The multiple facets of drug resistance: one history,different approaches

Some cancers like melanoma and pancreatic and ovarian cancers, for example, commonly display resistance to chemotherapy, and this is the major obstacle to a better prognosis of patients. Frequently, literature presents studies in monolayer cell cultures, 3D cell cultures or in vivo studies, but rarely the same work compares results of drug resistance in different models. Several of these works are presented in this review and show that usually cells in 3D culture are more resistant to drugs than monolayer cultured cells due to different mechanisms. Searching for new strategies to sensitize different tumors to chemotherapy, many methods have been studied to understand the mechanisms whereby cancer cells acquire drug resistance. These methods have been strongly advanced along the years and therapies using different drugs have been increasingly proposed to induce cell death in resistant cells of different cancers. Recently, cancer stem cells (CSCs) have been extensively studied because they would be the only cells capable of sustaining tumorigenesis. It is believed that the resistance of CSCs to currently used chemotherapeutics is a major contributing factor in cancer recurrence and later metastasis development. This review aims to appraise the experimental progress in the study of acquired drug resistance of cancer cells in different models as well as to understand the role of CSCs as the major contributing factor in cancer recurrence and metastasis development, describing how CSCs can be identified and isolated.     

Fatal outcome of a lumbar incisional hernia originating at the surgical site of hip arthroplasty: An exceptionally rare case

This article discusses an uncommon case of complicated incisional lumbar hernia secondary to total hip arthroplasty. A female patient with a history of bilateral total hip arthroplasty at another institution was hospitalized for acute oedematous pancreatitis and was treated conservatively. An initial abdominal computerized tomography showed the incidental finding of a left lumbar hernia in close relationship with a hip prosthesis. During the 30^th day of hospital stay, the incisional hernia became incarcerated, and the intestinal contents strangulated. The severity of this complication finally led to the death of the patient. Despite their rarity, these hernias should be included within the differential diagnosis of flank masses and late hip arthroplasty symptomatic complications.     

Salvage treatment of disseminated strongyloidiasis in an immunocompromised patient: therapy success with subcutaneous ivermectin

Disseminated strongyloidiasis is a disease with high mortality rate, especially in immunocompromised individuals. Paralytic ileus and intestinal malabsorption are frequent symptoms caused by this severe disease. As there are no licensed parenteral anthelmintic drugs for human use, off-label formulations are often used in the treatment of this disease. In this case report, the use of subcutaneous ivermectin is described as a successful therapy for this life-threatening infection.     

3D left ventricular extracellular volume fraction by low-radiation dose cardiac CT: Assessment of interstitial myocardial fibrosis

BackgroundMyocardial fibrosis leads to impaired cardiac function and events. Extracellular volume fraction (ECV) assessed with an iodinated contrast agent and measured by cardiac CT may be a useful noninvasive marker of fibrosis.ObjectiveThe purpose of this study was to develop and evaluate a 3-dimensional (3D) ECV calculation toolkit (ECVTK) for ECV determination by cardiac CT.MethodsTwenty-four subjects (10 systolic heart failure, age, 60 ± 17 years; 5 diastolic failure, age 56 ± 20 years; 9 matched healthy subjects, age 59 ± 7 years) were evaluated. Cardiac CT examinations were done on a 320-multidetector CT scanner before and after 130 mL of iopamidol (Isovue-370; Bracco Diagnostics, Plainsboro, NJ, USA) was administered. A calcium score type sequence was performed before and 7 minutes after contrast with single gantry rotation during 1 breath hold and single cardiac phase acquisition. ECV was calculated as (ΔHU_myocardium/ΔHU_blood) × (1 ? Hct) where Hct is the hematocrit, and ΔHU is the change in Hounsfield unit attenuation = HU_{after iodine} ? HU_{before iodine}. Cardiac magnetic resonance imaging was performed to assess myocardial structure and function.ResultsMean 3D ECV values were significantly higher in the subjects with systolic heart failure than in healthy subjects and subjects with diastolic heart failure (mean, 41% ± 6%, 33% ± 2%, and 35% ± 5%, respectively; P = 0.02). Interobserver and intraobserver agreements were excellent for myocardial, blood pool, and ECV (intraclass correlation coefficient, >0.90 for all). Higher 3D ECV by cardiac CT was associated with reduced systolic circumferential strain, greater end-diastolic and -systolic volumes, and lower ejection fraction (r = 0.70, r = 0.60, r = 0.73, and r = ?0.68, respectively; all P < 0.001).Conclusion3D ECV by cardiac CT can be performed with ECVTK. We demonstrated increased ECV in subjects with systolic heart failure compared with healthy subjects. Cardiac CT results also showed good correlation with important functional heart biomarkers, suggesting the potential for myocardial tissue characterization with the use of 3D ECV by cardiac CT. This trial is registered at www.ClinicalTrials.gov as NCT01160471.     

Enfermedad pulmonar intersticial difusa por metaplasia peribronquiolar

Peribronchiolar metaplasia is a histologic lesion characterized by fibrosis and bronchiolar epithelial proliferation, affecting peribronchiolar alveolar septa and terminal bronchioles. It has been considered a nonspecific tissue reaction secondary to the action of external factors, such as tobacco smoke and microbes, and is a common histologic finding in several diffuse interstitial lung diseases. Several such cases with clinical, radiologic, and lung function manifestations characteristic of idiopathic interstitial pneumonia have been described recently, all having peribronchiolar metaplasia as the only histologic abnormality. We report 2 cases of interstitial lung disease in which peribronchiolar metaplasia was the only finding of pathology.     

Transvaginal ultrasound for diagnosis of deeply infiltrating endometriosis

Deeply infiltrating endometriosis is the clinical form of the disease that is generally associated with conditions of more intense pain and may require more complex surgical management, consequently resulting in greater risks to the patient. In recent years, various investigators have confirmed the usefulness of methods such as magnetic resonance imaging (MRI), transrectal ultrasound and transvaginal ultrasound (TVUS) for the diagnosis of deep endometriotic lesions. The objectives of the present study are to describe the method used to perform TVUS for the detection of deeply infiltrating endometriosis, and to discuss the clinical benefits that the data obtained may offer clinicians providing care for patients suspected of having this type of endometriosis.     

Myocardial oxidative metabolic supply-demand relationships in patients with nonischemic dilated cardiomyopathy.

BACKGROUND: Nonischemic dilated cardiomyopathy (NIDCM) is associated with left ventricular remodeling, hypertrophy, and mitochondrial metabolic abnormalities in vitro. We evaluated the hypothesis that energy supply, as judged by the rate of myocardial oxidative metabolism, is inadequate to meet oxygen demand in patients with NIDCM compared with normal subjects. METHODS AND RESULTS: We used positron emission tomography to determine the myocardial carbon 11 acetate decay rate (kmono) as an index of energy supply, and we compared kmono with the rate-pressure product (RPP) as an index of metabolic demand in 7 patients with NIDCM and 7 normal subjects. The mean kmono value (SEM) was 0.060 +/- 0.006 min(-1) in NIDCM patients versus 0.054 +/- 0.002 in normal subjects (P = not significant). The RPP was 9949 +/- 931 beats/min.mm Hg in NIDCM patients and 6521 +/- 476 in normal subjects (P = .007). The relationship of kmono to this index of demand (kmono/RPP) was 6.2 x 10(-6) in NIDCM patients but was 8.5 x 10(-6) in normal subjects (P = .003). Thus RPP, as an index of myocardial oxygen demand, was poorly matched by the rate of oxidative metabolism in those patients with NIDCM. The kmono was closely related to RPP in normal subjects (r = 0.83, P = .02) but not in NIDCM patients. Furthermore, there was no significant relationship between kmono and wall stress as another index of oxygen demand. CONCLUSIONS: These results are consistent with a mitochondrial metabolic abnormality in heart failure. This metabolic mismatch detected by positron emission tomography may contribute to the pathophysiology of congestive heart failure and left ventricular remodeling.     

Chagas disease in rural areas of Chaco Province, Argentina: epidemiologic survey in humans, reservoirs, and vectors

We studied the seroprevalence of antibodies against Trypanosoma cruzi in the human population along with domiciliary infestation by triatomine bugs in an area endemic for Chagas disease in the Chaco Province of Argentina. In addition, we carried out parasitologic surveys in patients, dogs, wild mammals, and vectors. The mean seroprevalence in humans was 27.81% (109 of 392) and 24.14% (63 of 261) in 1-15-year-old children. The minimum domiciliary infestation rate was 13.33%, with certain areas reaching 53.85%. The prevalence was 15.09% (16 of 106) in dogs and 35.71% (10 of 28) in opossums. Infection with T. cruzi was detected in 30.10% (59 of 196) of the Triatoma infestans tested. Compared with nationwide studies, our data suggest that 1) there are zones requiring immediate sanitary action, and 2) nationwide estimates are based on very heterogeneous epidemiologic situations. This heterogeneity emphasizes the importance of in-depth studies of restricted areas to provide additional information for a better understanding of the present status of Chagas disease in Argentina.