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2.
Clin Med (Lond) ; 21(1): 79-80, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33479073

ABSTRACT

We present the case of a 71-year-old woman with bilateral pneumonia who continued to deteriorate despite multiple courses of antibiotics. When dexamethasone was added to cover the possibility of COVID-19 pneumonia, she rapidly improved. Subsequently, she was found to have a strongly positive PR3 anti-nuclear cytoplasmic antibody (ANCA) and clinical features consistent with granulomatosis with polyangiitis (GPA) with upper respiratory tract and renal involvement. The case highlights how the COVID-19 pandemic can create new challenges in the diagnosis of GPA.


Subject(s)
COVID-19/epidemiology , Granulomatosis with Polyangiitis/diagnosis , Lung/diagnostic imaging , Radiography, Thoracic/methods , SARS-CoV-2 , Aged , COVID-19/diagnosis , Comorbidity , Diagnosis, Differential , Female , Granulomatosis with Polyangiitis/epidemiology , Humans , Pandemics , Tomography, X-Ray Computed
3.
Drug Ther Bull ; 56(12): 150-153, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30470710

ABSTRACT

In conjunction with BMJ Case Reports, DTB will feature occasional drug-related cases that are likely to be of interest to readers. These will include cases that involve recently marketed drugs for which there is limited knowledge of adverse effects and cases that highlight unusual reactions to drugs that have been marketed for several years.


Subject(s)
Adalimumab/adverse effects , Lung Diseases, Interstitial/chemically induced , Anti-Inflammatory Agents/adverse effects , Diagnosis, Differential , Humans , Lung Diseases, Interstitial/diagnostic imaging , Male , Middle Aged
4.
BMJ Case Rep ; 20182018 May 15.
Article in English | MEDLINE | ID: mdl-29764848

ABSTRACT

We report a rare case of drug-induced intestinal lung disease (ILD) secondary to adalimumab, a tumour necrosis factor alpha-receptor blocker. A 52-year-old smoker with ankylosing spondylitis, treated with adalimumab, presented with progressive breathlessness. A high resolution CT chest demonstrated predominantly upper-zone patchy ground glass changes and small bilateral pleural effusions. Bronchoscopy and bronchoalveolar lavage showed no evidence of infection or malignant cells and an echocardiogram was normal. The working diagnosis was that of possible adalimumab-induced ILD. Adalimumab was subsequently stopped. The patient's breathlessness and cough improved on cessation of the drug. A further CT chest several months later showed resolution of the ground glass changes. Adalimumab-induced ILD is rare. We review the literature surrounding this and discuss the diagnostic challenges. This case highlights the importance of considering the possibility of drug-induced lung disease in patients taking adalimumab.


Subject(s)
Adalimumab/adverse effects , Anti-Inflammatory Agents/adverse effects , Lung Diseases, Interstitial/chemically induced , Spondylitis, Ankylosing/drug therapy , Adalimumab/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Echocardiography , Humans , Male , Middle Aged , Pleural Effusion/diagnostic imaging , Tomography, X-Ray Computed
5.
Respir Med Case Rep ; 20: 198-200, 2017.
Article in English | MEDLINE | ID: mdl-28331796

ABSTRACT

We report the case of a 47-year old Caucasian man with a history of depression and high alcohol intake who presented with a one-month history of weight loss, dry cough and abdominal pain. He had no smoking history of note. The patient was treated for a suspected chest infection, however developed respiratory failure and was intubated. A CT showed multiple pulmonary nodules, left pleural thickening extending to the mediastinum and bilateral pleural effusions-larger on the left, suggestive of disseminated malignancy. A broncho-alveolar lavage surprisingly contained numerous acid-fast bacilli and no malignant cells. Treatment for tuberculosis was initiated and the patient recovered gradually. After several weeks, a pyrazinamide-resistant organism was cultured and subsequently identified to be Mycobacterium Bovis. We discuss this unexpected finding and review the literature on Bovine Tuberculosis in humans.

6.
J Dent ; 53: 64-72, 2016 10.
Article in English | MEDLINE | ID: mdl-27472955

ABSTRACT

OBJECTIVE: Numerous studies have proposed that smooth metal surfaces reduce initial bacterial attachment in the establishment of an early biofilm formation. However, these studies have largely examined single bacterial species, which are not always relevant as pathogens identified as initiators of inflammatory peri-implantitis. This study investigated the adherence of four periodontally-relevant bacterial species to implant and abutment surfaces in current clinical use. METHODS: Discs of polished cobalt chromium (CoCr-polished) and milled titanium (Ti-milled), representing two clinically relevant surfaces, were prepared and surfaces were characterised. Bacterial species Porphyromonas gingivalis, Fusobacterium nucleatum, Prevotella intermedia and Aggregatibacter actinomycetemcomitans were cultured to mid-log or stationary growth phase. Co-cultures of P. gingivalis, F. nucleatum and P. gingivalis, F. nucleatum, Pr. intermedia were similarly prepared. Bacteria were inoculated onto discs for 2h, stained with a live/dead fluorescent stain and percentage bacterial coverage was calculated by confocal microscopy and image analysis. RESULTS: CoCr-polished discs had smooth surfaces with gentle valley structures, whilst Ti-milled discs had sharp edged peaks. Both discs demonstrated a partial wetting ability capable of initiating bacterial adhesion. P. gingivalis, F. nucleatum and co-cultures, at both mid-log and stationary concentrations, demonstrated equally high coverage of both the smooth CoCr-polished and the rougher Ti-milled metal surfaces. Pr. intermedia and A. actinomycetemcomitans demonstrated lower surface coverage which was slightly higher for Ti-milled. CONCLUSION: Variability was noted in the adherence potential for the respective periodontal pathogens examined. Particularly high adherence was noted for P. gingivalis and F. nucleatum, despite the manufacture of a smooth surface. CLINICAL SIGNIFICANCE: Both surfaces studied may be used at implant-abutment junctions and both possess an ability to establish a bacterial biofilm containing a periodontally-relevant species. These surfaces are thus able to facilitate the apical migration of bacteria associated with peri-implantitis.


Subject(s)
Dental Implants , Aggregatibacter actinomycetemcomitans , Fusobacterium nucleatum , Humans , Peri-Implantitis , Porphyromonas gingivalis , Prevotella intermedia
7.
Am J Orthod Dentofacial Orthop ; 148(5): 862-7, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26522047

ABSTRACT

The aim of this study was to fabricate a resin appliance incorporating "wire" components without the use of an analog impression and dental casts using an intraoral scanner and computer technology to build the appliance. This unique alignment of technology offers an enormous reduction in the number of fabrication steps when compared with more traditional methods of manufacture. The prototype incorporated 2 Adams clasps and a fitted labial bow. The alloy components were built from cobalt-chromium in an initial powdered form using established digital technology methods and then inserted into a build of a resin base plate. This article reports the first known use of computer-aided design and additive manufacture to fabricate a resin and alloy appliance, and constitutes proof of the concept for such manufacturing. The original workflow described could be seen as an example for many other similar appliances, perhaps with active components. The scan data were imported into an appropriate specialized computer-aided design software, which was used in conjunction with a force feedback (haptic) interface. The appliance designs were then exported as stereolithography files and transferred to an additive manufacturing machine for fabrication. The results showed that the applied techniques may provide new manufacturing and design opportunities in orthodontics and highlights the need for intraoral-specific additive manufacture materials to be produced and tested for biocompatibility compliance. In a trial, the retainer was fitted orally and judged acceptable by the clinician according to the typical criteria when placing such appliances in situ.


Subject(s)
Chromium Alloys/chemistry , Composite Resins/chemistry , Computer-Aided Design , Dental Materials/chemistry , Orthodontic Appliance Design , Orthodontic Retainers , Dental Clasps , Dental Impression Technique , Humans , Imaging, Three-Dimensional/methods , Orthodontic Wires , Technology, Dental , User-Computer Interface , Workflow
9.
BMJ Case Rep ; 20132013 Aug 05.
Article in English | MEDLINE | ID: mdl-23917367

ABSTRACT

We describe a 42-year-old British man of Indo-Caribbean origin with immunodeficiency, centromeric region instability and facial anomalies (ICF) syndrome. Most patients with ICF syndrome die of infection at a young age, usually in the first or second decade of life. The patient was born 3.5 weeks premature to non-consanguineous parents. He had a mild bird-like face abnormality, but had no other congenital malformations, cognitive impairment or developmental delays. He had recurrent ear and chest infections during childhood and developed bronchiectasis. Investigations revealed IgG, IgA and IgM deficiencies with a normal lymphocyte count and normal T cell proliferation to in vitro mitogenic stimulation. Following several unsuccessful attempts to make a diagnosis during childhood, a recent chromosomal analysis showed centromeric region instability of chromosomes 1 and 16, diagnosing ICF syndrome. The patient receives immunoglobulin replacement for hypogammaglobulinameia and has chest physiotherapy and antibiotics for bronchiectasis. Recently, he developed liver cirrhosis of unknown cause.


Subject(s)
Face/abnormalities , Immunologic Deficiency Syndromes , Survivors , Adult , Humans , Immunologic Deficiency Syndromes/diagnosis , Male , Primary Immunodeficiency Diseases
10.
Acute Med ; 12(2): 96-7, 2013.
Article in English | MEDLINE | ID: mdl-23732133

ABSTRACT

A 25-year man presented to the Accident and Emergency Department complaining of dizziness and shortness of breath after taking 70 grams of cocaine over 10 hours. He said a friend had noticed that his skin had turned dark blue. On examination the patient was severely centrally and peripherally cyanosed. His pulse oximeter oxygen saturations were 88% on air. An arterial blood gas showed a methaemoglobin level of 45.6%. The patient was diagnosed with cocaine-induced methaemoglobinaemia and given methyl thioninium chloride (methylene blue). He made an uneventful recovery.


Subject(s)
Cocaine/poisoning , Methemoglobinemia/chemically induced , Adult , Cocaine/blood , Cyanosis/blood , Cyanosis/chemically induced , Dizziness/chemically induced , Dyspnea/chemically induced , Enzyme Inhibitors/therapeutic use , Humans , Male , Methemoglobinemia/blood , Methemoglobinemia/drug therapy , Methylene Blue/therapeutic use , Oximetry/methods , Treatment Outcome
11.
BMJ Case Rep ; 20132013 Jan 11.
Article in English | MEDLINE | ID: mdl-23314877

ABSTRACT

A 75-year-old woman presented 9 days post-total hip replacement with sudden onset of shortness of breath and fever. She had been discharged taking dabigatran. The patient was treated for sepsis with antibiotics and fluids. However, she deteriorated and was transferred to the intensive care unit. Following a 10 s asystolic episode the patient was thrombolysed with alteplase for presumed massive pulmonary embolism. Initially, her blood pressure and oxygen saturation improved. However, over the next few days, she remained persistently hypotensive. A CT scan of her chest, abdomen and pelvis demonstrated bilateral adrenal haemorrhages. A short synacthen test confirmed acute adrenal failure.


Subject(s)
Adrenal Insufficiency/etiology , Antithrombins/adverse effects , Benzimidazoles/adverse effects , Fibrinolytic Agents/adverse effects , Pulmonary Embolism/drug therapy , Tissue Plasminogen Activator/adverse effects , beta-Alanine/analogs & derivatives , Adrenal Gland Diseases/chemically induced , Adrenal Gland Diseases/complications , Aged , Arthroplasty, Replacement, Hip , Dabigatran , Female , Hemorrhage/chemically induced , Hemorrhage/complications , Humans , beta-Alanine/adverse effects
12.
Respirology ; 18(2): 246-54, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23039264

ABSTRACT

Despite 50-60% of intensive care patients demonstrating evidence of pleural effusions, there has been little emphasis placed on the role of effusions in the aetiology of weaning failure. Critical illness and mechanical ventilation lead to multiple perturbations of the normal physiological processes regulating pleural fluid homeostasis, and consequently, failure of normal pleural function occurs. Effusions can lead to deleterious effects on respiratory mechanics and gas exchange, and when extensive, may lead to haemodynamic compromise. The widespread availability of bedside ultrasound has not only facilitated earlier detection of pleural effusions but also safer fluid sampling and drainage. In the majority of patients, pleural drainage leads to improvements in lung function, with data from spontaneously breathing individuals demonstrating a consistent symptomatic improvement, while a meta-analysis in critically ill patients shows an improvement in oxygenation. The effects on respiratory mechanics are less clear, possibly reflecting heterogeneity of underlying pathology. Limited data on clinical outcome from pleural fluid drainage exist; however, it appears to be a safe procedure with a low risk of major complications. The current level of evidence would support a clinical trial to determine whether the systematic detection and drainage of pleural effusions improve clinical outcomes.


Subject(s)
Critical Illness , Intensive Care Units , Pleural Effusion/diagnosis , Pleural Effusion/therapy , Respiration, Artificial , Drainage/methods , Humans , Lung/diagnostic imaging , Lung/physiopathology , Respiratory Mechanics , Ultrasonography , Ventilator Weaning
13.
BMJ Case Rep ; 20122012 Sep 18.
Article in English | MEDLINE | ID: mdl-22989422

ABSTRACT

A 59-year-old man presented with a 4-year history of productive cough, shortness of breath and wheeze. He had been treated for asthma and given several courses of antibiotics which improved his symptoms. Medical history was unremarkable. There was no history respiratory disease in childhood although he was prone to chest infections in adult life. A high-resolution chest CT showed marked proximal cystic bronchiectasis associated with collapse of distal bronchi on expiration. A diagnosis of cystic bronchiectasis due to undiagnosed adult Williams-Campbell syndrome was made on the basis of these characteristic radiological features and the exclusion of other possible causes.


Subject(s)
Tracheobronchomalacia/diagnosis , Bronchiectasis/diagnosis , Bronchiectasis/diagnostic imaging , Bronchiectasis/etiology , Diagnosis, Differential , Humans , Lung/diagnostic imaging , Male , Middle Aged , Tomography, X-Ray Computed , Tracheobronchomalacia/complications , Tracheobronchomalacia/diagnostic imaging
14.
Respir Med ; 105(10): 1413-21, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21684732

ABSTRACT

Pulmonary-renal syndromes are a group of disorders characterised by necrotising glomerulonephritis and pulmonary haemorrhage. Small vessel systemic vasculitis is the most common cause of pulmonary-renal syndromes presenting to respiratory physicians. Rarer causes include systemic lupus erythematosus and connective tissue diseases though severe pneumonia or cardiac failure may mimic their presentation. Some forms of small vessel vasculitides have a predilection for the pulmonary and renal vascular beds and if left untreated can result in fulminant organ failure. Whilst the aetiology of these syndromes remains unclear, much is known about the disease mechanisms including the pathogenic role of autoantibodies, immune-complex mediated inflammation and microangiopathic in-situ thrombosis. Despite established treatments achieving successful remission induction, patient tolerability and side effect profiles have limited their use which has led to searches for more targeted treatments. Consequently newer biological therapies have gained wider acceptance despite little being known about their long term safety and efficacy. The European Vasculitis Study Group (EUVAS) have recently formulated guidelines to provide consensus on diagnosis and management in this area and work to define survival rates in these conditions with longer term follow-up studies is ongoing. This review summarises the current aetiopathogenesis thought to underlie these complex diseases, the diagnostic definitions and classification criteria currently in use and the evidence base for modern therapies. Though unusual for respiratory specialists to coordinate overall management of these patients, an update on their current management is regarded as important to their practice given the recently changing trends in treatments.


Subject(s)
Glomerulonephritis/pathology , Hemorrhage/pathology , Lung Diseases/pathology , Lupus Erythematosus, Systemic/pathology , Practice Guidelines as Topic , Pulmonary Alveoli/pathology , Vasculitis/pathology , Glomerulonephritis/therapy , Hemorrhage/prevention & control , Hemorrhage/therapy , Humans , Lung Diseases/therapy , Lupus Erythematosus, Systemic/therapy , Syndrome , Vasculitis/therapy
16.
J Virol ; 79(9): 5653-64, 2005 May.
Article in English | MEDLINE | ID: mdl-15827180

ABSTRACT

Equine infectious anemia virus (EIAV) is a lentivirus with in vivo cell tropism primarily for tissue macrophages; however, in vitro the virus can be adapted to fibroblasts and other cell types. Tropism adaptation is associated with both envelope and long terminal repeat (LTR) changes, and findings strongly suggest that these regions of the genome influence cell tropism and virulence. Furthermore, high levels of genetic variation have been well documented in both of these genomic regions. However, specific EIAV nucleotide or amino acid changes that are responsible for cell tropism changes have not been identified. A study was undertaken with the highly virulent, macrophage-tropic strain of virus EIAV(wyo) to identify LTR changes associated with alterations in cell tropism. We found the stepwise generation of a new transcription factor binding motif within the enhancer that was associated with adaptation of EIAV to endothelial cells and fibroblasts. An LTR that contained the new motif had enhanced transcriptional activity in fibroblasts, whereas the new site did not alter LTR activity in a macrophage cell line. This finding supports a previous prediction that selection for new LTR genetic variants may be a consequence of cell-specific selective pressures. Additional investigations of the EIAV(wyo) LTR were performed in vivo to determine if LTR evolution could be detected over the course of a 3-year infection. Consistent with previous in vivo findings, we observed no changes in the enhancer region of the LTR over that time period, indicating that the EIAV(wyo) LTR was evolutionarily stable in vivo.


Subject(s)
Infectious Anemia Virus, Equine/genetics , Terminal Repeat Sequences/genetics , Adaptation, Physiological , Amino Acid Motifs , Animals , Base Sequence , Biological Evolution , Cells, Cultured , Disease Models, Animal , Endothelial Cells , Enhancer Elements, Genetic/genetics , Equine Infectious Anemia/virology , Fibroblasts , Horses , Infectious Anemia Virus, Equine/pathogenicity , Macrophages , Molecular Sequence Data , Sequence Alignment , Serial Passage , Virulence/genetics
17.
Virus Res ; 92(1): 83-7, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12606079

ABSTRACT

Lactate dehydrogenase-elevating virus (LDV) is a macrophage-tropic arterivirus which generally causes a persistent viremic infection in mice. LDV replication in vivo seems to be primarily regulated by the extent and dynamics of a virus-permissive macrophage population. Previous studies have shown that glucocorticoid treatment of chronically LDV-infected mice transiently increases viremia 10-100-fold, apparently by increasing the productive infection of macrophages. We have further investigated this phenomenon by comparing the effect of dexamethasone on the in vivo and in vitro replication of two LDV quasispecies that differ in sensitivity to immune control by the host. The single neutralizing epitope of LDV-P is flanked by two N-glycans that impair its immunogenicity and render LDV-P resistant to antibody neutralization. In contrast, replication of the neuropathogenic mutant LDV-C is suppressed by antibody neutralization because its epitope lacks the two protective N-glycans. Dexamethasone treatment of mice 16 h prior to LDV-P infection, or of chronically LDV-P infected mice, stimulated viremia 10-100-fold, which correlated with an increase of LDV permissive macrophages in the peritoneum and increased LDV infected cells in the spleen, respectively. The increase in viremia occurred in the absence of changes in total anti-LDV and neutralizing antibodies. The results indicate that increased viremia was due to increased availability of LDV permissive macrophages, and that during a chronic LDV-P infection virus replication is strictly limited by the rate of regeneration of permissive macrophages. In contrast, dexamethasone treatment had no significant effect on the level of viremia in chronically LDV-C infected mice, consistent with the view that LDV-C replication is primarily restricted by antibody neutralization and not by a lack of permissive macrophages. beta-Glucan, the receptor of which is induced on macrophages by dexamethasone treatment, had no effect on the LDV permissiveness of macrophages.


Subject(s)
Dexamethasone/pharmacology , Glucocorticoids/pharmacology , Lactate dehydrogenase-elevating virus/drug effects , Lactate dehydrogenase-elevating virus/physiology , Macrophages/drug effects , Macrophages/virology , Virus Replication/drug effects , Animals , Antibodies, Viral/biosynthesis , Arterivirus Infections/immunology , Arterivirus Infections/virology , Female , Lactate dehydrogenase-elevating virus/immunology , Lactate dehydrogenase-elevating virus/pathogenicity , Mice , Neutralization Tests , Spleen/drug effects , Spleen/virology
18.
Viral Immunol ; 16(4): 511-23, 2003.
Article in English | MEDLINE | ID: mdl-14733738

ABSTRACT

Persistent infection of mice with lactate dehydrogenase-elevating virus (LDV) is associated with polyclonal B cell activation, autoimmunity, and circulating hydrophobic IgG-containing immune complexes (ICs), which bind to the surfaces of uncoated ELISA plates in the presence of 0.05% Tween 20. We demonstrate here that hydrophobic IgG-containing ICs also appear naturally in the plasma of autoimmune MRL/lpr mice. These and the similar hydrophobic ICs of LDV-infected mice as well as pigs coincide on ELISA plate surfaces with TGF-beta, apparently in the form of an IgG-TGF-beta complex. Circulating hydrophobic IgG-containing ICs are also susceptible to considerable amplification in vitro by exposure to alkaline conditions. By this latter method, the fraction of in vivo hydrophobic IgG, relative to the maximum in vitro chemically inducible IgG, was found to be about 20% in the plasma of LDV-infected mice, 5% in normal mouse plasma, and less than about 2% in pig plasma. These results indicate the potential for both chemically induced and protein-binding contributions to the generation of hydrophobic IgG-containing molecules, and have implications for immunopathological mechanisms in autoimmunity and persistent virus infections.


Subject(s)
Antigen-Antibody Complex/blood , Arterivirus Infections/immunology , Autoimmunity , Immunoglobulin G/blood , Lactate dehydrogenase-elevating virus/immunology , Transforming Growth Factor beta/blood , Animals , Arterivirus Infections/virology , Hydrogen-Ion Concentration , Hydrophobic and Hydrophilic Interactions , Mice , Mice, Inbred MRL lpr , Swine
19.
J Gen Virol ; 81(Pt 9): 2167-2175, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10950973

ABSTRACT

The common biologically cloned isolates of lactate dehydrogenase-elevating virus (LDV-P and LDV-vx) invariably cause a polyclonal activation of B cells in immunocompetent mice. It is recognized by an at least 10-fold increase in plasma IgG2a levels and the de novo formation of immune complexes that most likely consist of autoantibodies and their antigens. The present study indicates that three closely spaced N-glycans on the short ectodomain of the primary envelope glycoprotein, VP-3P, of LDV-P/vx, play a major role in inducing the polyclonal proliferation of B cells. IFN-gamma then seems to mediate the differentiation of the activated B cells to IgG2a-producing plasma cells. These conclusions are based on the finding that the IgG2a hypergammaglobulinaemia and immune complex formation were much lower in mice that were infected with LDV variants (LDV-C and LDV-v) whose VP-3P ectodomains lack two of the three N-glycans than in LDV-P/vx infected mice. In contrast, the VP-3P ectodomains of three neutralization escape variants of LDV-C/v whose VP-3P ectodomains possess three N-glycosylation sites caused a polyclonal activation of B cells comparable to that of LDV-P/vx.


Subject(s)
B-Lymphocytes/immunology , Gene Products, env/chemistry , L-Lactate Dehydrogenase/metabolism , Membrane Glycoproteins/immunology , Polysaccharides/immunology , Amino Acid Sequence , Animals , Enzyme-Linked Immunosorbent Assay , Glycosylation , Immunoglobulin G/biosynthesis , Mice , Mice, Inbred C57BL , Mice, SCID , Mice, Transgenic , Molecular Sequence Data , Structure-Activity Relationship , Viral Envelope Proteins/immunology , Viremia/immunology
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