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PubMed2005

Evolutionary conservation suggests a regulatory function of AUG triplets in 5'-UTRs of eukaryotic genes.

By comparing sequences of human, mouse and rat orthologous genes, we show that in 5'-untranslated regions (5'-UTRs) of mammalian cDNAs but not in 3'-UTRs or coding sequences, AUG is conserved to a significantly greater extent than any of the other 63 nt triplets. This effect is likely to reflect, primarily, bona fide evolutionary conservation, rather than cDNA annotation artifacts, because the excess of conserved upstream AUGs (uAUGs) is seen in 5'-UTRs containing stop codons in-frame with the start AUG and many of the conserved AUGs are found in different frames, consistent with the location in authentic non-coding sequences. Altogether, conserved uAUGs are present in at least 20-30% of mammalian genes. Qualitatively similar results were obtained by comparison of orthologous genes from different species of the yeast genus Saccharomyces. Together with the observation that mammalian and yeast 5'-UTRs are significantly depleted in overall AUG content, these findings suggest that AUG triplets in 5'-UTRs are subject to the pressure of purifying selection in two opposite directions: the uAUGs that have no specific function tend to be deleterious and get eliminated during evolution, whereas those uAUGs that do serve a function are conserved. Most probably, the principal role of the conserved uAUGs is attenuation of translation at the initiation stage, which is often additionally regulated by alternative splicing in the mammalian 5'-UTRs. Consistent with this hypothesis, we found that open reading frames starting from conserved uAUGs are significantly shorter than those starting from non-conserved uAUGs, possibly, owing to selection for optimization of the level of attenuation.

5' Untranslated Regions↗
PubMed2006

Understanding ecosystem dynamics for conservation of biota.

1. Ecosystems have higher-order emerging properties that can affect the conservation of species. We identify some of these properties in order to facilitate a better understanding of them. 2. Nonlinear, indirect effects of food web interactions among species can produce counterintuitive changes in populations. 3. Species differ in their roles and linkages with other species in the system. These roles are a property of the system. Such differences in roles influence how we conserve individual species. 4. Ecosystems operate at a multitude of interacting spatial and temporal scales, which together structure the system and affect the dynamics of individual populations. 5. Disturbance also structures an ecosystem, producing both long-term slow changes and sudden shifts in ecosystem dynamics. 6. Ecosystems therefore can have multiple states, determined both by disturbance regimes and biotic interactions. Conservation should recognize a possible multiplicity of natural states while avoiding aberrant (human-induced) states. 7. Ecosystem processes are influenced by the composition of the biota they contain. Disturbances to the biota can distort processes and functions, which in turn can endanger individual species. 8. The goal of ecosystem conservation is the long-term persistence of the biota in the system. There are two paradigms: community-based conservation (CBC) and protected area conservation. Both have their advantages but neither is sufficient to protect the biota on its own. 9. CBC is required to conserve the majority of the world's biota not included in protected areas. However, current CBC methods favour a few idiosyncratic species, distort the species complex, and ignore the majority. More comprehensive methods are required for this approach to meet the goal of ecosystem conservation. 10. Protected areas are essential to conserve species unable to coexist with humans. They also function as ecological baselines to monitor the effects of humans on their own ecosystems. 11. However, protected areas suffer from loss of habitat through attrition of critical areas. Thus, renewal (addition) of habitat is required in order to achieve the long-term persistence of biota in functioning ecosystems. Identification of minimum habitat areas and restoration of ecosystems become two major priorities for future research.

Animals↗
PubMed2005

Conservation programmes for African cattle: design, cost and benefits.

Information on costs and benefits of conservation programmes for cattle is scarce in the literature and mainly available for Europe. This study aims at simulating cost of and benefits from different kinds of conservation programmes designed for indigenous African cattle. The programmes include installation of a herdbook and activities to promote the breed (HB), in situ conservation with a sire rotation scheme (IS), cryoconservation of semen (CC) and CC combined with in situ conservation (IC). The results indicate that cost of the analysed conservation programmes was generally higher than those reported in the literature for comparable schemes. If cost per effective population size conserved is considered, programmes analysed in this study do not appear to be more expensive. The proposed rotation scheme in IS can be applied to many different production systems and prove to be effective with regard to low increase in kinship. Reduction in extinction probability is found to be higher for conservation programmes that strongly involve farmers and give them part of the responsibility for the breeding population. IC was most efficient with regard to cost per effective population size conserved. However, if cost per reduction in endangerment is considered as criterion for the efficiency of a programme, IS, HB and CC are superior to IC. These findings suggest that decisions on conservation programmes should be based on multiple criteria, and not just on cost per effective population size.

Africa↗
PubMed1999

Transcriptional activation signals found in the Epstein-Barr virus (EBV) latency C promoter are conserved in the latency C promoter sequences from baboon and Rhesus monkey EBV-like lymphocryptoviruses (cercopithicine herpesviruses 12 and 15).

The Epstein-Barr virus (EBV) EBNA2 protein is a transcriptional activator that controls viral latent gene expression and is essential for EBV-driven B-cell immortalization. EBNA2 is expressed from the viral C promoter (Cp) and regulates its own expression by activating Cp through interaction with the cellular DNA binding protein CBF1. Through regulation of Cp and EBNA2 expression, EBV controls the pattern of latent protein expression and the type of latency established. To gain further insight into the important regulatory elements that modulate Cp usage, we isolated and sequenced the Cp regions corresponding to nucleotides 10251 to 11479 of the EBV genome (-1079 to +144 relative to the transcription initiation site) from the EBV-like lymphocryptoviruses found in baboons (herpesvirus papio; HVP) and Rhesus macaques (RhEBV). Sequence comparison of the approximately 1,230-bp Cp regions from these primate viruses revealed that EBV and HVP Cp sequences are 64% conserved, EBV and RhEBV Cp sequences are 66% conserved, and HVP and RhEBV Cp sequences are 65% conserved relative to each other. Approximately 50% of the residues are conserved among all three sequences, yet all three viruses have retained response elements for glucocorticoids, two positionally conserved CCAAT boxes, and positionally conserved TATA boxes. The putative EBNA2 100-bp enhancers within these promoters contain 54 conserved residues, and the binding sites for CBF1 and CBF2 are well conserved. Cp usage in the HVP- and RhEBV-transformed cell lines was detected by S1 nuclease protection analysis. Transient-transfection analysis showed that promoters of both HVP and RhEBV are responsive to EBNA2 and that they bind CBF1 and CBF2 in gel mobility shift assays. These results suggest that similar mechanisms for regulation of latent gene expression are conserved among the EBV-related lymphocryptoviruses found in nonhuman primates.

Animals↗
PubMed2005

Variation in conserved non-coding sequences on chromosome 5q and susceptibility to asthma and atopy.

BACKGROUND: Evolutionarily conserved sequences likely have biological function. METHODS: To determine whether variation in conserved sequences in non-coding DNA contributes to risk for human disease, we studied six conserved non-coding elements in the Th2 cytokine cluster on human chromosome 5q31 in a large Hutterite pedigree and in samples of outbred European American and African American asthma cases and controls. RESULTS: Among six conserved non-coding elements (> 100 bp, > 70% identity; human-mouse comparison), we identified one single nucleotide polymorphism (SNP) in each of two conserved elements and six SNPs in the flanking regions of three conserved elements. We genotyped our samples for four of these SNPs and an additional three SNPs each in the IL13 and IL4 genes. While there was only modest evidence for association with single SNPs in the Hutterite and European American samples (P < 0.05), there were highly significant associations in European Americans between asthma and haplotypes comprised of SNPs in the IL4 gene (P < 0.001), including a SNP in a conserved non-coding element. Furthermore, variation in the IL13 gene was strongly associated with total IgE (P = 0.00022) and allergic sensitization to mold allergens (P = 0.00076) in the Hutterites, and more modestly associated with sensitization to molds in the European Americans and African Americans (P < 0.01). CONCLUSION: These results indicate that there is overall little variation in the conserved non-coding elements on 5q31, but variation in IL4 and IL13, including possibly one SNP in a conserved element, influence asthma and atopic phenotypes in diverse populations.

Asthma↗
PubMed2005

Variation in structural location and amino acid conservation of functional sites in protein domain families.

BACKGROUND: The functional sites of a protein present important information for determining its cellular function and are fundamental in drug design. Accordingly, accurate methods for the prediction of functional sites are of immense value. Most available methods are based on a set of homologous sequences and structural or evolutionary information, and assume that functional sites are more conserved than the average. In the analysis presented here, we have investigated the conservation of location and type of amino acids at functional sites, and compared the behaviour of functional sites between different protein domains. RESULTS: Functional sites were extracted from experimentally determined structural complexes from the Protein Data Bank harbouring a conserved protein domain from the SMART database. In general, functional (i.e. interacting) sites whose location is more highly conserved are also more conserved in their type of amino acid. However, even highly conserved functional sites can present a wide spectrum of amino acids. The degree of conservation strongly depends on the function of the protein domain and ranges from highly conserved in location and amino acid to very variable. Differentiation by binding partner shows that ion binding sites tend to be more conserved than functional sites binding peptides or nucleotides. CONCLUSION: The results gained by this analysis will help improve the accuracy of functional site prediction and facilitate the characterization of unknown protein sequences.

Amino Acid Sequence↗
PubMed2002

The relationship of protein conservation and sequence length.

BACKGROUND: In general, the length of a protein sequence is determined by its function and the wide variance in the lengths of an organism's proteins reflects the diversity of specific functional roles for these proteins. However, additional evolutionary forces that affect the length of a protein may be revealed by studying the length distributions of proteins evolving under weaker functional constraints. RESULTS: We performed sequence comparisons to distinguish highly conserved and poorly conserved proteins from the bacterium Escherichia coli, the archaeon Archaeoglobus fulgidus, and the eukaryotes Saccharomyces cerevisiae, Drosophila melanogaster, and Homo sapiens. For all organisms studied, the conserved and nonconserved proteins have strikingly different length distributions. The conserved proteins are, on average, longer than the poorly conserved ones, and the length distributions for the poorly conserved proteins have a relatively narrow peak, in contrast to the conserved proteins whose lengths spread over a wider range of values. For the two prokaryotes studied, the poorly conserved proteins approximate the minimal length distribution expected for a diverse range of structural folds. CONCLUSIONS: There is a relationship between protein conservation and sequence length. For all the organisms studied, there seems to be a significant evolutionary trend favoring shorter proteins in the absence of other, more specific functional constraints.

Animals↗
PubMed2006

[Impact of rural land market on farm household's behavior of soil & water conservation and its regional difference: A case study of Xingguo, Shangrao, and Yujiang County in Jiangxi province ecologically vulnerable districts].

The paper analyzed the farm households' decision-making progress of soil & water conservation and its two-stage conceptual model. It also discussed the impacts of rural land market on the farm households' behavior of soil & water conservation. Given that, the article established models for the relations between the land market and soil & water conservation, and the models' parameters were estimated with Heckman's two-stage approach by using the farm household questionnaires in Xingguo, Shangrao and Yujiang counties of Jiangxi province. The paper analyzed the impact o f rural land market on farm household's behavior of soil & water conservation and its regional difference with the result of model estimation. The results show that the perception of soil & water loss and the tax & fee on the farm land have significant influence upon the soil and water conservation from the view of the population; however, because of different social and economic condition, and soil & water loss, there are differences of the influence among the three sample counties. These differences go as follows in detail: In Xingguo County, the rent-in land area and its cost have remarkable effect on the farm households' soil & water conservation behavior; In Yujiang County, the rent-in land area, rent-in cost and rent-out land area remarkably influence the farm households' behavior of soil and water conservation, with the influence of the rent-in land area being greater than Xingguo County; In Shangrao County, only rent-out land area has significant influence on the behaviors of soil & water conservation; In all samples, Xingguo County and Yujiang County samples, the rent-out income has no significant influence on the farm household's decision-making behavior soil and water conservation. Finally, the paper put forward some suggestions on how to bring the soil & water loss under control and use land resource in sustainable ways.

Agriculture↗
PubMed1997

Change in the use of breast-conserving surgery in western Washington after the 1990 NIH Consensus Development Conference.

OBJECTIVE: To evaluate the use of breast-conserving surgery in western Washington before and after the National Institutes of Health Consensus Development Conference (June 18-21, 1990) during which breast-conserving surgery was recommended for most women with early invasive breast cancer. DESIGN: Survey. SETTING: Population-based cancer registry in the Seattle-Puget Sound (Washington) region. PARTICIPANTS: The survey included 13541 women in whom American Joint Committee on Cancer stage I or II breast cancer was diagnosed between January 1, 1983, and December 31, 1993. MAIN OUTCOME MEASURE: Proportion of participants who underwent breast-conserving surgery. RESULTS: From April 1985, after results of a US randomized controlled trial showing equivalent survival in women undergoing mastectomy or breast-conserving surgery were published, to the time of the Conference, breast-conserving surgery was performed on 44.8% of women with stage I and 25.8% with stage II breast cancer. These percentages increased to 54.9% and 35.2%, respectively, during the post-Conference period. While women with stage II breast cancer were less likely than women with stage I breast cancer to undergo breast-conserving surgery before and after the Conference, trends for age and education were attenuated after the Conference. Differences in the use of breast-conserving surgery observed before the Conference between countries of residence and among hospital types were also reduced after the Conference. CONCLUSIONS: These findings suggest that the Conference recommendations had an effect on the adoption of breast-conserving surgery, particularly among groups who were previously least likely to undergo such surgery. Despite progress toward the Conference recommendation that the majority of women with early invasive breast cancer undergo breast-conserving surgery, the majority of women with stage II breast cancer undergo mastectomy.

Aged↗
PubMed2006

Conservation biology of Malagasy strepsirhines: a phylogenetic approach.

The phylogenetic diversity of extant lemurs represents one of the most important but least studied aspects of the conservation biology of primates. The phylogenetic diversity of a species is inversely proportional to the relative number and closeness of its phylogenetic relatives. Phylogenetic diversity can then be used to determine conservation priorities for specific biogeographic regions. Although Malagasy strepsirhines represent the highest phylogenetic diversity among primates at the global level, there are few phylogenetic data on species-specific and regional conservation plans for lemurs in Madagascar. Therefore, in this paper the following questions are addressed for extant lemurs: 1) how does the measure of taxonomic uniqueness used by Mittermeier et al. (1992 Lemurs of Madagascar; Gland, Switzerland: IUCN) equate with an index of phylogenetic diversity, 2) what are the regional conservation priorities based on analyses of phylogenetic diversity in extant lemurs, and 3) what conservation recommendations can be made based on analyses of phylogenetic diversity in lemurs? Taxonomic endemicity standardized weight (TESW) indices of phylogenetic diversity were used to determine the evolutionary component of biodiversity and to prioritize regions for conserving lemur taxa. TESW refers to the standardization of phylogenetic diversity indices for widespread taxa and endemicity of species. The phylogenetic data came from recent genetic studies of Malagasy strepsirhines at the species level. Lemur species were assigned as being either present or absent in six biogeographic regions. TESW indices were combined with data on lemur complementarity and protected areas to assign conservation priorities at the regional level. Although there were no overall differences between taxonomic ranks and phylogenetic rankings, there were significant differences for the top-ranked taxa. The phylogenetic component of lemur diversity is greatest for Daubentonia madagascariensis, Allocebus trichotis, Lepilemur septentrionalis, Indri indri, and Mirza coquereli. Regional conservation priorities are highest for lemurs that range into northeast humid forests and western dry forests. Expansion of existing protected areas in these regions may provide the most rapid method for preserving lemurs. In the long term, new protected areas must be created because there are lemur species that: 1) are not found in existing protected areas, 2) exist only in one or two protected areas, and 3) are still being discovered outside the current network of protected areas. Data on the population dynamics and feeding ecology of phylogenetically important species are needed to ensure that protected areas adequately conserve lemur populations in Madagascar.

Animals↗
PubMed2006

Development and validation of nomograms for predicting residual tumor size and the probability of successful conservative surgery with neoadjuvant chemotherapy for breast cancer.

BACKGROUND: Neoadjuvant chemotherapy (NACT) increases the likelihood that breast conservation therapy for breast cancer patients will be successful. There is no available nomogram to predict breast conservation after NACT. The aim of the current study was to develop and validate nomograms for predicting residual tumor size and probability of a patient becoming eligible for breast conservation surgery after NACT. METHODS: A total of 1147 patients treated at M. D. Anderson Cancer Center (Houston, TX) and the Institut Gustave Roussy (Villejuif, France) who received anthracycline with or without paclitaxel NACT were included in the analysis. Clinicopathologic data from 1 series were used to construct logistic regression models for breast conservation and residual tumor size < 3 cm after NACT and were validated on an independent series. RESULTS: The discrimination and the calibration of the nomogram for predicting the probability of residual tumor size < 3 cm after anthracycline-based NACT were good when applied to the validation set (concordance index = 0.79; U-index = 10(-3)). The discrimination of the nomogram for predicting eligibility for breast conservation therapy was also good (concordance index = 0.67). However, the calibration had to be adjusted to take into account global rates of breast conservation surgery. A second nomogram adapted to preoperative chemotherapy regimens containing paclitaxel was established. The concordance index of the nomogram for predicting breast conservation was 0.71 (P < 10(-6)) for the independent dataset and the calibration was also good. The confrontation of both nomograms showed that predictions were highly correlated (r = 0.97), suggesting that eligibility for breast conservation therapy was independent of the preoperative chemotherapy regimen used. CONCLUSIONS: Nomograms were developed for breast cancer patients who received NACT to predict residual tumor size and whether the patient would thus become eligible for breast conservation therapy. These tools may be useful when counseling patients about treatment options, and a web-based interface is now available to help guide patients and physicians in these decisions.

Anthracyclines↗
PubMed2006

Conservation laryngeal surgery versus total laryngectomy for radiation failure in laryngeal cancer.

BACKGROUND: Total laryngectomy is the standard of care for surgical salvage of radiation failure in laryngeal cancer. However, the role of conservation laryngeal surgery in this setting remains unclear. The objective was to compare the efficacy of conservation versus total laryngectomy for salvage of radiation failure in patients who initially presented with T1 or T2 squamous cancer of the larynx. METHODS: A 21-year retrospective analysis of patients who received surgery at a single comprehensive cancer center after definitive radiation therapy is reported. At recurrence, the patients were reevaluated and then underwent a total laryngectomy or, if possible, a conservation laryngeal procedure. The charts of 105 patients who failed radiation treatment for primary laryngeal cancer and who subsequently underwent surgical salvage were reviewed for this study. Eighty-nine were male (84.8%). The mean age was 60.3 years. The median follow-up time after surgery was 69.4 months. Most patients with recurrence after radiotherapy required total laryngectomy (69.5%; 73/105). Conservation laryngeal surgery was performed for 32 patients (31.5%). Concomitant neck dissections were performed on 45 patients (45.5%). RESULTS: In 14 patients, local or regional recurrence developed after salvage surgery: 9 patients after total laryngectomy (12.3%; 9/73), and 5 patients (15.6%; 5/32) after conservation laryngeal surgery. This difference was not statistically significant, nor was there a difference in disease-free interval for the two procedures (p = .634, by log-rank test). Distant metastasis developed in 13 patients. Most developed in the setting of local and/or regional recurrence, but distant metastasis occurred as the only site of failure in 6 of the patients who had undergone total laryngectomy but in 1 of the conservation surgery patients treated for a supraglottic laryngeal cancer. The overall mortality for patients who underwent total laryngectomy was also higher: 73.74% (54/73) versus 59.4% (19/32) for patients who underwent a conservation approach (p = .011 by log-rank test). CONCLUSIONS: Although conservation laryngeal surgery was possible in a few patients with local failure after radiotherapy, conservation laryngeal surgery is an oncologically sound alternative to total laryngectomy for these patients.

Adult↗
PubMed1986

Sequence conservation in the protein coding and intron regions of the engrailed transcription unit.

Engrailed (en) is a gene involved in proper segmentation of the Drosophila embryo. The predicted en protein contains a homeodomain and regions rich in polyalanine, polyglutamine, polyglutamate/aspartate and serine. We have taken an evolutionary approach to define which regions may be of fundamental importance by examining the D. virilis genomic sequence homologous to the D. melanogaster en primary transcription unit. Sequence homology begins at the first ATG of a long open reading frame yielding proteins of 584 and 552 amino acids for the D. virilis and D. melanogaster proteins, respectively. The predicted amino acid sequence can be divided into conserved and non-conserved domains. The C-terminal 30% of the protein (which includes the homeodomain) is completely conserved. In the N-terminal 70% of the protein, the overall conservation is 71%, but non-conservative amino acid changes occur in clusters and there are short stretches of highly conserved sequence. A region rich in glutamate and aspartate is conserved and has homology to an 18-amino acid sequence present in members of the myc family of proteins. Major differences in the size of the two proteins occur in regions of non-conserved repeated sequences. In the introns of the engrailed transcription units there are long stretches of conservation, suggesting this DNA may be of functional importance.

Amino Acid Sequence↗
PubMed2003

Conserved residue clustering and protein structure prediction.

Protein residues that are critical for structure and function are expected to be conserved throughout evolution. Here, we investigate the extent to which these conserved residues are clustered in three-dimensional protein structures. In 92% of the proteins in a data set of 79 proteins, the most conserved positions in multiple sequence alignments are significantly more clustered than randomly selected sets of positions. The comparison to random subsets is not necessarily appropriate, however, because the signal could be the result of differences in the amino acid composition of sets of conserved residues compared to random subsets (hydrophobic residues tend to be close together in the protein core), or differences in sequence separation of the residues in the different sets. In order to overcome these limits, we compare the degree of clustering of the conserved positions on the native structure and on alternative conformations generated by the de novo structure prediction method Rosetta. For 65% of the 79 proteins, the conserved residues are significantly more clustered in the native structure than in the alternative conformations, indicating that the clustering of conserved residues in protein structures goes beyond that expected purely from sequence locality and composition effects. The differences in the spatial distribution of conserved residues can be utilized in de novo protein structure prediction: We find that for 79% of the proteins, selection of the Rosetta generated conformations with the greatest clustering of the conserved residues significantly enriches the fraction of close-to-native structures.

Acyl Coenzyme A↗
PubMed2006

Exploring structurally conserved solvent sites in protein families.

Protein-bound water molecules are important components of protein structure, and therefore, protein function and energetics. Although structural conservation of solvent has been studied in a few protein families, a lack of suitable computational tools has hindered more comprehensive analyses. Herein we present a semiautomated computational approach for identifying solvent sites that are conserved among proteins sharing a common three-dimensional structure. This method is tested on six protein families: (1) monodomain cytochrome c, (2) fatty-acid binding protein, (3) lactate/malate dehydrogenase, (4) parvalbumin, (5) phospholipase A2, and (6) serine protease. For each family, the method successfully identified previously known conserved solvent sites. Moreover, the method discovered 22 novel conserved solvent sites, some of which have higher degrees of conservation than the previously known sites. All six families studied had solvent sites with more than 90% conservation and these sites were invariably located in regions of the protein with very high sequence conservation. These results suggest that highly conserved solvent sites, by virtue of their proximity to conserved residues, should be considered as one of the defining three-dimensional structural characteristics of protein families and folds.

Animals↗
PubMed2004

Thrombosed external hemorrhoids: outcome after conservative or surgical management.

PURPOSE: Few data exist on the actual recurrence rates of thrombosed external hemorrhoids. We wished to determine the incidence of recurrence, intervals to recurrence, and factors predicting recurrence of thrombosed external hemorrhoids after conservative or surgical management. METHODS: Two hundred and thirty-one consecutive patients with thrombosed external hemorrhoids treated from 1990 to 2002 were identified. Recurrence was defined as complete resolution of the index lesion with subsequent return of a thrombosed external hemorrhoid and did not include patients with chronic symptoms. Data were gathered retrospectively. Multiple potential risk factors were reviewed. RESULTS: The index thrombosed external hemorrhoid was managed conservatively in 51.5 percent of cases and surgically in 48.5 percent. There were no differences between groups in gender, age, or race, and 44.5 percent of all patients had a prior history of thrombosed external hemorrhoid. A prior history was less common in the conservative group than in the surgical group (38.1 percent vs. 51.3 percent; P < 0.05). The frequency of pain or bleeding as the primary complaint was higher in the surgical group ( P < 0.001 and P < 0.002). In addition, the surgical group was more likely to report all three symptoms of pain, bleeding, and a lump ( P < 0.005). Mean follow-up was 7.6 months, with the range extending to 7 years. Time to symptom resolution averaged 24 days in the conservative group vs. 3.9 days in the surgical group ( P < 0.0001). The overall incidence to recurrence was 15.6 percent-80.6 percent in the conservative group vs. 19.4 percent in the surgical group. The rate of recurrence in the conservative group was 25.4 percent (4/29; 14 percent were excised) whereas only 6.3 percent of the surgical patients had recurrence ( P < 0.0001). Mean time to recurrence was 7.1 months in the conservative group vs. 25 months in the surgical group ( P < 0.0001). Survival analysis for time to recurrence of thrombosed external hemorrhoid indicated that time to recurrence was significantly longer for the surgical group ( P < 0.0001). Logistic regression analysis of multiple factors (including diverticular disease, constipation, straining, benign prostatic hypertrophy, diarrhea, skin tags, history of travel, anoreceptive sex, anal fissures, internal hemorrhoids, and obesity) was performed to determine the outcome of each group. None of these variables were significant predictors of recurrence. CONCLUSIONS: Patients whose initial presentation was pain or bleeding with or without a lump were more like to be treated surgically. Surgically treated patients had a lower frequency of recurrence and a longer time interval to recurrence than conservatively treated patients. None of the variables analyzed were significant predictors of a particular treatment, except for a prior history of thrombosed external hemorrhoids, which may represent patient choice. Although most patients treated conservatively will experience resolution of their symptoms, excision of thrombosed external hemorrhoids results in more rapid symptom resolution, lower incidence of recurrence, and longer remission intervals.

Adult↗
PubMed2006

Conservative versus surgical treatment of venous leg ulcers: a prospective, randomized, multicenter trial.

BACKGROUND: The prevalence of venous leg ulcers is as high as 1% to 1.5%, and the total costs of this disease are 1% of the total annual health care budget in Western European countries. Treatment modalities are conservative or surgical. Subfascial endoscopic perforating vein surgery (SEPS) combined with superficial vein ligation is performed in many centers to address vein incompetence in patients with chronic venous leg ulcers. Several reports describe good healing and low recurrence rates, although a randomized trial to compare surgical treatment including SEPS and treatment of the superficial venous system to conservative modalities has never been performed. Therefore, a prospective, randomized, multicenter trial was conducted to study whether ambulatory compression therapy with venous surgery is a better treatment than just ambulatory compression therapy in venous leg ulcer patients. METHODS: Patients with an active (open) venous leg ulcer (CEAP C6) qualified for the study. The study consisted of two treatment groups. All patients were treated by standardized ambulatory compression therapy, and half of the patients received SEPS. Concomitant superficial venous incompetence was also treated in the second group. For allocation to both treatment groups, each patient was assigned by a computer program at the randomization center. The primary goal of the study was to compare the ulcer-free period during follow-up in both study groups. Secondary end points were ulcer healing and recurrence rates. RESULTS: From April 1997 until January 2001, 200 ulcerated legs (170 patients) were included in the study in 12 centers in The Netherlands. A total of 97 ulcers were allocated to the surgical group and 103 to the conservative group. Patient characteristics were similar in the two treatment groups at baseline, with the exception of a higher proportion in the conservative group of diabetes mellitus. Healing rates were 83% in the surgical group and 73% in the conservative group (not significant; median time to healing, 27 months). Recurrence rates were the same in both treatment groups (22% surgical vs 23% conservative). During follow-up of a mean of 29 months (median, 27 months) in the surgical group and 26 months (median, 24 months) in the conservative group, we found that in the surgical group, the ulcer-free rate was 72%, whereas in the conservative group this rate was 53% (P = .11; Mann-Whitney test). Patients with recurrent ulceration or medially located ulcers in the surgical group had a longer ulcer-free period than those treated in the conservative group (P = .02 for both). A first-time ulcer and one of the centers also had a positive effect on the ulcer-free period during follow-up (P < .001 and P = .02), independent of the treatment group. Deep vein incompetence did not affect the ulcer-free period. CONCLUSIONS: In conclusion, we suggest that patients with medial and/or recurrent ulceration should receive surgery combined with ambulatory compression therapy. A dedicated center should provide care for those patients.

Aged↗
PubMed2000

The role of conservative management of vestibular schwannomas.

Although microsurgery is generally regarded as the conventional treatment of choice for most vestibular schwannomas, there remains a group of patients in whom a conservative management approach may be a desirable alternative. The aim of this study was to determine the natural history and outcome following the conservative management of 72 patients with unilateral vestibular schwannomas. The reasons for conservative management included poor general health, age, patient preference, small tumour size, minimal or no symptoms, and tumour in the only/better hearing ear. The mean duration of follow-up was 39.8 months (range 12-194 months). All patients underwent serial magnetic resonance imaging (MRI) for assessment of tumour growth. Patients were deemed to have failed conservative management if there was evidence of continuous or rapid radiological tumour growth and/or increasing symptoms or signs. The mean tumour growth rate, according to the 1995 guidelines of the American Academy of Otolaryngology/Head and Neck Surgery, was 1.16 mm/year (range: 0.75 9.65 mm/year). Approximately 83% of tumours grew at < 2 mm/year. Significant tumour growth was seen in 36.4%, no or insignificant growth in 50%, and negative growth in 13.6% of tumours. The growth rate of CPA tumours (1.4 mm/year) was significantly greater than that of IAC tumours (0.2 mm/year) (P = 0.001). Failure of conservative management, in which active treatment was required, occurred in 15.3%. The outcome of these patients appeared to be as favourable to a comparable group who underwent primary treatment, without a period of conservative management. The mean growth rate of tumours in patients who failed conservative management (4.2 mm/year) was significantly greater than that in patients who did not fail (0.5 mm/year) (P < 0.01). No factors predictive of tumour growth or failure of conservative management were identified. Deterioration of mean pure tone average (0.5, 1, 2, 3 kHz) and speech discrimination scores occurred regardless of whether radiological tumour growth was demonstrated or not. This study suggests that in a select number of cases of vestibular schwannoma, a conservative management approach may be appropriate. Regular follow-up with serial MRI is mandatory. Deterioration of auditory function occurs even in the absence of tumour growth.

Case-Control Studies↗