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At least 325 records · Page 18Linked to original sources
PubMed1985

The Angelchik anti-reflux prosthesis--some reservations.

A prospective study has been made of the use of the Angelchik prosthesis in the treatment of hiatus hernia and gastro-oesophageal reflux. Forty-one patients under the care of one surgeon were studied over a 3-year period. The operation is simple and safe to perform. Twelve patients suffered transient dysphagia which spontaneously resolved within 3 months. Satisfactory results were obtained thereafter in 80.9 per cent. Seven of the prostheses have been removed (17.1 per cent), all within 18 months of performing the operation. Dysphagia and recurrent symptoms were the main reasons for removal and in two of these stricturing was present pre-operatively. We feel the presence of an established stricture is a contraindication to the use of the device. We have, however, been impressed by its use as a second procedure when previous surgery has failed and when revisional surgery for recurrent hiatus hernia is difficult due to dense adhesion formation. While it is still early to assess the legacy that the use of this prosthesis might incur, we would recommend conservatism if not abandonment of its use until longer-term evaluation is available.

Adolescent↗
PubMed1987

Case for conservative management of selected fibro-adenomas of the breast.

To assess the safety of a conservative approach to fibro-adenoma of the breast we prospectively studied 321 women with this clinical diagnosis, and performed aspiration cytology and excision biopsy. There was histological confirmation of fibro-adenoma in 217 (68 per cent), the remainder having various benign conditions and 4 (1.3 per cent) had carcinoma. Aspiration cytology had a sensitivity of 87 per cent and a specificity of 76 per cent for fibro-adenoma. Three cases of carcinoma were identified cytologically and the fourth was regarded as suspicious. To estimate the risk of missing carcinoma we compared the annual frequency of carcinoma with fibro-adenoma in young women and found a ratio of 1:470 between 15 and 19 years, 1:133 between 20 and 24 years and 1:9 in the 25-29 age group. To assess patients' views on non-operative treatment of benign breast masses we asked 124 women, 10 days postoperatively, whether they preferred a conservative approach for a cytologically benign lump: 26 (21 per cent) opted for conservative management in the future and 8 (7 per cent) would have preferred conservatism rather than their recent excision. A conservative approach is safe for clinically and cytologically benign breast lumps in women under 25 years, but very few will accept it.

Adenofibroma↗
PubMed1991

Gunshot wound of the abdomen: role of selective conservative management.

This prospective study includes 146 patients with gunshot wounds of the abdomen. One hundred and five patients (72 per cent) had an acute abdomen on admission and were operated on immediately. The remaining 41 patients (28 per cent) had minimal or equivocal abdominal signs and were observed with serial clinical examinations. Seven of the observed patients needed subsequent laparotomy, but there was no mortality or serious morbidity. Had a policy of mandatory exploration for abdominal gunshot wound been applied the incidence of unnecessary or negative laparotomies would have been 27 per cent. By using a policy of selective conservatism this figure was only 5 per cent. We suggest that abdominal gunshot wounds should be assessed and managed exactly like knife wounds. Physical examination is reliable in detecting significant intra-abdominal injuries. Many carefully selected patients with abdominal gunshot wounds can safely be managed non-operatively.

Abdominal Injuries↗
PubMed1993

Non-therapeutic operations for penetrating trauma: early morbidity and mortality.

A prospective study was carried out to assess the incidence and type of complications after non-therapeutic operations for penetrating trauma. A total of 372 operations were performed on 368 patients with penetrating injuries to the abdomen (240 procedures), chest (49), neck (48) and extremities (35). There were 46 negative or non-therapeutic operations. The incidence of major complications directly related to anaesthesia or operation in this group of patients was 4 percent (two patients). The operation might have contributed to a further three major complications. The mean hospital stay for patients undergoing uncomplicated non-therapeutic operation was 4.1 days; for those with complications it was 21.2 days. It is concluded that non-therapeutic operations for penetrating trauma carry a significant morbidity rate. A policy of selective conservatism is advocated.

Abdominal Injuries↗
PubMed1991

Musculotopic organization of the hypoglossal nucleus in the grass frog, Rana pipiens.

Recent neural tracer studies in several mammalian species have demonstrated a similar musculotopic organization of the hypoglossal motoneurons which innervate individual tongue muscles. The distribution of this musculotopic organization in nonmammalian tetrapods, however, has not received detailed investigation. As part of an ongoing study on the comparative organization of the vertebrate hypoglossal nucleus, the musculotopic organization of the hypoglossal nucleus of Rana pipiens was studied by injection of lectin-conjugated horseradish peroxidase into four distinct tongue muscles and the geniohyoid muscle. Injections into the hyoglossus muscle label neurons in dorsal regions of the hypoglossal nucleus in middle and rostral nucleus levels. Injections into the genioglossus basalis muscle label neurons in ventral and lateral regions of the hypoglossal nucleus in caudal nucleus levels. Injections into the genioglossus medialis muscle label neurons in dorsal regions in caudal levels, throughout the nucleus in middle levels, and in ventral regions in more rostral levels. Injections into the geniohyoid muscle label neurons in the ventral tip of the hypoglossal nucleus and in the ventromedial corner of the medullary gray matter in middle and rostral nucleus levels. These results demonstrate that the organization of the hypoglossal nucleus in Rana pipiens is more complex than previous tracer studies indicated. Similarities in the musculotopic organization of the amphibian and mammalian hypoglossal nuclei suggest an evolutionary conservatism of the motor system controlling tongue movement.

Animals↗
PubMed1992

Extremely divergent histone H4 sequence from Trypanosoma cruzi: evolutionary implications.

Trypanosoma cruzi presents six histones electrophoretically resolved in three gel systems. Indirect evidence shows that one of these histones, named e, corresponds to H4 in other species. We present evidence that histone e is H4 by sequencing its amino terminal end. The amino terminal of T. cruzi histone H4, unlike that of other H4s examined thus far is not blocked. Moreover, this protein presents two variants. This partial amino acid sequence of T. cruzi histone H4 differs greatly from homologous sequences of human, yeast, or Tetrahymena. Since the conservatism of the core histones (H2A, H2B, H3, and H4) is clearly illustrated by comparative sequence analyses, the data shown here demonstrates that T. cruzi histone H4 is the most divergent reported. Quantitative analysis of the data suggests that the rate of substitutions in the histone H4 amino terminal sequence varies among different lineages. We postulate a slow-down in the evolutionary rate of histone H4 amino terminal domain in the metazoa branch related perhaps to the appearance of a novel function for this domain.

Amino Acid Sequence↗
PubMed1983

Preparation and cross-reactivity of anti-avian glutamine synthetase antibody.

Rabbit antibody to chicken liver mitochondrial glutamine synthetase was purified by immunoaffinity chromatography for analysis of the immunological relatedness of vertebrate glutamine synthetases. The antibody cross-reacted with enzymes from representatives of all five vertebrate classes, indicating a high degree of evolutionary conservatism in the structure of the enzymes. A unique aspect of the immunological similarity of these enzymes is that it exists between cytosolic and mitochondrial enzymes which are, in general, immunologically distinct. The antibody did not cross-react with two insect glutamine synthetases. Compositional difference indices, calculated from the amino acid compositions of glutamine synthetases from several species, gave a mean estimate of over 80% sequence homology for the vertebrate enzymes. The avian mitochondrial enzyme gave a mean 78% homology with the mammalian cytosolic enzyme.

Amino Acid Sequence↗
PubMed2007

Morphological changes in pedal phalanges through ornithopod dinosaur evolution: a biomechanical approach.

The evolution of ornithopod dinosaurs provides a well-documented example of the transition from digitigrady to subunguligrady. During this transition, the ornithopod pes was drastically altered from the plesiomorphic dinosaurian morphology (four digits, claw-shaped unguals, strongly concavo-convex joints, phalanges longer than wide, excavated collateral ligament fossae, presence of sagittal ridge, and prominent processes for the attachment of tendons) to a more derived condition (tridactyly, modification of the unguals into hooves, phalanges wider and thinner than long, lack of collateral ligament fossae, loss of sagittal ridge and tendon attachment processes, relatively flattened articular surfaces). These changes are particularly noteworthy given the overall conservatism in pedal morphology seen across Dinosauria. But what are the functional consequences of these specific morphological transitions? To study them, we examine a wide range of pedal morphologies in four non-avian dinosaurs and two birds. Our analyses of the external morphology, two-dimensional models (using Finite Element Analysis), and internal bone structure demonstrate that this evolutionary shift was accompanied by a loss of digit mobility and flexibility. In addition, pedal posture was modified to better align the pes with the main direction of the ground reaction force, thus becoming well suited to support high loads. These conclusions can be applied to other, parallel evolutionary changes (in both dinosaurs and mammals) that involved similar transitions to a subunguligrade posture.

Animals↗
PubMed2001

Year 2000 status of MRI in Mexico.

The development of clinical magnetic resonance imaging in Mexico has followed a different course from that in the U.S. and Europe. The first clinical unit was installed in Mexico in the late 1980s at the very beginning of clinical applications worldwide. Since then, installations have proceeded at a sedate pace that now brings the installed total to 66 imagers. The largest fraction of these units (28, or 42%) is in Mexico City, with a broad distribution across the remaining 23 Mexican states. There is a noticeable increase of the number of units (20, or 30%) in the states bordering the U.S., while the states bordering nations to the south have no units. More than half the units (38, or 58%) are 0.5 T units, while a further 35% are 1.0 T or higher. Slower addition of units in Mexico relative to the U.S. is attributed to the higher fraction of public-funded hospitals and the inherent conservatism of such institutions when considering new technologies. Present public planning for health care development suggests that the coming decade will see more rapid installation of units to meet growing demand in Mexico for the latest medical technology. Experience over the past two decades indicates the need for more systematic training of technical and clinical personnel to implement these additions. The National University (Universidad Nacional Autónoma de México (UNAM) and the Metropolitan University (Universidad Autónoma Metropolitana (UAM) are collaborating with diverse clinical facilities to create such a program. J. Magn. Reson. Imaging 2001;13:813-817.

Developing Countries↗
PubMed1989

Density changes at the proximal tibia after medial meniscectomy.

Trabecular bone density changes at the proximal tibia were studied after total and partial meniscectomy using quantitative computerized tomography. Thirty-seven medially meniscectomized patients (5- and 10-year follow-up) and 10 control persons were included. In the partially and the totally meniscectomized knees, the area of maximal density in the medial tibial condyle was displaced approximately 4 mm in a posteromedial direction relative to the position in the intact knees. In both partially and totally meniscectomized knees, the density in the region of tibiofemoral contact in the medial tibial condyle was higher compared with the density in the same region in the contralateral intact knees. This difference was of the same order in the 5- and 10-year follow-up groups. The density difference between the meniscectomized and the intact knees in the region of tibiofemoral contact in the medial condyle was significantly higher in totally than in partially meniscectomized patients. It is concluded that not only total but also partial medial meniscectomy is followed by density changes, occurring within the first 5 years after meniscectomy. The results emphasize the importance of the utmost conservatism in surgery on the meniscus.

Adult↗
PubMed1993

ATP binding to cytochrome c diminishes electron flow in the mitochondrial respiratory pathway.

Eukaryotic cytochrome c possesses an ATP-binding site of substantial specificity and high affinity that is conserved between highly divergent species and which includes the invariant residue arginine91. Such evolutionary conservatism strongly suggests a physiological role for ATP binding that demands further investigation. We report the preparation of adducts of the protein and the affinity labels 8-azido adenosine 5'-triphosphate, adenosine 5'-triphosphate-2',3'-dialdehyde, and 5'-p-fluorosulfonylbenzoyladenosine. The two former reagents were seen to react at the arginine91-containing site, yet the reaction of the latter, although specific, occurred elsewhere, suggesting caution is necessary in its use. None of the adducts displayed significant modification of global structure, stability, or physicochemical properties, leading us to believe that the 8-N3-ATP and oATP adducts are good stabilized models of the noncovalent interaction; yet modification led to significant, and sometimes pronounced, effects on biological activity. We therefore propose that the role of ATP binding to this site, which we have shown to occur when the phosphorylation potential of the system is high under the equivalent of physiological conditions, is to cause a decrease in electron flow through the mitochondrial electron transport chain. Differences in the degree of inhibition produced by differences in adduct chemistry suggest that this putative regulatory role is mediated primarily by electrostatic effects.

Adenosine↗
PubMed2003

Confidence intervals for the binomial parameter: some new considerations.

Several methods have been proposed to construct confidence intervals for the binomial parameter. Some recent papers introduced the "mean coverage" criterion to evaluate the performance of confidence intervals and suggested that exact methods, because of their conservatism, are less useful than asymptotic ones. In these studies, however, exact intervals were always represented by the Clopper-Pearson interval (C-P). Now we focus on Sterne's interval, which is also exact and known to be better than the C-P in the two-sided case. Introducing a computer intensive level-adjustment procedure which allows constructing intervals that are exact in terms of mean coverage, we demonstrate that Sterne's interval performs better than the best asymptotic intervals, even in the mean coverage context. Level adjustment improves the C-P as well, which, with an appropriate level adjustment, becomes equivalent to the mid-P interval. Finally we show that the asymptotic behaviour of the mid-P method is far poorer than is generally expected.

Binomial Distribution↗
PubMed2003

Design and analysis of non-inferiority mortality trials in oncology.

The recent revision of the Declaration of Helsinki and the existence of many new therapies that affect survival or serious morbidity, and that therefore cannot be denied patients, have generated increased interest in active-control trials, particularly those intended to show equivalence or non-inferiority to the active-control. A non-inferiority hypothesis has historically been formulated in terms of a fixed margin. This margin was historically designed to exclude a 'clinically meaningful difference', but has become recognized that the margin must also be no larger than the assured effect of the control in the new study. Depending on how this 'assured effect' is determined or estimated, the selected margin may be very small, leading to very large sample sizes, especially when there is an added requirement that a loss of some specified fraction of the assured effect must be ruled out. In cases where it is appropriate, this paper proposes non-inferiority analyses that do not involve a fixed margin, but can be described as a two confidence interval procedure that compares the 95 per cent two-sided CI for the difference between the treatment and the control to a confidence interval for the control effect (based on a meta-analysis of historical data comparing the control to placebo) that is chosen to preserve a study-wide type I error rate of about 0.025 (similar to the usual standard for a superiority trial) for testing for retention of a prespecified fraction of the control effect. The approach assumes that the estimate of the historical active-control effect size is applicable in the current study. If there is reason to believe that this effect size is diminished (for example, improved concomitant therapies) the estimate of this historical effect could be reduced appropriately. The statistical methodology for testing this non-inferiority hypothesis is developed for a hazard ratio (rather than an absolute difference between treatments, because a hazard ratio seems likely to be less population dependent than the absolute difference). In the case of oncology, the hazard ratio is the usual way of comparing treatments with respect to time to event (time to progression or survival) endpoints. The proportional hazards assumption is regarded as reasonable (approximately holding). The testing procedures proposed are conditionally equivalent to two confidence interval procedures that relax the conservatism of two 95 per cent confidence interval testing procedures and preserve the type I error rate at a one-sided 0.025 level. An application of this methodology to Xeloda, a recently approved drug for the treatment of metastatic colorectal cancers, is illustrated. Other methodologies are also described and assessed - including a point estimate procedure, a Bayesian procedure and two delta-method confidence interval procedures. Published in 2003 by John Wiley & Sons, Ltd.

Antimetabolites, Antineoplastic↗
PubMedDate not supplied

Multiple comparisons for relative risk regression: extension of the kappa-ratio method.

We propose a kappa-ratio method for multiple comparisons among disjoint groups in survival analysis, specifically among relative risk estimates from a proportional hazards regression analysis. The new method relates the magnitude of critical values to an overall measure of group heterogeneity. That is, large critical values result from small values of a chi-square statistic for testing between-groups homogeneity. Conversely, large values of the overall statistic lead to small critical values for individual comparisons, even if there are many groups. The adaptivity of the kappa-ratio method contrasts sharply with the conservatism of competing methods.

Analysis of Variance↗
PubMed1991

Approximate multinormal probabilities applied to correlated multiple endpoints in clinical trials.

Clinical trials with multiple endpoints incur increased familywise type I errors. The Bonferroni correction is a common method used to modify the p-values to account for multiple significance testing. For independent endpoints the Bonferroni method is slightly conservative whereas with high correlation the conservatism is extreme, as demonstrated by Pocock et al. This paper presents a procedure which allows for the correlation present, whilst adjusting the multiple p-values. The method is based on an approximation derived for multinormal probabilities.

Analysis of Variance↗
PubMed1992

k-ratio t tests for multiple comparisons involving several treatments and a control.

We consider the problem of simultaneously comparing several treatment means with a control mean and also with one another. Following an elementary decision-theoretic Bayesian approach requiring the choice of a type-I to type-II error-seriousness ratio k, a posteriori t tests are derived for testing both treatment versus control (TvC) and treatment versus treatment (TvT) differences. These k-ratio t tests are strictly comparisonwise in nature. That is, the test applied to any TvC or TvT difference d, depends in no way at all on whether the other differences are being tested. The test for d, however, does depend on the sizes of the other differences through tG, the standardized average of the observed TvC differences, and through FT, the observed between-treatments F ratio. From these adaptive dependences on tG and FT, the critical t values can be large or small, thus avoiding the intuitive objections of under- or over-conservatism in classical comparisonwise or experimentwise level testing rules.

Bayes Theorem↗
PubMed1994

A unified method for monitoring and analysing controlled trials.

Group sequential methods are becoming increasingly popular for monitoring and analysing large controlled trials, especially clinical trials. They not only allow trialists to monitor the data as it accumulates, but also reduce the expected sample size. Such methods are traditionally based on preserving the overall type I error by increasing the conservatism of the hypothesis tests performed at any single analysis. Using methods which are based on hypothesis testing in this way makes point estimation and the calculation of confidence intervals difficult and controversial. We describe a class of group sequential procedures based on a single parameter which reflects initial scepticism towards unexpectedly large effects. These procedures have good expected and maximum sample sizes, and lead to natural point and interval estimates of the treatment difference. Hypothesis tests, point estimates and interval estimates calculated using this procedure are consistent with each other, and tests and estimates made at the end of the trial are consistent with interim tests and estimates. This class of sequential tests can be considered in both a traditional group sequential manner or as a Bayesian solution to the problem.

Bayes Theorem↗
PubMed1994

Dose-response assessment for developmental toxicity. II. Comparison of generic benchmark dose estimates with no observed adverse effect levels.

Developmental toxicity risk assessment currently relies on the estimation of reference doses (RfDDTS) of reference concentrations (RfCDTS) based on the use of no observed adverse effect levels (NOAELS) divided by uncertainty factors (UFs). The benchmark dose (BMD) has been proposed as an alternative basis for reference value calculations. A large database of 246 developmental toxicity experiments representing 1825 endpoints related to dead implants or malformed fetuses has been compiled for use in evaluating alternative approaches to developmental toxicity risk assessment. Using this database we have compared two approaches for BMD estimation with each other and with corresponding statistically derived NOAELS. Comparisons have been based on proportion of affected litters (litters with one or more affected offspring, a quantal response variable) and on the proportion of affected offspring within each litter (a continuous response variable). A quantal Weibull model was used to calculate generic BMDs for the quantal response variable (QBMDs) and a continuous power model was used to calculate generic BMDs for the continuous response variable (CBMDs) at three levels of additional risk (10, 5, and 1%). CBMD05s (continuous benchmark doses for 5% risk) and CNOAELs (statistically derived NOAELs based on the continuous response variable) were similar, with over 98% of the data subsets having CBMD05 and CNOAEL values that differed by less than an order of magnitude. In contrast, QNOAELs tended to be greater than corresponding QBMD10s. The observed conservatism of the QBMD values relative to the corresponding CBMD values was attributed to two factors, lower maximum likelihood estimates for the quantal model and wider confidence intervals around the maximum likelihood estimates, compared to the continuous model.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗