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PubMedDate not supplied

Incidence of surgery in conservatively treated patients with scoliosis.

UNLABELLED: The effectiveness of bracing and the effectiveness of conservative treatment of scoliosis as a whole is widely denied and rejected. We therefore carried out the present study in order to establish whether the work involved in the conservative treatment of scoliosis is reasonable and worthwhile, including as it does the education of patients, techniques of brace moulding, time-consuming follow-ups and the strain put on patients by the treatment itself. STUDY DESIGN: A retrospective analysis of the incidence of surgery in patients with scoliosis presenting every kind of aetiology. To improve comparison with data already published by other centres, this group of patients was matched with the study design of the control group. MATERIALS AND METHODS: Since 1992, in addition to the intensive inpatient rehabilitation programme developed at our centre, we have also been practising moulding techniques according to Chêneau in order to construct scoliosis orthoses of high correction. For the purposes of this study we chose a number of scoliosis patients from our data bank who had had conservative treatment at our centre between 1993 and 1996. All the patients, like those of the untreated control group, were at least 15 years of age at the time they were last investigated or questioned. The incidence of surgery in our group was compared statistically with data published by other centres. RESULTS: Three hundred and forty-three patients (females only) with a curvature of 33.4 degrees (SD = 18.9) were included in our study and could be followed up under the described pre-conditions. Forty-one patients (11.95%) had had surgery. In patients with adolescent idiopathic scoliosis, we found an incidence of surgery of only 7.3% compared with 28% in the control group with the same diagnosis. Statistically, therefore, the incidence of surgery in our group was highly significantly lower than the incidence of surgery in the control group from Ireland and other centres described in literature. CONCLUSIONS: The conservative treatment of scoliosis (which includes outpatient physiotherapy, inpatient intensive scoliosis rehabilitation (SIR) and high-correction-effect bracing based on plastercasting) shows an obvious reduction in the rate of surgery in patients with idiopathic scoliosis compared with untreated scoliosis patients. Thus it can be seen that the conservative treatment of scoliosis may reduce the incidence of surgery, which not only causes considerable medical expenses but also carries with it the risk of repeated operations and further complications. In our study, we also found highly significant differences by comparison with the work of a bracing centre in the USA. Therefore, the quality of the bracing itself and the effects of primary correction must receive greater consideration in future scientific studies on the subject of "conservative" treatment of scoliosis.

Germany↗
PubMed2005

Genome-wide analysis of the functions of a conserved surface on the corepressor Tup1.

The general transcriptional repressor Tup1 is responsible for the regulation of a large, diverse set of genes in Saccharomyces cerevisiae, and functional homologues of Tup1 have been identified in many metazoans. The crystal structure for the C-terminal portion of Tup1 has been solved and, when sequences of Tup1 homologues from fungi and metazoans were compared, a highly conserved surface was revealed. In this article, we analyze five point mutations that lie on this conserved surface. A statistical analysis of expression microarrays demonstrates that the mutant alleles are deficient in the repression of different subsets of Tup1-regulated genes. We were able to rank the mutant alleles of TUP1 based on the severity of their repression defects measured both by the number of genes derepressed and by the magnitude of that derepression. For one particular class of genes, the mutations on the conserved surface disrupted recruitment of Tup1 to the repressed promoters. However, for the majority of the genes derepressed by the Tup1 point mutants, recruitment of Tup1 to the regulated promoters is largely unaffected. These mutations affect the mechanism of repression subsequent to recruitment of the complex and likely represent a disruption of a mechanism that is conserved in fungi and metazoans. This work demonstrates that the evolutionarily conserved surface of Tup1 interacts with two separate types of proteins-sequence-specific DNA-binding proteins responsible for recruiting Tup1 to promoters as well as components that are likely to function in a conserved repression mechanism.

Alanine↗
PubMed2005

Conservation analysis of large biochemical networks.

MOTIVATION: Large biochemical networks pose a unique challenge from the point of view of evaluating conservation laws. The computational problem in most cases exceeds the capability of available software tools, often resulting in inaccurate computation of the number and form of conserved cycles. Such errors have profound effects on subsequent calculations, particularly in the evaluation of the Jacobian which is a critical quantity in many other calculations. The goal of this paper is to outline a new algorithm that is computationally efficient and robust at extracting the correct conservation laws for very large biochemical networks. RESULTS: We show that our algorithm can perform the conservation analysis of large biochemical networks, and can evaluate the correct conserved cycles when compared with other similar software tools. Biochemical simulators such as Jarnac and COPASI are successful at extracting only a subset of the conservation laws that our algorithm can. This is illustrated with examples for some large networks which show the advantages of our method.

Algorithms↗
PubMed1997

Synteny conservation and chromosome rearrangements during mammalian evolution.

An important problem in comparative genome analysis has been defining reliable measures of synteny conservation. The published analytical measures of synteny conservation have limitations. Nonindependence of comparisons, conserved and disrupted syntenies that are as yet unidentified, and redundant rearrangements lead to systematic errors that tend to overestimate the degree of conservation. We recently derived methods to estimate the total number of conserved syntenies within the genome, counting both those that have already been described and those that remain to be discovered. With this method, we show that approximately 65% of the conserved syntenies have already been identified for humans and mice, that rates of synteny disruption vary approximately 25-fold among mammalian lineages, and that despite strong selection against reciprocal translocations, inter-chromosome rearrangements occurred approximately fourfold more often than inversions and other intra-chromosome rearrangements, at least for lineages leading to humans and mice.

Animals↗
PubMed1999

Temporal and regional variation in the use of breast-conserving surgery and radiotherapy for older women with early-stage breast cancer from 1983 to 1995.

BACKGROUND: Authorities recommend radiation therapy after breast-conserving surgery for breast cancer. Numerous studies have reported that older women diagnosed with breast cancer are less likely to receive radiation after breast-conserving surgery. It is unclear how care of older women with breast cancer has changed over time. METHODS: Women with local or regional stage breast cancer diagnosed between 1983-1995 were identified from the Surveillance, Epidemiology, and End Results (SEER) Cancer Registries. The treatment information in SEER includes type of surgical procedures and receipt of radiation therapy. RESULTS: There were small increases in the percentage of women receiving breast-conserving surgery during the 1980s followed by substantial increases in the 1990s. Age was a major factor in determining receipt of radiation therapy after breast-conserving surgery. A large increase in use of radiotherapy after surgery was observed in women aged > or = 75, from below 30% in 1983 to over 50% in 1995. Women aged > or = 75 diagnosed in 1992-1995 were 1.76 and 2.34 times more likely to receive radiation for local and regional stage respectively, as compared to those in 1983-1987. There was no increase in use of radiation for women aged < 65. CONCLUSIONS: There has been a substantial increase in use of breast-conserving surgery and in receipt of radiation therapy after breast-conserving surgery in older women. However, there was a net increase in the percentage of all women with breast cancer who received this surgery without radiotherapy, due to the large increase in the overall percentage of women receiving this surgery.

Aged↗
PubMed2004

Comparison of diverse protein sequences of the nuclear-encoded subunits of cytochrome C oxidase suggests conservation of structure underlies evolving functional sites.

Interspecific comparisons of protein sequences can reveal regions of evolutionary conservation that are under purifying selection because of functional constraints. Interpreting these constraints requires combining evolutionary information with structural, biochemical, and physiological data to understand the biological function of conserved regions. We take this integrative approach to investigate the evolution and function of the nuclear-encoded subunits of cytochrome c oxidase (COX). We find that the nuclear-encoded subunits evolved subsequent to the origin of mitochondria and the subunit composition of the holoenzyme varies across diverse taxa that include animals, yeasts, and plants. By mapping conserved amino acids onto the crystal structure of bovine COX, we show that conserved residues are structurally organized into functional domains. These domains correspond to some known functional sites as well as to other uncharacterized regions. We find that amino acids that are important for structural stability are conserved at frequencies higher than expected within each taxon, and groups of conserved residues cluster together at distances of less than 5 A more frequently than do randomly selected residues. We, therefore, suggest that selection is acting to maintain the structural foundation of COX across taxa, whereas active sites vary or coevolve within lineages.

Animals↗
PubMed2006

Comparison of Pax1/9 locus reveals 500-Myr-old syntenic block and evolutionary conserved noncoding regions.

Identification of conserved genomic regions within and between different genomes is crucial when studying genome evolution. Here, we described regions of strong synteny conservation between vertebrate deuterostomes (tetrapods and teleosts) and invertebrate deuterostomes (amphioxus and sea urchin). The shared gene contents across phylogenetically distant species demonstrate that the conservation of the regions stemmed from an ancestral segment instead of a series of independent convergent events. Comparison of the syntenic regions allows us to postulate the primitive gene organization in the last common ancestor of deuterostomes and the evolutionary events that occurred to the 3 distinct lineages of sea urchin, amphioxus, and vertebrates after their separation. In addition, alignment of the syntenic regions led to the identification of 8 noncoding evolutionarily conserved regions shared between amphioxus and vertebrates. To our knowledge, this is the first report of conserved noncoding sequences shared by vertebrates and nonvertebrates. These noncoding sequences have high possibility of being elements that regulate neighboring genes. They are likely to be a factor in the maintenance of conserved synteny over long phylogenetic distance in different deuterostome lineages.

Amino Acid Sequence↗
PubMed2001

Snake alpha-neurotoxin binding site on the Egyptian cobra (Naja haje) nicotinic acetylcholine receptor Is conserved.

Evolutionary success requires that animal venoms are targeted against phylogenetically conserved molecular structures of fundamental physiological processes. Species producing venoms must be resistant to their action. Venoms of Elapidae snakes (e.g., cobras, kraits) contain alpha-neurotoxins, represented by alpha-bungarotoxin (alpha-BTX) targeted against the nicotinic acetylcholine receptor (nAChR) of the neuromuscular junction. The model which presumes that cobras (Naja spp., Elapidae) have lost their binding site for conspecific alpha-neurotoxins because of the unique amino acid substitutions in their nAChR polypeptide backbone per se is incompatible with the evolutionary theory that (1) the molecular motifs forming the alpha-neurotoxin target site on the nAChR are fundamental for receptor structure and/or function, and (2) the alpha-neurotoxin target site is conserved among Chordata lineages. To test the hypothesis that the alpha-neurotoxin binding site is conserved in Elapidae snakes and to identify the mechanism of resistance against conspecific alpha-neurotoxins, we cloned the ligand binding domain of the Egyptian cobra (Naja haje) nAChR alpha subunit. When expressed as part of a functional Naja/mouse chimeric nAChR in Xenopus oocytes, this domain confers resistance against alpha-BTX but does not alter responses induced by the natural ligand acetylcholine. Further mutational analysis of the Naja/mouse nAChR demonstrated that an N-glycosylation signal in the ligand binding domain that is unique to N. haje is responsible for alpha-BTX resistance. However, when the N-glycosylation signal is eliminated, the nAChR containing the N. haje sequence is inhibited by alpha-BTX with a potency that is comparable to that in mammals. We conclude that the binding site for conspecific alpha-neurotoxin in Elapidae snakes is conserved in the nAChR ligand binding domain polypeptide backbone per se. This conclusion supports the hypothesis that animal toxins are targeted against evolutionarily conserved molecular motifs. Such conservation also calls for a revision of the present model of the alpha-BTX binding site. The approach described here can be used to identify the mechanism of resistance against conspecific venoms in other species and to characterize toxin-receptor coevolution.

Acetylcholine↗
PubMed1997

Amino acid substitutions preserve protein folding by conserving steric and hydrophobicity properties.

We present a comprehensive analysis of amino acid substitution patterns (sets of residues in a position of a multiple alignment) and conservation of physicochemical properties in alignments of protein sequences. Of the one million possible substitution patterns, only a few hundred account for the majority of aligned positions. Very similar distributions of substitution patterns are observed in all but one of the diverse databases of multiple alignments. In these substitution patterns we analyzed the conservation of 511 physicochemical and steric amino acid properties. Highest conservation was observed in those steric and transfer free energy-related properties that are crucial for folding. The best conserved steric properties include the minimal width of the side chains and their interactions with other residues. Among the hydrophobicity-related properties, charge and those properties that provide information on propensities to form secondary structures or side chain conformation, appear to be better conserved than pure hydrophobicity measures. Physicochemical sequence analysis based on the most conserved properties is expected to aid searching a protein sequence query against a database of multiple alignments, prediction of secondary and tertiary structures and protein engineering.

Amino Acids↗
PubMed1994

Evolutionary divergence and conservation of trypsin.

The trypsin sequences currently available in the data banks have been collected and aligned using first the amino acid sequence homology and, subsequently, the superposed crystal structures of trypsins from the cow, the bacterium Streptomyces griseus and the fungus Fusarium oxysporum. The phylogenetic tree constructed according to this multiple alignment is consistent with a continuous evolutionary divergence of trypsin from a common ancestor of both prokaryotes and eukaryotes. Comparison of crystal structures reveals a strict conservation of secondary structure. Similarly, in the alignment of all the sequences, insertions and deletions occur only in regions corresponding to loops between the secondary structure elements in the known crystal structures. The conserved residues cluster around the active site. Almost all conserved residues can be associated with one of the basic functional features of the protein: zymogen activation, catalysis and substrate specificity. In contrast, the residues of the hydrophobic core of the protein and the calcium ion binding sites are generally not conserved. The conserved features of trypsin and the nature of the conservation are discussed in detail.

Amino Acid Sequence↗
PubMed1999

Role of magnetic resonance imaging and magnetic resonance imaging--guided surgery in the evaluation of patients with early-stage breast cancer for breast conservation treatment.

Magnetic resonance imaging (MRI) may be more sensitive than mammography for detecting breast cancer and may have an adjunctive role in assessing patients with early-stage disease for breast conservation treatment. This study was performed to analyze the impact of breast MRI on the clinical management of 83 patients being considered for breast conservation treatment. Eighty-three consecutive cases of patients undergoing breast MRI during standard workup and evaluation for breast conservation treatment from 1993 to 1996 were retrospectively reviewed. Records were reviewed for patient and tumor characteristics, mammographic findings, MRI findings, timing of MRI study, findings from MRI-guided surgery (when done), and whether the patient underwent breast conservation treatment. MRI definitely altered management in 15 patients (18%), may have affected management in 4 patients (5%), and did not change management in 64 patients (77%). Thirteen patients underwent additional surgery because of MRI findings; the positive predictive value for MRI-guided surgery was 38% (5 of 13). Ultimately, 82% of the patients received breast conservation treatment. No predictive factor was identified to characterize the patients most likely to have management affected by MRI findings. These findings suggest that breast MRI may be useful in the evaluation of patients with early-stage breast cancer for breast conservation treatment. A larger study population and outcome data will be required to confirm these findings and to define those patients most likely to benefit from breast MRI.

Adult↗
PubMed1995

Conservative surgery without radiotherapy in the treatment of patients with early-stage invasive breast cancer. A review.

OBJECTIVE: The authors determined whether some patients with clinical stage I or II invasive breast cancer can be adequately treated by conservative surgery without radiotherapy. SUMMARY BACKGROUND DATA: Currently, there are many patients who are being treated in this manner in both academic and community hospitals. This approach is not as effective as either mastectomy or conservative surgery followed by radiotherapy in preventing local recurrence. However, there may be subsets of patients who might be adequately treated by surgery alone with acceptably low recurrence rates. METHODS: The authors reviewed retrospective studies of conservative surgery alone and of randomized trials comparing the results of treatment with and without postoperative radiotherapy. RESULTS: The local recurrence rate is unacceptably high when random patients are treated with conservative surgery without radiotherapy. More favorable results may be possible when relatively wide excisions are performed on selected postmenopausal patients with small lesions without an extensive intraductal component, lymphatic or blood-vessel invasion, and histologically negative axillary nodes. The role of tamoxifen in reducing the risk of breast recurrence is uncertain. Despite salvage therapy, some individuals may develop disseminated disease as a result of local recurrence. CONCLUSIONS: The authors believe that conducting carefully designed prospective studies of conservative surgery alone is reasonable for patients who are adequately informed of the potential risks of omitting radiation therapy. However, currently, patients should not be treated with conservative surgery alone (without radiotherapy) without such stringent guidelines.

Adult↗
PubMed2005

Conservative management of acoustic neuroma: a meta-analysis and proposed treatment algorithm.

OBJECTIVES/HYPOTHESES: Conservative management is a viable treatment alternative for acoustic neuroma. Using previous studies to provide evidence-based support, we have attempted to more clearly define the role of conservative management. STUDY DESIGN: Retrospective review of literature and patient charts. METHODS: Published studies on conservative management of acoustic neuroma were found using a key word search through PubMed in addition to the bibliographies of these selected studies. A spreadsheet was made to tabulate the selection criteria for conservative management, duration and frequency of follow-up, patient demographics, initial tumor size and rate of growth, change in hearing status, and the need for definitive treatment. RESULTS: A total of 21 studies comprising 1,345 patients were included in our meta-analysis. The average length of follow-up these studies was 3.2 years. The average initial tumor size was 11.8 mm (n = 900); 43% of 1,244 acoustic neuromas showed growth, whereas 57% showed either no growth or tumor regression. The average growth rate was 1.9 mm/year in 793 individuals. Hearing loss occurred in 51% of 347 individuals. In 15 studies, 20.0% of 1,001 individuals eventually failed conservative management. CONCLUSIONS: Our meta-analysis supports the role of conservative management of acoustic neuromas in properly selected patients on the basis of a slow overall rate of growth and a substantial incidence of no growth. However, the lack of predictive factors, the relatively short duration of follow-up, and the variability of inclusion criteria underscore the need for continued collection of long-term data. An algorithm for acoustic neuroma management is proposed based on initial tumor size, patient age, and hearing status.

Algorithms↗
PubMed1984

Operative and conservative treatment of tubo-ovarian abscess due to pelvic inflammatory disease.

Of 83 patients with tubo-ovarian abscess studied retrospectively, 18 were treated within 24 hours of admission with total abdominal hysterectomy and bilateral salpingoo-ophorectomy. The other 65 patients were treated conservatively. In six patients, conservative therapy proved an immediate failure, and 14 patients had delayed failure. Thirty-nine patients were successfully treated conservatively, and six were lost to follow-up. We examined the length of hospital stay in the surgically treated group and the conservatively treated group. Immediate operation and delayed operation were examined in terms of mortality, morbidity, and hospital stay. Conservative therapy consisting of broad spectrum antibiotics combined with conservative operation when applicable is an effective method of treating unruptured tubo-ovarian abscess.

Abscess↗
PubMed2001

Relationships between outcomes of conservative treatment and magnetic resonance imaging findings in patients with mild cervical myelopathy caused by soft disc herniations.

STUDY DESIGN: A retrospective follow-up study of conservatively treated patients with mild cervical myelopathy caused by cervical soft disc herniation. OBJECTIVE: To investigate the outcome of conservative treatment for patients with mild myelopathy caused by cervical soft disc herniation and to evaluate usefulness of magnetic resonance findings in the prediction of the outcomes. SUMMARY OF BACKGROUND DATA: Recent studies on conservative treatment for cervical soft disc herniation have focused mainly on radiculopathy, and not on myelopathy. METHODS: Twenty-seven patients with mild cervical myelopathy secondary to cervical soft disc herniation were treated conservatively for more than 6 months by cervical bracing and restriction of daily activities. Of the 27 patients, 17 patients (Group A) underwent conservative treatment only and it was associated with improvement in their neurologic deficits, while the other 10 patients (Group B) ultimately underwent decompression surgery because of neurologic deterioration. Comparisons between the two groups were made in regard to JOA scores, patient satisfaction, and magnetic resonance findings, including location of the disc herniation (focal or diffuse in the sagittal plane, median or paramedian in the axial plane). RESULTS: The JOA scores were 13.6 +/- 1.6 in Group A and 14.1 +/- 1.6 in Group B before treatment, 14.9 +/- 1.0 and 12.9 +/- 2.1, respectively, at 3 months, and 16.2 +/- 0.8 and 16.0 +/- 1.2, respectively, at the final follow-up. The JOA scores at 3 months were significantly lower in Group B than in Group A. Satisfaction with the results of treatment at the final follow-up was reported by 77% of the patients in Group A and 90% in Group B. Focal-type herniation was present in 47% of the patients in Group A and 70% in Group B, while median-type herniation was diagnosed in 77% in Group A and 30% in Group B. Follow-up magnetic resonance imaging of the patients in Group A showed spontaneous regression of a herniated mass in 10 patients (59%). Diffuse-type herniations were more likely to regress spontaneously than focal-type herniations (78% vs. 37%). CONCLUSIONS: Conservative treatment is an effective treatment option for mild cervical myelopathy caused by cervical soft disc herniation. A good outcome can be expected in patients with a median-type and/or diffuse-type herniation on magnetic resonance imaging.

Adult↗
PubMed2005

The prognosis of conservative treatments for lumbar spinal stenosis: analysis of patients over 70 years of age.

STUDY DESIGN: A prospective study. OBJECTIVES: To identify outcomes of aged patients with lumbar spinal stenosis (LSS) treated conservatively and to examine factors that control the prognosis. SUMMARY AND BACKGROUND DATA: There have been no reports evaluating the outcomes of conservative treatments for elderly LSS patients. METHODS: A total of 89 patients, 70 years of age and older, who underwent in-hospital conservative treatment were included. The Japanese Orthopedic Association's score (JOA score) and the disturbance level of activities of daily living (ADL) were used for evaluation. Nerve involvement was classified into radicular, cauda equina, and mixed type. Myelographic findings were classified into central defect with or without block and root defect. Associations between disturbance level of ADL, nerve involvement, and myelographic classifications were investigated. RESULTS: The mean JOA score increased from 11.1 points at admission to 15.9 points at discharge, with 14.3 points maintained at the follow-up; 48.8% of radicular type showed no obstacle in ADL at the follow-up compared with 33.3% of the other types; 13.3% of central defect with block showed no obstacle in ADL compared with 47.8% of the other types with significant difference. CONCLUSION: The prognosis of conservative treatment for aged LSS was relatively good. Radicular type may be a candidate for conservative treatment. However, patients with complete block in the myelogram may not respond favorably to conservative treatment.

Activities of Daily Living↗
PubMed2004

Accelerated partial breast irradiation after conservative surgery for breast cancer.

OBJECTIVE: To critically review the theoretical and actual risks and benefits of accelerated partial breast irradiation (APBI) after breast-conserving surgery. SUMMARY BACKGROUND DATA: Because of rapid evolution of radiation therapy techniques related to brachytherapy and three-dimensional conformal radiation therapy, APBI has very recently come to the forefront as a potential local treatment option for women with breast cancer. This review aims to give an overview of the biologic rationale for APBI techniques, and benefits and limitations of APBI techniques. METHODS: The authors reviewed the currently available published world medical literature on breast-conserving surgery with and without postoperative irradiation; all studies involving partial breast irradiation, including brachytherapy, for breast cancer; and currently accruing and planned APBI trials. The focus of this review was the early results of treatment in terms of toxicity, complications, cosmesis, and local control. RESULTS: On average, approximately 3% of patients treated with breast-conserving surgery will have an in-breast local recurrence away from the original lumpectomy site with or without postoperative standard whole-breast irradiation. The results of phase I-II studies involving approximately 500 patients treated with APBI after breast-conserving surgery have been published. Although many of the studies have limited long-term follow-up and potential selection bias, early results suggest that toxicity, cosmesis, and local control are comparable to outcomes seen after breast-conserving surgery followed by standard whole-breast irradiation. CONCLUSIONS: Recent advances in radiation delivery and published series of partial breast irradiation support large randomized trials comparing APBI with standard whole-breast irradiation after breast-conserving surgery.

Brachytherapy↗
PubMed2004

Prediction of functional sites by analysis of sequence and structure conservation.

We present a method for prediction of functional sites in a set of aligned protein sequences. The method selects sites which are both well conserved and clustered together in space, as inferred from the 3D structures of proteins included in the alignment. We tested the method using 86 alignments from the NCBI CDD database, where the sites of experimentally determined ligand and/or macromolecular interactions are annotated. In agreement with earlier investigations, we found that functional site predictions are most successful when overall background sequence conservation is low, such that sites under evolutionary constraint become apparent. In addition, we found that averaging of conservation values across spatially clustered sites improves predictions under certain conditions: that is, when overall conservation is relatively high and when the site in question involves a large macromolecular binding interface. Under these conditions it is better to look for clusters of conserved sites than to look for particular conserved sites.

Algorithms↗