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Infant heart rate response to trigeminal airstream stimulation: determination of normal and deviant values.

In this study, trigeminal airstream stimulation is used on a group of normal, sleeping infants to screen for reflex bradycardia. Infants were tested at 1--3 days and at 4, 8, 12, and 16 weeks of age. The usual heart rate response was acceleration above the prestimulus level. The amount of heart rate change was seen to depend on prestimulus rate and, to a lesser extent, postconceptional age. Multiple regression analysis of the data provided estimates of expected responses, given postconceptional age and prestimulus heart rate. From these, ranges were established for classification of normal or abnormal responses. Six deviant data points over 2 SDs from expected values were identified. Two of these represented heart rate increases and four were heart rate decreases. One deviant heart rate decrease was over 3 SDs from the mean. Although the deviant increases were thought to represent exaggerated startles, the more severe heart rate decreases were believed to be a reflex resembling the diving reflex.

Heart Rate↗

Primary degenerative cerebellar ataxias in ethnic Bengalees in West Bengal: some observations.

Seventy cases of primary degenerative cerebellar ataxias in ethnic Bengalees from southern West Bengal, India, were studied by the authors. Of these, 50 cases were of the familial type (hereditary ataxias) encountered in 23 families and the remaining 20 were of sporadic onset. 18 cases (from 11 families) were of "probable" autosomal recessive (AR) inheritance, 12 cases (8 families) had Friedreich's type ataxia (FA), 4 cases (2 families) had FA type ataxia with retained reflexes and in 2 cases (1 family) the exact phenotypic characterization could not be made. AR inheritance in these cases seemed most likely in view of the occurrence in a single generation with unaffected parents and history of consanguinity in many of the families studied. Genotypic confirmation of FA type ataxia and its variants could not be done in any case due to the non-availability of technology for studying the FA locus but some common dominant ataxia genotypes could be excluded. Thirty-two cases (from 12 families) with autosomal dominant ataxias (ADCA) were studied. Genotype analysis revealed 4 families with SCA2 genotype, 5 families with SCA3 and 3 families where genotypic characterization could not be made (phenotypically 2 were of ADCA I and 1 of ADCA II). No clear preponderance of one particular genotype of SCA over another could be demonstrated in our ethnic Bengalee patients. We also noted significant intra and inter-family variations in phenotypes within the same genotypic form as well as overlapping of clinical signs between different genotypes. Slow saccades and peripheral neuropathy were not seen consistently in our ethnic Bengalee subjects with SCA2 genotype. Similarly, extrapyramidal features, ophthalmoplegias and distal amyotrophy were seen in some but not all families with the SCA3 genotype. Phenotypic expression appeared to be an inconsistent marker of the SCA genotype in our patients. Of the 20 sporadic cases with cerebellar ataxia, genotype analysis revealed 2 cases with SCA1 and 1 with SCA2. Some of the sporadic ataxia cases had extracerebellar involvement and may warrant classification as Multiple System Atrophy. In all the 3 subjects with genotype characterization, phenotype correlation was lacking. The clinical pattern of hereditary ataxias in ethnic Bengalees seems to be somewhat different from that seen in Western India. The need for clinical and genetic studies of ataxias in different specific ethnic populations of India has been stressed.

Adolescent↗

Xenobiotic regulation of glutathione S-transferase Ya gene expression.

The gene for the rat GST Ya subunit has been examined in detail as a model for understanding the molecular mechanisms of inducibility by xenobiotics and their tissue-specific regulation. The focus of this article is to describe our current understanding of these mechanisms. The discussion will begin with the classification of the types of inducing agents. These pioneering studies suggested that there were multiple mechanisms for the inducibility of GSTs. In fact, the analysis of GST Ya gene expression has identified two different upstream activating elements and putative protein factors through which different classes of inducers act. Finally, the position-specific and tissue-specific regulation of the GST Ya gene will be discussed.

Animals↗

Read Codes Version 3: a user led terminology.

Version 3 of the Read Codes was designed in response to a new set of requirements generated by three new terming initiatives in the UK, the Clinical Terms Project, the Professions Allied to Medicine Terms Project and the Nursing Terms Project. The challenge was to cope with the detail required by clinical specialists for maintaining a computerised record, to capture the natural language used by clinicians in their everyday work, and to support efficient analysis across medical records required to extract information from clinicians' individual patient data. The structure of Version 3 allows a directed acyclic graph to replace the traditional hierarchy; permits multiple such graphs if necessary; introduces qualifiers, embedding these in an information model to support analysis; introduces one-to-many mapping to external classifications where this is necessary; and maintains the tradition of a dynamic terminology that stresses the inclusion of natural clinical terms.

Artificial Intelligence↗

Computerized analysis of multiple-mammographic views: potential usefulness of special view mammograms in computer-aided diagnosis.

PURPOSE: To investigate the potential usefulness of special view mammograms in the computer-aided diagnosis of mammographic breast lesions. MATERIALS AND METHODS: Previously, we developed a computerized method for the classification of mammographic mass lesions on standard-view mammograms, i.e., mediolateral oblique (MLO) view and/or cranial caudal (CC) views. In this study, we evaluate the performance of our computerized classification method on an independent database consisting of 70 cases (33 malignant and 37 benign cases), each having CC, MLO, and special view mammograms (spot compression or spot compression magnification views). The mass lesion identified in each of the three mammographic views was analyzed using our previously developed and trained computerized classification method. Performance in the task of distinguishing between malignant and benign lesions was evaluated using receiver operating characteristic analysis. On this independent database, we compared the performance of individual computer-extracted mammographic features, as well as the computer-estimated likelihood of malignancy, for the standard and special views. RESULTS: Computerized analysis of special view mammograms alone in the task of distinguishing between malignant and benign lesions yielded an Az of 0.95, which is significantly higher (p < 0.005) than that obtained from the MLO and CC views (Az values of 0.78 and 0.75, respectively). Use of only the special views correctly classified 19 of 33 benign cases (a specificity of 58%) at 100% sensitivity, whereas use of the CC and MLO views alone correctly classified 4 and 8 of 33 benign cases (specificities of 12% and 24%, respectively). In addition, we found that the average computer output of the three views (Az of 0.95) yielded a significantly better performance than did the maximum computer output from the mammographic views. CONCLUSIONS: Computerized analysis of special view mammograms provides an improved prediction of the benign versus malignant status of mammographic mass lesions.

Breast Neoplasms↗

The quantitative parameters of intrathecal IgG synthesis. A comparison.

Cerebrospinal fluid IgG/Albumin, IgG Index, Tourtellotte's formula and Schuller's formula have been calculated in 258 patients with definite Multiple Sclerosis and oligoclonal bands at isoelectrofocusing examination of cerebrospinal fluid. A step wise discriminant analysis was performed on single parameters and on a combination of IgG Index, Tourtellotte's and Schuller's formulas. The latter showed the highest percentage of right classification.

Female↗

Evaluating technologies for classification and prediction in medicine.

Modern technologies promise to provide new ways of diagnosing disease, detecting subclinical disease, predicting prognosis, selecting patient specific treatment, identifying subjects at risk for disease, and so forth. Advances in genomics, proteomics and imaging modalities in particular hold great potential for assisting with classification/prediction in medicine. Before a classifier can be adopted for routine use in health care, its classification accuracy must be determined. Standards for evaluating new clinical classifiers however, lag far behind the well established standards that exist for evaluating new clinical treatments. In this paper, we discuss a phased approach to developing a new classifier (or biomarker). It mirrors the internationally established phase 1-2-3 paradigm for therapeutic drugs. The defined phases lead to a logical sequence of studies for classifier development. We emphasize that evaluating classification accuracy is fundamentally different from simply establishing association with outcome. Therefore, study objectives and designs differ from the familiar methods of clinical trials. We discuss these briefly for each phase.Finally, we argue that classifier development requires some rethinking of traditional data analysis techniques. As an example we show that maximizing the likelihood function to fit a logistic regression model to multiple predictors, can yield a poor classifier. Instead we demonstrate that an approach that maximizes an alternative objective function characterizing classification accuracy performs better.

Diagnostic Techniques and Procedures↗

Increased risk of obesity resulting from the interaction between high energy intake and the Trp64Arg polymorphism of the beta3-adrenergic receptor gene in healthy Japanese men.

BACKGROUND: Few studies have investigated the interaction between the Trp64Arg polymorphism of the beta3-adrenergic receptor gene (ADRB3) and environmental factors. This study aimed to investigate whether energy intake affects the relationship between this polymorphism and obesity. METHODS: Healthy Japanese men (n=295; age 46.1+/-11.5 years (mean +/-standard deviation); waist circumference 83.9+/-9.3 cm; body mass index (BMI) 23.3+/-3.3 kg/m2) recruited in a Japanese chemical industry firm were eligible for analysis. Daily energy intake, protein, fat, and carbohydrate (PFC) ratio and daily physical activity were assessed by self-reported questionnaires. Genotyping for the polymorphism was performed with written informed consent. RESULTS: When the subjects were classified into two groups according to presence of the polymorphism, the groups were not significantly different in waist circumference or BMI. Quartile classification of energy intake, however, demonstrated a significantly larger ratio of obese subjects to non-obese subjects in the group with the polymorphism in the highest 4th quartile alone. Multiple logistic regression analysis also revealed that the presence of the polymorphism increased the risk of obesity significantly in the 4th quartile alone (adjusted odds ratio=3.37, 95% confidence interval=1.12-10.2). CONCLUSION: Presence of the polymorphism alone does not significantly increase the risk of obesity. However, high energy intake interacts with the polymorphism and leads to a significant increase in risk of obesity. The Trp64Arg polymorphism of ADRB3 warrants consideration, along with other polymorphisms involved in the development of obesity, for tailor-made prevention of obesity.

Body Mass Index↗

Effects of multiple somatostatin treatment on rat gonadotrophic cells and ovaries.

The effect of multiple somatostatin (SRIH-14) treatment on the pituitary gonadotrophs, follicle stimulating harmone (FSH) and luteinizing harmone (LH), and ovaries of adult female Wistar rats was examined. Females received two 20 microg/100 g body wt. doses daily subcutaneously, for five consecutive days. FSH and LH cells were studied using a peroxidase-antiperoxidase immunocytochemical procedure. Morphometry and stereology were used to evaluate changes in the number per unit area (mm2), cell volume and volume densities of LH- and FSH-immunoreactive cells. Ovaries were analysed by simple point counting of follicles and corpora lutea. Follicles were divided by size according to the classification of Gaytán and Osman. Morphometric and stereological analysis of the pituitary showed that the number, volume and the volume density of FSH- and LH-immunoreactive cells were decreased after multiple SRIH-14 treatment, particularly in the latter. In the ovary, SRIH-14 induced decreases in the number of healthy follicles in all phases of folliculogenesis and corpora lutea, but the large antral follicle stage was most affected. The number of atretic follicles was increased. It can be concluded that multiple SRIH-14 treatment markedly inhibited LH cells, but affected FSH cells as well. In the ovary, SRIH- 14 acted by inhibiting folliculogenesis and enhancing atretic processes.

Animals↗

Incidence, outcome and prediction of early clinical events following percutaneous transluminal coronary angioplasty. A comparison between treatment with reviparin and unfractionated heparin/placebo (results of a substudy of the REDUCE trial).

BACKGROUND: Unfractionated heparin and its low molecular weight fragments possess antithrombotic properties, properties that are routinely exploited in coronary angioplasty (PTCA). OBJECTIVES: In the setting of the REDUCE trial, a randomized, double-blind, multicentre trial, the occurrence of acute or early clinical events was compared in patients treated with either unfractionated heparin/placebo or low molecular weight heparin (reviparin). METHODS AND RESULTS: Six hundred and twelve patients with native coronary artery obstructions randomized between unfractionated heparin/placebo and reviparin, were analysed. Baseline characteristics were similar in both groups. Using the intention-to-treat analysis, major acute or early events (myocardial infarction, re-PTCA, bypass surgery, death) occurred in 42 patients (7%), 29 in the control group and 13 in the treatment group (P=0.027). In order to develop a predictive model for the risk of early events following coronary balloon angioplasty, clinical as well as pre-PTCA and procedural characteristics were analysed. Thrombi at the treated lesion site (P=0.02), dissection (P<0.001), lesion type B2 and C according to the NHLBI classification (P<0.001), diameter stenosis >50% post-PTCA (P<0.001), and length of stenosis >20mm (P=0.005) were significantly associated with the occurrence of acute events. By multiple logistic regression analysis, in which these variables and the treatment regimen were entered, dissection (P=0.042), diameter stenosis >50% (P<0.028) and lesion type B2 and C (P=0.017) were found to be independently predictive of early adverse events. Bleeding complications were similar in the two treatment groups. CONCLUSIONS: Reviparin, given in a very early stage of vascular injury, compares favourably with unfractionated heparin/placebo, by reducing abrupt closure and acute-phase adverse outcome following PTCA. With respect to the evaluated risk factors for acute events, the positive effect of reviparin on early adverse outcome after PTCA may be due to improved antithrombotic properties as compared to unfractionated heparin.

Angina Pectoris↗

Analysis of the flow patterns of liquid organic compounds between blade electrodes by classification models

The flow patterns of 20 organic liquids with diverse structures and functionalities between electrodes were measured under a dc electric field. The results clearly showed the existence of a strong relationship between the flow pattern of a compound and its molecular structure. On the basis of a variety of 23 molecular descriptors including those obtained by quantum-chemical calculations, multiple regression analysis and discriminant analysis were applied to identify the significant factors contributing to the flow patterns. For the flow rate dipole moment, nucleophilic delocalizability and lipophilicity as expressed by the 1-octanol/water partition coefficient were found to be the key factors as judged by a five-value regression model with a squared correlation coefficient (r2) of 0.881. For the direction of the flow, just two quantum-chemical parameters, namely, absolute hardness and the self-polarizability normalized by molecular volume, were identified as significant factors by using linear discriminant analysis. The numbers of misclassified compounds were only one and two for training and prediction (leave-one-out cross-validation), respectively, by the best discriminant model.

Journal Article↗

Classification of spider neurotoxins using structural motifs by primary structure features. Single residue distribution analysis and pattern analysis techniques.

In recent years the data on the novel structures of spider toxins have been greatly increasing. The sequence data should be classified. We introduced two primary structure analysis techniques-single residue distribution analysis (SRDA) and pattern analysis for classifying spider polypeptide toxins with molecular weight less than 10kDa. For multiple sequence alignment, we also introduced three novel sequence representation formats named as a simple record, motif record and a pattern record, which can be useful for large-scale analysis of structures. About 300 sequences of spider toxins were analyzed and nine primary structure motifs were identified. New classification of spider toxins was proposed on the basis of previously described principal structural motif (PSM) and extra structural motif (ESM) [Kozlov, S.A., Malyavka, A.A., McCutchen, B., Lu, A., Schepers, E., Herrmann, R., Grishin, E.V., 2005. A novel strategy for the identification of toxin-like structures in spider venom. Proteins 59 (1), 131-140]. Five main structural classes were revealed, and for putative ion channel inhibitors from the most numerous classes 1, 2, and 3, five-digital personal ID numbers were introduced. A reference table with simple, motif and pattern representation sequence formats was created for all analyzed structures.

Amino Acid Motifs↗

Importance of adjusting for correlated concomitant variables in psychiatric research.

The potential importance of adjusting for correlated concomitant variables in psychiatric research to avoid possible erroneous or misleading results is demonstrated through examples of "suppression effects" and "spurious associations." Special reference is made to correlational studies and unbalanced factorial analysis of variance. Methods of adjusting for correlated covariates are noted, and the usefulness of multiple regression for this purpose in certain situations is shown. Simulated and real data examples are provided. Part I discusses these issues in relation to correlational studies, and also lays a general groundwork for understanding them in terms of simple path analysis models. Part 2 relates the problems of correlated covariates to factorial analysis of variance (ANOVA). As in Part I, "suppression effects" and "spurious associations" are discussed, this time as they result from confounded main effects and interaction effects in ANOVA. Confounding in this case is synonymous with cell sample size imbalances in the factorial cross-classification. A useful method for dealing with these problems without loss of information is discussed. This method involves viewing the ANOVA from a "general linear model" perspective and performing the analysis as a multiple regression.

Analysis of Variance↗

Importance of organ dysfunction in determining hospital outcomes in children.

OBJECTIVES: To use measures of organ dysfunction derived from administrative data to assess clinical and economic outcomes in hospitalized children. STUDY DESIGN: We used the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnostic and procedure codes to evaluate organ dysfunction in all patients, excluding neonates, in the Healthcare Cost and Utilization Project Kids' Inpatient Database (KID). We adapted consensus clinical definitions to characterize organ dysfunction in terms of degree of impairment, type of organ system involvement, and number of dysfunctional organ systems. Univariate and multivariable models were constructed to determine the impact of organ dysfunction on in-hospital mortality and resource use. RESULTS: Patients with organ dysfunction (n=51,386) were younger and more often male than those without organ dysfunction, and they had significantly higher in-hospital mortality and resource use. Organ dysfunction, assessed in terms of degree, type, and number of dysfunctional organ systems, was consistently associated with all hospital outcomes. In multivariable models, types of organ system failures were most predictive of in-hospital mortality, whereas degree of organ system involvement allowed for a better assessment of resource use. CONCLUSIONS: Administrative data can be used to characterize multiple dimensions of organ dysfunction in children. Hospitalizations involving organ dysfunction are associated with significant clinical and economic consequences.

Adolescent↗

[Clinical research of correlation between osteonecrosis and steroid].

OBJECTIVE: To explore the correlation between the dosage of corticosteroid, time of onset and incidence of osteonecrosis (ON) in patients with SARS. METHODS: From July 2003 to January 2004, general survey carried out for ON in 551 patients with SARS. Five hundred and fifty-one patients except 12 were administrated by corticosteroid from 80 mg to 30 000 mg. The age of patients was (33 +/- 9) years old ranging from 19 to 59 years old. One hundred and thirty-one were male, and four hundred and twenty were female. MRI and X-ray film were taken in all patients including both hips, knees, shoulders, ankles and wrists. CT scan was taken in partial patients. Common classification system were used for staging of hip (ARCO), knee (Lotka) and shoulder (Cruess). Independent test, rank-sum test and multiple factor logistic regression analysis were used for statistical analysis. RESULTS: No osteonecrosis was detected in 12 patients without corticosteroid. Osteonecrosis was detected in 176 patients (32.7 percent) among 539 patients. There were ON of femoral head in 130 cases (210 hips), ON of knee in 98 cases (130 knees), ON of humeral head in 21 cases (36 shoulders), ON of talus and calcaneus in 16 cases (26 ankles), ON of scaphoid and lunate in 11 cases (17 wrists), ON of patella in 3 cases (4 patella), ON of ilium in 1 case and bone infarction (femur, tibia) in 18 cases. One hundred and nineteen cases (195 hips) with ONFH were in stage I (IA 45 hips, IB 77 hips, IC 73 hips). Eleven cases (15 hips) were in stage II. All osteonecrosis of the knee and humoral head was stage I. Thirty-four patients with ON had one joint affected, 45 patients had 2 joints, 93 patients had more than 3 joints. The dosage of corticosteroid was (5842 +/- 4988) mg in ON group and (2719 +/- 2571) mg in non-ON group (P < 0.0001). The duration of steroid was (38 +/- 17) d in ON group and (27 +/- 15) d in non-ON group (P < 0.01). The dosage of pulse treatment was (340 +/- 207) mg/d in ON group and (211 +/- 160) mg/d in non-ON group (P < 0.01). The duration of pulse treatment was (28 +/- 13) d in ON group and (18 +/- 11) d in non-ON group (P < 0.01). All patients with ON were detected within 6 months from administration. CONCLUSION: About one-third patients with SARS who were treated with a high dose of corticosteroid occurred osteonecrosis. ON is frequently multiple focuses. The actual time of onset of ON is early of steroid used. MRI is golden standard for early diagnosis of ON. The patients who were treated with a high dose of corticosteroid should be inspected initially by MRI.

Adrenal Cortex Hormones↗

Relative efficiency in rural primary health care: an application of data envelopment analysis.

This study applied data envelopment analysis (DEA) to the evaluation of rural primary health care programs, which are known to be very heterogeneous. DEA is a mathematical programming technique that optimizes the relative efficiency ratio of current inputs over current outputs for each decision-making unit (DMU). It produces a summary scalar efficiency ratio for each DMU and identifies the amount of inefficiency. The data came from the National Evaluation of Rural Primary Health Care Programs. Despite the demands of the software used for homogeneous units and nonzero values, the efficiency analysis was useful to the evaluation. It assessed multiple inputs and multiple outputs simultaneously, and identified directly those units that are performing efficiently or inefficiently when compared to specific peer programs. This then allowed us to compare this efficient-inefficient classification with other data, first, to verify the classification and, second, to assist with the evaluation. DEA can contribute to the evaluation of heterogeneous health programs, especially when used in conjunction with other methods of analysis.

Evaluation Studies as Topic↗

Brain MRI lesion load quantification in multiple sclerosis: a comparison between automated multispectral and semi-automated thresholding computer-assisted techniques.

Brain magnetic resonance imaging (MRI) lesion volume measurement is an advantageous tool for assessing disease burden in multiple sclerosis (MS). We have evaluated two computer-assisted techniques: MSA multispectral automatic technique that is based on bayesian classification of brain tissue and NIH image analysis technique that is based on local (lesion by lesion) thresholding, to establish reliability and repeatability values for each technique. Brain MRIs were obtained for 30 clinically definite relapsing-remitting MS patients using a 2.0 Tesla MR scanner with contiguous, 3 mm thick axial, T1, T2 and PD weighted modalities. Digital (Dicom 3) images were analyzed independently by three observers; each analyzed the images twice, using the two different techniques (Total 360 analyses). Accuracy of lesion load measurements using phantom images of known volumes showed significantly better results for the MSA multispectral technique (p < 0.001). The mean intra-and inter-observer variances were, respectively, 0.04 +/- 0.4 (range 0.04-0.13), and 0.09 +/- 0.6 (range 0.01-0.26) for the multispectral MSA analysis technique, 0.24 +/- 2.27 (range 0.23-0.72) and 0.33 +/- 3.8 (range 0.47-1.36) for the NIH threshold technique. These data show that the MSA multispectral technique is significantly more accurate in lesion volume measurements, with better results of within and between observers' assessments, and the lesion load measurements are not influenced by increased disease burden. Measurements by the MSA multispectral technique were also faster and decreased analysis time by 43%. The MSA multispectral technique is a promising tool for evaluating MS patients. Non-biased recognition and delineation algorithms enable high accuracy, low intra-and inter-observer variances and fast assessment of MS related lesion load.

Analysis of Variance↗

[Prognosis of hepatocellular carcinoma according to new staging classifications].

BACKGROUND AND OBJECTIVE: We investigated prognostic factors and survival of patients with hepatocellular carcinoma (HCC) in North-Germany. Established staging systems (Child-Pugh, Okuda and UICC classification) were compared with new prognostic scores from Italy (CLIP) and Spain (BCLC). PATIENTS AND METHODS: The clinical course of 62 consecutive patients (34-82 years, 48 males, 14 females) with HCC observed in the Medical School of Hannover from October 1996 to September 1998 were retrospectively analyzed. The patients were classified according to the staging systems of Child Pugh, Okuda, UICC, CLIP and BCLC. Follow-up ended on December 31 (st) 2001. RESULTS: Overall median survival was 11,3 (1 - 59,5) months. At univariate analysis (log-rank test) Okuda, UICC, CLIP and BCLC Score were each associated with a shorter survival. In contrast Child Pugh score provided no significant prognostication. By multiple regression analysis (Cox regression analysis), only the CLIP and UICC score and chronic hepatitis B infection were shown to be independent risk factors. CONCLUSION: Our investigations indicate, that the CLIP and UICC classifications identified those patients with the best prognosis and they, as well as chronic hepatitis C, were shown to be independent risk factors.

Adult↗