Efficacy of concomitant administration of clarithromycin and acetylcysteine in bronchiolitis obliterans in seventeen sulfur mustard—exposed patients: An open-label study

Background:

Victims of sulfur mustard (SM) gas exposure experience different types of chronic pulmonary disease, manifested as cough, sputum production, and dyspnea. Conventional therapies (eg, immunosuppressive drugs, corticosteroids) have not been effective in these patients.

Objective:

This study was carried out to determine the efficacy of concomitant administration of the macrolide clarithromycin and the mucolytic agent acetylcysteine in the treatment of bronchiolitis obliterans in SM-exposed patients.

Methods:

This open-label clinical study was conducted at the Research Center of Chemical Injuries, Baqiyatallah Medical Sciences University, Tehran, Iran. Clarithromycin and acetylcysteine were administered concomitantly for 6 months to male SM-exposed patients with chronic bronchitis and bronchiolitis obliterans who were nonresponsive to conventional treatments. Efficacy analysis included symptom assessment and pulmonary function tests (forced expiratory volume in 1 second [FEV₁], forced vital capacity [FVC], and FEV₁/FVC ratio) using spirometry, performed at baseline and after 2 and 6 months of treatment.

Results:

Seventeen male patients (mean [SD] age, 38.3 [5.3] years [range, 31-50 years]; mean [SD] body weight, 77.9 [15.7] kg) were included in the study. Cough and sputum production were each found in 10 of 17 patients (58.8%) at baseline and were improved in all 10 patients after the administration of clarithromycin and acetylcysteine. FEV₁ and FVC also were improved, by mean (SD) 10.6% (9.7%) (P < 0.001 vs baseline) and 12.9% (13.6%) (P = 0.001 vs baseline). No significant change in FEV₁/FVC ratio was found.

Conclusions:

In this study of concomitant administration of clarithromycin and acetylcysteine for the treatment of bronchiolitis obliterans in SM-exposed patients, symptoms and pulmonary function were improved. These results may have been related to the therapeutic effects of a macrolide antibiotic on chronic bronchitis and bronchiolitis obliterans in these patients. Based on the results of this study, we recommend this treatment for chemical warfare victims with recurrent exacerbation of bronchitis who do not respond to conventional treatment.     

Neutrophils stimulated by apolipoprotein(a) generate fragments that are stronger inhibitors of plasmin formation than apo(a)

Apolipoprotein(a), the plasminogen-like component of lipoprotein(a), is transformed into fragments by polymorphonuclear neutrophils (PMNs) elastase. Since stimulated PMNs express urokinase-type plasminogen activator (uPA), we sought to investigate the relevance of apo(a) fragmentation on plasminogen activation by neutrophils. Freshly isolated human PMNs stimulated by a 10 kringle recombinant apo(a), r-apo(a), activate plasminogen in a specific and saturable manner (Km = 476 +/- 42 nM, Vmax = 896 +/- 18 pmol min(-1)).This activation is prevented by amiloride, an inhibitor of u-PA, and epsilon-aminocaproic acid, epsilon-ACA, a lysine analogue that blocks plasminogen binding to PMNs. Stimulation of PMNs by apo(a) results in the formation of elastase-derived apo(a) fragments. These fragments produce a concentration-dependent decrease in the formation of plasmin. Addition of elastase inhibitors to PMNs prevented degradation of apo(a) and partially restored the formation of plasmin. In a similar manner, isolated r-apo(a) fragments were able to produce a 100% decrease in plasmin generation as compared to intact r-apo(a). These data indicate that apo(a) fragments produce a more pronounced inhibition in the generation of cell-bound plasmin by uPA than the parent apo(a). These effects of apo(a) and its fragments were neutralised by a monoclonal antibody directed against the lysine-binding site of apo(a). This mechanism may be of biological relevance to the effects of Lp(a) in conditions where PMNs accumulate and release elastase, i.e. thrombus lysis and inflammatory lesions.     

Mortality in primary immunodeficient patients, registered in Iranian primary immunodeficiency registry

Primary immunodeficiencies (PID) are a group of disorders, characterized by an unusual susceptibility to infections. Delay in diagnosis results in increased morbidity and mortality in affected patients. The purpose of this study was to determine the mortality rate of Iranian immunodeficient patients referred to Children Medical Center Hospital affiliated to Tehran University of Medical Sciences over a period of 20 years.In this study, records of 235 (146 males, 89 females) patients with immunodeficiency who were diagnosed and followed in our center, during 22 years period (1979-2001) were reviewed. The diagnosis of immunodeficiency was based on the standard criteria. The cause of death was determined by review of death certificates.Antibody deficiency was the most common diagnosis made in our patients. The overall five-year survival rate was 22.7% in our studied patient group; this was greatest in antibody deficiency. During the 22 year period of study, 32 patients died. As some of the patients could not be located, the true mortality rate ranged between 13.6% and 17.5%. The main leading cause of death were lower respiratory tract involvement in 14 cases (44%). The most common pathogenic microorganisms causing fatal infections were psudomonas and staphylococcus in 9 cases (28.1%) followed by E. coli in 7 (21.9%), tuberculosis in 13 (40.6%) and salmonella in 1 (3.1%).Based on our study, delay in diagnosis in patients with PID results in tissue and organ damage and several complications. Mortality and morbidity are increased in undiagnosed patients.     

Gastrointestinal manifestations of patients with chronic granulomatous disease

Chronic Granulomatous Disease (CGD) represents a group of inherited disorders of phagocytic system, manifesting recurrent infections at different sites. The present study was accomplished in order to determine the gastrointestinal manifestations of CGD patients. Fifty-seven patients (38 males and 19 females) with CGD, who had been referred to three immunodeficiency referral centers in Iran, were studied during a 24-year period (1980-2004). The median age at the time of study was 14.5 years old (1-56 years). The median onset age of symptoms was 5 months (1 month- 13.75 years), and that of diagnostic age was 5 years (2 months- 54.1 years), with a diagnostic delay of 33 months, on average. Seven patients were presented with acute diarrhea, 3 with oral candidiasis, and 2 with liver abscesses as the first chief complaints. Twenty-four cases (42.1%) had been complicated by gastrointestinal manifestations during their course of the disease. Of those, 12 cases (21.1%) had diarrhea, 7 (12.3%) oral candidiasis, 5 (8.8%) hepatitis, 4 (7.0%) hepatic abscess, and 2 cases (3.5%) gastric outlet obstruction. Also, failure to thrive was detected in 6 patients (10.5%). Four patients died (7%). CGD should be excluded in any patient with gastrointestinal manifestations especially chronic diarrhea, hepatic abscess, and gastric outlet obstruction.     

Prostate cancer: evaluation with endorectal MR imaging and three-dimensional proton MR spectroscopic imaging

PURPOSE: To establish the additional value of MR Spectroscopy (3D CSI MRS Three-dimensional Chemical Shift Imaging Magnetic Resonance Spectroscopy) to endorectal MR in the diagnosis and grading of prostate cancer. MATERIALS AND METHODS: MR and 3D CSI MR spectroscopy were performed in 53 patients with suspicion of prostate cancer on the basis of rectal exploration and/or transrectal ultrasound and/or the PSA levels. All the examinations were performed with a 1.5 T imager using an endorectal coil. We acquired axial and coronal T2-weighted FSE sequences, axial T1-weighted SE sequences and PRESS 3D CSI (Point Resolved Spectroscopy 3D Chemical Shift Imaging) sequences localized on the axial T2 images so as to include the prostatic gland while excluding the periprostatic fat. The MR examinations were evaluated by two radiologists unaware of the clinical data, transrectal ultrasound findings, PSA levels and histological findings. The MR and 3D CSI MRS findings were compared with the biopsy findings in 22 cases and with material obtained from laparoscopic prostatectomy in 31 cases. RESULTS: The histological examination revealed adenocarcinoma in 37 cases, prostatitis in 2 cases and no alterations in the remaining 14 cases. The morphologic MR scan showed a sensitivity of 76%, a specificity of 56%, an accuracy of 70%, a PPV of 80% and a NPV of 50%. By combining MR and 3D CSI MRS we obtained a sensitivity of 95%, a specificity of 81%, an accuracy of 91%, a PPV of 92% and a NPV of 87%. Elevated choline concentrations were found both in tumours with a low Gleason score (18 cases) and in those with a high Gleason score (19 cases); instead we found markedly reduced (n=9) or absent (n=4) citrate only in the tumours with a high Gleason score, while we found normal citrate levels in the 18 tumours with a low Gleason score. CONCLUSIONS: The 3D CSI MRS improved the reliability of endorectal MR in the diagnosis and characterisation of prostatic cancer. Moreover, the 3D CSI MRS findings demonstrated a linear correlation with tumour grade.     

Magnetic resonance imaging of benign adnexal disease

Magnetic resonance imaging (MRI) plays an important role in localizing and characterizing pelvic masses, particularly adnexal masses. The multiplanar capability of MRI helps to locate an abnormality outside the ovary and facilitate the exclusion of malignancy. Its superior soft-tissue contrast features help to diagnose specific benign masses, including teratoma, endometrioma, and ovarian fibroma. In addition, cystic ovarian neoplastic lesions can be further characterized as benign versus malignant, particularly after gadolinium administration. An approach to adnexal evaluation using MRI is discussed based on these features.     

Adverse events during radiofrequency treatment of 582 hepatic tumors

OBJECTIVE: We describe the rates and potential risk factors of complications of radiofrequency ablation of hepatic tumors. SUBJECTS AND METHODS. Over a 5-year period, 312 patients underwent 350 sessions of radiofrequency ablation (124 intraoperative and 226 percutaneous) for treatment of 582 liver tumors including 115 hepatocellular carcinomas and 467 metastatic tumors. The chi-square test was used for a group-to-group comparison of the occurrence of adverse events. RESULTS: Thirty-seven (10.6%) adverse events and five (1.4%) deaths were related to radiofrequency treatment. The deaths were caused by liver insufficiency (n = 1), colon perforation (n = 1), and portal vein thrombosis (n = 3). Portal vein thrombosis was significantly (p < 0.00001) more frequent in cirrhotic livers (2/5) than in noncirrhotic livers (0/54) after intraoperative radiofrequency ablation performed during a Pringle maneuver. Liver abscess (n = 7) was the most common complication. Abscess occurred significantly (p < 0.00001) more frequently in patients bearing a bilioenteric anastomosis (3/3) than in other patients (4/223). We encountered five pleural effusions, five skin burns, four hypoxemias, three pneumothoraces, two small subcapsular hematomas, one acute renal insufficiency, one hemoperitoneum, and one needle-tract seeding. The 6.3% of minor complications did not require specific treatment or a prolonged hospital stay. Among the 5.7% major complications, 3.7% required less than 5 days of hospitalization for treatment or surveillance and 2% required more than 5 days for treatment. CONCLUSION: Radiofrequency ablation of liver tumors is a well-tolerated technique, but caution should be exercised when treating patients with a bilioenteric anastomosis, and radiofrequency ablation during vascular occlusion in cirrhotic livers should be avoided.     

An evaluation of the Laryngeal Tube during general anesthesia using mechanical ventilation

The Laryngeal Tube is a new supraglottic ventilatory device for airway management. It has been developed to secure a patent airway during either spontaneous or mechanical ventilation. In this study, we sought to determine the effectiveness of the Laryngeal Tube for primary airway management during routine surgery with mechanical ventilation. One-hundred-seventy-five subjects classified as ASA physical status I and II, scheduled for elective surgery, were included in the study. After the induction of general anesthesia and insertion of a Size 4 Laryngeal Tube, measurements of oxygen saturation, end-tidal CO(2) and isoflurane concentration, and breath-by-breath spirometry data were obtained every 5 min throughout surgery. The lungs were ventilated with volume-controlled mechanical ventilation. The number of attempts taken to insert the Laryngeal Tube and the insertion time were recorded. In 96.6% of patients, it was possible to maintain oxygenation, ventilation, and respiratory mechanics by using mechanical ventilation throughout the surgical procedure. The results of this study suggest that the Laryngeal Tube is an effective and safe airway device for airway management in mechanically ventilated patients during elective surgery. IMPLICATIONS: In 96.6% of patients intubated with the Laryngeal Tube, it was possible to maintain oxygenation, ventilation, and respiratory mechanics during mechanical ventilation.     

Postdural puncture headache: an imaging-guided management protocol

IMPLICATIONS: We propose an imaging-based algorithm for the management of headache caused by the inadvertent puncture of dura that occurs sporadically during epidural analgesia. Its implementation can identify those postdural puncture headache cases that cannot benefit from epidural blood patches, and their unnecessary application can consequently be avoided.