Plasma viral load threshold for sustaining intrahost HIV type 1 evolution

The objective of the present study was to determine if natural suppression of plasma viremia below the detection limit of commercial assays (50-80 copies HIV-1 RNA/ml) can contain the HIV-1 evolution. HIV-1 quasispecies complexity in PBMC DNA was assessed in the env gene at two time points in 14 long-term nonprogressors (LTNPs). Sequence changes consistent with viral evolution was found in all patients with a median plasma RNA viral load >100 copies/ml. Evidence of low-level viral evolution was detected in two of four patients with intermittent viremia and a median plasma HIV-1 RNA load of >80 copies/ml. No significant evolution was observed in the three LTNPs with persistent viral suppression below the detection limit. Overall, a significant positive correlation (p < 0.001) was observed between viral evolution and plasma RNA viral load in the LTNPs analyzed. These results suggest that the detection limit of ultrasensitive viremia assays could represent an important threshold below which intrahost HIV-1 evolution does not occur.     

Pharmacological dose of {alpha}-tocopherol induces cardiotoxicity in Wistar rats determined by echocardiography and histology

The effect of pharmacological dose of α-tocopherol on heart health was determined in Wistar rats. Animals were randomly assigned to either C (control, n = 11) or E (α-tocopherol, n = 11) group. Animals received corn oil (C) or α-tocopherol dissolved in corn oil (250 mg α-tocopherol/[kg body wt/day]) (E) by gavage for a 7-week period. Rats underwent echocardiogram and were analyzed for cardiomyocyte histology and cardiac α-tocopherol absorption at the end of the study period. As compared to the C group, α-tocopherol-supplemented group showed significantly (p < 0.05) lower body weight (E, 412.8 g vs C, 480.3 g) and total cardiac weight (E, 0.94 g vs C, 1.08 g); cardiomyocyte histological impairment; smaller left ventricle (LV) (LV end-diastolic diameter (E, 7.22 mm vs C, 7.37 mm), lower LV systolic [left ventricle fractional shortening (E, 47.6% vs C, 53.6%) and ejection fraction ratio (E, 85.4 vs C, 89.9)] and diastolic [early peak velocities of diastolic transmitral flow (E, 64.6 cm/sec vs C, 75.1 cm/sec)] function. The α-tocopherol uptake in target tissue was confirmed by determination of α-tocopherol concentration medians in cardiac tissue (E, 109.91 nmol/kg vs C, 52.09 nmol/kg). The current study indicates that pharmacological dose of α-tocopherol supplementation can induce cardiotoxicity in healthy rats.     

Positron Emission Tomography Detection of Distant Metastatic or Synchronous Disease in Patients with Locally Advanced Rectal Cancer Receiving Preoperative Chemoradiation

Background Patients with locally advanced rectal cancer may present with synchronous distant metastases. Choice of optimal treatment—neoadjuvant chemoradiation versus systemic chemotherapy alone—depends on accurate assessment of distant disease. We prospectively evaluated the ability of [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography (PET) to detect distant disease in patients with locally advanced rectal cancer who were otherwise eligible for combined modality therapy (CMT). Methods Ninety-three patients with locally advanced rectal cancer underwent whole-body [¹⁸F]FDG PET scanning 2–3 weeks before starting CMT. Sites other than the rectum, mesorectum, or the area along the inferior mesenteric artery were considered distant and were divided into nine groups: neck, lung, mediastinal lymph node (LN), abdomen, liver, colon, pelvis, peripheral LN, and soft tissue. Two nuclear medicine physicians blinded to clinical information used PET images and a five-point scale (0–4) to determine certainty of disease. A score greater than 3 was considered malignant. Confirmation was based on tissue diagnosis, surgical exploration, and subsequent imaging. Results At a median follow-up of 34 months, the overall accuracy, sensitivity, and specificity of PET in detecting distant disease were 93.7%, 77.8%, and 98.7% respectively. Greatest accuracy was demonstrated in detection of liver (accuracy = 99.9%, sensitivity = 100%, specificity = 98.8%) and lung (accuracy = 99.9%, sensitivity = 80%, specificity = 100%) disease; PET detected 11/12 confirmed malignant sites in liver and lung. A total of 10 patients were confirmed to have M1 stage disease. All 10 were correctly staged by pre-CMT PET; abdominopelvic computed tomography (CT) scans accurately detected nine of them. Conclusion Baseline PET in patients with locally advanced rectal cancer reliably detects metastatic disease in liver and lung. PET may play a significant role in defining extent of distant disease in selected cases, thus impacting the choice of neoadjuvant therapy. An erratum to this article can be found at     

New anti-angiogenic compound based on chemically modified heparin

Graefe's Archive for Clinical and Experimental Ophthalmology - The purpose of this study was to measure the anti-angiogenic effect of N-desulfated Re–N-acetylated, a chemically modified...     

Surgical considerations for ‘intrinsic＇ brainstem gliomas： proposal of a modification in classification

BACKGROUND： Brainstem gliomas are highly heterogeneous tumors both in their clinical manifestation and in their pathology. Despite significant advances in the surgery for brainstem gliomas many aspects of this pathology are still unelear. OBJECTIVE： To evaluate the clinical, radiological and surgical outcome of 40 focal ＂intrinsic＂ brainstem gliomas and propose a surgical strategyoriented classification. MATERIALS AND METHODS： A total of 40 focal ‘intrinsie’ （＂expanding variety＂） tumors have been operated over a period of 8.5-years （January 1998-June 2007）. Our criteria included patients with （1） well-defined gadolinium enhancing tumor, （2） relatively long duration of symptoms （〉 six months） and （3） good neurological functional status and independent for all activities of davy living. The cutoff size of 2 cm was not rigidly adhered to. RESULTS： The ＂intrinsic＂ brainstem tumors were classified into three types： Expanding, diffuse infiltrative and pure ventral varieties.     

Single-session endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography for evaluation of pancreaticobiliary disorders

Background  

Endoscopic ultrasonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) often are required in the evaluation and treatment of patients with pancreaticobiliary disorders. Few reports of single-session EUS-ERCP have raised questions regarding its safety and accuracy or about which procedure should be performed first.