Diabetic retinopathy at high altitude

The objective of this study was to determine whether altitude hypoxia favors the development of diabetic retinopathy (DR) in healthy type 1 diabetic climbers with tight glycemia control. The retinas of 7 type 1 diabetic climbers with a history of stays at high altitude were studied through nonmydriatic chamber retinography (Ffo-CNM). The retinographies were performed before and after a 7,143 m peak expedition. One of the subjects presented evidence of DR prior to the ascent, in addition to a microhemorrhage afterward; the rest of the retinographies were normal. Fine glycemia management and adequate acclimatization are not the only cautions for diabetics going to altitude; an ophthalmologic exam beforehand is also recommended.     

Planned neck dissection before combined chemoradiation for pyriform sinus carcinoma

CONCLUSIONS: A pretreatment neck dissection in a chemoradiation regimen for pyriform sinus carcinoma provides no delay for radiation, low complication rates, optimal radiation doses and a high nodal disease control. OBJECTIVES: The aims of this study were to evaluate the clinical feasibility, therapeutic consequences and neck nodes control of a pretreatment neck dissection in a chemoradiation regimen for organ preservation strategy for pyriform sinus carcinoma. PATIENTS AND METHODS: Seventy-six patients with untreated stage III and IV squamous cell carcinoma of the pyriform sinus were included in this study. Eighty neck dissections were performed according to the N status. Dose of radiotherapy was delivered according to the pathologic finding of neck dissections. RESULTS: The mean time between neck dissection and the chemoradiation was 24 days (+/-12 days). Only two patients (2.5%) experienced wound complications. A 'boost' radiation of 14 Gy was delivered after 49 neck dissections (61%) in patients with extracapsular spread. The rate of disease control within the regional nodes was 90%. The Kaplan-Meier 1- and 2- year overall survival rates were 78% and 43%, respectively, and specific survival rates were 88% and 67%, respectively.     

Monocytic suppressive cells mediate cardiovascular transplantation tolerance in mice

One of the main unresolved questions in solid organ transplantation is how to establish indefinite graft survival that is free from long-term treatment with immunosuppressive drugs and chronic rejection (i.e., the establishment of tolerance). The failure to achieve this goal may be related to the difficulty in identifying the phenotype and function of the cell subsets that participate in the induction of tolerance. To address this issue, we investigated the suppressive roles of recipient myeloid cells that may be manipulated to induce tolerance to transplanted hearts in mice. Using depleting mAbs, clodronate-loaded liposomes, and transgenic mice specific for depletion of CD11c⁺, CD11b⁺, or CD115⁺ cells, we identified a tolerogenic role for CD11b⁺CD115⁺Gr1⁺ monocytes during the induction of tolerance by costimulatory blockade with CD40L-specific mAb. Early after transplantation, Gr1⁺ monocytes migrated from the bone marrow into the transplanted organ, where they prevented the initiation of adaptive immune responses that lead to allograft rejection and participated in the development of Tregs. Our results suggest that mobilization of bone marrow CD11b⁺CD115⁺Gr1⁺ monocytes under sterile inflammatory conditions mediates the induction of indefinite allograft survival. We propose that manipulating the common bone marrow monocyte progenitor could be a useful clinical therapeutic approach for inducing transplantation tolerance.     

Minimal Removal of Raltegravir by Hemodialysis in HIV-Infected Patients with End-Stage Renal Disease

Little is known about raltegravir removal by hemodialysis in patients with end-stage renal disease (ESRD). We therefore measured raltegravir concentrations in plasma in pre- and postdialyzer blood samples from 2 ESRD HIV-infected patients. The hemodialysis extraction ratio and raltegravir hemodialysis clearance were 5.5% and 9.1 ml/min in patient 1 and 9.5% and 19.1 ml/min in patient 2, respectively. Our results suggest minimal raltegravir removal by hemodialysis with no specific raltegravir dosage adjustments required in HIV-infected patients undergoing hemodialysis.The prevalence of chronic renal disease in HIV-infected patients has been estimated to be 5% to 40% (1, 6), depending on the definition applied in each study, and on the racial composition and comorbidity of the population studied. In any case, the progressive aging of the HIV-infected population together with the presence of some comorbid diseases (such as diabetes or hypertension), as well as direct toxicity derived from the antiretroviral drugs, provides a basis for growing concern that the prevalence of chronic renal disease and end-stage renal disease (ESRD) may increase in the future (8). This means that an increasing number of HIV-infected patients will need renal replacement therapy.Raltegravir is an integrase inhibitor of HIV with demonstrated efficacy in naïve and treatment-experienced HIV-infected patients (5, 9). It is mainly metabolized by glucuronidation through UGT1A1 in the liver, with only 9% of the raltegravir dose excreted unchanged in the urine. Raltegravir is approximately 83% bound to plasma proteins, has a low molecular weight, and presents a relatively high solubility in water (blood-to-plasma partition coefficient, 0.6) (4). These characteristics make it possible for hemodialysis to remove raltegravir from plasma in patients with ESRD. As a result, subtherapeutic concentrations of raltegravir after the dialysis sessions might be possible.Here we report two cases of ESRD HIV-infected patients undergoing routine hemodialysis who were receiving antiretroviral therapy with raltegravir. To evaluate the effect of hemodialysis on raltegravir clearance, predialyzer and postdialyzer blood samples were collected at the beginning and end of a single dialysis session. Both patients gave their oral informed consent before sampling.Blood samples for raltegravir determinations were collected into potassium and EDTA-containing 10-ml tubes. Plasma was isolated by centrifugation (3,200 × g for 15 min) and stored at −20°C until analysis. Raltegravir concentrations in plasma were determined by high-performance liquid chromatography with a fluorescence detector (HPLC multifluorescence detector 2475; Waters) according to a validated method (7). Chromatographic separation was performed on a Sunfire C₁₈ column (5 μm; 4.6 by 150 mm) (Waters). The mobile phase was phosphate buffer-acetonitrile (25 mM, pH 3). The fluorescence detector was set at 299 and 396 nm for excitation and emission wavelengths, respectively. The drug was extracted from plasma by liquid-liquid extraction with tert-butyl methyl ether. The method was linear over the range of 10 to 5,000 ng/ml, with quality controls at 840 ng/ml, 360 ng/ml, and 60 ng/ml. At least 98% of raltegravir was recovered at the three levels of concentration assessed. The intra- and interday coefficients of variation were less than 10%.The hemodialysis extraction ratio (ER) for raltegravir was calculated at the beginning of the dialysis session as ER = (C_in − C_out)/C_in (2), where C_in is predialyzer raltegravir concentration in plasma (i.e., blood entering the kidney machine) and C_out is postdialyzer raltegravir concentration in plasma (i.e., blood leaving the kidney machine).Raltegravir dialysis clearance (CL_D) in terms of plasma was calculated as CL_D = ER × Q_p (2), where Q_p is plasma flow through the dialyzer.Because raltegravir is minimally distributed into red blood cells (4), correction for hematocrit was made according to the equation Q_p = Q_b(1 − H) (2), where Q_b is the blood flow through the dialyzer and H is the patient''s hematocrit.Patient 1 was a 53-year-old man who was diagnosed with HIV infection in 1984. The patient had received multiple antiretroviral regimens and at the time of the study had been receiving therapy with nevirapine (200 mg twice daily) and raltegravir (400 mg twice daily) for the previous 6 months. HIV-1 RNA load in plasma was <50 copies/ml, and CD4⁺ T-cell count was 863 cells/mm³. His most relevant underlying diseases included hepatitis C virus (HCV) coinfection, hypertension, hyperlipidemia, and severe ischemic heart disease. The patient had ESRD and had been undergoing hemodialysis three times a week (Fresenius F8HPS) for the previous 2 years. Each hemodialysis session lasted approximately 4 h. On hemodialysis days, the patient delayed the morning raltegravir dose until the end of the dialysis session. Dialysate and blood flows were held constant at 500 ml/min and 300 ml/min, respectively.Patient 2 was a 50-year-old man who was diagnosed with HIV infection in 1992. He had been receiving antiretroviral therapy with efavirenz (600 mg once daily) plus tipranavir-ritonavir (500/200 mg twice daily, respectively) and raltegravir (400 mg twice daily). HIV-1 RNA load in plasma was <50 copies/ml, and CD4⁺ T-cell count was 976 cells/mm³. He had been diagnosed with hypertension. The patient had been undergoing 4-hour hemodialysis sessions three times a week (Polyflux 17C). Dialysate and blood flows were 500 ml/min and 300 ml/min, respectively.Table ​Table11 summarizes raltegravir concentrations in plasma in pre- and postdialyzer samples at the beginning and end of the dialysis session. At the end of the session, raltegravir concentrations had decreased by 68% in patient 1 and by 45% in patient 2. However, the hemodialysis extraction ratio and raltegravir hemodialysis clearance were only 5.5% and 9.1 ml/min in patient 1 and 9.5% and 19.1 ml/min in patient 2, respectively. Both patients maintained raltegravir concentrations in plasma higher than the protein-binding-adjusted 95% inhibitory concentration of 15 ng/ml at the end of the dialysis session (M. Miller, M. Witmer, K. Stilmock, P. Felock, L. Ecto, J. Flynn, W. Schleif, G. Dornadula, R. Danovich, and D. Hazuda, presented at the 16th International AIDS Conference, 2006).

TABLE 1.

Raltegravir concentrations in plasma in pre- and postdialyzer samples during the hemodialysis session^a

A review of automatic mass detection and segmentation in mammographic images

The aim of this paper is to review existing approaches to the automatic detection and segmentation of masses in mammographic images, highlighting the key-points and main differences between the used strategies. The key objective is to point out the advantages and disadvantages of the various approaches. In contrast with other reviews which only describe and compare different approaches qualitatively, this review also provides a quantitative comparison. The performance of seven mass detection methods is compared using two different mammographic databases: a public digitised database and a local full-field digital database. The results are given in terms of Receiver Operating Characteristic (ROC) and Free-response Receiver Operating Characteristic (FROC) analysis.