18 research outputs found
Complications of chronic necrotizing pulmonary aspergillosis: review of published case reports
Chronic necrotizing pulmonary aspergillosis (CNPA), a form of chronic pulmonary aspergillosis (CPA), affects immunocompetent or mildly immunocompromised persons with underlying pulmonary disease. These conditions are associated with high morbidity and mortality and often require long-term antifungal treatment. The long-term prognosis for patients with CNPA and the potential complications of CNPA have not been well documented. The aim of this study was to review published papers that report cases of CNPA complications and to highlight risk factors for development of CNPA. The complications in conjunction associated with CNPA are as follows: pseudomembranous necrotizing tracheobronchial aspergillosis, ankylosing spondylarthritis, pulmonary silicosis, acute respiratory distress syndrome, pulmonary Mycobacterium avium complex (MAC) disease, superinfection with Mycobacterium tuberculosis, and and pneumothorax. The diagnosis of CNPA is still a challenge. Culture and histologic examinations of bronchoscopically identified tracheobronchial mucus plugs and necrotic material should be performed in all immunocompromised individuals, even when the radiographic findings are unchanged. Early detection of intraluminal growth of Aspergillus and prompt antifungal therapy may facilitate the management of these patients and prevent development of complications
First reported case of fulminant TB with progression of infection from lungs to the genitourinary region
Although tuberculosis (TB) is a curable disease, it continues to be one of the leading infections associated with death in the world. Extra-pulmonary TB (EPTB) occurs in approximately 10% of the total cases, presenting with lymph nodes, pleura, bone and genitourinary tract as the most common locations. Genitourinary tuberculosis, the second most common EPTB, is very difficult to diagnose unless there is a high index of suspicion. Isolated TB orchitis or prostatitis without clinical evidence of renal involvement is a rare entity among genitourinary tuberculosis. We presented the first reported case of TB prostatitis and orchitis associated with pulmonary TB and the presence of an acute massive caseous pneumonia in an immunocompetent man. Despite the anti-TB therapy, the patient presented a rapid progression of disease and deterioration of general conditions taking to death, which occurred four days after TB treatment had started. Disseminated TB is a relatively uncommon cause of acute massive caseous pneumonia; however, there should always be suspicion of the disease, since it is a potentially treatable cause. This rare case supports the assertion that TB should be considered as an important differential diagnosis of genitourinary tumors irrespective of evidence of active TB elsewhere in the body
Alpha-1-antitrypsin deficiency: Molecular basis, clinical presentation, therapeutic options and an integrative approach in diagnostics
Primarna uloga alfa-1-antitripsina (AAT) jeste da zaÅ”titi pluÄni parenhim od proteolize dejstvom neutrofilne elastaze. Njegovu biosintezu kontroliÅ”e izuzetno polimorfni GEN SERPINA1. Deficijencija AAT (AATD) jeste autozomalno recesivno oboljenje i smatra se najÄeÅ”Äim genetskim uzrokom oboljenja jetre kod dece i emfizema kod odraslih. Prema uÄestalosti, deficijentni aleli se mogu podeliti na "Äeste" (Z i S) i "retke" (Mmalton, Mheerlen, Mprocida itd.). Za vrstu, intenzitet i vremenski period u kome se razvijaju kliniÄke manifestacije smatra se odgovornim interakcija AATD i dodatnih genetskih i steÄenih faktora rizika (puÅ”enje, izloženost aerozagaÄenju i sl.). Kod obolelih se najÄeÅ”Äe javljaju preuranjen emfizem, hroniÄni hepatitis, ciroza i hepatocelularni karcinom. EpidemioloÅ”ke studije naglaÅ”avaju potrebu poveÄanja dijagnostiÄke efikasnosti kod AATD. PreporuÄuje se da dijagnostiÄki pristup integriÅ”e precizne, meÄunarodno identifikovane, kliniÄke kriterijume i standardizovan laboratorijski protokol, zasnovan na biohemijskim i molekularno-bioloÅ”kim metodama. Terapijski pristup zavisi od vrste kliniÄkih manifestacija. Kod pulmoloÅ”kih bolesnika je moguÄe primeniti terapiju nadoknade, dok kod osoba sa terminalnom fazom oÅ”teÄenja jetre uzrokovanog AATD transplantacija trenutno predstavlja jedinu specifiÄnu terapiju. Kod svih obolelih je neophodno preventivno uticati na smanjenje Å”tetnog uticaja životnih navika i faktora sredine. OÄekuje se da zdravstveni ishodi kod obolelih budu znaÄajno unapreÄeni uvoÄenjem genske terapije. DosadaÅ”nji rezultati istraživanja efikasnosti integrativnog pristupa detekciji AATD u populaciji Srbije su ohrabrujuÄi i upuÄuju na potrebu njegovog omasovljenja, Äime bi se ostvarili uslovi za formiranje nacionalnog registra obolelih.The primary role of Alpha-1-antitrypsin (AAT), encoded by the highly polymorphic SERPINA1 gene, is to protect the lung parenchyma from proteolysis by neutrophil elastase. AAT deficiency (AATD) is an autosomal recessive disease, considered as the most important genetic cause of liver disease in children and emphysema in adults. According to frequency, deficient alleles can be classified as "common" (Z and S) and "rare" (Mmalton, Mheerlen, Mprocida etc). Type, intensity and onset of clinical disease associated with AATD occur as a result of interaction between AATD and additional genetic and acquired factors (tobacco smoking, air pollution exposure etc). The most frequent clinical manifestations include premature emphysema, chronic hepatitis, cirrhosis and hepatocellular carcinoma. Epidemiological studies highlight the need for improvement in diagnostic efficiency for AATD. It is recommended for a diagnostic approach to integrate precise, internationally recognized clinical criteria and a standardized laboratory protocol, based on a combination of biochemical and molecular methods. The predilection site of clinical manifestations guides the therapeutic approach. Augmentation therapy is possible in lung disease, while currently the only specific measure in patients with severe liver failure due to AATD is transplantation. In all patients, preventive measures, ammeliorating the deleterious effects of habits and environmental factors are recommended. Introduction of gene therapy is expected to additionally improve health outcomes in affected persons. Current results with an integrative AATD diagnostic strategy in the Serbian population are highly encouraging, prompting towards its further implementation in common medical practice with the ultimate goal to establish a national register of affected individuals
Questionable reliability of homocysteine as the metabolic marker for folate and vitamin B12 deficiency in patients with chronic obstructive pulmonary disease
Uvod: PoviÅ”ena koncentracija homocisteina (Hey) može predstavljati metaboliÄki marker nedostatka folata i vitamina B12, znaÄajnih problema javnog zdravlja. Bolesnici sa hroniÄnom opstruktivnom boleÅ”Äu pluÄa (HOBP) skloni su nedostatku ovih vitamina usled razliÄitih razloga. Prikazana studija procenjuje pouzdanost koncentracije Hcy kao prediktora nedostatka folata i vitamina B12 kod ovih bolesnika. Metode: Studija je sprovedena u grupi od 50 osoba obolelih od HOBP (28 muÅ”karaca/22 žene, starosti (xĀ±SD = 49,0Ā±14,5) godina. Koncentracije Hcy, folata i vitamina B12 su odreÄivane hemiluminiscentnim imunoodreÄivanjem na mikroÄesticama. StatistiÄka analiza je ukljuÄila testove Kolmogorov-Smirnov, Mann-Whitney U and x2, Spearman-ovu korelaciju i ROC analizu, uz nivo znaÄajnosti od 0,05. Rezultati: ProseÄne (SD) koncentracije folata i vitamina B-12 su iznosile 4,15 (2,16) pg/L i 465,6 (271,0) ng/L, pri Äemu je samo kod vitamina B12 uoÄena korelacija sa nivoom Hcy (R =-0,510 (P=0,029)). Koncentracije vitamina se nisu razlikovale izmeÄu polova, a starost je bila u korelaciji samo sa nivoom folata (R= 0,279 (P=0,047)). Incidenca nedostatka vitamina znaÄajno se razlikovala (P=0,000 i P lt 0,000 za folat odn. vitamin B12) u zavisnosti od cut-off vrednosti u odnosu na koju je definisana (4,4; 6,6 i 8,0 pg/L - folat; 203 i 473 ng/L - vitamin B-12)-ROC analizom nije bilo moguÄe dokazati znaÄaj hiperhomocisteinemije kao prediktora deficijencije. ZakljuÄak: Pouzdanost koncentracije Hey kao markera nedostatka folata ili vitamina B12 kod bolesnika sa HOBP nije zadovoljavajuÄa, pa se deficijencija ovih vitamina ne može predvideti na osnovu pojave hiperhomocisteinemije.Background: An increased homocysteine (Hey) concentration may represent a metabolic marker of folate and vitamin Bi2 deficiency, both significant public health problems. For different reasons, patients with chronic obstructive pulmonary disease (COPD) are prone to these deficiencies. The study evaluates the reliability of Hey concentration in predicting folate or vitamin B12 deficiency in these patients. Methods: A group of 50 COPD patients (28 males/22 females, age (xĀ±S D = 49.0Ā±14.5) years was enrolled. A chemiluminescent microparticle immunoassay was applied for homocysteine, folate and vitamin B12 concentration. Kolmogorov-Smirnov, Mann-Whitney U and x2 tests, Spearman's correlation and ROC analysis were included in the statistical analysis, with the level of significance set at 0.05. Results: Average (SD) concentrations of folate and vitamin B12 were 4.15 (2.16) pg/L and 465.6 (271.0) ng/L, whereas only vitamin B12 correlated with the Hey level (P =-0.510 (R=0.029)). Gender related differences were not significant and only a borderline significant correlation between age and folate was confirmed (R = 0.279 (P=0.047)). The incidence of folate and vitamin B12 deficiency differed significantly (P=0.000 and PcO.OOO for folate and vitamin B12 respectively), depending on the cutoff used for classification (4.4, 6.6 and 8.0 pg/L - folate; 203 and 473 ng/L - vitamin B12)-ROC analyses failed to show any significance of hyperhomocysteinemia as a predictor of folate or vitamin B12 deficiency. Conclusion: Reliability of the Hey concentration as a biomarker of folate or vitamin B12 depletion in COPD patients is not satisfactory, so their deficiency cannot be predicted by the occurrence of HHcy
Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?
Introduction: Alpha-1-antitrypsin deficiency (AATD), genetic risk factor for premature chronic obstructive pulmonary disease (COPD), often remains undetected. The aim of our study was to analyse the effectiveness of an integrative laboratory algorithm for AATD detection in patients diagnosed with COPD by the age of 45 years, in comparison with the screening approach based on AAT concentration measurement alone. Subjects and methods: 50 unrelated patients (28 males / 22 females, age 52 (24-75 years) diagnosed with COPD before the age of 45 years were enrolled. Immunonephelometric assay for alpha-1-antitrypsin (AAT) and PCR-reverse hybridization for Z and S allele were first-line, and isoelectric focusing and DNA sequencing (ABI Prism BigDye) were reflex tests. Results: AATD associated genotypes were detected in 7 patients (5 ZZ, 1 ZM(malton), 1 ZQ0(amersfoort)), 10 were heterozygous carriers (8 MZ and 2 MS genotypes) and 33 were without AATD (MM genotype). Carriers and patients without AATD had comparable AAT concentrations (P = 0.125). In majority of participants (48) first line tests were sufficient to analyze AATD presence. In two remaining cases reflex tests identified rare alleles, M-malton and Q0(amersfoort), the later one being reported for the first time in Serbian population. Detection rate did not differ between algorithm and screening both for AATD (P = 0.500) and carriers (P = 0.063). Conclusion: There is a high prevalence of AATD affected subjects and carriers in a group of patients with premature COPD. The use of integrative laboratory algorithm does not improve the effectiveness of AATD detection in comparison with the screening based on AAT concentration alone
Questionable Reliability of Homocysteine As the Metabolic Marker for Folate and Vitamin B12 Deficiency in Patients with Chronic Obstructive Pulmonary Disease
Background: An increased homocysteine (Hcy) concentration may represent a metabolic marker of folate and vitamin B-12 deficiency, both significant public health problems. For different reasons, patients with chronic obstructive pulmonary disease (COPD) are prone to these deficiencies. The study evaluates the reliability of Hcy concentration in predicting folate or vitamin B-12 deficiency in these patients. Methods: A group of 50 COPD patients (28 males/22 females, age ((X) over bar +/- SD=49.0 +/- 14.5) years was enrolled. A chemiluminescent microparticle immunoassay was applied for homocysteine, folate and vitamin B-12 concentration. Kolmogorov-Smirnov, Mann-Whitney U and chi(2) tests, Spearman's correlation and ROC analysis were included in the statistical analysis, with the level of significance set at 0.05. Results: Average (SD) concentrations of folate and vitamin B-12 were 4.13 (2.16) mu g/L and 463.6 (271.0) ng/L, whereas only vitamin B-12 correlated with the Hcy level (P=-0.310 (R=0.029)). Gender related differences were not significant and only a borderline significant correlation between age and folate was confirmed (R=0.279 (P=0.047)). The incidence of folate and vitamin B-12 deficiency differed significantly (P=0.000 and P lt 0.000 for folate and vitamin B12 respectively), depending on the cutoff used for classification (4.4, 6.6 and 8.0 mu g/L folate; 203 and 473 ng/L - vitamin B-12). ROC analyses failed to show any significance of hyperhomocysteinemia as a predictor of folate or vitamin B-12 deficiency. Conclusion: Reliability of the Hcy concentration as a biomarker of folate or vitamin B-12 depletion in COPD patients is not satisfactory, so their deficiency cannot be predicted by the occurrence of HHcy
Isoelectrofocusing and PCR Amplification-Reverse Hybridization Assay in Evaluation of Alpha-1-Antitrypsin Deficiency
Alpha-1-antitrypsin deficiency is a potentially lethal genetic disorder, which has pulmonary and liver manifestations. The standardized biochemical and molecular diagnostic protocol for detection of clinically relevant alleles is needed. The paper summarizes current concepts about AATD, describes the potentials of isoelectric focusing and PCR amplification-reverse allele specific oligonucleotide hybridization assay in the detection of affected individuals and shortly presents our experiences in the evaluation of AATD. We conclude that the systematic clinical laboratory approach to AATD might be based on the combination of mentioned methods, coordinated by alpha-1-antritrypsin quantification. Additionally, its complete medical implementation is achieved through teamwork between clinical chemists, molecular biologists and clinicians
Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?
Introduction: Alpha-1-antitrypsin deficiency (AATD), genetic risk factor for premature chronic obstructive pulmonary disease (COPD), often remains undetected. The aim of our study was to analyse the effectiveness of an integrative laboratory algorithm for AATD detection in patients diagnosed with COPD by the age of 45 years, in comparison with the screening approach based on AAT concentration measurement alone. Subjects and methods: 50 unrelated patients (28 males / 22 females, age 52 (24-75 years) diagnosed with COPD before the age of 45 years were enrolled. Immunonephelometric assay for alpha-1-antitrypsin (AAT) and PCR-reverse hybridization for Z and S allele were first-line, and isoelectric focusing and DNA sequencing (ABI Prism BigDye) were reflex tests. Results: AATD associated genotypes were detected in 7 patients (5 ZZ, 1 ZM(malton), 1 ZQ0(amersfoort)), 10 were heterozygous carriers (8 MZ and 2 MS genotypes) and 33 were without AATD (MM genotype). Carriers and patients without AATD had comparable AAT concentrations (P = 0.125). In majority of participants (48) first line tests were sufficient to analyze AATD presence. In two remaining cases reflex tests identified rare alleles, M-malton and Q0(amersfoort), the later one being reported for the first time in Serbian population. Detection rate did not differ between algorithm and screening both for AATD (P = 0.500) and carriers (P = 0.063). Conclusion: There is a high prevalence of AATD affected subjects and carriers in a group of patients with premature COPD. The use of integrative laboratory algorithm does not improve the effectiveness of AATD detection in comparison with the screening based on AAT concentration alone
Anti-TNF treatment and miliary tuberculosis in Crohnās disease
Introdution. Tumour necrosis factor alpha (TNFĪ±) has a central role in the host immune response to mycobacterial infection. TNFĪ± blockade may therefore result in reactivation of recent or remotely acquired infection. In reported mycobacterium tuberculosis infections, extra-pulmonary and disseminated tuberculosis (TB) was common, appeared rapidly, and if unrecognized, with fatal outcome. We present a female patient with miliary TB following treatment with infliximab for fistulizing Crohnās disease. Case Outline. Five years before admission, the patient was diagnosed with Crohnās disease, with inflammation limited to the terminal ileum and sigmoid colon and has been on azathioprine 100 mg/day for the last 10 months. Three months before admission to the hospital she developed an enterocutaneous fistula for which therapy with infliximab was started in addition to azathioprine therapy. A tuberculin skin test and a chest x-ray were performed prior to the first infusion with normal findings. She presented with a 6-week history of fever, weakness, weight-loss and a 2-week dry cough. Chest x-ray and computed tomography displayed remarkable bilateral hilar and mediastinal lymphadenopathy and uniformly distributed fine nodules throughout both lung fields varying in size from 2 to 3 mm, without any signs of cavitation. Since there were clinical and morphological signs that indicated miliary TB, the treatment with antituberculous therapy was started and six weeks later all of the symptoms completely resolved and the lesions visible on x-ray diminished. Conclusion. The clinical use of TNF-inhibitors is associated with increased risk of developing tuberculosis. Physicians should be aware of the increased risk of reactivation of TB among patients treated with anti-TNF agents and regularly look for usual and unusual symptoms of TB