[Screening for violence against women. Validation and feasibility studies of a French screening tool]. / Dépistage de la violence faite aux femmes. Epreuves de validation et de fiabilité d'un instrument de mesure français.

OBJECTIVE: To replicate, in a Francophone community, our prior work determining the reliability and validity of the full Woman Abuse Screening Tool (WAST) and a two-item version (WAST-Short). DESIGN: Questionnaires completed by abused and nonabused women. SETTING: Two women's shelters in Francophone communities in Ontario and Quebec and participants' homes or workplaces. PARTICIPANTS: A convenience sample of 25 abused women currently residing in two women's shelters and a convenience sample of 21 women who reported they were not abused. MAIN OUTCOME MEASURES: Women's responses to French versions of the WAST, the Abuse Risk Inventory (ARI), and comfort in answering the questions were compared. Also, the reliability and validity of French versions of WAST and WAST-Short were assessed. RESULTS: Abused (n = 23) and not abused (n = 21) women were demographically similar. A strong single-factor structure that accounted for 81% of total variance in the French WAST items was identified. The French WAST was found to be highly reliable with a coefficient alpha of .95 and demonstrated construct and discriminant validity. The WAST-Short correctly classified all the nonabused women and 78.7% of the abused women. The abused women reported feeling less comfortable responding to the WAST questions than the nonabused women. CONCLUSION: The French version of the WAST demonstrated good reliability and validity and discriminated between known samples of abused and nonabused women. Even though the French WAST-Short did not perform as well as the English version, results of this study support further evaluation of the WAST for screening women in Francophone or bilingual family practice settings.

Identification of mutations in 15 Hungarian families with hereditary protein C deficiency.

Hereditary protein C deficiency represents about 2-9% of inherited thrombophilias. Our aim was to elucidate the molecular basis of protein C deficiency in 25 members of 15 Hungarian families with venous thromboembolic diseases and to identify hitherto undescribed genetical defects in the protein C (PROC) gene. The exons of the PROC gene were screened for mutations with the combination of polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE), and/or PCR and single-strand conformation polymorphism (SSCP) analysis. The amplified DNA fragments with aberrant migration during DGGE and SSCP were sequenced. Mutations were determined in the PROC gene in all of the examined families: one nonsense mutation, one rare frameshift deletion and nine different missense mutations, of which three were novel (1493 A-->G, 35Asp-->Gly; 6231 G-->A, 173Gly-->Glu; 8476 C-->T, 254Thr-->Ile). The combination of hereditary protein C deficiency with other hereditary thrombophilias was rather common. DGGE and SSCP were proved to be efficient and cost-effective screening methods in the genetic analysis of hereditary protein C deficiency.

Application of the Woman Abuse Screening Tool (WAST) and WAST-short in the family practice setting.

BACKGROUND: Our study objectives were to assess the validity and reliability of the Woman Abuse Screening Tool (WAST) in the general population within the family practice setting; to determine the comfort levels of family physicians administering the WAST, their perceptions of its ability to help them identify abused women, and their willingness to continue using it in practice; and to determine the self-reported comfort of patients being asked the WAST questions by their family physicians. METHODS: We included a stratified random sample of 20 physicians practicing in both urban and rural settings drawn from 400 family physicians in London, Ontario, Canada, and the surrounding area. These physicians administered the WAST to 10 to 15 eligible and consenting patients during the course of regular care. Following the physician-patient encounter, patients were asked to complete both a measure about their comfort in being asked each of the WAST questions and the Abuse Risk Inventory (ARI). RESULTS: Scores on the WAST correlated well with those on the ARI. The reliability of the WAST among this sample was demonstrated by a coefficient alpha of 0.75. With the WAST-Short (the first 2 questions of the WAST), 26 of the 307 patients screened (8.5%) were identified as experiencing abuse. The physicians were comfortable administering the WAST to their women patients, and 91% of the patients reported being comfortable or very comfortable when asked the WAST questions by their family physician. CONCLUSIONS: The WAST was found to be a reliable and valid measure of abuse in the family practice setting, with both patients and family physicians reporting comfort with it being part of the clinical encounter.

Pregnancy-associated risk for venous thromboembolism and pregnancy outcome in women homozygous for factor V Leiden.

INTRODUCTION: To evaluate the pregnancy-associated risk of venous thromboembolism and the risk of stillbirth and miscarriage a multicenter, retrospective and controlled study was conducted in women carrying the homozygous factor V Leiden mutation and in an agematched control group of women from the normal population. PATIENTS AND METHODS: In 64 homozygous (median age 44 years, range 21-75 years) and in 52 control women from five different centers data on venous thromboembolism and pregnancy outcome were obtained. RESULTS: The 64 homozygous women had in total 212 pregnancies, the 52 control women had 118 pregnancies. In homozygous women 65% of pregnancies ended with delivery of a viable infant, 15% with fetal loss (3.3% stillbirth, 12% miscarriage) and 20% by pregnancy termination. In the control women 75% of pregnancies ended with delivery of a viable infant, 12% with fetal loss (1.7% stillbirth, 10% miscarriage) and 13% by pregnancy termination. The differences were statistically not significant. Venous thromboembolism occurred significantly more often in the homozygous women, in 4.2% (9/212) during pregnancy and in 4.7% (10/212) after delivery or pregnancy termination. None of the control women had a thromboembolic episode. CONCLUSION: Our data indicate that women with homozygous factor V Leiden have a high probability for a favorable pregnancy outcome. The increased risk for venous thromboembolism during pregnancy and after delivery would favor heparin prophylaxis during and after pregnancy in women homozygous for factor V Leiden.

[Clinical evaluation of factors VIII and IX manufactured in Hungary, based on results of the first half year]. / Hazai elöállítású VIII és IX faktor készítményekkel nyert tapasztalatok a klinikai alkalmazás elsö fél évének eredményei alapján.

The development of anti-factor VIII/IX antibodies (inhibitor-induction) and the transmission of viral infections are the most significant complications of haemophilia treatment. The Humafactor-8 and Humafactor-9 are high-purity pasteurized factor VIII and IX concentrates, which are produced from pooled plasma of Hungarian donors by ion-exchange chromatography. The clinical study has been accomplished in two steps: first we have demonstrated the biological efficacy of the concentrates in a phase IV trial. After that we followed 13 patients with severe haemophilia for 6 months in respect of virus-safety and inhibitor-induction. According to our results the recently developed domestic FVIII/FIX concentrates display appropriate biological activities and they are safe as blood-borne virus-transmission and immunogenicity are concerned.

[Indirect methods in the genetic diagnosis of hemophilia A]. / Indirekt módszerek a haemophilia A genetikai diagnosztikájában.

In haemophilia A (HA), besides the direct detection of the most common mutation of the factor VIII gene (the gene inversion), it was necessary to establish indirect methods which are suitable to reveal the pattern of inheritance of the genes examined, regardless of the mutations they carry. This task can be achieved by the analysis of DNA polymorphisms located within and in the near proximity of the factor VIII gene. For diagnostic purposes we used an RFLP and two microsatellite polymorphisms. The aim of our program is to provide carrier and also prenatal diagnostics for affected families. So far we completed the analyses of 15 HA patients and 68 of their family members, and we gave prenatal diagnoses in 3 cases. According to the information content of the polymorphisms used, we expect to be able to provide DNA diagnoses to 95% of the Hungarian HA families requesting the test.

Development of the Woman Abuse Screening Tool for use in family practice.

BACKGROUND: This study developed a screening tool for use by family physicians to identify and assess women patients experiencing emotional and/or physical abuse by their partner. METHODS: An initial set of eight questions developed for the Woman Abuse Screening Tool (WAST) was completed by both abused and non-abused women. Participants were also asked to indicate their comfort in answering the questions in both research and family practice contexts. They also completed the Abuse Risk Inventory and a demographic questionnaire. Analysis of the WAST included 1) standard assessment of the validity and reliability of the measure and 2) examination of the efficacy of further reducing the number of questions on the WAST for screening purposes. RESULTS: The final samples of abused (n = 24) and non-abused women (n = 24) differed significantly on a number of demographic and abuse variables. After eliminating one of the original items, a strong single factor structure was identified for the WAST that accounted for 85% of the total variance in responses to the WAST items. The WAST was found to be a highly reliable measure; coefficient alpha was estimated at.95. The scale also demonstrated construct and discriminant validity. The abused women reported being less comfortable responding to the WAST questions, in both the research and family practice contexts, than the non-abused women. The two WAST questions the abused women reported being most comfortable with were used to construct the WAST-Short for initial screening purposes. The WAST-Short correctly classified 100% of the non-abused women and 91.7% of the abused women. CONCLUSIONS: The WAST demonstrated good reliability and validity and discriminated between abused and non-abused women. Development of the WAST-Short provides physicians with a relatively unobtrusive screening tool for assessing abuse. The use of additional WAST questions can be used to further explore the possibility that a woman patient is experiencing abuse by her partner. Further study includes field testing the WAST in the family practice setting.

Focus groups in family practice research: an example study of family physicians' approach to wife abuse.

Focus groups have been extensively used in marketing research and recently adapted for studies in the behavioral sciences and primary care. The purpose of this paper is two-fold: 1) to describe the application of focus group methodology to research in family practice, and 2) to demonstrate the use of this qualitative method to examine a specific issue--family physicians' approach to wife abuse.

Microheterogeneity of antithrombin III: effect of single amino acid substitutions and relationship with functional abnormalities.

Microheterogeneity of antithrombin III (AT-III) was investigated by crossed immunoelectrofocusing (CIEF) on eleven molecular variants. A normal pattern was found in five variants while two different abnormal CIEF patterns were found in the other four and two variants, respectively. Point mutations causing a major pI change (exceeding 4.0) of the amino acid substituted lead to alterations in the overall microheterogeneity. The variants thus substituted share a first type of abnormal CIEF pattern with alterations throughout the pH range, regardless of the location of the mutation (reactive site and adjacent regions or heparin binding region). Minor amino acid pI changes in these regions do not alter the AT-III overall microheterogeneity, whatever the resulting functional defect. However, if the mutation is placed in the region around positions 404 or 429, then even minor changes of the amino acid pI seem able to alter the overall charge, leading to a second type of abnormal CIEF pattern with the main alteration at pH 4.8-4.6. Neuraminidase treatment leads to disappearance of microheterogeneity except for the variants with the Arg393 to Cys substitution. Addition of thrombin induces CIEF modifications specifically related to the functional defect. A normal formation of thrombin-antithrombin complexes induces a shift towards the more acid pH range, whereas in the variants substituted at the reactive site the CIEF pattern is substantially unaffected by thrombin; variants substituted at positions 382-384 show a maximal thrombin-induced increase of the isoforms at pI 4.8-4.6. Therefore mutant antithrombins with different functional abnormalities but sharing a common CIEF pattern were well distinguished.(ABSTRACT TRUNCATED AT 250 WORDS)

(ATT) trinucleotide repeats in the antithrombin gene and their use in determining the origin of repeated mutations.

Two (ATT) trinucleotide repeat polymorphisms have been identified in the tails of Alu repeat elements in intron 5 of the antithrombin gene. The frequency and distribution of allele sizes for the Alu 5 and Alu 8 tail polymorphisms have been defined in a sample Caucasian population. The Alu 5 polymorphism has two alleles while that of Alu 8 has 10 alleles with a heterozygosity of 0.83. These polymorphisms have been used in combination with four previously described polymorphisms within the antithrombin gene to construct antithrombin gene haplotypes in the sample Caucasian population. Twenty-two different haplotypes were observed, with the Alu 8 polymorphism being particularly useful in subdividing the core haplotype based on the previously identified polymorphisms. The haplotype data were used to investigate the origin of repeat mutations within the antithrombin locus. We compared the haplotypes associated the mutant antithrombin genes in five families with the mutation 2759C-->T (L99F) and five families with the mutation 5381C-->T (R129Stop). The mutation 2759C-->T (L99F), which occurs within a non-CpG dinucleotide, was carried on a gene associated with an identical haplotype in each of the five families. The mutation 5381C-->T (R129Stop), a single base substitution within a CpG dinucleotide, was associated with at least two different haplotypes. The findings suggest a founder effect in the five families sharing the 2759C-->T (L99F) and at least two independent origins for the CpG dinucleotide mutation 5381C-->T (R129Stop).

Generation of activated protein C during thrombolysis.

The observation that urokinase infusion increases circulating levels of the anticoagulant activated protein C (APC) in baboons implies that APC might be elevated during thrombolytic therapy. Patients undergoing coronary thrombolysis showed an 11-fold increase (means from 6 to 69 micrograms/L) in APC during infusion of streptokinase. Thrombolytic therapy thus generates at least two potent antithrombotic factors in the circulation--the fibrinolytic enzyme, plasmin, and the anticoagulant enzyme, APC. APC may help prevent reocclusion during or after thrombolysis.

Identifying and treating wife abuse.

BACKGROUND: Wife abuse, acknowledged as a critical problem in our society, is often undetected by family physicians. The purpose of this study was to identify the problems and potential solutions encountered by family physicians in the identification and treatment of wife abuse in London, Ontario. METHODS: Family physicians in London were recruited to participate in four focus groups. The groups' discussions were audiotaped and transcribed. The transcripts were analyzed using qualitative methodology to determine relevant themes. RESULTS: Thirty-two physicians (16 male and 16 female) participated in the focus groups. The majority were in group practice (81%). The average number of years in practice was 11.75. An analysis of the focus group session identified two major clinical themes with subcategories: (1) physician issues (ie, identification, treatment); and (2) patient issues (ie, barriers to identification, symptom presentation). CONCLUSIONS: The focus groups served as an effective method to engage family physicians in isolating their own as well as their patients' difficulties in confronting this serious problem.

A no bleed implant.

Breast implants have evolved from the original saline-filled, smooth-surfaced silicone rubber bag to silicone gel-filled smooth-walled sacs to a combination of a silicone gel-filled bag within a saline-filled sac, and, most recently, a reversed, double-lumen implant with a saline bag inside of a gel-filled bag. Texture-surfaced implants were first used in 1970 when the standard silicone gel-filled implant was covered with a polyurethane foam. Because of concerns about the degradation products of this foam, they were removed from the market in 1991. In 1975 double-lumen silicone textured implants were developed, followed by silicone gel-filled textured implants. In 1990 a new radiolucent, biocompatible gel was produced that reduced the problem of radioopacity of silicone implants. Because of the gel's sufficiently low coefficient of friction, leakage caused by fold flaw fracture may also be decreased. We present a case where this new biocompatible gel implant was repositioned after four months. The resulting scar capsule in this soft breast was thin [< 0.002 cm (0.008 in.)] and evenly textured as a mirror image of the textured silicone surface. Scanning electron microscopy and x-ray defraction spectrophotometry revealed no silicone bleed.

Pleiotropic effects of antithrombin strand 1C substitution mutations.

Six different substitution mutations were identified in four different amino acid residues of antithrombin strand 1C and the polypeptide leading into strand 4B (F402S, F402C, F402L, A404T, N405K, and P407T), and are responsible for functional antithrombin deficiency in seven independently ascertained kindreds (Rosny, Torino, Maisons-Laffitte, Paris 3, La Rochelle, Budapest 5, and Oslo) affected by venous thromboembolic disease. In all seven families, variant antithrombins with heparin-binding abnormalities were detected by crossed immunoelectrophoresis, and in six of the kindreds there was a reduced antigen concentration of plasma antithrombin. Two of the variant antithrombins, Rosny and Torino, were purified by heparin-Sepharose and immunoaffinity chromatography, and shown to have greatly reduced heparin cofactor and progressive inhibitor activities in vitro. The defective interactions of these mutants with thrombin may result from proximity of s1C to the reactive site, while reduced circulating levels may be related to s1C proximity to highly conserved internal beta strands, which contain elements proposed to influence serpin turnover and intracellular degradation. In contrast, s1C is spatially distant to the positively charged surface which forms the heparin binding site of antithrombin; altered heparin binding properties of s1C variants may therefore reflect conformational linkage between the reactive site and heparin binding regions of the molecule. This work demonstrates that point mutations in and immediately adjacent to strand 1C have multiple, or pleiotropic, effects on this serpin, leading ultimately to failure of its regulatory function.

Antithrombin Budapest 3. An antithrombin variant with reduced heparin affinity resulting from the substitution L99F.

The molecular basis and functional properties of a variant antithrombin (AT) protein. AT Budapest 3, were studied. A single base substitution was identified in codon 99, CTC----TTC, altering the normal leucine to phenylalanine. The proband presented with a history of venous thrombotic disease and was found to be homozygous for the mutation. The variant protein demonstrated reduced heparin affinity and reduced antiproteinase activity in the presence of either unfractionated heparin or the AT-binding heparin pentasaccharide, when compared to normal AT. A small change in the isoelectric point was also identified. The substituted amino acid residue of AT Budapest 3 is located near to the proposed AT heparin binding site, and it is suggested that reduced heparin affinity of the variant protein may result from substitution-induced distortion of positive charge geometry in the binding site and/or changes in its position relative to the rest of the inhibitor molecule.

Antithrombin III Budapest: a single amino acid substitution (429Pro to Leu) in a region highly conserved in the serpin family.

Antithrombin III (AT) is a major plasma serine protease inhibitor and a member of the serpin family of proteins. We have characterized the molecular and genetic basis of AT Budapest, an inherited variant of AT that is associated with thrombotic disease in affected family members. A single amino acid substitution, 429Pro to Leu, was identified, occurring in a region of the molecule that is highly conserved in members of the serpin family. Two forms of variant protein were present in approximately equal amounts in the plasma of the propositus, who is homozygous for the mutation. One form, which had apparently normal Mr, bound heparin strongly and retained some residual thrombin inhibitory activity. The other form had only weak heparin affinity and no antiproteinase activity, and had slightly decreased mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under nonreducing conditions; this normalized in the presence of a reducing agent, suggesting it was caused by a change in conformation. Additional support for a difference in conformation of the two forms of variant was provided by the finding that the fraction that bound heparin-Sepharose was recognized by a monoclonal antibody raised against normal AT, whereas the weak-affinity fraction was not.

[Homozygous (or double heterozygous) antithrombin III defect: AT-III, Budapest 4]. / Homozygota (vagy dupla heterozygota) antithrombin-III defektus: AT-III, Budapest 4.

A quantitative-qualitative AT-III deficiency was found in a young woman with severe thromboembolic episodes. Only AT-III molecules with a low heparin affinity were detected in her plasma and these pathological AT-III molecules could not increase the rate of the thrombin-inactivation at all. The pathological AT-III molecules were present in the blood of her father and one of her sisters, but only in a 50% quantity, the other half of the AT-III molecules proved to be functionally normal. The mother of the proposita had deceased earlier, thus she could not be investigated. However, the authors suggest a heterozygous state for her as well, because this assumption can explain the homozygous (or double heterozygous) state of the proposita. In accordance with the convention, this abnormality was designated as AT-III Budapest 4, and the exact biochemical and genetic background of the disorders can be clarified only by further investigations.