as revealed by native electrophoresis. Aliquots of such samples were observed under the electron microscope, and the symmetric particles were classified using neuronal networks and multivariate statistical analysis. Three different populations of symmetric particles were obtained which contained substrate in none, one or both GroEL cavities, respectively. The presence of substrate in the symmetric complexes under functional conditions supports their role as active intermediates in the protein folding cycle. These results also suggest that symmetric GroEL-GroES complexes can use both rings simultaneously for folding, probably increasing the efficiency of the reaction.

Adenosine Triphosphate↗
PubMedDate not supplied

Multivariate independent prognostic factors in endometrial carcinoma: a clinicopathologic study in 181 patients: 10 years experience at the Department of Obstetrics and Gynecology of the Mainz University.

The aim of this study was to evaluate the biologic outcome of endometrial carcinomas as compared to clinical and pathologic parameters and to identify multivariate independent prognostic factors. Charts were abstracted from patients with endometrial carcinoma from 1985 to 1995. Data on clinicopathologic variables, adjuvant treatment, site of recurrence, and survival were collected. chi2 test was used to test association between variables. Kaplan-Maier method was used for survival analysis and Cox proportional hazards model for multiple regression analysis. Univariate analysis revealed that FIGO stage, tumor grade, depth of myometrial invasion, biochemical analysis of progesterone receptor status, age, additional diabetes mellitus, lymph node metastasis, and type of tumor were significantly associated with the overall-survival. For disease-free interval, FIGO stage, tumor grade, depth of myometrial invasion, biochemical analysis of progesterone receptor status, lymph node metastasis, and type of tumor were also significantly associated. Multivariate analysis revealed that FIGO stage, tumor grading, tumor type, depth of myometrial invasion, and biochemically measured progesterone receptor status were associated significantly with overall survival. A significant correlation as independent prognostic factors were also seen for recurrence free interval for FIGO stage, tumor grade, and biochemical progesterone receptor status. In multivariate statistical analysis we identified FIGO stage, tumor type, tumor grade, biochemical analysis of progesterone receptor status, and depth of myometrial invasion as independent prognostic factors for overall survival, and FIGO stage, biochemical analysis of progesterone receptor status, and tumor grade as independent prognostic factors for recurrence-free interval.

Adenocarcinoma↗
PubMed1996

The relationship between psychological distress during pregnancy and birth weight for gestational age.

BACKGROUND: Fetal growth may be determined by genetic as well as environmental factors. Whether psychological distress during pregnancy influences fetal growth is a matter of debate. MATERIAL AND METHODS: A prospective population-based study with repeated measures of psychological distress (General Health Questionnaire) during pregnancy, based on the use of questionnaires. Danish speaking women with singleton pregnancies attending antenatal care between August 1, 1989 and September 30, 1991 were eligible to the study (n = 8719). Of these women 5868 women (67%) completed all questionnaires. The main outcome measure was fetal growth (assessed as birth weight for gestational age (continuous)) and birth weight below the 10th percentile of birth weight for gestational age (light for gestational age (LGA) (dichotomous). Gestational age was calculated primarily from an early ultrasound scan. Confounders were controlled using multivariate statistical methods. RESULTS: Birth weight for gestational age and risk of delivering a LGA baby were not associated with psychological distress, neither distress in 16th week nor in 30th week of pregnancy. CONCLUSION: To the extent that fetal growth can be explored at birth, the results indicate that psychological distress does not influence fetal growth.

Adult↗