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PubMed2000

Topology prediction of Brucella abortus Omp2b and Omp2a porins after critical assessment of transmembrane beta strands prediction by several secondary structure prediction methods.

In order to propose a reliable model for Brucella porin topology, several structure prediction methods were evaluated in their ability to predict porin topology. Four porins of known structure were selected as test-cases and their secondary structure delineated. The specificity and sensitivity of 11 methods were separately evaluated. Our critical assessment shows that some secondary structure prediction methods (PHD, Dsc, Sopma) originally designed to predict globular protein structure are useful on porin topology prediction. The overall best prediction is obtained by combining these three "generalist" methods with a transmembrane beta strand prediction technique. This "consensus" method was applied to Brucella porins Omp2b and Omp2a, sharing no sequence homology with any other porin. The predicted topology is a 16-stranded antiparallel beta barrel with Omp2a showing a higher number of negatively charged residue in the exposed loops than Omp2b. Experiments are in progress to validate the proposed topology and the functional hypotheses. The ability of the proposed consensus method to predict topology of complex outer membrane protein is briefly discussed.

Amino Acid Sequence↗

PubMed2006

Heartburn severity does not predict disease severity in patients with erosive esophagitis.

BACKGROUND: For patients with gastroesophageal reflux disease (GERD), it is often assumed by treating physicians that the severity of heartburn correlates with the severity of erosive esophagitis (EE). OBJECTIVE: This is a post hoc analysis of data from 5 clinical trials that investigate the relationship between the baseline severity of heartburn and the baseline severity of EE. METHODS: Patients with endoscopically confirmed EE were assessed for heartburn symptoms with a 4-point scale at baseline and during treatment for 8 weeks with various proton pump inhibitors in 5 double-blind trials in which esomeprazole was the common comparator. EE was graded with the Los Angeles (LA) classification system. In these trials, healing and symptom response were evaluated by endoscopy and questionnaire after 4 weeks of treatment. Patients who were not healed were treated for an additional 4 weeks and reevaluated. RESULTS: A total of 11,945 patients with endoscopically confirmed EE participated in the 5 trials, with patients receiving esomeprazole 40 mg (n = 5068), esomeprazole 20 mg (n = 1243), omeprazole 20 mg (n = 3018), or lansoprazole 30 mg (n = 2616). Approximately one quarter of the 11,945 GERD patients in these 5 trials had severe EE (defined as LA grades C or D), regardless of their baseline heartburn severity. CONCLUSION: The severity of GERD symptoms does not correlate well with disease severity. These findings indicate that endoscopy may have value in GERD patients in identifying those with EE, and if empirical therapy is chosen, then longer courses (4-8 weeks) of antisecretory therapy may be necessary to ensure healing of unrecognized esophagitis.

Clinical Trials as Topic↗

PubMed2002

Early prediction of severity in acute pancreatitis. Is this possible?

One out of ten cases of acute pancreatitis develops into severe acute pancreatitis which is a life threatening disorder with a high mortality rate. The other nine cases are self limiting and need very little therapy. The specificity of good clinical judgement on admission, concerning the prognosis of the attack, is high (high specificity) but misses a lot of severe cases (low sensitivity). The prediction of severity in acute pancreatitis was first suggested by John HC Ranson in 1974. Much effort has been put into finding a simple scoring system or a good biochemical marker for selecting the severe cases of acute pancreatitis immediately on admission. Today C-reactive protein is the method of choice although this marker is not valid until 48-72 hours after the onset of pain. Inflammatory mediators upstream from CRP like interleukin-6 and other cytokines are likely to react faster and preliminary results for some of these mediators look promising. Another successful approach has been to study markers for the activation of trypsinogen such as TAP and CAPAP. This is based on studies showing that active trypsin is the initial motor of the inflammatory process in acute pancreatitis. In the near future a combined clinical and laboratory approach for early severity prediction will be the most reliable. Clinical judgement predicts 1/3 of the severe cases on admission and early markers for either inflammation or trypsinogen activation should accurately identify 50-60% of the mild cases among the rest, thus missing only 2-4% of the remaining severe cases. One problem is that there is no simple and fast method to analyze any of these parameters.

Acute Disease↗

PubMed2005

Computed tomography severity index, APACHE II score, and serum CRP concentration for predicting the severity of acute pancreatitis.

CONTEXT: The assessment of the severity of pancreatitis is important for proper management of this challenging disease. A highly accurate system which could predict the severity and identify the local extent and complications of a serious inflammation, is beneficial for patient outcome. OBJECTIVE: The aim was to establish the value of the computed tomography severity index in predicting the severity of acute pancreatitis and to compare it with the accuracy of the APACHE II score and serum CRP concentrations. DESIGN: Prospective clinical series. PATIENTS: Fifty-five consecutive patients (37 women, 18 men; mean age 57 years) with a clinical and laboratory diagnosis of acute pancreatitis. INTERVENTIONS: Clinical evaluation, biochemical analysis of blood and contrast-enhanced abdominal CT. MAIN OUTCOME MEASURES: Computed tomography severity index within the first 5 days, serum CRP level, and clinical APACHE II score at 48 hours after admission. RESULTS: Thirteen patients had severe pancreatitis according to the Atlanta classification. The mean values of predictive markers in the mild and the severe pancreatitis groups were: computed tomography severity index 1.26 and 6.30 (P<0.001); APACHE II 4.14 and 8.61 (P<0.001); and CRP 96.0 mg/L and 192.4 mg/L (P<0.001), respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated for the CTSI (greater than 3: 85%, 98%, 92%, 95%, and 95%), for APACHE II (equal to, or greater than 7: 62%, 86%, 57%, 88%, and 80%) and for CRP (equal to, or greater than 150 mg/L: 85%, 74%, 50%, 94%, and 76%). CONCLUSION: The computed tomography severity index is a reliable method for staging the severity of acute pancreatitis; moreover, CT has the ability of showing the local extent of the inflammation and the occurrence of local complications.

APACHE↗

PubMed1993

Can severe cardiorespiratory dysregulation induced by clozapine monotherapy be predicted?

Severe orthostatic and cardiorespiratory dysregulation may occur during institution of clozapine therapy both during concomitant benzodiazepine medication and on reinstitution of clozapine after a washout period. Extensive medical and neurological workup before and after the trials can nevertheless be normal. The absence of similar previous reactions to other drugs, adhering to monotherapy with clozapine, increasing dosage slowly or performing a single test for orthostatic reactions after initiating clozapine are insufficient precautionary measures. Cardiorespiratory complications can occur without the challenge of assuming an erect position but appear to otherwise run an initial course similar to that of severe orthostatic reactions. A significantly abnormal response to testing for orthostatic reactions may be established, but only during the period of vulnerability to cardiorespiratory dysregulation. Repeated testing for this predisposition during the first weeks of clozapine therapy is suggested.

Adult↗

PubMed2005

Immunosuppressive therapy for aplastic anemia in children: a more severe disease predicts better survival.

Severe acquired aplastic anaemia (SAA) is a life-threatening disease characterized by pancytopenia and hypoplastic bone marrow. Autologous T lymphocytes are thought to cause bone marrow failure by immune-mediated excessive apoptosis of stem and progenitor cells. The disease is subclassified into a severe (neutrophil count, > 0.2 x 10(9)/L [> 200/microL]) and a very severe (< 0.2 x 10(9)/L [< 200/microL]) (vSAA) form. We report the results of a prospective multicenter trial with a combined immunosuppressive regimen of cyclosporin A (CSA), anti-thymocyte globulin (ATG) and, in cases with neutrophil counts fewer than 0.5 x 10(9)/L (< 500/microL), granulocyte colony-stimulating factor (G-CSF) for treatment of SAA in children. Children with vSAA showed a higher rate of complete response than did children with SAA (68% versus 45%; P = .009), as well as better survival (93% versus 81%; P < .001). Thus, in children with SAA a more severe disease stage at diagnosis indicates a favorable outcome with immunosuppressive therapy.

Adolescent↗

PubMed1984

Prognostic factors in acute pancreatitis.

Prognostic factor scoring systems provide one method of predicting severity of acute pancreatitis. This paper reports the prospective assessment of a system using nine factors available within 48 hours of admission. This assessment does not include patient data used to compile the system. Of 405 episodes of acute pancreatitis occurring in a seven year period, 72% had severity correctly predicted by the system; 31% of 131 episodes with three or more factors present were severe and 8% of 274 episodes with less than three factors were severe. Assessment of individual factors revealed only one which did not predict severity. A scoring system based on the other eight factors correctly predicted severity in 79% of episodes. Prognostic factor scoring systems (i) alert the clinician to potentially severe disease, (ii) allow comparison of severity within and between patient series and (iii) will allow rational selection of patients for trials of new treatment.

Acute Disease↗

PubMed1988

ERCP findings and the role of endoscopic sphincterotomy in acute gallstone pancreatitis.

A total of 131 patients with acute pancreatitis (of whom 100 had gallstones) underwent endoscopic retrograde cholangiopancreatography (ERCP) during the same hospital admission. Urgent ERCP (less than 72 h) was performed in 68 cases and early ERCP (3-30 days) in 63 cases; 47 had predicted severe attacks and 84 had predicted mild attacks (modified Glasgow criteria). The highest incidence of common bile duct stones occurred in those with predicted severe attacks and those who had urgent ERCP. Highly significant correlations were found between age and common bile duct and pancreatic duct diameters. Significant correlations were also found between the common bile duct and pancreatic duct (correcting for age) and between these and the admission serum bilirubin. The common bile duct diameter was greatest in those with common bile duct stones and predicted severe attacks. A considerably lower incidence of pancreatic duct filling occurred in those with predicted severe attacks and common bile duct stones; in predicted mild attacks the pancreatic duct diameter was greater in those with common bile duct stones. In gallstone patients complications were highest in those with predicted severe attacks but more significantly in those with common bile duct stones. Endoscopic sphincterotomy was undertaken in 37 patients with common bile duct stones without mortality. The overall complication rate in gallstone patients was 19 per cent and the mortality rate was 2 per cent. These findings suggest that common bile duct stones cause acute common bile duct and pancreatic duct obstruction and are closely associated with complications. Urgent ERCP for detection of common bile duct stones, and endoscopic sphincterotomy for treatment, is strongly recommended for patients with predicted severe attacks due to gallstones and should also be considered for others who fail to show clinical improvement.

Acute Disease↗

PubMed1997

Upper abdominal surgery: does a lung function test exist to predict early severe postoperative respiratory complications?

We evaluated the capacity to predict severe respiratory complications (SRCs) following upper abdominal surgery (UAS) by using the results of a respiratory questionnaire and preoperative pulmonary function tests. Lung volumes, flows and transfer factor of the lung for carbon monoxide (TL,CO,sb) were assessed in 361 consecutive adult patients (248 males and 113 females). SRCs were diagnosed 24 h after UAS by clinical examination and chest radiography. Univariate and stepwise multiple logistic regression analyses were performed to estimate the odds ratio (OR) and 95% confidence interval (95% CI) of each single input variable, and to determine which indices best predicted outcome. These patients had a 1% mortality rate and 14% incidence of SRCs, with a male:female ratio of 0.86. The best predictors for SRCs by multiple analysis were: preoperative current hypersecretion of mucus (OR=133; p<0.0001); an increase in residual volume (RV) (OR=3.11; p=0.01); and, to a lesser extent, low percentage of predicted values both of forced expiratory volume in one second (FEV1 % pred) and TL,CO,sb. The algorithm thus obtained (logit theta) was extremely sensitive (84%), specific (99%), and accurate (95%) for preoperative prediction of SRCs. We have found that preoperative current hypersecretion of mucus and pulmonary hyperinflation, and to a lesser extent percentage predicted values both of forced expiratory volume in one second and transfer factor of the lung for carbon monoxide, have a significant predictive capacity for severe respiratory complications following upper abdominal surgery.

Abdomen↗

PubMed2004

Classification and regression tree for prediction of outcome after severe head injury using simple clinical and laboratory variables.

Many previous studies have constructed several predictive models for outcome after severe head injury, but these have often used expensive, time consuming, or highly specialized measurements. The goal of this study was to develop a simple, easy to use a model involving only variables that are rapidly and easily achievable in daily routine practice. To this end, a classification and regression tree (CART) technique was employed in the analysis of data from 345 patients with isolated severe brain injury who were admitted to Asclepeion General Hospital of Athens from January, 1993, to December, 2000. A total of 16 prognostic indicators were examined to predict neurological outcome at 6 months after head injury. Our results indicated that Glasgow Coma Scale was the best predictor of outcome. With regard to the other data, not only the most widely examined variables such as age, pupillary reactivity, or computed tomographic findings proved again to be strong predictors, but less commonly applied parameters, indirectly associated with brain damage, such as hyperglycemia and leukocytosis, were found to correlate significantly with prognosis too. The overall cross-validated predictive accuracy of CART model for these data was 86.84%, with a cross-validated relative error of 0.308. All variables included in this tree have been shown previously to be related to outcome. Methodologically, however, CART is quite different from the more commonly used statistical methods, with the primary benefit of illustrating the important prognostic variables as related to outcome. This technique may prove useful in developing new therapeutic strategies and approaches for patients with severe brain injury.

Adolescent↗

PubMed2004

Combination of APACHE-II score and an obesity score (APACHE-O) for the prediction of severe acute pancreatitis.

BACKGROUND: The advent of specific therapeutic or preventive treatments for severe acute pancreatitis creates a need to determine the risk of complications for each individual. Scoring systems used in acute pancreatitis identify groups of patients at risk of complications, but the pancreatitis-specific scores require 48 h of hospital admission to give full information. The APACHE-II score is useful within 24 h, but ignores simple clinical features, such as obesity, known to predict severity. The aim of this study was to evaluate a combination of the APACHE-II score with an obesity score in patients with acute pancreatitis, to predict severity using information available during the first 24 h of hospital admission. METHODS: Data were collected prospectively from 186 consecutive patients with acute pancreatitis, to allow calculation of the APACHE-II score and body mass index (BMI). BMI was categorised as normal (score = 0), overweight (BMI 26-30: score = 1), or obese (BMI >30: score = 2). A logistic regression model was used to identify factors significantly associated with complications (Atlanta criteria; 104 complications in 60 patients). RESULTS: Age, BMI and the acute physiology score independently predicted complications. Addition of the score for obesity to the APACHE-II score gave a composite score (APACHE-O) with greater predictive accuracy. At cut-off of >8, APACHE-O had sensitivity 82%, specificity 86%, positive predictive value 74%, negative predictive value 91% and overall accuracy 85%. CONCLUSIONS: This study confirms that age, obesity and APACHE-II measured in the first 24 h of hospital admission can predict complications in acute pancreatitis. Combination of the APACHE-II and obesity scores by simple addition improved categorical prediction of severity (mild or severe) in patients with acute pancreatitis.

APACHE↗

PubMed1995

Pathologic voice type and the acoustic prediction of severity.

We hypothesized that acoustic measures would predict dysphonic severity with differential results for pathological voice types. An instructional program based upon synthesized voice signals was developed to facilitate an awareness of prototypical voice types. Eighty phonatory samples representing normal subjects as well as patients with unilateral vocal fold paralysis, vocal nodules, and functional dysphonia were analyzed acoustically on the basis of four measures: average fundamental frequency (F0), jitter, shimmer, and harmonic/noise ratio (H/N ratio). Following training, 29 listeners classified 62% of the phonatory samples on the basis of breathy, hoarse, rough, and normal. Dysphonic severity of rough voices was predicted more successfully by H/N ratio (r2 = .73) than by shimmer (r2 = .43). Dysphonic severity of breathy voices was predicted only by the combined features of less jitter, more shimmer, and lower H/N ratio (r2 = .74). No combination of acoustic variables was successful in the prediction of the hoarse voice type.

Adolescent↗

PubMedDate not supplied

Prediction of severe coronary artery disease and long-term outcome in patients undergoing vasodilator SPECT.

BACKGROUND: Vasodilator perfusion imaging has not been extensively evaluated for predicting severe coronary artery disease (CAD) or long-term prognosis. METHODS AND RESULTS: The goals of this study were to develop a model to predict left main/3-vessel CAD in patients undergoing vasodilator thallium 201 imaging and coronary angiography (angiographic population) and to test the long-term prognostic value of this model in a separate cohort of patients who were not referred for angiography (prognostic population). In the angiographic population (n = 653) the chi2 value of the clinical model (containing the variables age, sex, and prior myocardial infarction) in the prediction of severe CAD was 32. The addition of 3 vasodilator Tl-201 variables (magnitude of ST-segment depression, summed reversibility score, and increased lung uptake) increased the model chi2 value to 114 (P <.001). Only 9% of predicted low-risk patients versus 57% of predicted high-risk patients had severe CAD. In the prognostic population (n = 521) survival rates free of cardiac death or myocardial infarction at 7 years were 91%, 73%, and 51%, respectively, for patient groups predicted to be at low, intermediate, and high risk of severe CAD (P <.001). CONCLUSIONS: Clinical and vasodilator Tl-201 variables can accurately predict the risk of severe CAD. Stress Tl-201 variables add incremental information to clinical variables. The same model also predicts patient outcome.

Adenosine↗

PubMed1980

Early prediction of severity of acute pancreatitis using peritoneal lavage.

Diagnostic peritoneal lavage was attempted in 96 out of a consecutive series of 168 attacks of acute pancreatitis, in order to evaluate its ability to predict severe disease. Lavage was successful in 89 instances, and resulted in relief of pain in many patients, and in one complication. Lavage indicated (by the presence of numerous organisms) that the diagnosis was incorrect in 1 patient with suspected acute pancreatitis; the correct diagnosis, biliary peritonitis, was revealed at post mortem examination. The severity of the attack was predicted by the clinician prior to lavage, and each attack was classified as mild or severe when the patient left hospital according to a simple clinical scheme. Although there was a strong correlations between severe attacks and the concentrations of G. O. T., albumin, protein, magnesium, potassium and phosphate in the lavage fluid, a simple and immediate classification based upon the physical features of the free peritoneal fluid and the lavage return fluid was adopted. The presence of brown free fluid, or more than 10 ml of free fluid, or mild-straw coloured lavage was taken as the lavage criterion of a severe attack. Of the 89 attacks with a successful lavage, 68 were classified as mild and 21 as severe according to the clinical outcome. Clinical assessment of the attack on the day of admission to hospital successfully predicted only 8 (38%) of the severe attacks, but 17 (76%) were correctly predicted by lavage, carried out at an average time of 7 hours after admission. False positive results of lavage were seen in only 4 (6%) of the 68 mild attacks. All attacks in which a shock-like illness developed, or which resulted in death (4) were predicted as severe by lavage. We feel that diagnostic lavage especially suited to select patients who may be expected to benefit from therapeutic peritoneal lavage.

Acute Disease↗

PubMed1995

Chronotropic response to exercise predicts angiographic severity in patients with suspected or stable coronary artery disease.

Inappropriate chronotropic response to exercise has been observed to correlate with poor prognosis in patients with coronary disease, but the mechanism for this association is not well defined. We attempted to examine the association between chronotropic response to exercise and angiographic severity of coronary disease in patients with suspected or stable coronary artery disease. The chronotropic response, expressed as peak heart rate, chronotropic index (ratio of heart rate reserve and metabolic reserve utilized), or percent maximal heart rate achieved, was correlated with angiographic findings obtained within 180 days of the test. Significant coronary disease was defined as > or = 1 stenosis of > or = 50% in a major epicardial artery or its main branches; severe coronary disease was defined as > or = 50% stenosis in all 3 epicardial arteries, or in the left main coronary trunk, or 2-vessel disease with > or = 70% proximal left anterior descending artery stenosis. We observed that peak heart rate and percent maximal heart rate achieved were independent negative predictors of both significant and severe coronary disease by logistic regression. The chronotropic index predicted severe coronary disease only. All 3 parameters of chronotropic response exhibited a significant gradient of abnormality across the spectrum of coronary disease (p < 0.01 for all), expressed by the number of vessels involved and correlated with left anterior descending artery involvement (p < 0.05 for all). We conclude that chronotropic response to exercise predicts the presence and angiographic severity of coronary disease. This association is likely related to the proportion of left ventricular myocardium rendered ischemic during stress.

Aged↗

PubMed1991

Prediction of severe adverse reactions to ionic and nonionic contrast media in Japan: evaluation of pretesting. A report from the Japanese Committee on the Safety of Contrast Media.

In a nationwide prospective study of adverse reactions to intravenous contrast media (CM), the Japanese Committee on the Safety of Contrast Media compared high-osmolar ionic CM with low-osmolar nonionic CM. A total of 337,647 cases were analyzed. The reliability of pretesting with an intravenous injection of a small amount of CM as a means of predicting severe or fatal reactions was also evaluated. The predictive values of the pretest were 1.2% for ionic and 0.0% for nonionic CM, and the sensitivity values were 3.7% and 0.0%, respectively. Such low values render this test meaningless for predicting which patients are at risk of a severe adverse reaction. A comparison of the incidence of severe adverse reactions between the nonpretested and pretested patients, as well as between the nonpretested and pretested patients with negative results, disclosed no statistically significant differences. Also, no beneficial effects of premedication in patients with a positive pretest were proved. The authors therefore conclude that pretesting with an intravenous injection of a small amount of CM is not useful in predicting severe reactions to ionic or nonionic CM.

Contrast Media↗

PubMed1989

Prediction of severity of acute pancreatitis: an alternative approach.

Admission laboratory data of 203 patients suffering from acute pancreatitis were analysed to search for a simpler method of prediction of severity than the traditional multifactor prognostic scoring system. By discriminant analysis, admission serum urea and plasma glucose were identified to be factors with independent significance in predicting severity. If the presence of either factor higher than the cutoff point (urea greater than 7.4 mmol/l, glucose greater than 11.0 mmol/l) was considered as an indication of severe disease, then the sensitivity of this method was 75.0%, specificity 80.3% and the accuracy 79.3%. The predictive ability of this method was comparable with the Glasgow multifactor scoring system when the latter was also used to grade severity of our patients. It has the advantage, however, of simplicity and the ability of predicting severity at the time of admission.

Acute Disease↗

PubMed1995

Severity and predicted outcome of postoperative Pseudomonas aeruginosa infections.

The severity and predicted outcome of postoperative Pseudomonas aeruginosa (P. aeruginosa) infections (PPAI) was evaluated using a severity scoring system based on a simplification and modification of the APACHE II system. A total of 86 patients in whom P. aeruginosa was isolated from various sources were examined. PPAI developed in 50 patients, resulting in an overall mortality rate of 24%. An increased severity score (SS) correlated with an increased risk of developing PPAI. Thus, PPAI developed in 33% of the patients with an SS of 0-1, in 66.7% of those with an SS of 2-3, and in 100% of those with an SS of 6 or higher. Moreover, the mortality rate of the patients with an initial score of 6 or higher was 50%. The mean (+/- SD) initial severity score was 5.4 +/- 2.9 for survivors and 2.9 +/- 2.6 for nonsurvivors (P < 0.01). In the patients who subsequently died, the SS remained high throughout the clinical course despite therapy, whereas in the survivors the SS decreased progressively, reflecting a favorable clinical course. These results suggest that our severity scoring system was useful for predicting outcome and monitoring the response of PPAI to therapy.

Adult↗