False-positive fecal immunochemical test results in colorectal cancer screening and gastrointestinal drug use.

PURPOSE: The study aimed to determine the influence of drug treatments (proton pump inhibitors [PPIs] combined with other drugs) on the false-positive (FP) rate in the fecal immunochemical test (FIT). METHODS: Patients undergoing colonoscopy in the setting of a CRC screening program due to a positive FIT result were included prospectively. Demographic data and drug intake of PPIs, antiplatelet therapy (APA), anticoagulants, selective serotonin reuptake inhibitors (SSRIs), and nonsteroidal anti-inflammatory drugs (NSAIDs) were collected. An FP FIT result was considered normal colonoscopy or with nonneoplastic pathology (NNP). Logistic regression models were used to evaluate the effect of these drugs on the rate of FP FIT results. RESULTS: We included 515 patients, and 59% (304/515) were males. The rate of FP FIT results was 48% (249/515). Study drug use was higher in patients > 60 years old and females than in those < 60 years old and males (p < 0.001 and p = 0.049, respectively). Multivariate logistic regression revealed that female sex (OR = 2.7 95% CI 1.9-3.9), NNP (OR = 1.5 95% CI 1.1-2.2), and the use of any of the study drugs (OR = 1.4 95% CI 0.9-2.0) were independent risk factors for FP FIT results. The risk of FP FIT results was significantly higher in PPI users than in nonusers (OR = 1.8 95% CI 1.1-2.9), specifically when PPIs were combined with other drugs (OR = 2.01 95% CI 1.1-3.6) only in men. CONCLUSION: Female sex, NNP, and PPIs combined with other drugs in males were identified as independent risk factors for FP FIT results.

Effect of in-hospital glycemic variability on mortality in patients with diabetes. / Efecto de la variabilidad glucémica intrahospitalaria en la mortalidad de los pacientes con diabetes.

INTRODUCTION: The aim of this study was to evaluate the impact of mean blood glucose (MBG) and glycaemic variability (GV) during hospitalisation on mortality after discharge. MATERIAL AND METHODS: We conducted a retrospective longitudinal analytical cohort study that included patients discharged form a department of internal medicine with a diabetes-related diagnosis The evaluated prognosis was mortality. During hospitalisation, the patients' clinical, laboratory and glycaemic control-related variables were recorded (MBG, GV and hypoglycaemia). The GV was measured with the coefficient of variation (CV). We calculated the mortality rates for every 1000 patient-years and compared them with Kaplan-Meier curves. We determined the predictors of mortality by performing a Cox regression. RESULTS: The study included 276 patients with a mean age of 77.6 (SD, 10.2) years. The median outpatient follow-up duration was 2.7 years. In the multivariate analysis, an MBG >140mg/dl (HR, 1.72; 95% CI 1.14-2.61; p=.01) and a CV >0.29 (HR, 1.52; 95% CI 1.12-2.06; p=.006) but not the presence of hypoglycaemia were additively and independently associated with an increased risk of mortality. An MBG >140mg/dl with a CV >0.29 increased the mortality rates (123 vs. 317 per 1000 patient-year; p <.001) and the adjusted mortality risk (HR, 2.70; 95% CI 1.71-4.27; p<.001) compared with having an MBG ≤140mg/dl. CONCLUSION: The simultaneous presence of a high MBG level and CV constitutes a powerful tool for stratifying mortality risk after hospital discharge.

Putative Secondary Structure at 5'UTR as a Potential Antiviral Target against SARS-CoV-2.

SARS-CoV-2 is an enveloped positive-sense single-stranded RNA coronavirus that causes COVID-19, of which the current outbreak has resulted in a high number of cases and fatalities throughout the world, even vaccine doses are being administered. The aim of this work was to scan the SARS-CoV-2 genome in search for therapeutic targets. We found a sequence in the 5'UTR (NC\_045512:74-130), consisting of a typical heptamer next to a structured region that may cause ribosomal frameshifting. The potential biological value of this region is relevant through its low similarity with other viruses, including coronaviruses related to SARS-CoV, and its high sequence conservation within multiple SARS-CoV-2 isolates. We have predicted the secondary structure of the region by means of different bioinformatic tools. We have suggested a most probable secondary structure to proceed with a 3D reconstruction of the structured segment. Finally, we carried out virtual docking on the 3D structure to look for a binding site and then for drug ligands from a database of lead compounds. Several molecules that could be probably administered as oral drugs show promising binding affinity within the structured region, and so it could be possible interfere its potential regulatory role.

Anaphylaxis associated with the ingestion of Goji berries (Lycium barbarum).

Goji berry (wolfberry), a member of the Solanacea family, has been recently introduced in Western countries and its consumption has increased rapidly. The objectives of the study were to describe the cases of 2 patients who experienced allergic symptoms after Goji berry consumption, to identify the protein profile of the extract, to analyze the allergenic profile of individuals, and to determine cross-reactivity with other members of the Solanaceae family (tomato). We describe 2 cases of allergic reaction, 1 of which was an anaphylactic reaction, after Goji berry ingestion. A Goji berry extract was manufactured and immunochemically characterized. The patients were skin prick tested with a battery of common aeroallergens including mites, epithelia, and molds. Individuals were also skin prick tested with food allergens, including Goji berries. A positive skin prick test and specific immunoglobulin (Ig) E to Goji berry was detected in both cases. Serum samples recognized a 9-kDa band, probably related to lipid transfer proteins (LTPs). Cross-reactivity with tomato was analyzed by inhibition studies, which showed that the 9-kDa band was totally inhibited by the tomato extract. This study describes the first 2 cases of allergic reaction following Goji berry ingestion. LTPs seem to be involved in allergic sensitization to Goji berries, as evidenced by cross-reactivity with tomato.

Direct oral anticoagulants for the treatment and prevention of venous thromboembolism in patients with cancer: current evidence.

Venous thromboembolic disease (VTED) is a common and clinically important complication in patients with cancer, contributing to its mortality and morbidity. Direct oral anticoagulant agents (DOACs), including direct thrombin inhibitors and direct factor Xa inhibitors, are as effective as vitamin K antagonists for the treatment of VTED and are associated with less frequent and severe bleeding. They have advantages over low-molecular-weight heparin, but comparative long-term efficacy and safety data are lacking for these compounds. Recent randomized clinical trials suggest a role for DOACs in the treatment of VTED in patients with cancer. This review will discuss the existing evidence and future perspectives on the role of DOACs in the treatment of VTE based on the current evidence about their overall efficacy and safety and the limited information in patients with cancer; in addition, we will briefly review their pharmacokinetic properties with special reference to potential interactions.

Effect of in-hospital glycemic variability on mortality in patients with diabetes.

INTRODUCTION: The aim of this study was to evaluate the impact of mean blood glucose (MBG) and glycaemic variability (GV) during hospitalisation on mortality after discharge. MATERIAL AND METHODS: We conducted a retrospective longitudinal analytical cohort study that included patients discharged form a department of internal medicine with a diabetes-related diagnosis. The evaluated prognosis was mortality. During hospitalisation, the patients' clinical, laboratory and glycaemic control-related variables were recorded (MBG, GV and hypoglycaemia). The GV was measured with the coefficient of variation (CV). We calculated the mortality rates for every 1000 patient-years and compared them with Kaplan-Meier curves. We determined the predictors of mortality by performing a Cox regression. RESULTS: The study included 276 patients with a mean age of 77.6 (SD, 10.2) years. The median outpatient follow-up duration was 2.7 years. In the multivariate analysis, an MBG > 140 mg/dL (HR = 1.72; 95% CI 1.14-2.61; p = .01) and a CV > 0.29 (HR = 1.52; 95% CI 1.12-2.06; p = .006), but not the presence of hypoglycaemia, were additively and independently associated with an increased risk of mortality. An MG > 140 mg/dL with a CV > 0.29 increased the mortality rates (123 vs. 317 per 1000 patient-year; p < .001) and the adjusted mortality risk (HR = 2.70; 95% CI 1.71-4.27; p < .001) compared with having an MBG ≤ 140 mg/dL. CONCLUSION: The simultaneous presence of a high MBG level and CV constitutes a powerful tool for stratifying mortality risk after hospital discharge.

Clinical outcomes of FOLFIRINOX and gemcitabine-nab paclitaxel for metastatic pancreatic cancer in the real world setting.

BACKGROUND/OBJECTIVES: The incidence of pancreatic cancer is increasing in developed countries. The incorporation of new therapies, to the first-line treatment of patients with good performance status led to better survival in clinical trials. However, there is a wide variability in their use and some concerns about the treatment of elderly patients who were not included in the clinical trials. METHODS: This is a retrospective multicenter study. Data from consecutive patients diagnosed with metastatic pancreatic cancer (mPC) treated with FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (GnP) were analysed to evaluate efficacy (overall survival-OS) and toxicity. RESULTS: A total of 119 patients were included. 49.6% were treated with FFX and 50.4% with GNP in first-line. The median OS was 12 months with no statistically significant differences between both regimens (12.7 m for FFX vs 10.2 m for GnP). Elevated Ca 19.9 levels and neutrophil-lymphocyte ratio (NLR) increased the risk of death. Patients who received both regimens in first/second line had a median OS longer than 15 months whichever the sequence. 32 patients (27%) were older than 70-y. 54% patients received a second-line treatment, 56% in the FFX group and 44% in the GnP group. The median OS for patients older than 70 was 9.5 m versus 12.3 m for patients younger than 70. Progression of the disease was the cause of death in 67.6% of the patients. CONCLUSIONS: In our setting, the use of FFX and GnP for treating mPC is quite similar, but superiority could not be demonstrated for any of the schemes in the first line. OS was determined by basal levels of Ca 19.9 and NLR. Patients receiving both regimens in first/second line whichever the sequence, exhibited the best survival rates. In our series, elderly patients had poorer survival rates.

[Pneumonitis associated to methotrexate]. / Neumonitis secundaria a metotrexate.

Methotrexate (MTX) is a folic acid antagonist that inhibits cellular reproduction. MTX has been shown to be an effective anti-inflammatory agent. Acute interstitial pneumonitis is the main pulmonary side effect during MTX treatment. We report a case of MTX pneumonitis in a 56-year old woman with autoimmune thrombocytopenia who presented with subacute nonproductive cough, dyspnea at rest, fever, and malaise. Chest roentgenogram demonstrated bilateral diffuse interstitial and alveolar infiltration. Infectious diseases were ruled out and methotrexate-induced pneumonitis was suspected. MTX was discontinued and methylprednisolone was prescribed. Patient improved progressively. After eight weeks, radiologic abnormalities and symptoms had disappeared.

Pleiotropic effects of heparins: does anticoagulant treatment increase survival in cancer patients?

The association between venous thromboembolism (VTE) and cancer has been recognized for more than 100 years. Numerous studies have been performed to investigate strategies to decrease VTE incidence and to establish whether treating VTE impacts cancer progression and overall survival. Accordingly, it is important to understand the role of the hemostatic system in tumorigenesis and progression, as there is abundant evidence associating it with cell survival and proliferation, tumor angiogenesis, invasion, and dissemination, and metastasis formation. In attempts to further the scientific evidence, several studies examine survival benefits in cancer patients treated with anticoagulant therapy, specifically treatment with vitamin K antagonists, unfractionated heparin, and low-molecular-weight heparin. Several studies and meta-analyses have been conducted with a special focus on brain tumors. However, no definitive conclusions have been obtained, and more well-designed clinical trials are needed.

Analysis of human antitopoisomerase-I idiotypes.

Antibodies to topoisomerase-I are present in approximately 26% of patients with scleroderma and are rarely found in patients with other diseases. In the current study, the expression of the antitopoisomerase-I (antitopo-I) idiotype from two scleroderma patients (E.M. and S.G.) and from a healthy individual (N.M.) were studied. Idiotype EM-SCL was restricted to the three classes of antitopo-I, whereas idiotypes SG-SCL and NM were found in all classes of antitopo-I as well as in their non-antitopo-I Igs. Sera from 9 of 10 antitopo-I-positive unrelated scleroderma patients expressed idiotype SG-SCL and some also expressed idiotype NM. Sera from N.M.'s 3 daughters and from 7 of 18 nonrelated normals expressed idiotype NM in the three immunoglobulin classes of non-antitopo-I. Two of the antitopo-I antibodies expressed a cross-reacting idiotype (CRI) that is present in non-antitopo-I antibodies from the same donor. Contrary to the natural CRI, SG-SCL's CRI is closely associated with the antigen binding site. Antitopo-I idiotypes are on the heavy chains. Like many other autoantibodies, Id-SG-SCL use VH4.2-1, DXP1, and JH4 in germline configuration.

An experimental study for biological nitrogen removal and control strategies in a sequencing batch reactor (SBR).

The aim of this work is to present an overview about an experimental study for biological nitrogen removal implemented in a pilot-scale plant, located in the Universidad Del Norte in Barranquilla, Colombia. This plant was studied in two different periods. The first period, which was carried out in 90 days, was dedicated to study the influence of the daily variations on the influent and effluent wastewater, and prove some control routines for nitrogen removal. In the second period, which was carried out in 120 days, the removal process was optimized with the addition of acetic acid as an external carbon source, and the implementation of the final control strategy was performed based on the results of the previous period.

Hepatocarcinoma fibrolamelar. Revisión de sus características diferenciales a partir de nuestra serie / Fibrolamellar hepatocellular carcinoma. Differencial characteristics based on our own case series

Introducción. El hepatocarcinoma fibrolamelar (CHCFL) es un tumor infrecuente, de aparición en adultos jóvenes y sobre hígado sano. Clásicamente considerado una variante del carcinoma hepatocelular (CHC), difieren en tantos aspectos, que debieranconceptuarse como entidades diferentes. El objetivo de este trabajo es refrescar sus características, haciendo hincapié en las diferenciales, para ser tenido en consideración ante lesiones hepáticas sólidas ocupantes de espacio en pacientes jóvenes. Material ymétodo.Estudio descriptivo retrospectivo de las características de 5 casos de CHCFL intervenidos en la unidad de cirugía hepatobiliopancreática un hospital de tercer nivel. Resultados. Cinco casos, edad media 31.8 años, mujer/hombre 4/1. Todos ellos sobrehígado sano, con clínica inespecífica. Radiológicamente e histopatológicamente cumplen las características típicas de este tumor.Sometidos en todos los casos a resecciones quirúrgicas amplias, y reintervenidos, por recidiva, 2 casos, uno de ellos en forma detrasplante hepático. La tabla 1 recoge todas las características epidemiológicas y clínicas, datos operatorios y supervivencia globaly libre de enfermedad de los pacientes incluidos en el estudio. Discusión. De curso clínico insidioso y silente en muchas ocasiones,el diagnóstico suele ser tardío, con grandes masas tumorales en las pruebas de imagen. Actualmente el tratamiento quirúrgico esel único potencialmente curativo. Pese a una supervivencia prolongada, la tasa de recidiva es muy elevada, precisando en muchoscasos intervenciones reiteradas. Los resultados en nuestra serie son acordes con la literatura y podrían calificarse como paradigmade las características anatomoclínicas, terapéuticas y pronósticas de este tipo de tumor. (AU)

Introduction. Fibrolamellar hepatocellular carcinoma is an infrequent tumour, which appears in young adults and on healthy liver.It has been classically considered a subtype of hepatocellular carcinoma, but they differ in such many aspects they could be considered separately. The objective of this review is to refresh its differential characteristics in order to take into account in the differentialdiagnosis of hepatic solid lessions in young adults. Material and methods. Descriptive retrospective study of the principles characteristics of the five fibrolamellar hepatocellular carcinoma operated patients by the hepatobilliary surgery team of our hospital.Results. Five cases, medium age 31.8 years, women/men 4/1. All of them in healthy liver with inespecific symptoms and radiollogicaland hystopathological typical characteristics. All of them having enlarged hepatic ressections and reoperated two of them becauseof recurrence, in one case in form of hepatic transplantation. Table 1 collect all the epidemiological and clinical characteristics, operation reports, global and recurrence free survival of all patientes included in the study. Discussion. Having insidious and silentdevelopment in many cases, diagnosis can be delayed, appearing big tumoral masses on the imaging tests. Nowadays, surgery is the only curative treatment. Despite long survival periods, the recurrence rate is very high, needing sometimes being reoperated. Our results are in the line of the literature results and could be classified as the paradigm of anatomoclinic, therapeutic and prognostic characteristics of this type of tumour. (AU)

Direct oral anticoagulants for the treatment and prevention of venous thromboembolism in patients with cancer: current evidence

Venous thromboembolic disease (VTED) is a common and clinically important complication in patients with cancer, contributing to its mortality and morbidity. Direct oral anticoagulant agents (DOACs), including direct thrombin inhibitors and direct factor Xa inhibitors, are as effective as vitamin K antagonists for the treatment of VTED and are associated with less frequent and severe bleeding. They have advantages over low-molecular-weight heparin, but comparative long-term efficacy and safety data are lacking for these compounds. Recent randomized clinical trials suggest a role for DOACs in the treatment of VTED in patients with cancer. This review will discuss the existing evidence and future perspectives on the role of DOACs in the treatment of VTE based on the current evidence about their overall efficacy and safety and the limited information in patients with cancer; in addition, we will briefly review their pharmacokinetic properties with special reference to potential interactions (AU)

Positron emission tomography: useful in detecting metastatic cancer of unknown primary site.

Metastatic cancer of unknown primary site represents approximately three percent of all new cancer diagnoses. Expensive and invasive diagnostic procedures are often performed although the primary tumour is detected in less than 25 percent of cases. We present a 63-year-old woman presenting with low back pain and was found on positron emission tomography (PET) to have lung cancer. The pros and cons of PET in the diagnostic process of patients with metastatic cancer of unknown primary site are reviewed. PET should be considered in the diagnostic process of patients with unknown primaries, and unnecessary invasive procedures may be avoided.

Prognostic importance of glycaemic variability on hospital mortality in patients hospitalised in Internal Medicine Departments.

INTRODUCTION: The objective was to assess the prognostic importance of various glycaemic control measures on hospital mortality. MATERIAL AND METHODS: Retrospective, analytical cohort study that included patients hospitalised in internal medicine departments with a diagnosis related to diabetes mellitus (DM), excluding acute decompensations. The clinical endpoint was hospital mortality. We recorded clinical, analytical and glycaemic control-related variables (scheduled insulin administration, plasma glycaemia at admission, HbA1c, mean glycaemia (MG) and in-hospital glycaemic variability and hypoglycaemia). The measurement of hospital mortality predictors was performed using univariate and multivariate logistic regression. RESULTS: A total of 384 patients (50.3% men) were included. The mean age was 78.5 (SD, 10.3) years. The DM-related diagnoses were type 2 diabetes (83.6%) and stress hyperglycaemia (6.8%). Thirty-one (8.1%) patients died while in hospital. In the multivariate analysis, the best model for predicting mortality (R(2)=0.326; P<.0001) consisted, in order of importance, of age (χ(2)=8.19; OR=1.094; 95% CI 1.020-1.174; P=.004), Charlson index (χ(2)=7.28; OR=1.48; 95% CI 1.11-1.99; P=.007), initial glycaemia (χ(2)=6.05; OR=1.007; 95% CI 1.001-1.014; P=.014), HbA1c (χ(2)=5.76; OR=0.59; 95% CI 0.33-1; P=.016), glycaemic variability (χ(2)=4.41; OR=1.031; 95% CI 1-1.062; P=.036), need for corticosteroid treatment (χ(2)=4.03; OR=3.1; 95% CI 1-9.64; P=.045), administration of scheduled insulin (χ(2)=3.98; OR=0.26; 95% CI 0.066-1; P=.046) and systolic blood pressure (χ(2)=2.92; OR=0.985; 95% CI 0.97-1.003; P=.088). CONCLUSION: An increase in initial glycaemia and in-hospital glycaemic variability predict the risk of mortality for hospitalised patients with DM.

[Evaluation of the effectiveness of a protocol designed to improve glycemic control in hospitalized internal medicine patients with hyperglycemia]. / Evaluación de la eficacia de un protocolo destinado a mejorar el control glucémico de los pacientes con hiperglucemia ingresados en servicios Hospitalarios.

BACKGROUND: Our aims were to assess the effectiveness of a diabetes (DM) management protocol to increase scheduled insulin therapy and to improve glycemic inpatient control. PATIENTS AND METHODS: We designed an analytical retrospective cohort study comparing 2 groups of medical services hospitalized patients with a primary of secondary discharge diagnosis of DM, before (group PRE) and after (group POS) the delivery of a DM management protocol. We analyzed the quality of attention by process indicators (cumulative probability of receive scheduled insulin therapy, evaluated with Kaplan-Meier analysis) and result indicators (adjusted glucose differences (group POS - group PRE), evaluated with multivariate regression models). RESULTS: A number of patients (355) were included (228 group PRE and 127 group POS). The median time to scheduled insulin regimen beginning was 1 (CI 95%: 0-2.5) day in group POS and 4 (CI 95%: 2-6) days in group PRE (p=0.056). First 48 hours mean glucose in patients without scheduled insulin therapy was lower in group POS than in group PRE (163.9 versus 186.7 mg/dl; p=0.025). The first 24 hours mean glucose was significantly lower in patients of group POS, with a difference between both groups of -24.8 mg/dl (CI 95%: -40.5-(-9); p=0.002). Stratified analysis showed statistically significant mean in-hospital glucose difference only in the nothing by mouth situation (-29.8 mg/dl; CI 95%: -58.9-(-0.6); p=0.045). CONCLUSION: The delivery of an institutional protocol can improve hospitalized DM patients management quality.

Autoantibodies in systemic sclerosis.

There are 3 major autoantibodies in sera from patients with scleroderma: 1) anticentromere antibodies (ACA), 2) anti-topoisomerase I (anti-topo I), and 3) anti-RNA polymerases. Each is present in about 25% of patients and are mutually exclusive. ACA are found in patients with primary and secondary Raynaud's disease and in patients with primary biliary cirrhosis. Anti-topo I and anti-RNA polymerases are found exclusively in scleroderma. Each autoantibody is present in specific subsets of scleroderma patients. ACA and anti-topo I have been well studied and their presence and titer are stable over time. The anti-topo I and ACA are of all three isotypes, recognize multiple epitopes on the antigens and have stable cross reactive or private idiotypes. The antigen, topoisomerase I, has domains which have homology to viral proteins. Other autoantibodies predominantly recognize nucleolar antigens, are found in less than 15% of patients, and are not specific for scleroderma.

Distinctive features of idiopathic inflammatory myopathies in French Canadians.

This is the first report on idiopathic inflammatory myopathies (IIM) in French Canadians. We reviewed retrospectively 30 French Canadian adults (20 women and 10 men) with IIM seen consecutively over 12 years. The median age at diagnosis was 45 years. The IIM were 8 (27%) primary polymyositis (PM), 9 (30%) primary dermatomyositis (DM), 5 (17%) IIM with neoplasia (lymphoma, breast, esophageal, colonic, and skin cancer) and 8 (27%) IIM with a connective tissue disease (4 with systemic sclerosis, 2 with mixed connective tissue disease, and 2 with rheumatoid arthritis). The most common presenting symptom was proximal muscle weakness (n = 10,33%). Of the remaining 20 patients, 6 (20%) had the onset of their weakness within 1 month of the presenting symptom. Only 3 (10%) patients did not have proximal muscle weakness. Twenty-six (87%) patients had weakness in the pelvic girdle, 25 (83%) in the shoulder girdle, and 7 (23%) in the neck muscles. Other common symptoms included dyspnea on exertion and dysphagia, each present in 13 (43%) patients. Gottron's papules and the heliotrope rash were the most common skin lesions documented in 11 (37%) and 10 (33%) patients, respectively. The serum creatine kinase (CK) level was between 171 and 1,000 U/L in 13 (43%) patients and between 1,001 and 6,000 U/L in 13 (43%) patients. Antinuclear antibodies (ANA) on HEp-2 cells were positive in 16 (53%) patients, of which 2 (13%) expressed autoantibodies to nuclear pore complexes. Autoantibody specificities were anti-La (n = 4, 13%), anti-U1RNP (n = 3, 10%), and anti-Ro (n = 2, 7%). None of the patients expressed anti-Jo-1, anti-topoisomerase I, or anticentromere antibodies. Twenty-eight (93%) patients received corticosteroid therapy, and 8 (27%) patients responded to prednisone alone. Thirteen (43%) patients were treated with methotrexate, and 9 (69%) responded. The mean follow-up was 62 months: 23 (77%) had their disease controlled, 3 (10%) patients were lost to follow-up, and 4 (13%) died (no death occurred because of IIM or its treatment). Therapy was discontinued because of remission in 5 (17%) patients. Cumulative survival rates at 2, 5, and 10 years were 89%, 89%, and 85%, respectively. The presence of autoantibodies to nuclear pore complexes and anti-La autoantibodies, the rare occurrence of anti-Jo-1 autoantibodies, the response to conventional therapies, and a high survival rate may distinguish IIM in French Canadians from that of other reported series.

Idiotypic analysis of human anti-topoisomerase I autoantibodies.

Anti-topoisomerase I autoantibodies (anti-topo I) are associated with proximal scleroderma and are of prognostic significance in patients with Raynaud's phenomenon. Polyclonal anti-idiotypic sera were raised against affinity-purified anti-topo I from 2 patients with scleroderma (EM, SG) and 1 healthy individual (NM). All 3 anti-topo I preparations expressed immunodominant private Ids in or near the antigen binding site of the autoantibody. Further analysis of Id-EM showed isotypic restriction to IgG and a stable Id-expression over the course of 9 years. Id-SG and Id-NM were expressed on IgG and on IgA. The idiotypic character of anti-topo I closely resembles that of anti-centromere autoantibodies which are associated with the CREST syndrome of scleroderma. The data suggest an antigen-driven process in the origin of autoantibodies in scleroderma.