Toxoplasma gondii is an intracellular protozoan parasite that infects approximately one third of the human popu- lation worldwide. Considering the toxicity and side effects of anti-toxoplasma medications, it is important to develop effec- tive drug alternatives with fewer and less severe off-target effects. In this study, we found that 4-hydroxybenzaldehyde (4- HBA) induced autophagy and the expression of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) in primary murine bone marrow-derived macrophages (BMDMs). Interestingly, treatment of BMDMs with 4-HBA significantly reduced the number of macrophages infected with T. gondii and the proliferation of T. gondii in infected cells. This effect was impaired by pretreating the macrophages with 3-methyladenine or wortmannin (selective autophagy inhibitors) or with sirtinol or EX527 (SIRT1 inhibitors). Moreover, we found that pharmacological inhibition of SIRT1 prevented 4-HBA-mediated expres- sion of LC3-phosphatidylethanolamine conjugate (LC3-II) and the colocalization of T. gondii parasitophorous vacuoles with autophagosomes in BMDMs. These data suggest that 4-HBA promotes antiparasitic host responses by activating SIRT1- mediated autophagy, and 4-HBA might be a promising therapeutic alternative for the treatment of toxoplasmosis.

Transarterial chemoembolization (TACE) is a widely accepted nonsurgical modality used for the treatment of multinodular hepatocellular carcinoma (HCC). The careful selection of the candidate is important due to the risk of developing various side effects. Fever, nausea, abdominal pain, and liver enzyme elevation are commonly known side effects of TACE. Hepatic failure, ischemic cholecystitis, and cerebral embolism are also reported, although their incidence might be low. Pulmonary complication after TACE is rare, and the reported cases of lipiodol pneumonitis are even rarer. A 53-year-old man was treated with TACE for ruptured HCC associated with hepatitis B virus infection. On day 19 after the procedure, the patient complained of dyspnea and dry cough. Chest computed tomography showed diffuse ground glass opacities in the wholelung fields, suggesting lipiodol-induced pneumonitis. After 2 weeks of conservative management, the clinical symptoms and radiologic abnormalities improved. Reported herein is the aforementioned case of lipiodol-induced pnemonitis after TACE, with literature review.
Abdominal Pain ; Carcinoma, Hepatocellular* ; Chemoembolization, Therapeutic ; Cholecystitis ; Cough ; Dyspnea ; Ethiodized Oil ; Fever ; Glass ; Hepatitis B virus ; Humans ; Incidence ; Intracranial Embolism ; Liver ; Liver Failure ; Middle Aged ; Nausea ; Pneumonia* ; Thorax

Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterized by the calcification and ossification of soft tissue, and can lead to severe cervical kyphosis, presenting with a spectrum of physical complaints including dysphagia, hoarseness, stridor, aspiration pneumonia, and dyspnea due to airway compromise. Restrictive ventilatory impairment is very rare. We encountered a 73-year-old man with DISH presenting with progressive dysphagia and dyspnea over a few months. The symptoms were evaluated with a video fluoroscopy swallowing study and pulmonary function tests (PFT). The PFT revealed restrictive ventilatory impairment. A neck magnetic resonance imaging (MRI) study showed anterior cervical osteophytes causing upper airway compromise and compression of the esophagus. Osteophytes were removed surgically and the patient improved clinically. Here, we describe the case with a literature review.
Aged ; Deglutition ; Deglutition Disorders* ; Dyspnea ; Esophagus ; Fluoroscopy ; Hoarseness ; Humans ; Hyperostosis, Diffuse Idiopathic Skeletal* ; Kyphosis ; Magnetic Resonance Imaging ; Neck ; Osteophyte* ; Pneumonia, Aspiration ; Respiratory Function Tests ; Respiratory Sounds

OBJECTIVE: We investigated low dose digital tomosynthesis (DT) for the evaluation of the paranasal sinus (PNS), and compared its diagnostic accuracy with a PNS radiography series (XR). MATERIALS AND METHODS: We enrolled 43 patients for whom XR, PNS DT, and OMU CT were performed. We measured effective doses (EDs) of XR, DT, and OMU CT using Monte Carlo simulation software. Two radiologists performed independent observation of both XR and DT. For seven PNSs, they scored anatomic conspicuity of sinuses and confidence on the presence of sinusitis using nine point scales. OMU CT was observed by the third radiologist and the findings were regarded as reference standard. We compared scores for conspicuity and sinusitis confidence between XR and DT. RESULTS: Mean EDs were 29 +/- 6 microSv, 48 +/- 10 microSv, and 980 +/- 250 microSv, respectively, for XR, DT, and CT. Mean scores for conspicuity were 6.3 and 7.4, respectively, for XR and DT. Sensitivity per patient basis for sinusitis detection were 52% and 96%, respectively, for XR and DT in observer 1 (p = 0.001) and 80% and 92% for observer 2 (p = 0.25). Specificities for sinusitis exclusion were 100% for both XR and DT for observer 1 and 89% and 100% for observer 2 (p = 0.50). Accuracies for sinusitis diagnosis were 72% and 98%, respectively, for XR and DT for observer 1 (p = 0.001) and 84% and 95% for observer 2 (p = 0.125). CONCLUSION: Patient radiation dose from low dose DT is comparable with that of PNS XR. Diagnostic sensitivity of DT for sinusitis was superior to PNS XR.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Monte Carlo Method ; Paranasal Sinuses/*radiography ; ROC Curve ; Radiation Dosage ; Radiographic Image Enhancement/*methods ; Sensitivity and Specificity ; Sinusitis/*radiography ; Statistics, Nonparametric ; Tomography, X-Ray Computed/*methods

BACKGROUND: Pneumonectomy remains the ultimate curative treatment modality for destroyed lung caused by tuberculosis despite multiple risks involved in the procedure. We retrospectively evaluated patients who underwent pneumonectomy for treatment of sequelae of pulmonary tuberculosis to determine the risk factors of early and long-term outcomes. MATERIALS AND METHODS: Between January 1980 and December 2008, pneumonectomy or pleuropneumonectomy was performed in 73 consecutive patients with destroyed lung caused by tuberculosis. There were 48 patients with empyema (12 with bronchopleural fistula [BPF]), 11 with aspergilloma and 7 with multidrug resistant tuberculosis. RESULTS: There were 5 operative mortalities (6.8%). One patient had intraoperative uncontrolled arrhythmia, one had a postoperative cardiac arrest, and three had postoperative respiratory failure. A total of 29 patients (39.7%) suffered from postoperative complications. Twelve patients (16.7%) were found to have postpneumonectomy empyema (PPE), 4 patients had wound infections (5.6%), and 7 patients required re-exploration due to postoperative bleeding (9.7%). The prevalence of PPE increased in patients with preoperative empyema (p=0.019). There were five patients with postoperative BPF, four of which occurred in right-side operation. The only risk factor for BPF was the right-side operation (p=0.023). The 5- and 10-year survival rates were 88.9% and 76.2%, respectively. The risk factors for late deaths were old age (> or =50 years, p=0.02) and low predicted postoperative forced expiratory volume in one second (FEV1) (<1.2 L, p=0.02). CONCLUSION: Although PPE increases in patients with preoperative empyema and postoperative BPF increases in right-side operation, the mortality rates and long-term survival rates were found to be satisfactory. However, the follow-up care for patients with low predicted postoperative FEV1 should continue for prevention and early detection of pulmonary complication related to impaired pulmonary function.
Arrhythmias, Cardiac ; Empyema ; Fistula ; Follow-Up Studies ; Forced Expiratory Volume ; Heart Arrest ; Hemorrhage ; Humans ; Lung ; Pneumonectomy ; Postoperative Complications ; Prevalence ; Respiratory Insufficiency ; Retrospective Studies ; Risk Factors ; Survival Rate ; Tuberculosis ; Tuberculosis, Pulmonary ; Wound Infection

BACKGROUND/AIMS: The findings of several recent studies suggest that antinuclear antibodies (ANAs) are frequently detected in patients with acute hepatitis A (AHA). However, the clinical significance of a positive ANA test remains uncertain. This study was performed to evaluate the clinical significance of ANAs in AHA patients. METHODS: All patients admitted with AHA were consecutively enrolled in this study. An ANA assay was performed by indirect immunofluorescence during hospitalization. ANA positivity was defined as an ANA titer > or =1:80. The peak international normalized ratio (INR), peak alanine aminotransferase (ALT) and peak bilirubin levels were assessed over the duration of the hospitalization, and the incidence of AHA complications was evaluated. RESULTS: A total of 422 patients were enrolled in this study (age, 31+/-7 years), of which 260 (61.6%) were men. ANAs were detected in 179 AHA patients (42.4%). The proportion of ANA-positive patients varied significantly with AHA status on the day of the ANA assay (4.7% during the prodromal period vs 52.1% during the icteric or recovery period, p<0.001) and sex (56.2% in women vs 33.8% in men, p<0.001). The ANAs became undetectable in all ANA-positive patients within 3 months. The incidence of complications, including mortality, fulminant hepatic failure, renal dysfunction, relapse, and cholestatic hepatitis, did not differ significantly between ANA-positive and ANA-negative patients. CONCLUSIONS: ANAs were detected frequently and transiently in patients with AHA, especially after their peak-ALT day. The presence of ANAs may not be associated with the clinical outcome of AHA, but simply with AHA status on the ANA assay day.
Alanine Transaminase ; Antibodies, Antinuclear ; Bilirubin ; Female ; Fluorescent Antibody Technique, Indirect ; Hepatitis ; Hepatitis A ; Hospitalization ; Humans ; Incidence ; International Normalized Ratio ; Liver Failure, Acute ; Male ; Prodromal Symptoms ; Recurrence

BACKGROUND: Growing tumors adapt to a hypoxic environment and increase anaerobic glycolysis. This metabolic switch is related to aggressive behavior. We investigated the relationship between glycolytic metabolism biomarkers associated with hypoxia-inducible factor (HIF)-1alpha and prognosis. METHODS: We performed immunohistochemical staining of HIF-1alpha, pyruvate dehydrogenase kinase (PDK) 1 and lactate dehydrogenase (LDH) 5 in 74 patients with oral squamous cell carcinoma (SCC) who had received curative radical resection. RESULTS: High reactivity of HIF-1alpha, PDK 1 and LDH 5 was observed in 29 (39.2%), 32 (43.2%) and 54 (73.0%) patients, respectively. Expression levels of the three biomarkers were significantly correlated. All three markers were highly expressed in 16 (21.6%) patients. Elevated expression of the three markers was associated with increased invasiveness (p = 0.043) and recurrence (p = 0.017) of tumors. In survival analysis, upregulation of the three markers was additionally associated with shorter disease free survival (DFS, p = 0.001) and overall survival (OS, p = 0.002). High expression of all three markers was a strong independent prognostic factor for DFS (p = 0.030) and OS (p = 0.026). CONCLUSIONS: Oral SCC with altered glycolytic metabolism exhibits a more invasive and aggressive phenotype. Our results indicate that glycolytic metabolism biomarkers related to HIF-1alpha may be independent prognostic factors in patients with oral SCC.
Biomarkers ; Carcinoma, Squamous Cell ; Disease-Free Survival ; Glycolysis ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; Isoenzymes ; L-Lactate Dehydrogenase ; Oxidoreductases ; Phenotype ; Phosphotransferases ; Prognosis ; Protein-Serine-Threonine Kinases ; Pyruvic Acid ; Recurrence ; Up-Regulation

OBJECTIVE: We aimed to evaluate the results of endovascular coil embolization for very small aneurysms (< or = 3 mm). MATERIALS AND METHODS: Between March 2005 and December 2008, a total of 31 very small aneurysms in 30 patients were treated by coil embolization. Of the 31 aneurysms, five (16%) were ruptured, as opposed to 26 (84%) that were not. We assessed the procedural complications, immediate angiographic outcome after coiling, clinical outcome, and follow-up MR angiography (MRA). RESULTS: Two thromboembolic complications occurred during the procedure, but did not lead to any persistent neurologic deficit. No procedural aneurysmal rupture was observed and procedure-related morbidity and mortality were both 0%. Occlusion was adequate in 25 aneurysms (81%) and incomplete in six aneurysms (19%). The clinical outcomes of five patients with ruptured aneurysms were good (Glasgow outcome scale > or = 4), with no bleeding of the treated aneurysms during a mean follow-up period of 13.3 months. On 27 follow-up MRA, there was no recurrence, and the five incompletely occluded aneurysms showed a spontaneous amelioration resulting in an adequate occlusion. CONCLUSION: Coil embolization of very small aneurysms is technically feasible with good results. The long-term efficacy and the potential as a standard treatment strategy remain to be determined by randomized large trials.
Adult ; Aged ; Aged, 80 and over ; Aneurysm, Ruptured/*therapy ; Cerebral Angiography ; Embolization, Therapeutic/*methods ; Female ; Humans ; Intracranial Aneurysm/*therapy ; Magnetic Resonance Angiography ; Male ; Middle Aged ; Treatment Outcome

BACKGROUND/AIMS: The aim of our study was to define the potential role of virologic response at 12 months of treatment (VR12) in predicting subsequent virologic and clinical outcomes in adefovir (ADV)-treated lamivudine-resistant chronic hepatitis B. METHODS: Two hundred and four patients with lamivudine-resistant chronic hepatitis B virus (HBV) treated with ADV monotherapy were included. Serum HBV DNA was quantified by real-time polymerase chain reactions. VR12 was defined as a HBV DNA level of less than 4 log10 copies/mL after 12 months of ADV treatment. RESULTS: VR12 was observed in 110 of the 204 patients (54%). The mean HBV DNA reductions from baseline after 12 months of ADV treatment were 3.8 and 1.9 log10 copies/mL in patients with and without VR12, respectively (p<0.001). The hepatitis B "e" antigen (HBeAg) seroconversion rates in patients with and without VR12 were 32% and 14% at 12 months treatment, respectively (p=0.018), and 40% and 27% at 24 months of treatment (p=0.032). The genotypic mutation rates to ADV in patients with and without VR12 were 0% and 6% at 12 months of treatment, respectively (p=0.033), and 21% and 42% at 24 months (p=0.012). The rates of viral breakthrough in patients with and without VR12 were 0% and 7% at 12 months of treatment, respectively (p=0.072), and 9% and 25% at 24 months (p=0.006). CONCLUSIONS: Patients without VR12 may need to switch to or add on other potent antiviral drugs in their medical regimens.
Adenine ; Antiviral Agents ; DNA ; Drug Resistance ; Hepatitis B ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Mutation Rate ; Organophosphonates ; Polymerase Chain Reaction ; Viruses

PURPOSE: We aimed to determine the treatment of choice criteria for benign prostatic hyperplasia (BPH) by analyzing the factors causing alpha-adrenergic receptor blocker (alpha-blocker) monotherapy failure. MATERIALS AND METHODS: This retrospective study enrolled 129 patients with BPH who were prescribed an alpha-blocker. Patients were allocated to a transurethral resection of prostate (TURP) group (after having at least a 6-month duration of medication) and an alpha-blocker group. We compared the differences between the two groups for their initial prostate volume, serum prostate-specific antigen (PSA), maximum urinary flow rate (Qmax), International Prostate Symptom Score (IPSS), and postvoid residual urine volume (PVR). RESULTS: Of the 129 patients, 54 were in the TURP group and 75 were in the alpha-blocker group. Statistically significant differences (p<0.05) between the two groups were found in the prostate volume (50.8 ml vs. 34.4 ml), PSA (6.8 ng/ml vs. 3.6 ng/ml), Qmax (6.84 ml/sec vs. 9.99 ml/sec), and IPSS (27.3 vs. 16.8). According to the multiple regression analysis, the significant factors in alpha-blocker monotherapy failure were the IPSS (p<0.001) and prostate volume (p=0.015). According to the receiver operating characteristic (ROC) curve-based prediction regarding surgical treatment, the best cutoff value for the prostate volume and IPSS were 35.65 ml (sensitivity 0.722, specificity 0.667) and 23.5 (sensitivity 0.852, specificity 0.840), respectively. CONCLUSIONS: At the initial diagnosis of BPH, patients with a larger prostate volume and severe IPSS have a higher risk of alpha-blocker monotherapy failure. In this case, combined therapy with 5-alpha-reductase inhibitor (5-ARI) or surgical treatment may be useful.
Adrenergic alpha-Antagonists ; Diagnosis ; Factor Analysis, Statistical* ; Humans ; Prostate ; Prostate-Specific Antigen ; Prostatic Hyperplasia* ; Retrospective Studies ; ROC Curve ; Sensitivity and Specificity ; Transurethral Resection of Prostate