Oro-Naso-Sino-Orbital-Cutaneous Fistula From Prolonged Cocaine Use.

Presentation We present the case of a 48-year-old man with nasal cellulitis and subsequent oro-naso-sino-orbital-cutaneous fistula from prolonged cocaine use. Diagnosis Initial laboratory investigations reported a raised white cell count (WBC) and C-Reactive Protein (CRP) and subsequently a positive atypical anti-neutrophil cytoplasm antibodies (ANCA) and positive anti-proteinase (PR3). Perihilar lung nodularity on chest imaging raised the possibility of a systemic autoimmune response. His urinalysis was positive for cocaine. Treatment He was commenced on Augmentin, Amphotericin B and Prednisolone. An obturator was created to manage the oro-nasal fistula. A subsequent naso-cutaneous defect was re-approximated. Daily nasal saline douche and abstinence of cocaine were recommended. Discussion Cocaine use in the community is rising and poses a challenge to multiple facets of our health care system.

Community Priority setting for Fetal Alcohol Spectrum Disorder Research in Australia.

INTRODUCTION: Fetal Alcohol Spectrum Disorder (FASD) is a neurodevelopmental disorder caused by prenatal alcohol exposure (PAE). FASD research is a rapidly growing field that crosses multiple disciplines. To ensure research is relevant and meaningful for people living with FASD, their families, and the broader public there is a need to engage community members in setting priorities for research. OBJECTIVES: Our primary objective was to formally identify the views of people living with FASD, their parents/caregivers, service providers, and the general community on the research priorities for FASD and alcohol use in pregnancy in Australia. Our secondary objective was to provide an overview of current research in the highest priority areas identified. METHODS: The approach for this study involved two community surveys and a consensus workshop, followed by a rapid literature review. Survey responses (n = 146) were collected and grouped using qualitative thematic analysis. The themes identified were then ranked in a second survey (n = 45). The 22 highest ranked themes were considered in a workshop with 21 community members, and consensus on the top ten priority areas was sought. The priority areas were grouped into conceptually similar topics and rapid literature reviews were undertaken on each. RESULTS: A diverse range of priorities was identified within key areas of prevention, diagnosis, and therapy. On request from participants, separate priority lists were developed by Aboriginal and non-Aboriginal participants. CONCLUSION: There is need for a national network of researchers to take forward the research commenced by the Centre of Research Excellence, FASD Research Australia, in addressing community priorities. KEY WORDS: Community, priorities, FASD, rapid review, Australia.

Increased T Cell Plasticity With Dysregulation of Follicular Helper T, Peripheral Helper T, and Treg Cell Responses in Children With Juvenile Idiopathic Arthritis and Down Syndrome-Associated Arthritis.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is the most common inflammatory arthritis in children; however, an aggressive, erosive arthritis of little-known immunologic mechanism occurs 20 times more frequently in children with Down syndrome. This study was undertaken to characterize T cell and B cell polyreactivity, follicular helper T (Tfh) cell, peripheral helper T (Tph) cell, and Treg cell responses, and synovial inflammation in Down syndrome-associated arthritis (DA). METHODS: Multiparametric flow cytometric analysis and Simplified Presentation of Incredibly Complex Evaluations (SPICE) software were used to examine peripheral blood B cell populations and T cell cytokine responses in patients with DA, JIA, Down syndrome (trisomy 21 [T21]), and in healthy controls. Tfh and Tph cell frequency and origin, in addition to Treg cell frequency, were also evaluated. Synovial inflammation was assessed by immunohistology. RESULTS: Expansion of IgM-only memory B cells was demonstrated in DA compared to JIA (mean ± SEM 22.48 ± 3.278 versus 9.011 ± 1.317; P = 0.005), paralleled by decreased frequency of transitional B cells. T cell responses in DA were characterized by marked functional plasticity, as was evident from the increased frequency of polyfunctional CD8+ Th cells (P < 0.05), CD161+ Th cells (P < 0.05), and CD8- Th cells (P < 0.001), and positivity for tumor necrosis factor, interferon-γ, interleukin-17A, or granulocyte-macrophage colony-stimulating factor, compared to all other groups. Significant expansion of CXCR3+CCR6+ (Th1/Th17) Tfh cells (P = 0.003) and CXCR3+CCR6+ Tph cells (P = 0.01), paralleled by a decrease in CXCR3-CCR6- (Th2) Tfh cells was observed in DA compared to T21. Treg cells were significantly reduced in DA compared to T21 (mean ± SEM 7.111 ± 0.9518 versus 11.96 ± 1.055 versus; P = 0.0028), with a specific reduction in the naive:memory Treg cell ratio. Marked synovial tissue inflammation and increased T cell and B cell infiltrations were demonstrated in DA compared to JIA. CONCLUSION: DA is more common and more aggressive than JIA. It is characterized by increased polyreactive Th, Tfh, and Tph cell responses, reduced Treg cell frequency, and evidence of increased synovial inflammation, all of which are potentially distinct from JIA and T21.

Shrinking lung syndrome and systemic lupus erythematosus: a case series and literature review.

Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus, characterized by progressive dsypnoea, reduced lung volumes and associated restrictive lung physiology. Here, we provide two previously unreported cases, and review the available literature on the pathophysiology, clinical features and management of SLS. Effective treatment can prevent further deterioration or lead to improvement in abnormal lung function. A heightened awareness of SLS and its management is therefore required to prevent disease progression and increased morbidity.

Downregulation of the inhibitor of apoptosis protein survivin in keratinocytes and endothelial cells in psoriasis skin following infliximab therapy.

BACKGROUND: Survivin, an inhibitor of apoptosis protein (IAP), has been implicated in endothelial cell stability, through inhibition of apoptosis and in cell proliferation. OBJECTIVES: To evaluate the effect of antitumour necrosis factor (TNF)-alpha therapy on survivin expression in psoriasis skin at 0, 2 and 12 weeks after infliximab therapy. METHODS: Skin biopsies were obtained from 16 patients; 11 also had arthritis with active skin/joint disease. Clinical scores [Psoriasis Area and Severity Index (PASI), involved body surface area (BSA), Disease Activity Score (DAS28) and Health Assessment Questionnaire] were recorded. Inflammatory infiltration and survivin protein expression were examined and graded by immunohistochemical staining, and mRNA levels were determined by real-time polymerase chain reaction. RESULTS: Survivin mRNA and protein were demonstrated in all baseline lesional biopsies. Survivin mRNA and protein expression was significantly greater in lesional compared with nonlesional baseline skin (P < 0.05). Differential cellular localization of survivin was demonstrated with cytoplasmic survivin protein expression localized to the perivascular/endothelial regions and strong nuclear staining localized in the basal layer of the epidermis. Infliximab produced a dramatic clinical response in skin and joints (P < 0.05), paralleled by significant reduction in the inflammatory infiltrate and survivin protein expression (P < 0.05) which was reflected at the mRNA level where expression was significantly reduced by week 12 (P < 0.01). Survivin protein levels before and after treatment significantly correlated with PASI (r = 0.478, P < 0.05) and BSA scores (r = 0.528, P < 0.024). PASI strongly correlated with BSA (r = 0.949, P < 0.0001) and DAS28 (r = 0.717, P < 0.002) scores. CONCLUSIONS: Survivin correlates with disease activity in patients with psoriasis and is significantly downregulated following anti-TNF-alpha treatment. Understanding the role of IAPs in cell survival/antiapoptosis and proliferation mechanisms may provide important insights into downstream therapeutic targeting in inflammation.

Studying the deformation of arachnid slit sensilla by a fracture mechanical approach.

Slit sensilla are sensory organs which measure strains in the exoskeleton of arachnids. They occur as isolated slits, in loose groups and in close parallel arrangements known as lyriform organs or compound slit sensilla. The deformations of the slits' faces induced by far-field strains acting on groups of slits are studied using Kachanov's analytical approximations for the opening displacements of cracks, a method developed within the framework of fracture mechanics. The accuracy of the approach is assessed by comparisons with results obtained by finite element analysis. The limits of its applicability to slit sensilla are found to be reached when the lateral spacing between interacting slits is less than half their length, i.e., the method is suitable for studying single slits and loose groups but not lyriform organs. The influence of a number of geometrical parameters of slit sensilla on the deformation patterns of the faces of parallel slits in generic arrangements is studied, viz., spacing between slits, longitudinal shifts between slits, and slit length. The results are presented as opening distances along the length of the cracks and in terms of normalized diagrams that relate the opening distances at mid-length of the slits to the geometrical parameters. In addition, Kachanov's method is used to find a set of slit lengths that give rise to prescribed opening distances.

Disease-modifying anti-rheumatic drug therapy and structural damage in early rheumatoid arthritis.

The appearance of measurable structural damage in rheumatoid arthritis (RA) is an indicator of disease severity and future disability. Disease-modifying anti-rheumatic drugs (DMARDs) used in combination appear to be more effective than monotherapies at reducing the rate of progressive joint damage during randomized controlled trials. In clinical practice, however, combination DMARD therapy is still largely reserved for patients who have failed to respond to monotherapy. High dose corticosteroid, when given in early disease with combination DMARD therapy, may continue to ameliorate disease severity and progression for years after discontinuation of the high dose. To date, no DMARD combination has totally arrested joint damage in all patients with early RA. Future randomised controlled trials should always include prospective radiographic data as a primary outcome measure.

Pulmonary cystic hydatid disease in Ireland.

BACKGROUND: Hydatid disease is rare in Ireland and its incidence and prevalence are unknown. Most cases are diagnosed by a combination of clinical findings, morphological features on imaging and by serological testing. AIMS: We describe an Irish case of pulmonary hydatid disease detected at bronchoscopy by bronchoalveolar lavage, and discuss the diagnosis and treatment of the disorder. CONCLUSION: The diagnosis of this rare disease requires a high index of suspicion. Treatment is primarily surgical, with a role for antihelminthic agents.

Characterization and localization of expression of an erythropoietin-induced gene, ERIC-1/TACC3, identified in erythroid precursor cells.

Gene expression profiles during erythropoietin (Epo)-induced differentiation of erythroid progenitor cells derived from the Friend virus anaemia (FVA) and phenylhydrazine (PHZ) murine models have been examined using differential display polymerase chain reaction (PCR). Ten cDNA fragments upregulated by Epo were isolated. The ribonuclease protection assay confirmed differential expression between Epo-stimulated and Epo-deprived cells for one of these, provisionally named ERIC-1. Sequencing of the full-length cDNA predicted a protein of 558 amino acids, 17 amino acids longer than mTACC3, the third member of a novel family of proteins that contain a coiled-coil domain. The human homologue, cloned using rapid amplification of cDNA ends (RACE)-PCR, encodes a larger protein of 838 amino acids that is identical to hTACC3. In addition to erythroid precursor cells, ERIC-1/TACC3 is expressed at high levels in the testes, at moderate levels in the thymus and peripheral leucocytes, and at lower levels in the spleen and intestinal tissue. Immunohistochemical analysis using an antibody to a GST fusion product of the C-terminus of hERIC-1/TACC3 revealed that it is localized to Sertoli cells in the human testes. Confocal microscopy demonstrated hERIC-1/TACC3 protein concentrated in the perinuclear vesicles of dermal microvascular endothelial cells. Although ERIC-1/TACC3 is expressed in a wide range of tissues, its upregulation by Epo in erythroid progenitors implies that it has a role in terminal erythropoiesis.

Evaluation of the effectiveness of targeted lookback for HCV infection in the United States-interim results.

BACKGROUND: As part of a nationwide program to identify persons at increased risk for HCV infection, persons who received blood from donors who later tested positive for anti-HCV are being directly notified. STUDY DESIGN AND METHODS: In December 1999, all 198 blood collection establishments (BCEs) and 5442 hospital transfusion services (TSs) in the United States were surveyed by mailed questionnaire to evaluate their progress in carrying out this notification. RESULTS: Eighty-one percent of the BCEs and 64 percent of the TSs responded. After correcting for nonresponse, an estimated 98,484 components at potential risk for transmitting HCV, according to previous testing of multiantigen-screened donors, were identified nationwide, of which 85 percent had been transfused to recipients. Lookback for these recipients was completed for 80 percent, of whom 69 percent had died. Of those living, 78 percent were successfully notified. An estimated 49.5 percent of those notified were tested; 18.9 percent of those tested were anti-HCV positive, and 32 percent of that group knew they were positive before notification. On the basis of an 85.5 percent reported completion rate for component notifications back through 1988, an estimated 1520 persons will have been newly identified as anti-HCV-positive when lookback related to multiantigen screening of donors is completed. CONCLUSION: Targeted lookback related to previous multiantigen screening of donors will identify <1 percent of the estimated 300,000 HCV-positive persons in the United States who may have acquired their infection via blood transfusion.

TB infection control recommendations from the CDC, 1994: considerations for dentistry. United States Centers for Disease Control and Prevention.

Between 1989 and 1992, reports of outbreaks and transmissions of tuberculosis in institutional settings prompted the Centers for Disease Control and Prevention to review the guidelines for TB infection control it had published in 1990. The CDC published an updated version of the guidelines in October 1994. This article gives dentists an overview of the guidelines' recommendations that are applicable to most outpatient dental settings.

Respirators, recommendations, and regulations: the controversy surrounding protection of health care workers from tuberculosis.

Recent nosocomial outbreaks of tuberculosis have increased concern about the occupational acquisition of tuberculosis by health care workers. The Centers for Disease Control and Prevention (CDC), Department of Health and Human Services, and the Occupational Safety and Health Administration, Department of Labor, have issued recommendations and regulations in an effort to decrease health care workers' risk for exposure to patients with infectious tuberculosis. Within the CDC, the National Center for Infectious Diseases, the National Center for Prevention Services, and the National Institute for Occupational Safety and Health collaborated to produce the 1994 Guidelines for Preventing the Transmission of Tuberculosis in Health-Care Facilities. As stated in the Draft Guidelines, the major components of health care worker protection from Mycobacterium tuberculosis infection include administration or source controls, engineering controls, and respiratory protective devices. We review the evolution of the seemingly conflicting recommendations for respiratory protective devices made by these Centers of the CDC and explain how the recommendations in the current CDC Guidelines were reached.

HIV safety guidelines and laboratory training. NIOSH.

At the Centers for Disease Control (CDC), educational activities concerning acquired immunodeficiency syndrome (AIDS) are directed to many target audiences; important among these are health care and public safety workers. Several CDC programs are designed to address the specific education and training needs of these groups. The National Institute for Occupational Safety and Health (NIOSH) has developed a set of occupational safety guidelines directed to fire service personnel, emergency medical technicians, paramedics, and law enforcement and correctional facility personnel. These guidelines provide information on modes of transmission of human immunodeficiency virus (HIV) in the workplace, the risk of transmission, the control of risk, and specific risk-control recommendations. NIOSH also has developed a model curriculum, based on the principles and practices discussed in the guidelines, for use in training workers. The Hospital Infections Program (HIP) at CDC's National Center for Infectious Diseases is responsible for assessing the risk of HIV infection for both health care workers and patients. As part of this effort, HIP has developed guidelines to prevent transmission of HIV and other bloodborne pathogens in health care settings, as well as statements regarding management of occupational exposure to HIV. The Public Health Practice Program Office provides laboratory training to health care workers who are performing HIV- and AIDS-related testing. This training is delivered through the National Laboratory Training Network and through courses given at CDC headquarters in Atlanta. The delivery of laboratory training is supported by the development of training materials and by performance evaluation programs.

Occupational sentinel health events: an up-dated list for physician recognition and public health surveillance.

An occupational sentinel health event (SHE[O]) is a disease, disability, or untimely death, which is occupationally related and whose occurrence may: 1) provide the impetus for epidemiologic or industrial hygiene studies; or 2) serve as a warning signal that materials substitution, engineering control, personal protection, or medical care may be required. Following survey of scientific literature, a list of 50 disease conditions linked to the workplace was presented in 1983; these were codable within the framework of the International Classification of Diseases system (ICD-9). Three criteria were used for inclusion: documentation of associated agent(s), of involved industries, and of involved occupations. The up-dated list contains 64 diseases or conditions and a bibliography of literature citations. The list is useful for the practicing physician in occupational disease recognition, for occupational morbidity and mortality surveillance, and as a periodically up-dated database of occupationally related diseases.

Guidelines for preventing the transmission of tuberculosis in health-care settings, with special focus on HIV-related issues.

The transmission of tuberculosis is a recognized risk in health-care settings. Several recent outbreaks of tuberculosis in health-care settings, including outbreaks involving multidrug-resistant strains of Mycobacterium tuberculosis, have heightened concern about nosocomial transmission. In addition, increases in tuberculosis cases in many areas are related to the high risk of tuberculosis among persons infected with the human immunodeficiency virus (HIV). Transmission of tuberculosis to persons with HIV infection is of particular concern because they are at high risk of developing active tuberculosis if infected. Health-care workers should be particularly alert to the need for preventing tuberculosis transmission in settings in which persons with HIV infection receive care, especially settings in which cough-inducing procedures (e.g., sputum induction and aerosolized pentamidine [AP] treatments) are being performed. Transmission is most likely to occur from patients with unrecognized pulmonary or laryngeal tuberculosis who are not on effective antituberculosis therapy and have not been placed in tuberculosis (acid-fast bacilli [AFB]) isolation. Health-care facilities in which persons at high risk for tuberculosis work or receive care should periodically review their tuberculosis policies and procedures, and determine the actions necessary to minimize the risk of tuberculosis transmission in their particular settings. The prevention of tuberculosis transmission in health-care settings requires that all of the following basic approaches be used: a) prevention of the generation of infectious airborne particles (droplet nuclei) by early identification and treatment of persons with tuberculous infection and active tuberculosis, b) prevention of the spread of infectious droplet nuclei into the general air circulation by applying source-control methods, c) reduction of the number of infectious droplet nuclei in air contaminated with them, and d) surveillance of health-care-facility personnel for tuberculosis and tuberculous infection. Experience has shown that when inadequate attention is given to any of these approaches, the probability of tuberculosis transmission is increased. Specific actions to reduce the risk of tuberculosis transmission should include a) screening patients for active tuberculosis and tuberculous infection, b) providing rapid diagnostic services, c) prescribing appropriate curative and preventive therapy, d) maintaining physical measures to reduce microbial contamination of the air, e) providing isolation rooms for persons with, or suspected of having, infectious tuberculosis, f) screening health-care-facility personnel for tuberculous infection and tuberculosis, and g) promptly investigating and controlling outbreaks. Although completely eliminating the risk of tuberculosis transmission in all health-care settings may be impossible, adhering to these guidelines should minimize the risk to persons in these settings.

Occupational lead poisoning in Ohio: surveillance using workers' compensation data.

To determine the utility of workers' compensation (WC) data in a system for the surveillance of occupational lead poisoning, we reviewed workers' compensation claims for lead poisoning in Ohio. For the period 1979 through 1983, 92 (81 per cent) of the 114 claims attributed to lead met our case definition of lead poisoning. The likelihood that a company had a case of lead poisoning was strongly correlated with the number of claims against the company. Thirty companies accounted for the 92 cases; two companies accounted for 49 per cent of these. Inspection by the Occupational Safety and Health Administration (OSHA) occurred at 14 of these companies, all of which were cited for violations of the OSHA lead standard. Comparison of the Standard Industrial Classification (SIC) codes for the 14 companies inspected by OSHA with the 15 companies not inspected by OSHA revealed that OSHA inspected battery manufacturers, non-ferrous foundries, secondary smelters, and primary lead smelters, but not bridge painters, manufacturers of electronic components, mechanical power transmission equipment, pumps, and paints, nor a sheriff's office where firing range slugs were remelted to make new bullets. Neither the number of cases of lead poisoning at a company nor the size of a company was related to the likelihood of being inspected by OSHA. Claims for WC appear to be a useful adjunct to an occupational lead poisoning surveillance system; their usefulness should be compared to that of other systems such as laboratory reports of elevated blood lead levels in adults.