Abdurrahman Senyigit

Mutations in SLC34A2 Cause Pulmonary Alveolar Microlithiasis and Are Possibly Associated with Testicular Microlithiasis

Pulmonary alveolar microlithiasis (PAM) is a rare disease characterized by the deposition of calcium phosphate microliths throughout the lungs. We first identified a PAM locus by homozygosity mapping to 4p15, then identified, by a candidate-gene approach, the gene responsible for the disease as SLC34A2 (the type IIb sodium-phosphate cotransporter gene), which is involved in phosphate homeostasis in several organs. We identified six homozygous exonic mutations in the seven unrelated patients with PAM we studied. Three of the mutations were frameshifts, one was a chain termination, one was an amino acid substitution, and one was a deletion spanning the minimal promoter and the first exon. Absence of functional protein product of the gene is compatible with calcium phosphate deposition in alveolar airspaces. We show that impaired activity of the phosphate transporter is presumably responsible for the microliths and that PAM is a recessive monogenic disease with full penetrance. Testicular microlithiasis (TM) is a disease that is more common than PAM. It is often associated with cancer and infertility. Since the gene we identified is also expressed in testis, we searched for mutations in subjects with TM. In 2 of the 15 subjects with TM we studied, we identified two rare variants, one synonymous and the other noncoding, that are possibly associated with the condition.

Is a complete blood cell count useful in determining the prognosis of pulmonary embolism

SummaryBackgroundPulmonary embolism (PE) is the third cardiovascular cause of hospital admission, following acute coronary syndrome and stroke. Despite high-tech diagnostic methods and new treatment modalities, PEs continue to have a high mortality rate within the first 3 months. This study was designed to assess the additional prognostic value of a complete blood cell count, renal function markers, C-reactive protein, and simplified pulmonary embolism severity index (sPESI) scoring system in PE 100-day mortality.Materials and methodsThe study retrospectively enrolled 208 consecutive patients who were hospitalized with the diagnosis of an acute PE. The patients’ demographic characteristics and clinical and laboratory parameters were recorded from the hospital electronic database and patient’s case notes. The primary end point of the study was an adverse 100-day outcome, defined as death from any cause.ResultsThe all-cause mortality in the first 100 days was 14.42 %. The mean age was 57.87 ± 18.17 (range: 16–93) years. We included 79 (38 %) male and 129 (62 %) female individuals. Red cell distribution width (RDW) and sPESI were found to be statistically significant predictors of PE mortality by multivariate regression analysis. On multivariate regression analysis, RDW was associated with a 4.08-fold (95 % confidence interval: 1.229–13.335, P = 0.021) increase in PE mortality.ConclusionThe results of this study demonstrated that RDW and sPESI may be a useful guide in predicting 100-day mortality. The elevated RDW may alert physicians to possible poor prognosis.ZusammenfassungGrundlagenDie Pulmonalembolie (PE) ist nach dem akuten Koronarsyndrom und dem Schlaganfall der dritthäufigste kardiovaskuläre Grund für eine Aufnahme ins Spital. Trotz hochtechnisierter Diagnostik und neuen Behandlungsmethoden haben Patienten mit einer PE noch immer eine hohe Mortalität innerhalb der ersten 3 Monate nach dem Ereignis. Die vorliegende Studie hat es sich zum Ziel gemacht, den zusätzlichen prognostischen Wert eines kompletten Blutbilds (kBB), des CRPs, von Markern der Nierenfunktion und von einem vereinfachten PE-Schweregrad Index (sPESI) in Bezug auf die Mortalität innerhalb der ersten 100 Tagen nach einer PE zu erheben.Material und MethodenDie Studie erfasste retrospektiv 208 konsekutive Patienten (79 (38 %) Männer, 129 (62 %) Frauen), die wegen der Diagnose einer akuten PE hospitalisiert worden waren. Die demographischen Charakteristika und Laborparameter wurden aus den elektronisch gespeicherten Spitalsdaten und individuellen Krankengeschichten erhoben. Der primäre Endpunkt der Studie war Tod jeder Ursache innerhalb der ersten 100 Tage.ErgebnisseDie Gesamtmortalität betrug 14,42 % innerhalb der ersten 100 Tage. Das mittlere Alter der Patienten lag bei 57,87 ± 18,17 (range: 16–93) Jahren. Die multivariate Regressionsanalyse ergab, dass die Verteilung der Erythrozytenbreite (RDW) und der erhobenen sPESI statistisch signifikante Prädiktoren der Mortalität nach PE waren. In dieser Analyse war die RDW mit einem 4,08 fachen (95 % CI: 1,229–13,335, P = 0,021) Anstieg der Mortalität nach PE verbunden.SchlussfolgerungenDie Ergebnisse dieser Studie zeigen, dass die RDW und sPESI im Bezug auf die Beurteilung der Prognose nach PE nützlich sein können. Erhöhte RDW könnten den Arzt auf eine möglicherweise schlechtere Prognose hinweisen.

Determination of environmental exposure to asbestos (tremolite) and mesothelioma risks in the southeastern region of Turkey.

Abstract In this study, the authors examined the concentrations and mineralogical analyses of asbestos, and investigated mesothelioma risk in southeastern Anatolia, Turkey. They used a gravimetric dust sampler to collect samples from 2 villages and 2 asbestos mines (1 active). Samples were then evaluated by an X-ray diffractometer and an electron microscope. The authors found high concentrations of asbestos in an active mine (4.9 fibers[f]/cm3) and at a house that was plastered with asbestos (1.24 f/cm3) and had a very active population. They found a low concentration (0.0042 f/cm3) in indoor measurements taken in Armutova village, and an even lower concentration (0.000081 f/cm3) in the inactive mine environment. Outdoor measurements included a low concentration of 0.007 f/cm3 in the village environment, and a high concentration of 1.17 f/cm3 on the mine road during the passing of a sheep herd. The people in the region are continuously exposed to asbestos during normal activities. This cumulative exposure to asbestos carries sufficient risks for mesothelioma development.

Fibulin-3 as a Diagnostic Biomarker in Patients with Malignant Mesothelioma

BACKGROUND New tumour biomarkers are being intensely investigated for malignant mesothelioma (MM). Fibulin-3 is produced in MM but its role remains uncertain. The aim of this study was to evaluate the validity of measuring serum fibulin-3 in the diagnosis and prognosis of MM. MATERIALS AND METHODS This prospective study was performed on 43 patients and 40 healthy controls who were admitted to our hospital between January 2012 and January 2014. Data from MM patients, including demographic and clinical features, routine laboratory data, levels of serum fibulin-3, and treatment outcomes were defined as potential prognostic factors. The receiver operating characteristic (ROC) curve for fibulin-3 was used to detect the cut-off value with highest sensitivity and specificity. Univariate survival analysis was performed using the Kaplan-Meier method in patients with MM. Afterwards, the possible factors identified with univariate analyses were entered into the cox regression analysis. RESULTS Our results revealed that patients with MM had significantly higher serum levels of fibulin-3 than controls. The results showed that the best cut-off point was 36.6 ng/ml with an AUC (area under the curve)=0.976, sensitivity=93.0% and specificity=90.0. In our study, the initial significant poor prognostic factors were advanced stage, high white blood cell count, high platelet count, high C-reactive protein (p<0.05 for each variable). Later, according to multivariate analysis the results showed only advanced stage as significant parameter (p=0.040). CONCLUSIONS We determined that real use for serum fibulin-3 was not for prognosis but for diagnosis in MM. Also advanced stage was associated with poor MM prognosis.

Follow-up results in tuberculous cervical lymphadenitis

OBJECTIVE To investigate the efficacy of medical antituberculous treatment in patients with tuberculous cervical lymphadenitis (TCL). METHODS In the period 1996-2002, 73 TCL patients were reviewed and the results of clinical and laboratory testing were documented. The efficacy of a four-drug chemotherapy regimen was investigated. RESULTS Purified protein derivatives (PPD) skin test results were positive in 58 (79 per cent) patients. Chest X-rays revealed changes consistent with tuberculosis in nine (12.3 per cent) patients. The mean duration of medical treatment was 10.04 months. In follow-up evaluation, 14 (20 per cent) patients were considered suspicious for resistant TCL and total excision of all nodes was performed. Histopathology confirmed TB in only 10 of these cases. CONCLUSION The high incidence of residual disease in our study indicates that medical treatment (at least nine months of four combined antituberculous drugs) did not seem to be effective. If lymphadenopathy persists, total surgical excision of lymph nodes should be the treatment of choice.

Clinical characteristics and treatment outcomes in 132 patients with malignant mesothelioma.

Purpose: Our objective is to scrutinize clinical, laboratory, radiological characteristics, treatment regimens, and treatment outcomes of malignant mesothelioma (MM) cases in our hospital. Materials and Methods: We investigated, retrospectively, the clinical characteristics and treatment outcomes of all 132 MM patients at Dicle University Hospital between January 2006 and April 2010. Results: A total of 82 (62.1%) patients were male, and 50 (37.9%) female. Median age was 56.0 years. Mean survival time was 9.6±6.9 months. Mean survival time of patients who had received best supportive care was 7.5 months, chemotherapy 10.4 months, and multimodality treatment regimen 12.6 months. Patients in the multimodality treatment group survived longer than did those in the other two groups (P=0.042). A total of 76 patients received chemotherapy, of whom 17 (22.3%) were administered Cisplatin/Carboplatin and Gemcitabine, 58 (76.4%) Cisplatin/Carboplatin and Pemetrexed, and one (1.3%) Cisplatin + Docetaxel. Complete and partial response to treatment in patients receiving Cisplatin/Carboplatin and Gemcitabine was found 47.1% and Cisplatin/Carboplatin and Pemetrexed was found 50.0% (P>0.05). Conclusions: MM related to asbestos exposure is seen frequently in Turkey. Patients present with the typical clinical features of dyspnea, weight loss, and chest pain. Survival analysis shows that patients receiving multimodality treatment may be better.

Oxidative Status and Acute Phase Reactants in Patients with Environmental Asbestos Exposure and Mesothelioma

Background and Objectives. The aim of this study was to investigate inflammatory indicators and oxidative status in patients with asbestos exposure with and without mesothelioma and to compare results with data from healthy subjects. Methods. Eighty people with exposure to environmental asbestos and without any disease, 46 mesothelioma patients, and a control group of 50 people without exposure to environmental asbestos were enrolled in this prospective study. Serum total oxidant level (TOL), total antioxidant capacity (TAC), and oxidative stress index (OSI), CRP, transferrin, ceruloplasmin, α-1 antitrypsin, ferritin, and copper levels were measured. Results. Mesothelioma group exhibited higher TOL, OSI, α1-antitrypsin, ferritin and copper levels as compared to the other groups (P < 0.001, P = 0.007, P < 0.0001, P < 0.001, and P < 0.001, resp.). Transferrin was lower in the mesothelioma group than in the other two groups (P < 0.001). The asbestos group had higher TOL, TAC, α1-antitrypsin, and transferrin levels (P < 0.001, P < 0.001, P < 0.001, and P < 0.001, resp.), as well as lower OSI and ferritin levels as compared to the control group (P < 0.001 and P < 0.001). Conclusions. We believe that elevated acute phase reactants and oxidative stress markers (TOL and OSI) in the mesothelioma group can be used as predictive markers for the development of asbestos-related malignancy.

Clinical and demographic characteristics of tracheobronchial variations

Background: There are various anatomic variations in tracheobronchial system (tracheal bronchus, ectopic bronchus, and accessory bronchus). We aimed to investigate the bronchoscopic findings of the patients with tracheobronchial variations (TBVs) during bronchoscopy and to describe their clinical characteristics. Materials and Methods: A total of 3322 records of bronchoscopic examinations in university hospital and 1560 in chest disease hospital total 4882 were retrospectively analyzed and 198 (134 male, 64 female) patients were diagnosed as TBV. Results: Mean age of patients was 48.5 ± 17.8 (range, 15–78) years. Most of the tracheobronchial variations (n = 68, 33.1%) were localized at the right upper lobe bronchus. The most common type of TBVs at this region was right upper lobe with two segments. Symptoms were found in 21 (10.2%) patients with TBVs (7 accessory cardiac bronchus, 5 tracheal bronchus, 5 accessory segmental bronchus in left main bronchus and 4 accessory segmental bronchus in right main bronchus). Their symptoms cough, hemoptysis and recurrent pneumonia with unknown etiologies were thought as related to TBVs. No other potential causes leading these symptoms were found in these patients. Conclusion: According to our best of knowledge our study population is one of the largest series of bronchoscopy for investigate of TBVs. Although TBVs were usually reported as asymptomatic, nearly 10% of our patients with TBVs had symptoms such as recurrent pneumonia, cough and hemoptysis. TBVs should be taken into consideration in symptomatic patients before fiber-optic bronchoscopic examination.

Two cases of extrapulmonary onset granulomatosis with polyangiitis which caused diffuse alveolar haemorrhage

Granulomatosis with polyangiitis (GPA) is a rare form of vasculitis. Multidisciplinary therapeutic approach and early diagnosis assume vital importance in management of patients with diffuse alveolar haemorrhage caused by GPA, which is a rare complication. The purpose of this study was to present the diagnostic and therapeutic challenges experienced by clinicians in management of two severe cases of GPA with insidious extrapulmonary manifestations which rapidly progressed into acute kidney injury, alveolar haemorrhage and acute respiratory failure.

Asthma COPD Overlap Syndrome

喘息と COPD はいずれも慢性の炎症性肺疾患であ り,喘息では好酸球と CD4 陽性 Th2 リンパ球を, COPD では好中球と CD8 陽性 T リンパ球をそれぞれ 主体とした気道炎症を特徴とする.典型的な症例では, その症状や発症年齢からも両者の鑑別は容易である が,喘息もCOPDもありふれた疾患であり,時にその 両者が合併した症例が存在することは古くから認識さ れていた.特に喫煙歴のある中高年の患者群では両疾 患の特徴を有する症例の頻度が増加する.最近になり, 喘息と COPD のいずれも単一の病態からなる均一な 疾患ではなく,多様な分子病態から構成される症候群 であり,さらに喘息とCOPDとの間でも複数の病態が オーバーラップすることが認識されるようになってき た.2014年にはGlobal Initiative for Asthma(GINA) とGlobal Initiative for Chronic Obstructive Lung Disease(GOLD)が共同で,持続的な気流閉塞とともに, それぞれ喘息と COPD とに特徴的ないくつかの症候 を有する患者を一つの疾患群とし,Asthma-COPD Overlap Syndrome(ACOS)と呼称することが提案さ れた.