Scientific and standardization committee communications: classification and nomenclature of disintegrins isolated from snake venoms

Summary.  Viper venoms from the Elapidae, Hydrophiidae, Atractaspididae, Viperidae and Colubridae families contain at least 25 separate classes of biologically active compounds, including enzymes and non-enzymatic molecules. Nomenclature standardization of these by structure and function has been reported for prothrombin activators. No such agreement has been made for the nomenclature and classification of disintegrins. At the 51st Annual SSC Meeting in Sydney Australia (August 2005), we reported the variety of names given to the 78 disintegrins then known, and proposed a nomenclature standardization method for the naming of future members in this protein family. The summary of these recommendations will provide guidance as disintegrin discoveries move beyond high pressure liquid chromatography (HPLC) separation methods to mass spectrometry, proteomics and cloned cDNA.
View the complete paper on the International Society on Thrombosis and Haemostasis website, http://www.isth.org . ( http://www.med.unc.edu/isth/ssc/communications/exogenous/disintegrins/disintegrins.htm ). This abstract is co-published in Toxicon .     

Large femoral bone loss after hip revision using the uncemented proximally porous-coated Bi-Metric prosthesis: 22 hips followed for a mean of 6 years

Background and purpose Periprosthetic bone loss after uncemented femoral hip revision is a matter of concern. We have used a proximally porous- and hydroxyapatite-coated prosthesis (Bi-Metric) in revision since 1989 and now we report the bone changes. This prosthesis is intended to distribute the forces more evenly and to avoid proximal femoral unloading.Methods 22 patients were unilaterally reoperated because of aseptic loosening. Only patients with a healthy contralateral hip were included. Mean age at revision was 69 (55–80) years. Bone defects were graded by Gustilo-Pasternak and Endo-Klinik classifications. Clinical assessment was performed with Harris hip score. We used radiographs and dual-energy X-ray absorptiometry to evaluate migration, femoral remodeling, and bone mineral density after 72 (30–158) months.Results The mean Harris hip score was 74 (30–100) points at follow-up. Mild thigh discomfort was present in 1 patient and moderate thigh pain in 3 patients. There was no loosening or subsidence. Osteolysis seen at revision had diminished in 19 of the 22 hips at follow-up. We noted a large reduction in bone mineral density. It was most pronounced in Gruen regions 1, 2, 6, and 7.Interpretation Revision with this stem is a reliable procedure; however, we noted a large degree of proximal bone loss that could lead to later mechanical complications or fractures.     

Validation of the Functional Status II questionnaire in the assessment of extremely-low-birthweight infants

Aim  The increased survival of infants born at extremely low birthweight (ELBW) has been associated with significant morbidity, including higher rates of neurodevelopmental disability. However, formalized testing to evaluate these problems is both time-consuming and costly. The revised Functional Status questionnaire (FS-II) was designed to assess caregivers' perceptions of the functional status of children with chronic diseases.
Method  We evaluated the reliability and validity of the FS-II for ELBW infants at 18 to 22 months corrected age using data from the US Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network (NRN). Exploratory factor analyses were conducted using data from the network's first follow-up study of 1080 children born in 1993 to 1994 (508 males, 572 females [53%]), and results were confirmed using data from the next network follow-up of 4022 children born in 1995 to 2000 (1864 males, 2158 females [54%]).
Results  Results suggest that a two-factor solution comprising measures of general health and independence is most appropriate for ELBW infants. These factors differed from those found among chronically ill children, and new, more appropriate scales are presented for screening ELBW survivors. Both scales demonstrated good internal consistency: Cronbach's α=0.87 for general health and α=0.75 for independence. Construct validity of the scales was assessed by comparing mean scores on the scales according to scores on the Bayley Scales of Infant Development, second edition (BSID-II), and medical conditions.
Interpretation  As hypothesized, infants with greater functional impairments according to their BSID-II scores or medical conditions had lower scores on the general health and independence scales, supporting the validity of the scales.     

Clinical outcome of patients with venous thromboembolism and recent major bleeding: findings from a prospective registry (RIETE)

BACKGROUND: Patients who have experienced a recent major bleeding episode are usually excluded from clinical studies of venous thromboembolism (VTE) treatment. Therefore, recommendations based on evidence from clinical trials may not be suitable for these patients. The Registro Informatizado de la Enfermedad TromboEmbolica (RIETE) is a multicenter, observational registry designed to gather and analyze data on VTE treatment practices and clinical outcomes in patients with acute VTE. OBJECTIVES: The aim of this analysis was to study outcomes of patients with VTE who had experienced recent major bleeding (< 30 days prior to VTE diagnosis). METHODS: Patients with objectively confirmed symptomatic acute VTE are consecutively enrolled into the RIETE registry. Patient characteristics, details of antithrombotic therapy, and clinical outcomes at 3 months were recorded. RESULTS: Of 6361 patients enrolled up to January 2004, 170 (2.7%) had experienced recent major bleeding: 69 (40.6%) gastrointestinal tract, 60 (35.3%) intracranial, 41 (24.1%) other. The incidences of major bleeding (4.1%) and recurrent pulmonary embolism (PE) (2.4%) were significantly higher in patients with recent major bleeding. Among them, patients with cancer had an increased incidence of major bleeding [odds ratio (OR) 10.0, 95% confidence interval (CI) 2.3, 50; P < 0.001] and fatal PE (OR 4.1, 95% CI 0.98, 17; P < 0.05). CONCLUSIONS: Patients with VTE and recent major bleeding prior to VTE diagnosis (2.7% of total enrolled patients) had poorer clinical outcomes compared with those who had not experienced recent major bleeding. In patients who had recent major bleeding prior to enrollment, those with cancer had a poorer clinical outcome than those without cancer.     

The prothrombin time/international normalized ratio (PT/INR) Line: derivation of local INR with commercial thromboplastins and coagulometers – two independent studies

Summary. Background: The WHO scheme for prothrombin time (PT) standardization has been limited in application, because of its difficulties in implementation, particularly the need for mandatory manual PT testing and for local provision of thromboplastin international reference preparations (IRP). Methods: The value of a new simpler procedure to derive international normalized ratio (INR), the PT/INR Line, based on only five European Concerted Action on Anticoagulation (ECAA) calibrant plasmas certified by experienced centres has been assessed in two independent exercises using a range of commercial thromboplastins and coagulometers. INRs were compared with manual certified values with thromboplastin IRP from expert centres and in the second study also with INRs from local ISI calibrations. Results: In the first study with the PT/INR Line, 8.7% deviation from certified INRs was reduced to 1.1% with human reagents, and from 7.0% to 2.6% with rabbit reagents. In the second study, deviation was reduced from 11.2% to 0.4% with human reagents by both local ISI calibration and the PT/INR Line. With rabbit reagents, 10.4% deviation was reduced to 1.1% with both procedures; 4.9% deviation was reduced to 0.5% with bovine/combined reagents with local ISI calibrations and to 2.9% with the PT/INR Line. Mean INR dispersion was reduced with all thromboplastins and automated systems using the PT/INR Line. Conclusions: The procedure using the PT/INR Line provides reliable INR derivation without the need for WHO ISI calibration across the range of locally used commercial thromboplastins and automated PT systems included in two independent international studies.