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Pneumonia, recurrent or persistent [keywords]
- Adenoid cystic carcinoma in the maxillary gingiva: a case report and immunohistochemical study. [JOURNAL ARTICLE]
- Cancer Biol Med 2013 Mar; 10(1):52-54.
Gingival adenoid cystic carcinoma (ACC) is a rare malignancy. We describe the diagnosis and treatment of a 43 year-old woman who presented with a persistent oral ulcer for approximately 1 year, and subsequent pain in the left posterior maxillary region. Clinical examination revealed an ulcer in the left upper molar gingiva, with swelling in the region from the second premolar to the third molar. X-ray images demonstrated the involvement of the maxillary alveolar bone. The histopathological and immunohistochemical features were diagnostic of ACC. ACC is often presented as a gingival lesion; thus, it may easily be neglected by patients. The identification of this tumor using specific pathological analyses prevents misdiagnosis and enables clinicians to determine the appropriate treatment. In this case, no recurrence or distant metastasis was observed after 2 years of follow-up.
- Early Poststroke Rehabilitation Using a Robotic Tilt-Table Stepper and Functional Electrical Stimulation. [JOURNAL ARTICLE]
- Stroke Res Treat 2013.:946056.
Background.Stroke frequently leaves survivors with hemiparesis. To prevent persistent deficits, rehabilitation may be more effective if started early. Early training is often limited because of orthostatic reactions. Tilt-table stepping robots and functional electrical stimulation (FES) may prevent these reactions.
Objective.This controlled convenience sample study compares safety and feasibility of robotic tilt-table training plus FES (ROBO-FES) and robotic tilt-table training (ROBO) against tilt-table training alone (control). A preliminary assessment of efficacy is performed. Methods. Hemiparetic ischemic stroke survivors (age 58.3 ± 1.2 years, 4.6 ± 1.2 days after stroke) were assigned to 30 days of ROBO-FES (n = 38), ROBO (n = 35), or control (n = 31) in addition to conventional physical therapy. Impedance cardiography and transcranial doppler sonography were performed before, during, and after training. Hemiparesis was assessed using the British Medical Research Council (MRC) strength scale.
Results.No serious adverse events occurred; 8 patients in the tilt-table group prematurely quit the study because of orthostatic reactions. Blood pressure and CBFV dipped <10% during robot training. In 52% of controls mean arterial pressure decreased by ≥20%. ROBO-FES increased leg strength by 1.97 ± 0.88 points, ROBO by 1.50 ± 0.85 more than control (1.03 ± 0.61, P < 0.05). CBFV increased in both robotic groups more than in controls (P < 0.05).
Conclusions.Robotic tilt-table exercise with or without FES is safe and may be more effective in improving leg strength and cerebral blood flow than tilt table alone.
- A Case of Persistent Hiccup after Laparoscopic Cholecystectomy. [JOURNAL ARTICLE]
- Case Rep Surg 2013.:206768.
A 79-year-old man, with history of recent laparoscopic cholecystectomy, came to our attention for persistent hiccup, dysphonia, and dysphagia. Noninvasive imaging studies showed a nodular lesion in the right hepatic lobe with transdiaphragmatic infiltration and increased tracer uptake on positron emission tomography. Suspecting a malignant lesion and given the difficulty of performing a percutaneous transthoracic biopsy, the patient underwent surgery. Histological analysis of surgical specimen showed biliary gallstones surrounded by exudative inflammation, resulting from gallbladder rupture and gallstones spillage as a complication of the previous surgical intervention. This case highlights the importance of considering such rare complication after laparoscopic cholecystectomy.
- Atypical Cogan's Syndrome. [JOURNAL ARTICLE]
- Case Rep Ophthalmol Med 2013.:476527.
Background.Cogan's syndrome is a rare clinical entity whose etiopathology is still unknown, and the treatment strategies are not clearly defined. Case. A 23-year-old male presented with symptoms of headache, peripheral facial palsy, persistent right hearing loss and bilateral papillitis. Workup excluded all infectious, granulomatous, neoplastic, and immune causes. The diagnosis of atypical Cogan's syndrome was established, and the patient was treated with systemic corticosteroids and later on with cyclophosphamide and methotrexate. There were improvement of visual symptoms and stabilisation of left hearing.
Conclusion.Cogan's syndrome is a very rare disease with no specific biological tests for the diagnosis. The diagnostic exams are mostly important to exclude other etiologies. The atypical ocular and audiovestibular manifestations make the diagnosis difficult, delaying the institution of appropriate therapy which may result in profound bilateral deafness.
- Increased Nitroxidative Stress Promotes Mitochondrial Dysfunction in Alcoholic and Nonalcoholic Fatty Liver Disease. [JOURNAL ARTICLE]
- Oxid Med Cell Longev 2013.:781050.
Increased nitroxidative stress causes mitochondrial dysfunctions through oxidative modifications of mitochondrial DNA, lipids, and proteins. Persistent mitochondrial dysfunction sensitizes the target cells/organs to other pathological risk factors and thus ultimately contributes to the development of more severe disease states in alcoholic and nonalcoholic fatty liver disease. The incidences of nonalcoholic fatty liver disease continuously increase due to high prevalence of metabolic syndrome including hyperlipidemia, hypercholesterolemia, obesity, insulin resistance, and diabetes. Many mitochondrial proteins including the enzymes involved in fat oxidation and energy supply could be oxidatively modified (including S-nitrosylation/nitration) under increased nitroxidative stress and thus inactivated, leading to increased fat accumulation and ATP depletion. To demonstrate the underlying mechanism(s) of mitochondrial dysfunction, we employed a redox proteomics approach using biotin-N-maleimide (biotin-NM) as a sensitive biotin-switch probe to identify oxidized Cys residues of mitochondrial proteins in the experimental models of alcoholic and acute liver disease. The aims of this paper are to briefly describe the mechanisms, functional consequences, and detection methods of mitochondrial dysfunction. We also describe advantages and limitations of the Cys-targeted redox proteomics method with alternative approaches. Finally, we discuss various applications of this method in studying oxidatively modified mitochondrial proteins in extrahepatic tissues or different subcellular organelles and translational research.
- CASE REPORT Pharyngocutaneous Fistula Closure Using Autologous Fat Grafting. [JOURNAL ARTICLE]
- Eplasty 2013.:e23.
Objective:Although the majority of pharyngocutaneous fistulas close spontaneously with conservative measures, 20% to 30% of patients do not respond to this approach, thereby necessitating major reconstruction with adjacent or free tissue transfers. These procedures carry considerable risk, particularly in patients with medical comorbidities or a history of prior surgery/radiation. Less invasive treatment approaches designed to reverse tissue damage or promote spontaneous healing would represent an important medical advance. Autologous fat grafts have been previously shown to promote healing of persistent wounds and improve the quality of radiation-damaged tissue. In this report, successful closure of a persistent pharyngocutaneous fistula with use of autologous fat grafting is described. Method: The history and details of pharyngocutaneous fistula closure in a patient with recurrent head and neck cancer are reported. Result: A 67-year-old patient with recurrent head and neck cancer and prior radiotherapy underwent reresection including partial pharyngectomy with pectoralis major myocutaneous flap closure. Postoperatively, he developed an enterocutaneous fistula, which failed to close with conservative measures including 8 months of nothing per os. Two rounds of autologous fat grafting were performed with successful fistula healing.
Conclusion:Autologous fat grafting is a useful treatment for closure of persistent pharyngocutaneous fistulas. Autologous fat grafting should be considered in poor surgical candidates, particularly in the setting of extensive radiation-induced tissue damage.
- Peroxisome Proliferator-Activated Receptor δ Agonist, HPP593, Prevents Renal Necrosis under Chronic Ischemia. [JOURNAL ARTICLE]
- PLoS One 2013; 8(5):e64436.
The Goldblatt's 2 kidney 1 clip (2K1C) rat animal model of renovascular hypertension is characterized by ischemic nephropathy of the clipped kidney. 2K1C rats were treated with a specific peroxisome proliferator-activated receptor δ (PPARδ) agonist, HPP593. Clipped kidneys from untreated rats developed tubular and glomerular necrosis and massive interstitial, periglomerular and perivascular fibrosis. HPP593 kidneys did not exhibit any histochemical features of necrosis; fibrotic lesions were present only in perivascular areas. Necrosis in the untreated clipped kidneys was associated with an increased oxidative stress, up regulation and mitochondrial translocation of the pro-death protein BNIP3 specifically in tubules. In the kidneys of HPP593-treated rats oxidative stress was attenuated and BNIP3 protein decreased notably in the mitochondrial fraction when compared to untreated animals. In untreated clipped kidneys, mitochondria were dysfunctional as revealed by perturbations in the levels of MCAD, COXIV, TFAM, and Parkin proteins and AMPK activation, while in HPP593-treated rats these proteins remained at the physiological levels. Nuclear amounts of oxidative stress-responsive proteins, NRF1 and NRF2 were below physiological levels in treated kidneys. Mitochondrial biogenesis and autophagy were inhibited similarly in both treated and untreated 2K1C kidneys as indicated by a decrease in PGC1-α and deficiency of the autophagy-essential proteins LC3-II and ATG5. However, HPP593 treatment resulted in increased accumulation of p62 protein, an autophagic substrate and an enhancer of NRF2 activity. Therefore, inhibition of BNIP3 activation by the preservation of mitochondrial function and control of oxidative stress by PPARδ is the most likely mechanism to account for the prevention of necrotic death in the kidney under conditions of persistent ischemia.
- Virtual and Biophysical Screening Targeting the γ-Tubulin Complex - A New Target for the Inhibition of Microtubule Nucleation. [JOURNAL ARTICLE]
- PLoS One 2013; 8(5):e63908.
Microtubules are the main constituents of mitotic spindles. They are nucleated in large amounts during spindle assembly, from multiprotein complexes containing γ-tubulin and associated γ-tubulin complex proteins (GCPs). With the aim of developing anti-cancer drugs targeting these nucleating complexes, we analyzed the interface between GCP4 and γ-tubulin proteins usually located in a multiprotein complex named γ-TuRC (γ-Tubulin Ring Complex). 10 ns molecular dynamics simulations were performed on the heterodimers to obtain a stable complex in silico and to analyze the residues involved in persistent protein-protein contacts, responsible for the stability of the complex. We demonstrated in silico the existence of a binding pocket at the interface between the two proteins upon complex formation. By combining virtual screening using a fragment-based approach and biophysical screening, we found several small molecules that bind specifically to this pocket. Sub-millimolar fragments have been experimentally characterized on recombinant proteins using differential scanning fluorimetry (DSF) for validation of these compounds as inhibitors. These results open a new avenue for drug development against microtubule-nucleating γ-tubulin complexes.
- Prediction of Response to Treatment by Gene Expression Profiling of Peripheral Blood in Patients with Microscopic Polyangiitis. [JOURNAL ARTICLE]
- PLoS One 2013; 8(5):e63182.
The JMAAV study was an open-labeled prospective clinical trial, which proposed severity-based treatment protocols for patients with microscopic polyangiitis (MPA). The results suggest that the proposed protocols are useful (remission rate: 89.4%), but are also indicative of relapse or patient demise regardless of the treatment (recurrence rate: 19.0%; mortality rate: 10.6%). The aim of this study is to develop the method to predict response to the treatment in patients with MPA. In the present study, transcriptome analysis was performed using peripheral blood from patients enrolled in the JMAAV study before and 1-week after the beginning of treatment. The gene expression profile before treatment was not directly related to the response to the treatment. However, when the samples from 9 patients with good response (persistent remission for 18 months) were examined, the expression of 88 genes was significantly altered by the treatment. Thirty statistically reliable genes were selected, and then the alteration of expression by the treatment was examined among 22 patients, including 17 with good response, which was defined as persistent remission for 18 months and 5 with poor response, which was defined as relapse after remission or no remission. Discrimination analysis between the alteration of expression of the 30 genes by the treatment and the response identified a combination of 16 genes as the most valuable gene set to predict the response to the treatment. This preliminary study identified IRF7, IFIT1, IFIT5, OASL, CLC, GBP-1, PSMB9, HERC5, CCR1, CD36, MS4A4A, BIRC4BP, PLSCR1, DEFA1/DEFA3, DEFA4, and COL9A2 as the important genes that can predict the response to the treatment in patients with MPA at an early point during the therapy.
- Differential IL-13 Production by Small Intestinal Leukocytes in Active Coeliac Disease versus Refractory Coeliac Disease. [JOURNAL ARTICLE]
- Mediators Inflamm 2013.:939047.
A small fraction of coeliac disease (CD) patients have persistent villous atrophy despite strict adherence to a gluten-free diet. Some of these refractory CD (RCD) patients develop a clonal expansion of lymphocytes with an aberrant phenotype, referred to as RCD type II (RCDII). Pathogenesis of active CD (ACD) has been shown to be related to gluten-specific immunity whereas the disease is no longer gluten driven in RCD. We therefore hypothesized that the immune response is differentially regulated by cytokines in ACD versus RCDII and investigated mucosal cytokine release after polyclonal stimulation of isolated mucosal lymphocytes. Secretion of the TH2 cytokine IL-13 was significantly higher in lamina propria leukocytes (LPLs) isolated from RCDII patients as compared to LPL from ACD patients (P = 0.05). In patients successfully treated with a gluten-free diet LPL-derived IL-13 production was also higher as compared to ACD patients (P = 0.02). IL-13 secretion correlated with other TH2 as well as TH1 cytokines but not with IL-10 secretion. Overall, the cytokine production pattern of LPL in RCDII showed more similarities with LPL isolated from GFD patients than from ACD patients. Our data suggest that different immunological processes are involved in RCDII and ACD with a potential role for IL-13.