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1.
Orphanet J Rare Dis ; 11: 42, 2016 Apr 18.
Article in English | MEDLINE | ID: mdl-27090393

ABSTRACT

BACKGROUND: We investigated the feasibility of using an online registry to provide prevalence data for multiple orphan lung diseases in Australia and New Zealand. METHODS: A web-based registry, The Australasian Registry Network of Orphan Lung Diseases (ARNOLD) was developed based on the existing British Paediatric Orphan Lung Disease Registry. All adult and paediatric respiratory physicians who were members of the Thoracic Society of Australia and New Zealand in Australia and New Zealand were sent regular emails between July 2009 and June 2014 requesting information on patients they had seen with any of 30 rare lung diseases. Prevalence rates were calculated using population statistics. RESULTS: Emails were sent to 649 Australian respiratory physicians and 65 in New Zealand. 231 (32.4%) physicians responded to emails a total of 1554 times (average 7.6 responses per physician). Prevalence rates of 30 rare lung diseases are reported. CONCLUSIONS: A multi-disease rare lung disease registry was implemented in the Australian and New Zealand health care settings that provided prevalence data on orphan lung diseases in this region but was limited by under reporting.


Subject(s)
Lung Diseases/epidemiology , Rare Diseases/epidemiology , Registries , Australia , Humans , New Zealand , Prevalence
2.
Intern Med J ; 45(11): 1134-40, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26337683

ABSTRACT

BACKGROUND: Screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) is now standard care in this disease. The existing Australian Scleroderma Interest Group algorithm (ASIGSTANDARD ) is based on transthoracic echocardiography (TTE) and pulmonary function tests (PFT). Recently, ASIG has derived and validated a new screening algorithm (ASIGPROPOSED ) that incorporates N-terminal pro-B-type natriuretic peptide level together with PFT in order to decrease reliance on TTE, which has some limitations. Right heart catheterisation (RHC) remains the gold standard for the diagnosis of PAH in patients who screen 'positive'. AIM: To compare the cost of PAH screening in SSc with ASIGSTANDARD and ASIGPROPOSED algorithms. METHODS: We applied both ASIGSTANDARD and ASIGPROPOSED algorithms to 643 screen-naïve SSc patients from the Australian Scleroderma Cohort Study (ASCS), assuming a PAH prevalence of 10%. We compared the costs of screening, the number of TTE required and both the total number of RHC required and the number of RHC needed to diagnose one case of PAH, and costs, according to each algorithm. We then extrapolated the costs to the estimated total Australian SSc population. RESULTS: In screen-naïve patients from the ASCS, ASIGPROPOSED resulted in 64% fewer TTE and 10% fewer RHC compared with ASIGSTANDARD , with $1936 (15%) saved for each case of PAH diagnosed. When the costs were extrapolated to the entire Australian SSc population, there was an estimated screening cost saving of $946 000 per annum with ASIGPROPOSED , with a cost saving of $851 400 in each subsequent year of screening. CONCLUSIONS: ASIGPROPOSED substantially reduces the number of TTE and RHC required and results in substantial cost savings in SSc-PAH screening compared with ASIGSTANDARD .


Subject(s)
Algorithms , Cost Savings/methods , Hypertension, Pulmonary/economics , Mass Screening/economics , Scleroderma, Systemic/economics , Aged , Cohort Studies , Echocardiography/economics , Echocardiography/methods , Female , Humans , Hypertension, Pulmonary/diagnosis , Male , Mass Screening/methods , Middle Aged , Prospective Studies , Respiratory Function Tests/economics , Respiratory Function Tests/methods , Scleroderma, Systemic/diagnosis
4.
Clin Exp Rheumatol ; 32(6 Suppl 86): S-133-7, 2014.
Article in English | MEDLINE | ID: mdl-24564981

ABSTRACT

OBJECTIVES: To determine the prevalence and correlates of antiphospholipid antibodies (APLA) in systemic sclerosis (SSc). METHODS: Nine hundred and forty SSc patients were tested for APLA using an ELISA assay at recruitment. Clinical manifestations were defined as present, if ever present from SSc diagnosis. Logistic regression analysis was used to determine the associations of APLA. RESULTS: One or more types of APLA were present in 226 (24.0%) patients. Anticardiolipin (ACA) IgG (ACA-IgG) antibodies were associated with right heart catheter-diagnosed pulmonary arterial hypertension (PAH), with higher titres corresponding with a higher likelihood of PAH (moderate titre (20-39 U/ml) ACA-IgG odds ratio [OR] 1.70, 95% CI: 1.01-2.93, p=0.047; high titre (>40 U/ml) ACA-IgG OR 4.60, 95% CI:1.02-20.8, p=0.047). Both ACA-IgM (OR 2.04, 95% CI: 1.4-3.0, p<0.0001) and ACA-IgG (OR 1.84, 95% CI: 1.2-2.8, p=0.005) were associated with interstitial lung disease (ILD). Increasing ACA-IgM and IgG titres were associated with increased likelihood of ILD. ACA-IgG was a marker of coexistent pulmonary hypertension and ILD (ILD-PH) (OR 2.10, 95% CI: 1.1-4.2, p=0.036). We also found an association between ACA-IgG and digital ulcers (OR 1.76, 95% CI: 1.16-2.67, p=0.008) and ACA-IgM and Raynaud's phenomenon (OR 2.39, 95% CI: 1.08-5.27, p=0.031). There was no association between APLA and SSc disease subtype, peak skin score, presence of other autoantibodies, mortality or other disease manifestations. CONCLUSIONS: The association of APLA with PAH, ILD, ILD-PH, Raynaud's phenomenon and digital ulcers suggests that endothelial abnormalities and small vessel thrombosis may be important in the pathogenesis of these disease features.


Subject(s)
Antibodies, Anticardiolipin/immunology , Heart Diseases/immunology , Hypertension, Pulmonary/immunology , Lung Diseases, Interstitial/immunology , Scleroderma, Systemic/immunology , Aged , Antibodies, Antiphospholipid/immunology , Cohort Studies , Female , Hand Dermatoses/etiology , Hand Dermatoses/immunology , Heart Diseases/etiology , Humans , Hypertension, Pulmonary/etiology , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Logistic Models , Lung Diseases, Interstitial/etiology , Male , Middle Aged , Prospective Studies , Raynaud Disease/etiology , Raynaud Disease/immunology , Scleroderma, Systemic/complications , Skin Ulcer/etiology , Skin Ulcer/immunology
5.
Intern Med J ; 43(5): 599-603, 2013 May.
Article in English | MEDLINE | ID: mdl-23668273

ABSTRACT

Pulmonary arterial hypertension (PAH) is a major cause of mortality in scleroderma and despite 'advanced' therapies confers a median survival of less than 5 years. Anticoagulation in systemic sclerosis-related PAH (SSc-PAH) is currently one of the most contentious issues in the management of patients with connective tissue disease. While some studies have shown a survival benefit with warfarin therapy in this disease, others have not. Accordingly, a state of clinical equipoise exists in relation to anticoagulation in SSc-PAH. With an over fivefold reduction in mortality demonstrated in some observational studies, the issue of anticoagulation in SSc-PAH demands resolution through a well-designed randomised controlled trial.


Subject(s)
Anticoagulants/therapeutic use , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/epidemiology , Scleroderma, Systemic/drug therapy , Scleroderma, Systemic/epidemiology , Familial Primary Pulmonary Hypertension , Humans
6.
Int J Clin Pract ; 66(11): 1117-24, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23067036

ABSTRACT

BACKGROUND: Pulmonary hypertension (PH) is a condition that affects more than 25 million individuals worldwide and causes premature disability and death. Despite advances in our understanding of this condition, education and training of health professionals has not kept pace with the rapid changes in diagnosis and treatment. The net effects of this gap between advancing knowledge and limited educational opportunity likely include clinically significant delays in both the diagnosis and commencement of effective evidence-based treatment - an unacceptable outcome for patients with a lethal condition. AIM: The Actelion Clinical Excellence Programme (ACEP) is an e-learning postgraduate curriculum, the purpose of which is to educate and mentor healthcare professionals, both theoretically and practically, in the diagnosis and treatment of patients with all forms of PH. This article reports on the development and delivery of the programme and outcomes from its first year of operation. RESULTS: Forty-three healthcare professionals from 22 institutions were enroled in the first iteration of the programme. In the 6 months from May to October 2011, participants successfully completed 285 lectures and/or activities. Overall, the programme was considered easily accessible, comprehensive in terms of both quality and quantity, provided an efficient means of self-paced learning, and was a highly regarded as reference source. Ninety-five per cent of participants said that they intended to change their clinical practice as a result of the information presented in the programme. CONCLUSION: ACEP represents a successful physician-industry partnership, which has resulted in a significant impact on clinical teaching and awareness of PH.


Subject(s)
Education, Medical, Graduate/organization & administration , Hypertension, Pulmonary/therapy , Internet , Pulmonary Medicine/education , Australia , Clinical Competence/standards , Curriculum , Evidence-Based Medicine/education , Humans , New Zealand , Program Evaluation
7.
Intern Med J ; 41(9): 679-87, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21470356

ABSTRACT

BACKGROUND: Exercise-induced pulmonary arterial hypertension (EIPAH) is associated with reduced peak exercise cardiac output (CO) and aerobic capacity (peak ). We investigated the validity of the encouraged 6-min walk test (6MWT) to identify exercise limitation and estimate aerobic capacity in subjects with EIPAH. METHODS: Seventeen subjects with EIPAH (56 ± 14 years, 15 women) and 20 healthy controls (57 ± 13 years, 19 women) underwent two encouraged 6MWTs and a symptom-limited cardiopulmonary exercise test (CPET). To measure central haemodynamics, subjects with EIPAH performed the CPET with a pulmonary artery catheter in situ. RESULTS: Compared with controls, subjects with EIPAH had reduced peak (1.2 ± 0.4 vs 1.7 ± 0.5, L/min, P < 0.01), 6-min walk distance (6MWD) (575 ± 86 vs 669 ± 76 m, P < 0.001) and 6-min walk work (6MWW) (39 ± 11 vs 45 ± 7 km.kg, P < 0.01). In subjects with EIPAH, there was a moderate correlation between 6MWD and peak (r= 0.72, P < 0.01) and a strong correlation between 6MWW and peak (r= 0.86, P < 0.001). There were significant correlations between 6MWD and peak CO (r= 0.59, P < 0.05), and between peak and peak CO (r= 0.55, P < 0.05). Peak heart rate was similar in the CPET and 6MWT in subjects with EIPAH (133 ± 15 vs 133 ± 19 beats/min, P= 0.8). CONCLUSIONS: The encouraged 6MWT identifies reduced exercise capacity and provides a valid estimate of aerobic capacity in EIPAH.


Subject(s)
Exercise Test/standards , Exercise Tolerance/physiology , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/physiopathology , Walking , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Databases, Factual , Exercise/physiology , Exercise Test/methods , Familial Primary Pulmonary Hypertension , Female , Humans , Male , Middle Aged , Prospective Studies
8.
Intern Med J ; 41(3): 227-34, 2011 Mar.
Article in English | MEDLINE | ID: mdl-20002851

ABSTRACT

BACKGROUND/AIMS: The Bosentan Patient Registry (BPR) was a prospective, multicentre, Australian registry funded by Actelion Pharmaceuticals. The primary aim of the registry was to collect survival data in patients with pulmonary arterial hypertension (PAH) treated with bosentan. METHODS: The BPR was initiated in 15 specialized PAH centres. All patients on or starting bosentan were invited to enrol. Treating physicians notified the registry if patients discontinued bosentan, because of either a change in therapy, transplantation, intervention or death. Survival data were validated against the Australian Institute of Health and Welfare National Death Index. RESULTS: Between 2004 and 2007, a total of 528 patients (mean age 59 ± 17 years) were enrolled representing 69% of patients either previously taking or initiated on bosentan during that time. The BPR population was generally older with more advanced functional deficit than patients enrolled in randomized, placebo-controlled trials. Aetiology was idiopathic (iPAH) in 58% and connective tissue disease related (scleroderma (SSc)-PAH) in 42%. For iPAH patients, World Health Organisation functional classes II, III and IV at enrolment was 8.2%, 66.4% and 20.5%, and for the SSc-PAH cohort, 3.2%, 75.8% and 17.9% respectively. The observed annual mortality was 11.8% in patients with iPAH and 16.6% in patients SSc-PAH. CONCLUSION: This large Australian registry provides 'real life' information on the characteristics and management of PAH in clinical practice. Treatment with bosentan improved survival outcomes in both iPAH and SSc-PAH compared with historical controls. Age, disease severity and aetiology were critical factors in determining clinical outcomes.


Subject(s)
Antihypertensive Agents/therapeutic use , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/mortality , Registries , Sulfonamides/therapeutic use , Adolescent , Adult , Aged , Australia/epidemiology , Bosentan , Familial Primary Pulmonary Hypertension , Female , Humans , Male , Middle Aged , Prospective Studies , Survival Rate/trends , Time Factors , Treatment Outcome , Young Adult
9.
Intern Med J ; 41(3): 235-44, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21118410

ABSTRACT

BACKGROUND: Several cellular pathways are implicated in the pathogenesis of pulmonary arterial hypertension (PAH) and attempts to arrest disease progression with a single drug would not be expected to succeed in the medium term. In clinical practice, combination therapy is often used in patients deteriorating on monotherapy, despite the absence of firm evidence from randomized controlled controls. METHODS: From January 2005 to August 2009, 112 patients with World Health Organisation Functional Class (FC) II-IV PAH deteriorating on monotherapy received non-parenteral combination therapy at six Australian PAH expert hospitals. Combination therapy included bosentan, sitaxentan, ambrisentan, iloprost and sildenafil. Data were prospectively collected for survival status, 6-min walk distance, FC and echocardiographic parameters at the start of monotherapy through to commencement of combination therapy and at 6-monthly intervals thereafter. RESULTS: After varying periods of monotherapy (18.7±13.4onths), survival estimates on combination therapy were 88%, 71% and 61% for the additional 1, 2 and 3years respectively. Survival on dual therapy in patients with idiopathic PAH/familial PAH was 93% at 1year and 79% at 2years, and for scleroderma-related PAH, 72% at 1 year and 48% at year 2 after initiation of combination therapy. In survivors, dual therapy reversed the deterioration in FC, from 3.1±0.6 on monotherapy to 2.2±0.6 at 12months. Similarly, dual therapy improved 6-min walk distance from 316±119m to 406±129m at 12months, and sequential echocardiography demonstrated a fall in pulmonary artery systolic pressure and improved right ventricular function. CONCLUSIONS: Dual non-parenteral therapy appears safe and effective and should be considered for PAH patients who are deteriorating on monotherapy to improve long-term outcomes.


Subject(s)
Cooperative Behavior , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/mortality , Adult , Aged , Australia/epidemiology , Bosentan , Drug Therapy, Combination , Familial Primary Pulmonary Hypertension , Female , Humans , Male , Middle Aged , Phenylpropionates/administration & dosage , Piperazines/administration & dosage , Prospective Studies , Purines/administration & dosage , Pyridazines/administration & dosage , Sildenafil Citrate , Sulfonamides/administration & dosage , Sulfones/administration & dosage , Survival Rate/trends , Young Adult
10.
Intern Med J ; 40(7): 494-502, 2010 Jul.
Article in English | MEDLINE | ID: mdl-19460060

ABSTRACT

BACKGROUND: Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) represent the leading causes of death in systemic sclerosis (SSc). Screening for these complications has assumed greater importance, but is not universal. The aim of this study is to determine the self-reported screening, diagnosis and treatment practices of rheumatologists and respiratory physicians for SSc-related lung disease. METHODS: Email survey of 270 rheumatologists and 600 respiratory physicians. RESULTS: Responses were received from 42 (16%) rheumatologists and 68 (11%) respiratory physicians. Of SSc patients seen by rheumatologists, 17% had ILD and 7.5% had a diagnosis of PAH compared with 31% and 21% for respiratory physicians. Forty per cent of all physicians screened asymptomatic SSc patients without a known diagnosis of ILD or PAH less than annually or not at all. The most commonly used screening investigations were pulmonary function tests (PFT) (95%) and transthoracic echocardiogram (TTE) (78%). In suspected ILD, both groups used high-resolution computed tomography scans and PFT in >90% of patients. In suspected PAH, both used TTE and PFT (>90%); right heart catheterisation was used by only 50% of physicians. In treatment of ILD, rheumatologists used intravenous (IV) cyclophosphamide more often (CYC) (59% vs 28%, P= 0.003) and more respiratory physicians used oral CYC (44% vs 28%, P= 0.012). In PAH, more respiratory physicians used warfarin (68% vs 40%, P= 0.006). Only approximately 65% of physicians had used specific PAH therapy, which may reflect lack of access to a designated PAH treatment centre. CONCLUSION: The heterogeneity of responses revealed in this study raises the importance of screening, diagnosis and treatment algorithms in the management of this potentially life-threatening disease.


Subject(s)
Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/drug therapy , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/drug therapy , Physicians , Rheumatology/methods , Scleroderma, Systemic/diagnosis , Scleroderma, Systemic/drug therapy , Cyclophosphamide/therapeutic use , Data Collection/methods , Diagnosis, Differential , Disease Management , Humans , Hypertension, Pulmonary/epidemiology , Lung Diseases, Interstitial/epidemiology , Mass Screening/methods , Respiration Disorders/diagnosis , Respiration Disorders/drug therapy , Scleroderma, Systemic/epidemiology , Treatment Outcome , Warfarin/therapeutic use
11.
Intern Med J ; 39(11): 766-70, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19912403

ABSTRACT

Pulmonary arterial hypertension (PAH) in pregnancy carries a mortality of 30-56%. There are few published data to guide clinicians in its management. Two pregnant women with severe PAH have been treated at Royal Perth Hospital with a successful result in both. Their presentation and management are described. We review the physiological changes in pregnancy, pathophysiology in PAH, and review the literature describing treatment of PAH in pregnancy.


Subject(s)
Hypertension, Pulmonary/diagnosis , Pregnancy Complications, Cardiovascular/diagnosis , Adult , Female , Humans , Hypertension, Pulmonary/physiopathology , Hypertension, Pulmonary/therapy , Infant, Newborn , Male , Pregnancy , Pregnancy Complications, Cardiovascular/physiopathology , Pregnancy Complications, Cardiovascular/therapy , Young Adult
13.
Intern Med J ; 39(10): 682-91, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19220532

ABSTRACT

BACKGROUND: We sought to determine the prevalence of pulmonary complications and especially pulmonary arterial hypertension (PAH) in an Australian scleroderma population. METHODS: Between July 2005 and June 2007, physicians in Western Australia were asked to refer patients with scleroderma specifically for pulmonary hypertension screening. All patients were assessed for PAH and other respiratory conditions using echocardiography, lung function testing and clinical assessments. Right heart catheterization was carried out in patients with evidence of increased right ventricular systolic pressure. RESULTS: Of the 184 patients analysed, 44 had possible PAH on echocardiography. Right heart catheterization confirmed the diagnosis in 24 (13%). Diffuse interstitial lung disease was found in 32 patients representing a point prevalence of 17.4%. The severity of PAH at diagnosis varied according to whether the patients were referred for screening (group A) or for diagnostic (group B) purposes. The 6-min-walk test distance and median pulmonary vascular resistance were significantly worse in group B versus group A (324 vs 402 m; P= 0.02 and 884 dynes/s per cm(-5) vs 486 dynes/s per cm(-5); P < 0.01, respectively). CONCLUSION: Screening may result in earlier diagnosis of PAH with, in general more mild disease. This is important, given that early treatment for PAH while patients are less symptomatic is associated with improved exercise tolerance and pulmonary haemodynamics: indices indicative of disease progression and clinical worsening.


Subject(s)
Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/epidemiology , Mass Screening , Scleroderma, Systemic/diagnosis , Scleroderma, Systemic/epidemiology , Adult , Aged , Aged, 80 and over , Early Diagnosis , Female , Humans , Hypertension, Pulmonary/complications , Male , Mass Screening/methods , Middle Aged , Prevalence , Prospective Studies , Scleroderma, Systemic/complications , Western Australia/epidemiology
15.
Intern Med J ; 37(1): 38-48, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17199843

ABSTRACT

Pulmonary arterial hypertension is a group of diseases which forms a small subset of those with elevated pulmonary artery pressure (pulmonary hypertension). The recent development of selective pulmonary vasodilator has lead to a substantial resurgence of interest in what have been previously regarded as rare and incurable diseases. This review aims to describe the spectrum of pulmonary vascular diseases, the evolving understanding as to pathogenesis, the evolving evidence of efficacy for drug therapies, trying to put this into a contemporary Australian context. Several key pathogenic pathways may be involved: prostacycline, Nitric Oxide-cGMP-phosphodiesterase 5 and endothelin- all of which are exploited for therapeutic benefit by newly available drug therapies. A recently modified classification system reasserts the importance of precise diagnosis. The cardinal symptom of exertional dyspnea warrants careful evaluation in an attempt to prevent (frequently occurring) substantial delay in diagnosis. Echocardiogram is the cornerstone of screening for pulmonary arterial hypertension; however, a detailed evaluation including a carefully performed right heart catheterisation with sufficient data to allow calculation of pulmonary vascular resistance is key to accurate diagnosis. These new approaches to therapy are already substantially improving quality of life and prognosis.


Subject(s)
Hypertension, Pulmonary/epidemiology , Adolescent , Adult , Aged , Arterioles/pathology , Arterioles/physiopathology , Australia/epidemiology , Bosentan , Cardiac Catheterization , Diagnostic Imaging , Disease Progression , Dyspnea/etiology , Endothelin A Receptor Antagonists , Epoprostenol/analogs & derivatives , Epoprostenol/therapeutic use , Exercise Test , Female , Forecasting , Heart-Lung Transplantation , Humans , Hypertension, Pulmonary/classification , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/therapy , Iloprost/therapeutic use , Lung Transplantation , Male , Middle Aged , Nitric Oxide/metabolism , Piperazines/therapeutic use , Prognosis , Pulmonary Artery/pathology , Pulmonary Artery/physiopathology , Purines , Randomized Controlled Trials as Topic , Sildenafil Citrate , Sulfonamides/therapeutic use , Sulfones , Vascular Resistance , Vasodilator Agents/therapeutic use , Ventricular Dysfunction, Right/etiology , Ventricular Dysfunction, Right/prevention & control
16.
Lymphology ; 37(4): 202-5, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15693538

ABSTRACT

The aim of this study was to determine whether lymphedema of the arm is associated with traumatic injury to the shoulder and to assess the role of lymphatic physiotherapy in reducing disabling shoulder pain. The study group consisted of 10 women aged 58-81 years (mean 66.9) with arm lymphedema after surgery for breast cancer. The average interval between the operation and the appearance of lymphedema was 9.8 years. All patients complained of shoulder pain. Five patients had a tear in the supraspinatus muscle diagnosed by ultrasound examination, and 5 had chronic bursitis; the nonaffected arm showed no pathology. The mean volume of the affected arm was 568 ml greater. Treatment consisted of manual lymphatic drainage and intermittent sessions of pneumatic compression with the LymphaPress device. This led to an average decrease in arm volume of 170 ml, with improvement of arm mobility and a drastic reduction in shoulder pain. In conclusion, lymphedema of the arm can cause severe shoulder trauma, pain and disability. Proper physiotherapy can reduce these effects. Patients should be referred for early treatment and follow-up to avoid permanent damage to the shoulder muscles.


Subject(s)
Arm Injuries/etiology , Lymph Node Excision/adverse effects , Lymphedema/etiology , Mastectomy/adverse effects , Shoulder Injuries , Aged , Aged, 80 and over , Arm Injuries/therapy , Axilla , Breast Neoplasms/surgery , Female , Humans , Middle Aged , Physical Therapy Modalities , Shoulder Pain/etiology
17.
J Med Virol ; 64(3): 275-82, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11424115

ABSTRACT

The relationship between quantitative PCR (COBAS Amplicor CMV Monitor, Roche Diagnostics) and quantitative antigenemia (Monofluor pp65, Sanofi Diagnostics) was examined for monitoring CMV viraemia. A total of 469 specimens from immunocompromised haematology and solid organ transplant patients were tested by quantitative antigenemia and qualitative PCR. Quantitative PCR (QPCR) was performed on the 245 specimens in which CMV DNA was detected by qualitative PCR. To exclude any effect due to specific anti-CMV treatment, analysis of antigenemia and QPCR results was only performed on the 164 of 245 specimens collected from patients not on ganciclovir or foscarnet treatment. Forty seven specimens had <400 CMV copies/mL and a negative antigen result, four specimens were antigen positive (all between 1 to 10 positive CMV cells/2 x 10(5) leucocytes) and had <400 CMV copies/mL. Fifty-one specimens had a CMV viral load > or = 400 copies/mL and a negative antigen result and 62 specimens had a CMV viral load > or = 400 copies/mL and a positive antigen. The viral load was shown to be as high as 43,000 copies/mL in some patients with a negative antigen and occurred in non-neutropenic patients. The correlation coefficient for antigen and QPCR results for specimens from bone marrow transplant patients, was 0.69 with an average CMV viral load of 3,200 copies/mL (SEM = 800) and an average antigen of nine positive CMV cells/2 x 10(5) leucocytes (SEM = 3). In the corresponding solid organ transplant group, the correlation coefficient for antigen and QPCR results was 0.71 with an average CMV viral load of 9,900 copies/mL (SEM = 2,100) and an average antigen of 26 positive CMV cells/2 x 10(5) leucocytes (SEM = 6). Both the average viral load and the average antigen result in specimens from solid organ transplant patients, were significantly higher than the average viral load and antigen result in the corresponding group of bone marrow transplant patients (Two-Sample-for-Means z-Test, P = 0.001 and P = 0.003, respectively). The differences in the kinetics of the two assays in monitoring CMV and their ability to predict CMV disease was also assessed in a sub-group of patients. In conclusion, the two assays used in this study do not always show parallel changes in CMV viral load, but may be complementary for the diagnosis and management of CMV disease. The observation that non-neutropenic patients can have a high viral load in plasma and a negative antigenemia has implications for laboratories using antigenemia alone to monitor patients for CMV disease.


Subject(s)
Antigens, Viral/blood , Bone Marrow Transplantation/adverse effects , Cytomegalovirus Infections/diagnosis , Cytomegalovirus/isolation & purification , DNA, Viral/analysis , Immunologic Tests/methods , Organ Transplantation/adverse effects , Polymerase Chain Reaction/methods , Reagent Kits, Diagnostic , Viremia/virology , Cytomegalovirus/immunology , Cytomegalovirus Infections/virology , DNA, Viral/blood , Humans , Immunocompromised Host , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/virology , Microscopy, Fluorescence , Predictive Value of Tests , Reproducibility of Results , Sensitivity and Specificity , Viral Load
18.
Am J Respir Crit Care Med ; 162(6): 2182-7, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11112135

ABSTRACT

In conditions characterized by airway inflammation, exhaled nitric oxide (eNO) levels are increased. Post-lung transplant bronchiolitis obliterans syndrome (BOS) is characterized by airway inflammation and development of progressive airway narrowing and fibrosis. We have previously shown that in stable lung transplant recipients (LTR), mean eNO levels were not elevated but were still related to the degree of airway neutrophilia within the group. The hypothesis now tested is that in BOS, eNO levels are increased in association with even greater airway neutrophilia and enhanced expression of inducible (iNOS) nitric oxide synthase in the bronchial epithelium. We determined eNO levels in 40 LTR in four groups: well and "stable": LTR (n = 20), BOS (n = 8), bacterial airway infection (BI, n = 6), and acute rejection (AR, n = 6). Following bronchoscopic sampling, we performed a quantitative assessment of iNOS and constitutive nitric oxide synthase (cNOS) expression in endobronchial biopsies by immunohistochemistry. Mean +/- SEM eNO levels in BOS and BI were significantly higher than in stable LTR (20 +/- 1.2 parts per billion [ppb] and 24.7 +/- 1.7 ppb versus 12.5 +/- 0.9 ppb; p < 0.01 for both). In AR, eNO levels (13.4 ppb +/- 0.5) were not different in stable LTR (p = 0.34). When compared with stable LTR, there was increased expression of iNOS in the bronchial epithelium and generally in the lamina propria (LP) in patients with BOS and BI. In AR, iNOS expression was increased but only in the LP in a perivascular distribution. Expression of cNOS was reduced in BOS but not in BI and AR compared with the stable group. Using regression analysis, only iNOS expression in the bronchial epithelium (r(2) = 0.77; p < 0.0001) and %BAL neutrophils (r(2) = 0. 79; p < 0.0001) were positively related to eNO in stable LTR and BOS. We conclude that epithelial iNOS appears to be the major source of eNO. Exhaled NO levels also appear to reflect the degree of airway neutrophilia in both stable LTR and BOS groups. This suggests that serial eNO measurements may be able to predict the early development of BOS.


Subject(s)
Bronchi/enzymology , Cryptogenic Organizing Pneumonia/metabolism , Lung Transplantation/adverse effects , Nitric Oxide Synthase/metabolism , Nitric Oxide/metabolism , Postoperative Complications/metabolism , Acute Disease , Analysis of Variance , Breath Tests , Bronchoscopy , Epithelium/enzymology , Female , Graft Rejection/metabolism , Humans , Immunohistochemistry , Lung Transplantation/physiology , Male , Nitric Oxide Synthase Type II , Statistics, Nonparametric
19.
Respirology ; 5(3): 301-3, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11022996

ABSTRACT

Chylothorax is an uncommon condition rarely seen outside the clinical scenario of trauma or malignancy, and management may be difficult. We report the case of a 52-year-old man with a right chylothorax occurring 23 years after mantle irradiation for Hodgkin's disease. In addition, a Medline literature search was performed. Chylothorax occurring post-irradiation is rare and the aetiology is uncertain. Recurrent malignancy must be excluded. There are a number of management options and our patient was successfully treated with a combination of thoracocentesis, medium chain triglyceride diet and thoracoscopy with talc pleurodesis. There was no evidence of recurrent chylothorax at 2 years follow up. Prompt assessment and treatment is required. Surgical measures need to be considered early if medical treatment is unsuccessful.


Subject(s)
Chylothorax/etiology , Hodgkin Disease/radiotherapy , Radiation Injuries/etiology , Chylothorax/therapy , Combined Modality Therapy , Humans , Male , Middle Aged , Time Factors
20.
Ann Thorac Surg ; 69(6): 1711-6, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10892912

ABSTRACT

BACKGROUND: Selection criteria for lung volume reduction surgery are still being refined. We sought to determine whether preoperative features could be used to predict early morbidity or mortality. METHODS: We reviewed preoperative characteristics of the first 89 patients who underwent lung volume reduction surgery at the Alfred Hospital. Data included arterial blood gases, prednisolone use, pulmonary function tests, 6-minute walk test, and anesthetic time. Length of stay and reintubation for respiratory failure were used as markers of morbidity. RESULTS: Findings included PaCO2 of 43 +/- 0.7 mm Hg, PaO2 70 +/- 1.1 mm Hg, percent predicted values for forced expiratory volume in 1 second 29.6% +/- 0.8%, TLCO% predicted 35.2 +/- 1.4%, and 6-minute walk test of 315 +/- 10.6 m (mean +/- SEM). Mean length of stay was 19 +/- 2 days, with 17 (19%) patients reintubated for respiratory failure. Mortality rate was 5.6% at 1 year post surgery, with no deaths in patients less than 65 years old. Multivariate analysis revealed that length of stay, reintubation and mortality were predicted by age and surgical time (p < 0.05), with no correlation with any other variables tested. Age greater than 70 years was associated with a significant risk of mortality (OR 9.0; p = 0.04). CONCLUSIONS: Age greater than 70 years and anesthetic time greater than 210 minutes predict both perioperative morbidity and mortality.


Subject(s)
Pneumonectomy , Postoperative Complications/etiology , Pulmonary Emphysema/surgery , Adult , Age Factors , Aged , Female , Humans , Male , Middle Aged , Patient Selection , Postoperative Complications/mortality , Pulmonary Emphysema/mortality , Risk Assessment , Risk Factors , Survival Rate
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