Improving the sensitivity of the sequence profile method.

The sequence profile method (Gribskov M, McLachlan AD, Eisenberg D, 1987, Proc Natl Acad Sci USA 84:4355-4358) is a powerful tool to detect distant relationships between amino acid sequences. A profile is a table of position-specific scores and gap penalties, providing a generalized description of a protein motif, which can be used for sequence alignments and database searches instead of an individual sequence. A sequence profile is derived from a multiple sequence alignment. We have found 2 ways to improve the sensitivity of sequence profiles: (1) Sequence weights: Usage of individual weights for each sequence avoids bias toward closely related sequences. These weights are automatically assigned based on the distance of the sequences using a published procedure (Sibbald PR, Argos P, 1990, J Mol Biol 216:813-818). (2) Amino acid substitution table: In addition to the alignment, the construction of a profile also needs an amino acid substitution table. We have found that in some cases a new table, the BLOSUM45 table (Henikoff S, Henikoff JG, 1992, Proc Natl Acad Sci USA 89:10915-10919), is more sensitive than the original Dayhoff table or the modified Dayhoff table used in the current implementation. Profiles derived by the improved method are more sensitive and selective in a number of cases where previous methods have failed to completely separate true members from false positives.

Risk of cardiovascular disease in a traditional African population with a high infectious load: a population-based study.

BACKGROUND: To test the inflammatory origin of cardiovascular disease, as opposed to its origin in western lifestyle. Population-based assessment of the prevalences of cardiovascular risk factors and cardiovascular disease in an inflammation-prone African population, including electrocardiography and ankle-arm index measurement. Comparison with known prevalences in American and European societies. METHODOLOGY/PRINCIPAL FINDINGS: Traditional population in rural Ghana, characterised by adverse environmental conditions and a high infectious load. Population-based sample of 924 individuals aged 50 years and older. Median values for cardiovascular risk factors, including waist circumference, BMI, blood pressure, and markers of glucose and lipid metabolism and inflammation. Prevalence of myocardial infarction detected by electrocardiography and prevalence of peripheral arterial disease detected by ankle-arm index. When compared to western societies, we found the Ghanaians to have more proinflammatory profiles and less cardiovascular risk factors, including obesity, dysglycaemia, dyslipidaemia, and hypertension. Prevalences of cardiovascular disease were also lower. Definite myocardial infarction was present in 1.2% (95%CI: 0.6 to 2.4%). Peripheral arterial disease was present in 2.8% (95%CI: 1.9 to 4.1%). CONCLUSIONS/SIGNIFICANCE: Taken together, our data indicate that for the pathogenesis of cardiovascular disease inflammatory processes alone do not suffice and additional factors, probably lifestyle-related, are mandatory.

Severe stroke: patient profile and predictors of favorable outcome.

Summary.  Background:  Severe stroke carries high rates of mortality and morbidity. The aims of this study were to determine the characteristics of patients who initially presented with severe ischemic stroke, and to identify acute and subacute predictors of favorable clinical outcome in these patients. Methods:  An observational cohort study, Acute Stroke Registry and Analysis of Lausanne (ASTRAL), was analyzed, and all patients presenting with severe stroke - defined as a National Institute of Health Stroke Scale score of ≥ 20 on admission - were compared with all other patients. In a multivariate analysis, associations with demographic, clinical, pathophysiologic, metabolic and neuroimaging factors were determined. Furthermore, we analyzed predictors of favorable outcome (modified Rankin scale score of ≤ 3 at 3 months) in the subgroup of severe stroke patients. Results:  Of 1915 consecutive patients, 243 (12.7%) presented with severe stroke. This was significantly associated with cardio-embolic stroke mechanism (odds ratio [OR] 1.74, 95% confidence interval [CI] 1.19-2.54), unknown stroke onset (OR 2.35, 95% CI 1.14-4.83), more neuroimaging signs of early ischemia (mostly computed tomography; OR 2.65, 95% CI 1.79-3.92), arterial occlusions on acute imaging (OR 27.01, 95% CI 11.5-62.9), fewer chronic radiologic infarcts (OR 0.43, 95% CI 0.26-0.72), lower hemoglobin concentration (OR 0.97, 95% CI 0.96-0.99), and higher white cell count (OR 1.05, 95% CI 1.00-1.11). In the 68 (28%) patients with favorable outcomes despite presenting with severe stroke, this was predicted by lower age (OR 0.94, 95% CI 0.92-0.97), preceding cerebrovascular events (OR 3.00, 95% CI 1.01-8.97), hypolipemic pretreatment (OR 3.82, 95% CI 1.34-10.90), lower acute temperature (OR 0.43, 95% CI 0.23-0.78), lower subacute glucose concentration (OR 0.74, 95% CI 0.56-0.97), and spontaneous or treatment-induced recanalization (OR 4.51, 95% CI 1.96-10.41). Conclusions:  Severe stroke presentation is predicted by multiple clinical, radiologic and metabolic variables, several of which are modifiable. Predictors in the 28% of patients with favorable outcome despite presenting with severe stroke include hypolipemic pretreatment, lower acute temperature, lower glucose levels at 24 h, and arterial recanalization.

The clinical profile of idiopathic and cat scratch neuroretinitis: who is at risk for recurrence?

Background: Most cases of neuroretinitis (NR) are idiopathic or due to cat scratch disease and occur as a single episode but a subgroup of patients experience recurrent attacks with cumulative visual loss. We reviewed our cases of NR to better characterize the clinical features of these subgroups in an effort to predict the risk of recurrence. Methods: Retrospective study of NR patients from a single institution. Sixty-seven patients were divided into three groups: 22 cases due to cat scratch disease (CSD-NR), 24 with idiopathic neuroretinitis (I-NR) and 21 (23 eyes) with recurrent neuroretinitis (R-NR). Results: Preceding systemic symptoms, predominantly central visual field (VF) loss and the combination of poor acuity with small relative afferent pupillary defect at presentation were common features of CSD-NR. There were no cases of recurrent CSD-NR. In the first attack of R-NR, the magnitude of VF loss at presentation was greater compared to the other two groups. While 39% of R-NR had a pattern of VF loss other than a central or cecocentral scotoma, only 13.6% of CSD-NR and 17% of I-NR showed this pattern. Visual recovery was least substantial for the R-NR group (average gain of 3.7 lines of Snellen acuity vs. 5 and 6.4 lines for CSD-NR and I-NR, respectively, and an average gain in VF score of 5.1 in the R-NR group compared to 8.2 and 11.5 for the other two groups). Conclusion: The main predictive factors for recurrence are absence of systemic symptoms, significant VF loss at presentation, particularly loss outside the central 30°, and less substantial visual recovery.