Presumed Etiology Research Articles

Molecular characterization of the largest mycoviral-like double-stranded RNAs associated with Amasya cherry disease, a disease of presumed fungal aetiology

The sequence of the four large (L) double-stranded RNAs (dsRNAs) associated with Amasya cherry disease (ACD), which has a presumed fungal aetiology, is reported. ACD L dsRNAs 1 (5121 bp) and 2 (5047 bp) potentially encode proteins of 1628 and 1620 aa, respectively, that are 37% identical and of unknown function. ACD L dsRNAs 3 (4458 bp) and 4 (4303 bp) potentially encode proteins that are 68% identical and contain the eight motifs conserved in RNA-dependent RNA polymerases (RdRp) of dsRNA mycoviruses, having highest similarity with those of members of the family Totiviridae. Both terminal regions share extensive conservation in all four RNAs, suggesting a functional relationship between them. As ACD L dsRNAs 1 and 2 do not encode RdRps, both are probably replicated by those from either ACD L dsRNA 3 or 4. Partial characterization of the equivalent L dsRNAs 3 and 4 associated with cherry chlorotic rusty spot revealed essentially identical sequences.

P21 Therapeutic Efficacy of Plasmapheresis for the Treatment of Refractory Pruritis of Primary Billiary Cirrhosis: 2 Case Reports.

Primary billiary cirrhosis (PBC), a chronic cholestatic disease of presumed autoimmune aetiology, is characterised by progressive intrahepatic bile duct destruction, liver cirrhosis, failure, and death, unless treated by liver transplantation. Distressing pruritis (skin itch), fatigue and metabolic bone diseases frequently complicate this disease, significantly reducing quality of life. The pathogenesis of pruritis remains uncertain. Some unknown pruritogen(s) produced by the liver have been implicated which accumulate in the plasma as a result of chronic cholestasis. Recent evidence also suggests a central mechanism, with increased neurotransmission/neuromodulation mediated by endogenous opioid agonists. Therapeutic interventions include unabsorbable oral resins, urso‐deoxycholeic acid, opiate antagonists and rifampicin. More experimental therapies include: partial diversion of bile; charcoal haemoperfusion; UVA; plasmapheresis and albumin‐based dialysis (for patients with renal impairment). We used plasma exchange for the treatment of intractable pruritis in two patients with primary billiary cirrhosis. Both were females between ages of 50–60 years, refractory to all medical treatments and severely disabled by intractable pruritis and fatigue. In the first patient, weekly to fortnightly plasmapheresis considerably reduced the intensity of itch and stabilized her condition until her liver transplant. The second patient was treated for a relapse of PBC following her liver transplant. She significantly improved with more than 50% reduction in the intensity of her generalized itch with healing of excoriations, and was able to sleep for 4 h undisturbed after only one procedure. We suggest that plasmapheresis may be helpful for the pruritis of chronic cholestasis refractory to medical management. It could also be considered for the initial treatment of selected patients in combination with other therapies.

AIDS Associated Arteriopathy as Etiology of Non-Infectious Recto-Colonic Ulcerations in an Adult

AIDS associated arteriopathy (AAA) of the gastrointestinal tract in adults has not been previously reported. We report the case of a young adult with AIDS and non-infectious recto-colonic ulcerations and postulate that the ulcerations may constitute a complication of AAA. Case Report: A 35 yo male with history of HIV with AIDS, non-Hodgkin's lymphoma, and MAI presented with fever, rectal pain and bleeding. Four months prior to admission, the patient underwent excision of a rectal ulcer, which revealed thick walled vessels with medial hypertrophy and intimal fibrosis within the granulation tissue. A few beaded acid-fast rods, consistent with Nocardia species were noted in adjacent crypts. Follow up colonoscopy revealed multiple ulcerations throughout the colon characterized microscopically as Candida associated colitis. The patient was treated for Nocardia and had complete resolution of his symptoms. 10 weeks later, he presented with diffuse abdominal pain and hematochezia. A repeat colonoscopy revealed a large, irregular fungating, friable cecal mass with biopsy changes similar to those in the rectal ulcer as well as luminal obliteration by organizing thrombi and no inflammation in the adjacent non-ulcerated cecal mucosa. Infectious, inflammatory and neoplastic etiologies were ruled out. The patient underwent a right hemicolectomy with ileo-colonic anastomosis with complete resolution of his pain. Microscopically, the cecal mass had vascular changes similar to those of the biopsy. AAA was the presumed etiology. Discussion: AAA is characterized by intimal fibrosis and fragmentation of the elastic fibers of medium sized arteries as well as fragmentation and calcification of the internal elastic membrane, with luminal narrowing. These changes have been described in children in organs such as the heart, lung, kidney, intestine, brain and spleen. Isolated cases complicated by coronary artery aneurysm, esophageal stricture and colonic perforation have been reported. Increased exposure to endogenous and exogenous elastases resulting from multiple infections secondary to the immunodeficiency in AIDS have been postulated as the pathogenetic mechanism. We report the first case of these vascular changes in the gastrointestinal tract of an adult with AIDS.

OP04.23: Impaired systolic and diastolic ventricular function after permanent extra‐embryonic venous obstruction, a pressure‐volume loop assessment in the stage‐24 chick embryo

Hydrops fetalis is the final common hemodynamic pathway for a variety of pathological states in the fetus, including high output states associated with fetal anemia or arterio-venous fistulas and abnormalities of both cardiac structure and rhythm. Hydrops fetalis secondary to cardiovascular decompensation is usually accompanied by elevations in fetal systemic venous pressure as evidenced by alterations in venous Doppler waveforms. We present two cases of severe fetal aortic stenosis with left ventricular fibroelastosis and mitral regurgitation and in utero closure or stenosis of the foramen ovale, with severe hydrops fetalis, despite normal systemic venous Doppler flow profiles. Both cases demonstrated markedly abnormal fetal pulmonary venous Doppler waveforms and after birth, both infants were hypoalbuminemic. The presence of normal systemic venous Doppler waveforms in fetuses with severe hydrops fetalis and structural cardiac disease challenges our understanding of the etiology of this pathological state. These cases have led us to reconsider the presumed etiology of cardiogenic hydrops fetalis in fetuses with severely impaired left ventricular pump function and secondary mitral regurgitation. We hypothesize that elevated pulmonary venous pressure, with only mildly increased central venous pressure, may negatively impact pulmonary lymphatic flow, decrease serum oncotic pressure due to loss of protein-rich fluid in the pulmonary interstitium, increase venous hydrostatic pressure, and lead to hydrops fetalis.

Virus discovery by sequence‐independent genome amplification

Genome sequences from several blood borne and respiratory viruses have recently been recovered directly from clinical specimens by variants of a technique known as sequence‐independent single primer amplification. This and related methods are increasingly being used to search for the causes of diseases of presumed infectious aetiology, but for which no agent has yet been found. Other methods that do not require prior knowledge of the genome sequence of any virus that may be present in the patient specimen include whole genome amplification, random PCR and subtractive hybridisation and differential display. This review considers the development and application of these techniques. Copyright © 2006 John Wiley & Sons, Ltd.

Vasospasm in Glaucoma: Clinical and Laboratory Aspects

During the last decade, the presumed etiology of glaucoma has moved from a pure pressure concept to a combined mechanical and vascular theory. Evidence of a localized vascular insufficiency leading to perfusion deficits of ocular structures, including the optic nerve head, the retina, the choroid, and the retrobulbar vessels, is now clear. This article evaluates the role of vasospasm as the primary cause of such a vascular failure. The role of both ocular and systemic vasospasms and their clinical correlations are discussed. At a cellular level, the function of the modulating role of the vascular endothelium is reviewed. Evidence of abnormalities of the vascular endothelium and its vasoactive peptides as a conduit for vasospasm is mounting. Herein lies exciting prospects for potential pharmacologic targets in future glaucoma management.

Autoimmune pancreatitis: proposal of IgG4-related sclerosing disease.

Autoimmune pancreatitis (AIP) is a peculiar type of pancreatitis of presumed autoimmune etiology. Many new clinical aspects of AIP have been clarified during the past 10 years, and AIP has become a distinct entity recognized worldwide. However, its precise pathogenesis or pathophysiology remains unclear. As AIP dramatically responds to steroid therapy, accurate diagnosis of AIP is necessary to avoid unnecessary surgery. Characteristic dense lymphoplasmacytic infiltration and fibrosis in the pancreas may prove to be the gold standard for diagnosis of AIP. However, since it is difficult to obtain sufficient pancreatic tissue, AIP should be diagnosed currently based on the characteristic radiological findings (irregular narrowing of the main pancreatic duct and enlargement of the pancreas) in combination with serological findings (elevation of serum γ-globulin, IgG, or IgG4, along with the presence of autoantibodies), clinical findings (elderly male preponderance, fluctuating obstructive jaundice without pain, occasional extrapancreatic lesions, and favorable response to steroid therapy), and histopathological findings (dense infiltration of IgG4-positive plasma cells and T lymphocytes with fibrosis and obliterative phlebitis in various organs). It is apparent that elevation of serum IgG4 levels and infiltration of abundant IgG4-positive plasma cells into various organs are rather specific to AIP patients. We propose a new clinicopathological entity, “IgG4-related sclerosing disease” and suggest that AIP is a pancreatic lesion reflecting this systemic disease.

Autoantibody profiles in microscopic colitis

The etiology of microscopic colitis is unclear; an autoimmune response and pharmacological induction have been proposed as possible mechanisms. We conducted a multicentre cross-sectional study to compare the antibody profiles of patients with collagenous and lymphocytic colitis with those of a control group. The medical histories and antibody profiles of 26 patients with collagenous and 16 patients with lymphocytic colitis were compared with the corresponding data of 43 controls without gastroenterological disease. Antibodies to the following structures were determined: intestinal goblet cells, antinuclear antibodies (ANA), antineutrophil cytoplasmic antibodies, anti-Saccharomyces cerevisiae antibody (ASCA), tissue transglutaminase, gliadin, pancreatic acini, glutamate decarboxylase, tyrosine phosphatase IA-2 and thyroid (microsomal anitbodies, MAB). Patients with collagenous and lymphocytic colitis had been treated significantly more often with H(2)-receptor antagonists and non-steroidal anti-inflammatory drugs (P = 0.026 and 0.014, respectively). Additional diseases of presumed autoimmune etiology were present in 43% (18/42) of patients. Comparison with the controls showed significantly more positive findings for ANA immunoglobulin G (IgG), gliadin immunoglobulin A (IgA) and ASCA (IgA and IgG) in patients with collagenous colitis but not in those with lymphocytic colitis. Collagenous colitis was associated with positive ASCA in 15% of patients and lymphocytic colitis in 13%. The autoantibodies investigated are of no diagnostic relevance to microscopic colitis. Positive ANA and strong associations with other autoimmune diseases point to an autoimmune etiology. H(2)-receptor antagonists and non-steroidal anti-inflammatory drugs might also be of pathogenetic significance.

New Manual Aids Diagnosis Of Sleep Disorders

New Manual Aids Diagnosis Of Sleep Disorders

A Comparison Between Post-Traumatic and Non-Traumatic Fibromyalgia

Objective: To compare clinical features of the fibromyalgia syndrome [FMS] patients of presumed traumatic etiology with those of non-traumatic origin, and correlate these findings with occupational status, using a prospective transversal study of symptom prevalences.Methods: Patients with FMS according to the American College of Rheumatology criteria were interviewed with a structured questionnaire about biodemographic characteristics, work and disability status, and the presence of 27 symptoms. They underwent pain evaluation by visual analog scale, pressure dolorimetry, and tender point count.Results: A total of 135 patients were evaluated, 48 with a history of trauma [group T] and 87 with a non-traumatic history [group NT]. Falls, automobile accidents, and aggressions were responsible for 13 of the traumatic events; work caused the other 35 events. Group T showed a longer period of formal education, but no other difference in terms of biodemographic data. A higher percentage of group T than group NT ind...

Use of Anti-Infective Drugs in Rheumatology

The clinical field of rheumatology utilizes numerous medications which are either structurally derived from antibiotic compounds or are actually originally track - record proven anti - infective agents adapted for use in this field. Though in many cases, exemplified by rheumatoid arthritis, a presumed infectious etiology brought about the introduction of these drugs into rheumatology, subsequent research has often failed to demonstrate an infectious agent; nevertheless such originally anti - infectious agents as hydroxychloroquine and sulfasalazine have gained a place in the rheumatologic armamentarium. This sequence of events implies that in many cases anti - infective agents posses anti - inflammatory or immuno - modulatory qualities not directly linked to their potential capacity to kill foreign pathogens. More recently agents such as cyclosporine and tacrolimus, both of antibiotic structure, have been developed specifically for their immuno - modulatory effects. This review covers the main events in the development of anti - infective agents for rheumatology and attempts to clarify the often enigmatic relationship between these two seemingly unrelated fields. Keywords: Rheumatology, sulfasalazine, hydroxychloroquine, minocycline, tetracylines, cyclosporine, tacrolimus, rheumatoid arthritis, systemic lupus erythematosus

Mortality in Patients with a First Unprovoked Seizure

The mortality after a first epileptic seizure is affected by the source of cases, the intensity of the diagnostic work-up, the type and the presumed etiology of the seizure, the length of follow-up, and the modalities of data collection (retrospective vs. prospective). We review the four studies of this topic. Four studies have been identified which focused on the mortality of the first unprovoked seizures or the first afebrile (provoked or unprovoked) seizure. These included two population-based surveys, one clinic-based community survey, and a randomized clinical trial on the treatment of the first unprovoked generalized tonic-clonic seizure. A standardized mortality ratio (SMR) of 2.3 (95% confidence interval, CI 1.5-3.3) for unprovoked first seizures was found in a retrospective cohort study in the population of Rochester, Minnesota. The SMR was higher during the first year after the seizures to progressively decrease thereafter. Acute symptomatic seizures carried the higher risk, followed by remote symptomatic seizures, while idiopathic and cryptogenic seizures carried no risk. The increased SMR found in women and in patients aged 0-19 years enrolled in the randomized trial differs from that seen in other mortality studies in epilepsy (SMR being highest in the youngest age groups) and may be a chance finding. Mortality is increased in patients with a first unprovoked seizure, particularly during the first year after the seizure. This increased mortality is associated with known etiology of the seizure, and is not present when etiology is unknown.

Pancreas Duct Abnormalities in Patients with Ulcerative Colitis.

The presumed etiology and prevalence of pancreatic abnormalities in patients with ulcerative colitis (UC) have been controversial. We conducted a controlled (cross-sectional) study of patients with UC compared with non-UC controls to determine the prevalence of pancreatic duct abnormalities in patients with UC and to determine if these are specific to UC using magnetic resonance cholangiopancreatography. Magnetic resonance cholangiopancreatography was performed on 79 unselected patients with UC and 45 non-UC controls, without a history of pancreatitis attack, between February 2000 and May 2003. Among patients with UC, the prevalence of pancreatic duct abnormalities was 16.4% (95% confidence interval, 8.3%-24.6%): coexisting dilatation and narrowing of the main pancreatic duct were found in 5; diffuse narrowing of pancreatic ducts in 5; and dilatation of pancreatic ductal branches in 3. These abnormalities were compatible with chronic pancreatitis. Among the controls, no pancreatic duct abnormality was found. Changes in the pancreatic duct were found in approximately one-sixth of patients with UC, none of whom had a history of overt pancreatitis. These pancreatic duct abnormalities are likely to be specific to patients with UC.

Antibiotic Use in Community-Based Pediatric Outpatients in Southern Region of Brazil

The irrational use of antibiotics is incriminated for the escalating antimicrobial resistance problem worldwide. This cross-sectional survey was conducted to describe patterns of antibiotic use in community-based pediatric outpatients in the southern region of Brazil. A sample of children (29 days to 18 years of age) was selected from each community-based outpatient clinic. Information related to antibiotic use in the child was obtained by interview with their parents using a structured questionnaire. Of 489 children, 201 (41.1 per cent) had received at least one antimicrobial course in the previous 2 months. The most commonly prescribed antibiotic was amoxicillin (54.0 per cent) and broad-spectrum agents were used in 15.3 per cent of antimirobial courses. Acute respiratory infections were the most frequent diagnosis for antibiotic prescribing (91.2 per cent), but at least 39.5 per cent were conditions of presumed viral etiology. Antibiotic use in the previous 2 months was more likely in children younger than 2 years (PR 1.36, 95 per cent CI 1.10-1.69); with chronic diseases (PR 1.38, 95 per cent CI 1.10-1.75); with higher paternal education level (PR 1.38, 95 per cent CI 1.11-1.72); with parents' pressure on physician for antibiotics (PR 1.66, 95 per cent CI 1.05-2.64) and with parental self-prescribing habit (PR 1.47, 95 per cent CI 1.06-2.04). Antibiotic use in children increased with mother's age (p=0.03 for linear trend). In conclusion, antibiotic prescribing is very common in community-based pediatric outpatients in the southern region of Brazil and inappropriate use is frequent. The independent risk factors for antibiotic use are child's age under 2 years, the presence of chronic diseases in the child, older mother, higher paternal education level, parents' pressure on physician and parental self-prescribing habit.

Fatores clínicos, etiológicos e evolutivos da audição na surdez súbita

Existem várias terapias preconizadas para o tratamento da surdez súbita, algumas apresentam riscos significativos necessitando inclusive de internação hospitalar. OBJETIVO: Este estudo prospectivo analisa aspectos clínicos, etiológicos e evolutivos nos casos de surdez súbita (SS) em pacientes tratados ambulatorialmente com medicação oral. FORMA DE ESTUDO: clínico com coorte transversal. MATERIAL E MÉTODO: 40 pacientes com perda súbita da audição submeteram inicialmente a avaliação clínica otorrinolaringológica, testes audiométricos, análise hematológica e ressonância magnética. Confirmado o diagnóstico de SS, todos os pacientes receberam inicialmente prednisona e pentoxifilina sendo acompanhados por pelo menos um ano. RESULTADO: 45% (n=18) apresentaram normalização dos limiares auditivos, 40% (n=16) apresentaram melhoras auditivas, 15% (n=6) mantiveram os mesmos limiares iniciais. Nove casos (22,5%) apresentaram manifestações clínicas que justificaram a perda auditiva (infecção viral, fatores imunomediados, alterações vasculares e outros), três (7,5%) apresentaram tumores na região do ângulo ponto-cerebelar. A evolução auditiva nestes 12 casos com etiologia presumida não apresentou diferença estatística significante em relação aos 28 casos sem etiologia definida. O tratamento clínico instituído nos primeiros sete dias de instalação da perda auditiva, nos pacientes que obtiveram melhora, foi o único parâmetro estatisticamente significante dos fatores prognóstico avaliado. CONCLUSÃO: A pesquisa exaustiva etiológica deve ser realizada em qualquer caso de perda auditiva neurossensorial aguda. A presença de 7,5% de tumores localizados na região do ângulo ponto-cerebelar nos casos de SS juntamente com outras causas tratáveis justifica a investigação clínica nestes pacientes. Nossos pacientes apresentaram uma boa melhora auditiva em 67,5% dos casos, independentemente da etiologia. O início da terapia nos primeiros sete dias de instalação da perda auditiva foi o único fator de melhora significante dos limiares auditivos.

Inflammatory Dilated Cardiomyopathy (DCMI)

Cardiomyopathies are heart muscle diseases, which have been defined by their central hemodynamics and macropathology and divided in five major forms: dilated (DCM), hypertrophic (HCM), restrictive (RCM), right ventricular (RVCM), and nonclassifiable cardiomyopathies (NCCM). Furthermore, the most recent WHO/WHF definition also comprises, among the specific cardiomyopathies, inflammatory cardiomyopathy as a distinct entity, defined as myocarditis in association with cardiac dysfunction. Idiopathic, autoimmune, and infectious forms of inflammatory cardiomyopathy were recognized. Viral cardiomyopathy has been defined as viral persistence in a dilated heart. It may be accompanied by myocardial inflammation and then termed inflammatory viral cardiomyopathy (or viral myocarditis with cardiomegaly). If no inflammation is observed in the biopsy of a dilated heart (< 14 lymphocytes and macrophages/mm(2)), the term viral cardiomyopathy or viral persistence in DCM should be applied according to the WHF Task Force recommendations. Within the German heart failure net it is the authors' working hypothesis, that DCM shares genetic risk factors with other diseases of presumed autoimmune etiology and, therefore, the same multiple genes in combination with environmental factors lead to numerous different autoimmune diseases including DCM. Therefore, the authors' primary goal is to acquire epidemiologic data of patients with DCM regarding an infectious and inflammatory etiology of the disease. Circumstantial evidence points to a major role of viral myocarditis in the etiology of DCM. The common presence of viral genetic material in the myocardium of patients with DCM provides the most compelling evidence, but proof of causality is still lacking. In addition, autoimmune reactions have been described in many studies, indicating them as an important etiologic factor. Nevertheless, data on the proportion of patients, in whom both mechanisms play a role are still missing.A pivotal role for autoimmunity in a substantial proportion of patients with DCM is supported by the presence of organ-specific autoantibodies, inflammatory infiltrates and pro-inflammatory cytotoxic cytokines. Furthermore, familial occurrence of DCM has been described in about 20-30% of cases, with the presence of autoantibodies and abnormal cytokine profiles in first-degree relatives with asymptomatic left ventricular enlargement. This suggests the involvement of a disrupted humoral and cellular immunity early in the development of the disease. A similar pattern of humoral and cellular immune dysregulation has been described in other autoimmune diseases. There is considerable evidence that genetic factors play an important role in the pathogenesis of DCM, either as contributors to the susceptibility to environmental factors or as determinants of functional and structural changes that characterize the phenotypic expression of the disease.Yet, it is not known whether the susceptibility to immunologically mediated myocardial damage reflects the presence of genetic risk factors shared by other autoimmune diseases. Preliminary investigations suggest, that this is the case, because the frequency of autoimmune disorders other than DCM was higher in first-degree relatives of the subjects with DCM including juvenile diabetes, rheumatoid arthritis, thyroiditis, psoriasis, and asthma. The nature of the genetic risk is undetermined and probably involves genes in the major histocompatibility (MHC) locus as well as other susceptibility loci. Therefore, the authors started their investigation with the search for MHC class 2 DQ polymorphisms in the peripheral blood of patients with DCM in parallel to the search for new interesting susceptibility loci by the use of the microarray analysis regarding genes responsible for inflammatory and autoimmune diseases. By this approach a new insight in the familial clustering of other autoimmune diseases in patients with DCM and in genetic predisposition can be expected.

Clinical, etiological and progression factors of hearing in sudden deafness

Out of the many forms of therapy for sudden deafness, some require hospitalization and present significant risks. This prospective study analyzes etiology and evolution in cases of sudden deafness (SD) where outpatient oral treatment was used. Clinical with transversal cohort. Forty cases of sudden hearing loss were followed for at least one year. All were submitted to initial clinical evaluation, auditory tests, routine blood analysis, and magnetic resonance imaging. All received initial treatment with pentoxifylline and prednisone. 45% (n=18) presented normal auditory thresholds, 40% (n=16) showed some improvement in hearing, 15% (n=6) maintained initial hearing level. Nine cases (22.5%) presented clinical conditions possibly implicated in hearing loss (viral infection, immunomediated hearing loss, vascular disorders, and so on); three (7.5%) had cerebellopontine tumors. Evolution of hearing in these 12 cases with presumed etiology presented no differences from hearing in the 28 cases without any known etiological factor. Clinical treatment within the first seven days was the only statistically significantly different condition in patients who improved hearing. An objective search for etiological bases should be conducted in any case of acute sensorineural hearing loss. The presence of cerebellopontine tumors in 7.5% of cases of SD, among other treated causes, justifies a thorough clinical investigation in these patients. Overall good evolution of hearing was observed in 67.5% of cases of SD, regardless of its etiology. Therapy within the first seven days of SD was significantly related to better outcomes in hearing.

Rare Causes of Hypercalcemia

Although hypercalcemia is usually caused by primary hyperparathyroidism or malignancy, a number of other conditions can be important to consider. This review considers unusual causes of hypercalcemia that are generally not found in reviews on this subject. Articles describing rarely reported associations between hypercalcemia and unusual causes were identified through a computer search of the terms hypercalcemia/etiology and through the references listed in those articles. We grouped the 58 different reports into categories defined by a presumed etiology: increased levels of 1,25-dihydroxyvitamin D or PTHrP, occult milk-alkali syndrome, and undefined mechanisms. Reports in infants and children are listed separately, as are reports of pseudohypercalcemia, situations that are not truly hypercalcemic because the ionized calcium is normal. In some situations, as this review points out, a number of unusual causes of hypercalcemia are important to consider. The search for an elusive cause of hypercalcemia is best accomplished by the most likely potential mechanism. An orderly search in this manner is likely to reveal the underlying cause. That so many patients have been described with rare and usually poorly understood causes of hypercalcemia highlights our incomplete understanding of calcium metabolism in humans and suggests additional areas in which directed clinical investigation might improve our knowledge of the normal metabolism of calcium.

Ocular cicatricial pemphigoid: Manifestations and management

Ocular cicatricial pemphigoid (OCP) is a chronic, progressive cicatrizing inflammatory disease of presumed autoimmune etiology affecting the mucous membranes and skin. It has sight-threatening ocular manifestations and potentially life-threatening extraocular manifestations. The ocular signs include: chronic cicatricial conjunctivitis, progressive conjunctival fibrosis, and corneal epitheliopathy. Systemic immunomodulatory therapy is the treatment of choice for controlling disease activity and limiting progression, given the systemic nature of the disease and the poor efficacy of current local or topical therapies. Systemic cyclophosphamide with short-term adjunctive high-dose prednisolone is the preferred treatment for severe and/or rapidly progressing OCP. Oral low-dose weekly methotrexate is a useful first-line treatment for mild-to-moderate OCP. The management of OCP requires a multidisciplinary approach to optimize the care of these patients.

Damage caused by Wegener's granulomatosis and its treatment: Prospective data from the Wegener's Granulomatosis Etanercept Trial (WGET)

To analyze damage occurring in patients with Wegener's granulomatosis (WG) enrolled in the WG Etanercept Trial (WGET) and to correlate that damage with disease activity, adverse events, and quality of life. The Vasculitis Damage Index (VDI) was applied to all 180 patients at trial entry and every 6 months throughout the trial. Items of damage were analyzed by presumed etiology (i.e., secondary to WG, to therapy, or both) and time of occurrence. Spearman's rank correlation coefficients were calculated between VDI scores and the Birmingham Vasculitis Activity Score for WG (BVAS/WG), frequency of flares, number of adverse events, and the patients' quality-of-life assessments. The mean VDI score was 1.3 at the study enrollment and 1.8 at the end of the trial. This increase was due to damage that occurred despite (or because of) therapy, including visual impairment, hearing loss, nasal blockade, pulmonary fibrosis, hypertension, renal insufficiency, peripheral neuropathy, gonadal failure, and diabetes mellitus. Only 11% of the enrolled patients had not sustained a single VDI item after 1 year of enrollment. When adjusted for baseline VDI, the baseline BVAS/WG correlated moderately well with the VDI score at 1 year (r = 0.20, P = 0.015). Increases in adjusted VDI scores also correlated with the number of adverse events, particularly among patients with limited WG (P = 0.06). Damage from both active disease and its treatment remain important problems for patients with WG. Despite the dramatic improvements in patient survival achieved over the last several decades, only a few patients with WG emerge from a period of active disease without sustaining some damage from the disease itself, its treatment, or both. An important measure of future therapeutic approaches will be their ability to reduce the damage accrued over time.