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Ultrasound therapy for acute ankle sprains.

BACKGROUND: Ultrasound is used in the treatment of a wide variety of musculoskeletal disorders. OBJECTIVES: To evaluate the effects of ultrasound therapy in the treatment of acute ankle sprains. SEARCH STRATEGY: MEDLINE and EMBASE up to December 1998 and databases of the Cochrane Rehabilitation and Related Therapies Field and Musculoskeletal Injuries Group were searched. This was supplemented with citation tracking, and contact with colleagues. Date of the most recent search: April 1999. SELECTION CRITERIA: Randomised or pseudo-randomised trials were included in the review if the following conditions were met: at least one study group was treated with active ultrasound; the study included patients with acute lateral ankle sprains; and outcome measures included general improvement, pain, swelling, functional disability, or range of motion. Final selection of papers was conducted by two independent reviewers. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality using a standardised checklist, and extracted data. Whenever possible, the results were analysed on an intention-to-treat basis. Fixed odds ratios together with 95% confidence intervals were calculated for dichotomous outcomes, and weighted or, where different scales were used, standardised mean differences together with 95% confidence intervals for continuous outcome measures. Pooling of data was undertaken where there was clinical homogeneity in terms of subjects, treatments, outcomes, and follow-up time points. MAIN RESULTS: The four included trials, involving 514 patients, were only of modest methodological quality. None of the three placebo-controlled trials (sham ultrasound) could demonstrate statistically significant differences between true and sham ultrasound therapy for any outcome measure at seven days of follow-up. The pooled odds ratio for general improvement was 1.19 (Peto fixed effects model, 95% confidence interval 0.73 to 1.93) for the comparison between ultrasound and sham ultrasound. The differences between intervention groups were generally small, between 0 and 6% for most dichotomous outcomes. However, one trial reported relatively large differences for pain free status (20%) and swelling (25%) in favour of ultrasound treatment. REVIEWER'S CONCLUSIONS: The extent and quality of the available evidence for the effects of ultrasound therapy for acute ankle sprains are limited. The results of three placebo-controlled trials do not support the use of ultrasound in the treatment of ankle sprains. The magnitude of most reported treatment effects appeared to be small, and may be of limited clinical importance. As yet, only few trials are available and no conclusions can be made regarding an optimal and adequate dosage schedule for ultrasound therapy, and whether such a schedule would improve on the reported effectiveness of ultrasound for ankle sprains.

Ankle Injuries↗

Topical treatments for fungal infections of the skin and nails of the foot.

OBJECTIVES: The objective of this review is to identify and evaluate the evidence of efficacy for topical treatments for fungal infections of the skin and nails of the human foot. To establish the effectiveness of topical treatments in achieving a cured condition and in preventing recurrence SEARCH STRATEGY: Randomised controlled trials were identified from the MEDLINE, EMBASE and CINHAL databases, from the beginning of these databases to December 1997. Also we screened the Cochrane Controlled Trials Register, the Science Citation Index BIOSIS, CAB - Health, Healthstar and Economic databases. References and unpublished studies were searched, podiatry journals handsearched and the pharmaceutical industry contacted. SELECTION CRITERIA: Only randomised controlled trials (RCTs) using participants who have mycologically diagnosed fungal infections of the skin and nails of the human foot are included in the analysis. DATA COLLECTION AND ANALYSIS: Two reviewers independently summarised the included trials and appraised their quality of reporting using a structured data extraction tool which assessed 12 quality criteria. MAIN RESULTS: Of 126 trials identified in 121 papers, 72 met the inclusion criteria. Placebo-controlled trials yielded the following pooled relative risks of failure to cure (RRFC) for skin infections: allylamines 0.30 (95% confidence interval 0.23 to 0.37); azoles 0.53 (0.42 to 0.68); undecenoic acid 0.28 (0.11 to 0.74); tolnaftate 0.46 (0.17 to 1.22). Though meta-analysis of 11 trials comparing allylamines and azoles showed an RRFC of 0.88 (0.78 to 0.99) in favour of allylamines, there was evidence of language bias. Seven English language reports favoured allylamines (RRFC = 0.79; 0.68 to 0.93) but four foreign language reports showed no difference between the two drugs (RRFC = 1.00; 0.90 to 1.12). The two trials of nail infections did not provide any evidence of benefit for topical treatments compared with placebo. REVIEWER'S CONCLUSIONS CONCLUSIONS: In placebo-controlled trials allylamines, azoles and undecenoic acid were efficacious. There are sufficient comparative trials to judge relative efficacy only between allylamines and azoles. Allylamines cure slightly more infections than azoles but are much more expensive. The most cost-effective strategy is first to treat with azoles or undecenoic acid and to use allylamines only if that fails.

Administration, Topical↗

Perioperative local anaesthesia for reducing pain following tonsillectomy.

BACKGROUND: Pain relief after tonsillectomy is an important part of post-operative management. Sometimes local anaesthetics are administed to the tonsillar region, but their effectiveness in relieving pain has not been formally assessed. OBJECTIVES: To assess the effects of pre- and post-operative local anaesthesia for pain reduction following tonsillectomy. SEARCH STRATEGY: Cochrane Controlled Trials Register, Medline, Embase and the Oxford Pain Database. Reference lists from identified publications, including those in non-English language publications, were scanned. Date of the most recent search was September 1998. SELECTION CRITERIA: Randomised controlled trials of adults and/or children undergoing tonsillectomy alone with local anaesthetic (a) injected into the tonsillar region immediately prior to removal of the tonsils (b) injected into the tonsillar region after removal of the tonsils (c) sprayed or otherwise applied to the tonsillar region after removal of the tonsils Outcome measures included the reduction in demand for post-operative analgesia, both in terms of time elapsed to request for first analgesia and of the total amount of analgesia used. DATA COLLECTION AND ANALYSIS: All three reviewers extracted data independently and assessed trials for quality. Four authors were contacted to obtain information on either the method of randomisation or the type of intervention used. MAIN RESULTS: Thirty trials were initially identified but only six trials met the inclusion criteria. These were all published in the English language literature between 1989 and 1997. Trials were excluded because procedures in addition to tonsillectomy were undertaken, inadequate randomisation techniques were used or because group sizes were inadequate. Of the six included studies, five involved local anaesthetic injection and one application of local anaesthetic spray. These studies used validated pain scores and measurement of supplemental analgesic intake for assessment of pain. However, some studies also included inappropriate, possibly post-hoc, outcome measures such as 'global pain scores' which may have resulted in bias. No included study showed a significant difference between intervention and control, other than for outcome measures which were felt to be inappropriate, such as the one mentioned above. REVIEWER'S CONCLUSIONS: There is no evidence that the use of perioperative local anaesthetic in patients undergoing tonsillectomy improves post-operative pain control. The trials identified were of small size and several involved the perioperative co-administration of intravenous opiates which may have masked any beneficial effect of the local anaesthetic. Further randomised controlled trials are necessary.

Anesthesia, Local↗

Protein restriction for diabetic renal disease.

OBJECTIVES: To determine whether protein restriction slows or prevents progression of diabetic nephropathy towards renal failure. SEARCH STRATEGY: Computerised databases MEDLINE (1976-1996) and EMBASE (1974-1996) were searched using keywords diabetes mellitus, diabetic nephropathy, dietary proteins, diet, protein restricted and uremia. Recent issues of selected journals (Diabetic Medicine, Diabetologia, Diabetes Care, Kidney International, Nephrology Dialysis and Transplantation) were handsearched for papers not yet in the computerised databases. Reference lists of papers were also checked. SELECTION CRITERIA: This review was not limited to randomised controlled trials. All trials involving people with insulin-dependent diabetes following a lower protein diet for at least 4 months were considered since the straight line nature of progression as reflected by GFR means that patients can act as their own controls in a before and after comparison. DATA COLLECTION AND ANALYSIS: Data were extracted for length of follow up, level of protein restriction, renal function and dietary compliance. No studies of the impact of protein restriction on outcomes such as the need for dialysis or transplantation were found. The trials reported only the effect on short-term indicators such as creatinine clearance. MAIN RESULTS: Overall a protein restricted diet (0.3-0. 8g/kg) does appear to slow the progression of diabetic nephropathy towards renal failure. REVIEWER'S CONCLUSIONS: The results show that reducing protein intake appears to slow progression to renal failure, but some questions remain unanswered. The first is what level of protein restriction we should be used? The trials aimed for a daily intake of between 0.3 to 0.8g/kg of protein. The second concerns compliance in routine care - what level would be acceptable to patients? The third concerns long term outcomes -the present trials use proxy indicators such as creatinine clearance rather than outcomes such as time to dialysis or prevention of ESRF. All trials were carried out in subjects with insulin-dependent diabetes. It remains to be seen if a lower protein intake would slow the progression of nephropathy affecting the non-insulin dependent diabetic population.

Diabetic Nephropathies↗

Inhaled steroids for neonatal chronic lung disease.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic disorder associated with prematurity. Systemic steroids induce at least a temporary improvement in respiratory function, but are associated with adverse side effects. Inhaled steroids have fewer side effects. OBJECTIVES: To determine if inhaled corticosteroids are effective in alleviating the morbidity of bronchopulmonary dysplasia (BPD) compared to 0-placebo. SEARCH STRATEGY: We identified randomised, controlled trials (RCT) within the Cochrane Database, references from retrieved trials, hand searches of journals and contact with pharmaceutical companies and experts in this field. SELECTION CRITERIA: Only randomised controlled trials involving infants with chronic lung disease of prematurity and treated with inhaled steroids versus placebo were included. Patients receiving systemic corticosteroids were excluded. Co-interventions included antenatal systemic steroids, routine neonatal intensive care, ventilatory support, surfactant replacement therapy, diuretics and bronchodilators. DATA COLLECTION AND ANALYSIS: Four of the seven included trials were of good methodological quality. There were five parallel-group trials in ventilated infants. These were comparable in terms of population, co-interventions and need for increased inspired oxygen concentration. They differed in terms of type, dose and duration (7-28 days) of inhaled steroids. Two cross-over trials were performed in non-ventilated patients. MAIN RESULTS: The inability to extubate during treatment was markedly reduced in infants treated with inhaled steroids; Peto Odds Ratio (OR) 0.12, 95% Confidence Interval (CI) 0.03 to 0.43. There was heterogeneity in this finding, however, with one study that contributed 30% of the total number of patients reporting no successful extubations in either treatment arm over one week. The risk of sepsis appeared similar between the two groups (N=3, OR=0.72, 95%CI: 0.21 to 2.43). The small number of trials precluded analysis to examine the effect of differences in drug, duration of therapy, delivery system, co-interventions, and disease severity. Reduced oxygen requirements were reported in one of the two trials performed in non-ventilated infants, but inadequate data reporting precluded pooling of data. REVIEWER'S CONCLUSIONS: In ventilated infants with BPD, inhaled steroids administered for 1 to 4 weeks improved the rate of extubation with no apparent increase in the risk of sepsis. No firm conclusion could be derived with regard to the efficacy of inhaled steroids in non-ventilated infants.

Administration, Inhalation↗

Pharmacotherapy for post traumatic stress disorder (PTSD).

BACKGROUND: Post traumatic stress disorder (PTSD) is a prevalent and disabling disorder. Evidence that PTSD is characterised by specific psychobiological dysfunctions has contributed to a growing interest in the use of medication in its treatment. OBJECTIVES: To assess the effects of medication for post traumatic stress disorder. SEARCH STRATEGY: We searched the Cochrane Depression, Anxiety and Neurosis Group specialised register (CCDANCTR-Studies) on 18 August 2005, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library issue 4, 2004), MEDLINE (January 1966 to December 2004), PsycINFO (1966 to 2004), and the National PTSD Center Pilots database. Reference lists of retrieved articles were searched for additional studies. SELECTION CRITERIA: All randomised controlled trials (RCTs) of pharmacotherapy for PTSD. DATA COLLECTION AND ANALYSIS: Two raters independently assessed RCTs for inclusion in the review, collated trial data, and assessed trial quality. Investigators were contacted to obtain missing data. Summary statistics were stratified by medication class, and by medication agent for the selective serotonin reuptake inhibitors (SSRIs). Dichotomous and continuous measures were calculated using a random effects model, heterogeneity was assessed, and subgroup/sensitivity analyses were undertaken. MAIN RESULTS: 35 short-term (14 weeks or less) RCTs were included in the analysis (4597 participants). Symptom severity for 17 trials was significantly reduced in the medication groups, relative to placebo (weighted mean difference -5.76, 95% confidence intervals (CI) -8.16 to -3.36, number of participants (N) = 2507). Similarly, summary statistics for responder status from 13 trials demonstrated overall superiority of a variety of medication agents to placebo (relative risk 1.49, 95% CI 1.28 to 1.73, number needed to treat = 4.85, 95% CI 3.85 to 6.25, N = 1272). Medication and placebo response occurred in 59.1% (N = 644) and 38.5% (628) of patients, respectively. Of the medication classes, evidence of treatment efficacy was most convincing for the SSRIs. Medication was superior to placebo in reducing the severity of PTSD symptom clusters, comorbid depression and disability. Medication was also less well tolerated than placebo. A narrative review of 3 maintenance trials suggested that long term medication may be required in treating PTSD. AUTHORS' CONCLUSIONS: Medication treatments can be effective in treating PTSD, acting to reduce its core symptoms, as well as associated depression and disability. The findings of this review support the status of SSRIs as first line agents in the pharmacotherapy of PTSD, as well as their value in long-term treatment. However, there remain important gaps in the evidence base, and a continued need for more effective agents in the management of PTSD.

Antidepressive Agents↗

Cranial irradiation for preventing brain metastases of small cell lung cancer in patients in complete remission.

BACKGROUND: Prophylactic cranial irradiation halves the rate of brain metastases in patients with small cell lung cancer. Individual randomized trials conducted on patients in complete remission were unable to clarify whether this treatment improves survival. OBJECTIVES: This study aims to test whether prophylactic cranial irradiation prolongs survival of patients with small cell lung cancer in complete remission. SEARCH STRATEGY: Published and unpublished trials were eligible. Electronic databases, reference lists of trial publications, review articles and relevant books were used to identify potentially eligible trials. The search was also guided by discussions with investigators and experts, and the examination of meeting proceedings and of the Physician Data Query clinical trial registry. SELECTION CRITERIA: Randomized trials comparing prophylactic cranial irradiation with no prophylactic cranial irradiation in patients with small cell lung cancer in complete remission. DATA COLLECTION AND ANALYSIS: Meta-analysis based on updated individual data. The main endpoint was survival. MAIN RESULTS: The relative risk of death in the treatment group compared to the control group was 0.84 (95% confidence interval=0.73 to 0.97, P=0.01), corresponding to a 5.4 percent increase in the 3-year survival rate (from 15.3 percent in the control group to 20.7 percent in the treatment group). Prophylactic cranial irradiation also increased disease-free survival (relative risk=0.75, 95% confidence interval=0.65 to 0.86, P<0.001) and decreased the risk of brain metastases (relative risk=0.46, 95% confidence interval=0.38 to 0.57, P<0.001). Increasing doses of irradiation decreased the risk of brain metastases when four groups (8 Gy, 24-25 Gy, 30 Gy, 36-40 Gy) were analyzed [trend test, P=0.02], but the effect on survival did not differ significantly according to the dose. We found a trend (P=0.01) for a decrease in the brain metastasis risk in favour of earlier administration of cranial irradiation after the initiation of induction treatment. REVIEWER'S CONCLUSIONS: Prophylactic cranial irradiation significantly improves survival and disease-free survival for patients with small cell lung cancer in complete remission. Further clinical trials are needed to confirm the potential greater benefit on brain metastasis rate suggested when cranial irradiation is given earlier or at higher doses.

Brain Neoplasms↗

Pharmacological interventions for treating acute heterotopic ossification.

BACKGROUND: Heterotopic ossification (HO) is the formation of mature lamellar bone in soft tissue sites outside the skeleton. HO frequently complicates burns, arthroplasty, fractures, and spinal cord and brain injuries. It can impair joint function. OBJECTIVES: To determine the efficacy of medications to treat acute HO on radiological, symptomatic, functional impairment, and disability outcomes. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group specialised register, the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2004), MEDLINE (1966 to August 2004), EMBASE (1980 to August 2004), CINAHL (1982 to August 2004), other databases, reference lists of articles, and contacted trialists and drug companies. No language restrictions were applied. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials that assessed the efficacy of any medication for treating acute HO (confirmed by bone scintigraphy, radiography, ultrasonography, or biopsy) and which used radiography to grade post-treatment HO severity. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the study quality and extracted data. We analysed two dichotomous outcomes: no progression in HO grade (versus progression) and improvement in HO grade (versus no improvement). MAIN RESULTS: Two randomised trials comparing disodium etidronate versus placebo were included (Ono 1988; Stover 1976), from which ninety-two participants with spinal cord injury had radiographically-proven HO at baseline. At the completion of the 12 week intervention, the Ono study but not the Stover study, suggested that disodium etidronate was associated with a significantly greater likelihood of successfully preventing the progression of radiographic HO grade, (relative risk (RR) 1.50; 95% confidence interval (CI) I 1.16 to 1.93; and RR 1.48; 95% CI 0.78 to 2.84 respectively) and a significantly greater likelihood of improvement in HO grade (RR 2.78; 95% CI 1.66 to 4.66; and RR 0.71; 95% CI 0.20 to 2.53 respectively). There was evidence of statistical heterogeneity for the latter outcome. Longer term radiographic, clinical or side effect outcomes were unavailable. Data was not pooled due to this heterogeneity and the inadequate duration of follow up. REVIEWERS' CONCLUSIONS: Given the absence of long term radiographic outcomes in the included studies, there is insufficient evidence to recommend the use of disodium etidronate or other pharmacological agents for the treatment of acute HO. It has been previously suggested that disodium etidronate acts by delaying, rather than preventing, the mineralization of HO, and that mineralization may occur after treatment cessation in many cases, thereby negating the benefit of disodium etidronate on eventual HO grade. Further studies are required to assess all pharmacological treatments for acute HO with sufficient follow-up duration.

Etidronic Acid↗

Interventions for treating mallet finger injuries.

BACKGROUND: Mallet finger, also called drop or baseball finger, is where the end of a finger cannot be actively straightened out due to injury of the extensor tendon mechanism. Treatment commonly involves splintage of the finger for six or more weeks. Less frequently, surgical fixation is used to correct the deformity. OBJECTIVES: To examine the evidence for the relative effectiveness of different methods of treating mallet finger injuries. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group trials register (November 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2004), MEDLINE (1966 to February week 2 2004), EMBASE (1988 to 2004 week 8), other databases, reference lists of articles and various conference proceedings. SELECTION CRITERIA: Randomised or quasi-randomised clinical trials evaluating different interventions, including no intervention, for treating mallet finger injuries. DATA COLLECTION AND ANALYSIS: Two reviewers independently performed study selection, quality assessment and data extraction. Study authors were contacted for additional information. MAIN RESULTS: Four trials were included. These involved a total of 278, mainly adult, participants with 283 mallet finger injuries. All four trials were methodologically flawed, including inadequate outcome assessment. Three trials compared different types of finger splints versus a standard Stack splint. One trial found a lower incidence of treatment failure in participants treated with a perforated custom-made splint. One trial found there were fewer complications in participants treated with a padded aluminium-alloy malleable finger splint; however, the incidence of treatment failure was similar in the two treatment groups. One trial evaluating the Abouna splint found a similar incidence of treatment failure in the two groups. However, the Abouna splint often needed replacing due to disintegration of its rubber cover and rusting of the exposed wires and was also less popular with participants. The fourth trial found no statistically significant differences between participants whose mallet finger was treated with Kirschner wire fixation and those with a Pryor and Howard splint. Similar numbers had complications in the two groups. REVIEWERS' CONCLUSIONS: There was insufficient evidence from comparisons tested within randomised trials to establish the relative effectiveness of different, either custom-made or off-the-shelf, finger splints used for treating mallet finger injury. There was a useful reminder that splints used for prolonged immobilisation should be robust enough for everyday use, and of the central importance of patient adherence to instructions for splint use. There was insufficient evidence to determine when surgery is indicated.

Adult↗

Methodology and application of gc-ms to study altered organic binding media from objects of the Kunsthistorisches Museum, Vienna.

Within the Kunsthistorisches Museum (KHM), Vienna, three off-line GC-MS analytical procedures for the identification of natural organic media have been refined, tested, and validated on a series of reference materials (partly artificially aged) to apply this knowledge for investigations of original, historic works of art from the museum's collections. At first, a set of artificially aged mockups has been prepared and a reference database has been built up for the identification of drying oils, resins, waxes, proteins and polysaccharides. Some interesting observations concerning the alteration of the composition of these organic media during different ageing steps are presented in the following text. In addition, some selected examples for the application of the refined techniques for the analysis of real samples from various museum objects are shown.

Art↗

An integrated map of the murine hippocampal proteome based upon five mouse strains.

With the advent of proteomics technologies it is possible to simultaneously demonstrate the expression of hundreds of proteins. The information offered by proteomics provides context-based understanding of cellular protein networks and has been proven to be a valuable approach in neuroscience studies. The mouse hippocampus has been a major target of analysis in the search for molecular correlates to neuronal information storage. Although human and rat hippocampal samples have been successfully subjected to proteomic profiling, no elaborate analysis providing the fundamental experimental basis for protein-expression studies in the mouse hippocampus has been carried out as yet. This led us to construct a master map generated from the individual hippocampal proteomes of five different mouse strains. A proteomic approach, based upon 2-DE coupled to MS (MALDI-TOF/TOF) has been chosen in an attempt to establish a comprehensive reference database of proteins expressed in the mouse hippocampus. 469 individual proteins, represented by 1156 spots displaying various functional states of the respective gene products were identified. Proteomic profiling of the hippocampus, a brain region with a pivotal role for neuronal information processing and storage may provide insight into the characteristics of proteins serving this highly sophisticated function.

Animals↗

Large-scale identification of cytosolic mouse brain proteins by chromatographic prefractionation.

Proteomic studies on mouse brain protein expression are still holding center stage as the generation of a reference database for the brain proteome, a need for designing expressional studies at the protein level. We therefore decided to extend the amount of identified brain proteins by the use of prefractionation. In order to reduce the complexity of mouse brain proteome we applied chromatographic prefractionations, ion-exchange and hydrophobic interaction chromatography, prior to 2-DE, followed by mass spectrometric identification (2-DE MALDI-MS). We analyzed about 17,000 protein spots in cytosolic fractions of mouse brain and identified about 10,000 spots. A total of 1841 proteins showing different pI or M(r), representing probably post-translational modifications or splice variants, were products of 789 different genes. Numerous proteins were clearly identified as metabolic, antioxidant, cytoskeleton, signaling, transcription/translation, nucleic acid-binding, proteolysis-related proteins. We additionally provided evidence for the existence of hypothetical proteins predicted from nucleic acid sequences. Moreover, observed pIs of proteins are listed thus enabling localization of proteins in a gel, information that cannot be obtained from theoretical pI's in databases. The results represent so far the largest database of mouse brain proteins and provide valuable information for the design of proteomic studies in the mouse.

Amino Acid Sequence↗

Systematic review of paramedical therapies for Parkinson's disease.

We evaluated the efficacy of physiotherapy, occupational therapy, and speech and language therapy in Parkinson's disease by synthesizing six Cochrane systematic reviews. All randomised, controlled trials examining the efficacy of a paramedical therapy versus control intervention and all those comparing the efficacy of two forms of active therapy in Parkinson's disease were included. Trials were identified by searching biomedical databases, reference lists, hand searching, and contacting investigators. The main outcome measures were quality of life, speech intelligibility, activities of daily living, and individual measures of motor and speech impairment. We identified 16 physiotherapy randomised controlled trials (399 patients), two occupational therapy trials (84 patients), and five speech and language therapy for dysarthria trials (154 patients). None of these studies examined nonpharmacological swallowing therapy for dysphagia. We were unable to perform meta-analysis of the results because the trials used heterogeneous therapy methods and outcome measures. The trials also had marked methodological flaws that could have introduced bias. In summary, we failed to find conclusive evidence of benefit for any form of paramedical therapy sufficient to recommend them in routine clinical practice. However, this lack of evidence is not proof of a lack of effect. Further large pragmatic randomised controlled trials are required to determine the effectiveness of paramedical therapies in Parkinson's disease.

Activities of Daily Living↗

Reproducibility of intracranial volume measurement by unsupervised multispectral brain segmentation.

To assess the inter-study variability of a recently published unsupervised segmentation method (Magn. Reson. Med. 1997;37:84-93), 14 brain MR studies were performed in five normal subjects. Standard deviations for absolute and fractional volumes of intracranial compartments, which reflect the experimental variability, were smaller than 16.5 ml and 1.1%, respectively. By comparing the experimental component of the variability with the variability observed in our reference database, an estimate of the biological variability of the intracranial fractional volumes in the database population was obtained.

Adolescent↗

High abundance protein profiling of cystic fibrosis lung epithelial cells.

Protein profiles of cultured cystic fibrosis (CF) lung epithelial cells were analyzed by two-dimensional gel electrophoresis and mass spectrometry (MS). The analysis gave rise to a protein map over the pI range of 4-7, and a molecular weight range of ca. 100-10 kDa. The map contains 194 identified proteins, which were detectable by silver stain. All silver stained features were identified by matrix-assisted laser desorption/ionization-time of flight MS of tryptic peptides. Some proteins were found to be represented by multiple features on the 2-D gel. Among the high abundance proteins identified were sets of proteins associated with inflammation, including the classical NFkappaB, p65 (RelA) and NFkappaB, p65 (RelB). We suggest that this composite atlas of the high abundance CF lung epithelial proteome will serve as a reference database for future studies of candidate CF drugs, validating different approaches to CFTR gene therapy, and analogous investigations of other types of human lung disorders.

Cell Culture Techniques↗

The accumulation of abundant soluble proteins changes early in the development of the primary roots of maize (Zea mays L.).

A reference database of the major soluble proteins of the primary root of the maize inbred line B73 was generated 5 days after germination (DAG) using a combination of 2-DE and MALDI-TOF MS. A total of 302 protein spots were detected with CBB in a pH 4-7 range and 81 proteins representing 74 distinct Genbank accessions were identified. Only 28% of the major proteins identified in 5 DAG primary roots were identified in similarly analyzed 9 DAG primary roots documenting remarkable changes in the accumulation of abundant soluble proteins early in primary root development.

Electrophoresis, Gel, Two-Dimensional↗

Proteomic analysis of the Gallus gallus embryo at stage-29 of development.

The chicken (Gallus gallus) is one of the primary models for embryological and developmental studies. In order to begin to understand the molecular mechanisms underlying the normal and abnormal development of the chicken, we used 2-DE to construct a whole-embryo proteome map. Proteins were separated by IEF on IPG strips, and by 11% SDS-PAGE) gels. Protein identification was performed by means of PMF with MALDI-TOF-MS. In all, 105 protein spots were identified, 35 of them implicated in embryo development, 10 related with some diseases, and 16, finally, being proteins that have never been identified, purified or characterized in the chicken before. This map will be updated continuously and will serve as a reference database for investigators, studying changes at the protein level under different physiological conditions.

Animals↗

Evaluation of Karhunen-Loève expansion for feature selection in computer-assisted classification of bioprosthetic heart-valve status.

This paper analyses the performance of four different feature-selection approaches of the Karhunen-Loève expansion (KLE) method to select the most discriminant set of features for computer-assisted classification of bioprosthetic heart-valve status. First, an evaluation test reducing the number of initial features while maintaining the performance of the original classifier is developed. Secondly, the effectiveness of the classification in a simulated practical situation where a new sample has to be classified is estimated with a validation test. Results from both tests applied to a reference database show that the most efficient feature selection and classification (> or = 97% of correct classifications (CCs)) are performed by the Kittler and Young approach. For the clinical databases, this approach provides poor classification results for simulated 'new samples' (between 50 and 69% of CCs). For both the evaluation and the validation tests, only the Heydorn and Tou approach provides classification results comparable with those of the original classifier (a difference always < or = 7%). However, the degree of feature reduction is particularly variable. The study demonstrates that the KLE feature-selection approaches are highly population-dependent. It also shows that the validation method proposed is advantageous in clinical applications where the data collection is difficult to perform.

Bioprosthesis↗