Coronary Calcification Is Associated With Lower Bone Formation Rate in CKD Patients Not Yet in Dialysis Treatment

Vascular calcification is a strong prognostic marker of mortality in hemodialysis patients and has been associated with bone metabolism disorders in this population. In earlier stages of chronic kidney disease (CKD), vascular calcification also has been documented. This study evaluated the association between coronary artery calcification (CAC) and bone histomorphometric parameters in CKD predialysis patients assessed by multislice coronary tomography and by undecalcified bone biopsy. CAC was detected in 33 (66%) patients, and their median calcium score was 89.7 (0.4-2299.3 AU). The most frequent bone histologic alterations observed included low trabecular bone volume, increased eroded and osteoclast surfaces, and low bone-formation rate (BFR/BS). Multiple logistic regression analysis, adjusted for age, sex, and diabetes, showed that BFR/BS was independently associated with the presence of coronary calcification [p=.009; odd ratio (OR) = 0.15; 95% confidence interval (Cl) 0.036-0.619] This study showed a high prevalence of CAC in asymptomatic predialysis CKD patients. Also, there was an independent association of low bone formation and CAC in this population. In conclusion, our results provide evidence that low bone-formation rate constitutes another nontraditional risk factor for cardiovascular disease in CKD patients. 2010 American Society for Bone and Mineral Research.

Behcet`s disease associated with celiac disease: a very rare association

There are common findings between Beh double dagger et`s disease (BD) and celiac disease (CD); however, association in the same patient is a rarity. We relate the third case in the literature of this overlap in a 40-year-old woman with history of obstipation since her childhood. She also presented asymmetric polyarthralgia, loss of weight, anemia, oral recurrent aphthas (> 3/year) and genital ulcerations, inflammatory lower back pain, bowel bleeding and abdominal colic. Afterwards, she presented episodes of erythema nodosum, superficial thrombophlebitis, pseudofolliculitis and aseptic meningitis, thus fulfilling criteria for BD. Due to persistence of the digestive complaints, a gastrointestinal endoscopy was performed. The biopsy showed chronic duodenitis with intraepithelial lymphocytosis, crypt hyperplasia, and villous atrophy. Endomysial antibody was positive. She fulfilled the diagnosis criteria for CD; a gluten-free diet was applied with clinical improvement. Ascertaining whether pathogenic mechanisms are common in these two conditions requires further investigation.

MR Imaging Findings of Iron Overload

Hemochromatosis can be classified as (a) primary, when it originates from a genetic disturbance that promotes the increase of iron absorption, or (b) secondary, when it relates to chronic diseases or to multiple transfusions. The distribution of iron accumulation differs between these two forms; therefore, they can be distinguished by using imaging methods in the majority of cases. Magnetic resonance (MR) imaging is the most sensitive and specific imaging modality in the diagnosis of hemochromatosis. The susceptibility effect caused by the accumulation of iron leads to signal loss in the affected tissues, particularly with the T2*-weighted sequences, which makes the diagnosis of iron overload possible. By using MR imaging techniques, it is possible to estimate the hepatic iron concentration in a noninvasive way, thereby avoiding repeated biopsies. Hemochromatosis can lead to complications, such as a higher frequency of neoplasia, particularly the development of hepatocellular carcinoma. Other neoplasms, such as colorectal tumors, are also associated. Complications related to the treatment of chronic anemia include the appearance of peliosis hepatis and tumors, which can regress after the suspension of treatment with drugs. Knowledge of the disease and of the patterns of iron deposition in patients with iron overload enables not only diagnosis, but also treatment, follow-up, and the detection of possible complications by using imaging methods. (C) RSNA, 2009 . radiographics.rsna.org

CLINICAL TUMOR DIMENSIONS MAY BE USEFUL TO PREVENT GEOGRAPHIC MISS IN CONVENTIONAL RADIOTHERAPY OF UTERINE CERVIX CANCER-A MAGNETIC RESONANCE IMAGING-BASED STUDY

Purpose: To evaluate the risk of geographic miss associated with the classic four-field ""box"" irradiation technique and to define the variables that predict this risk. Materials and Methods: The study population consisted of 80 patients with uterine cervix cancer seen between 2001 and 2006. Median age was 55 years (23-82 years), and 72 (90%) presented with squamous cell carcinoma. Most patients (68.7%) presented with locally advanced disease (IIb or more). Magnetic resonance imaging findings from before treatment were compared with findings from simulation of the conventional four-field ""box"" technique done with rectal contrast. Study variables included tumor volume; involvement of vagina, parametrium, bladder, or rectum; posterior displacement of the anterior rectal wall; and tumor anteroposterior diameter (APD). Margins were considered adequate when the target volume (primary tumor extension, whole uterine body, and parametrium) was included within the field limits and were at least 1 cm in width. Results: Field limits were inadequate in 45 (56%) patients: 29 (36%) patients at the anterior and 28 (35%) at the posterior border of the lateral fields. Of these, 12 patients had both anterior and posterior miss, and this risk was observed in all stages of the disease (p = 0.076). Posterior displacement of the anterior rectal wall beyond S2-S3 was significantly correlated with the risk of geographic miss (p = 0.043). Larger tumors (APD 6 cm or above and volume above 50 cm(3)) were also significantly correlated with this risk (p = 0.004 and p = 0.046, respectively). Conclusions: Posterior displacement of the anterior rectal wall, tumor APD, and volume can be used as guidance in evaluating the risk of geographic miss. (C) 2009 Elsevier Inc.

Review of genetic and epigenetic alterations in hepatocarcinogenesis

Hepatocellular carcinoma (HCC) is associated with multiple risk factors and is believed to arise from pre-neoplastic lesions, usually in the background of cirrhosis. However, the genetic and epigenetic events of hepatocarcinogenesis are relatively poorly understood. HCC display gross genomic alterations, including chromosomal instability (CIN), CpG island methylation, DNA rearrangements associated with hepatitis B virus (HBV) DNA integration, DNA hypomethylation and, to a lesser degree, microsatellite instability. Various studies have reported CIN at chromosomal regions, 1p, 4q, 5q, 6q, 8p, 10q, 11p, 16p, 16q, 17p and 22q. Frequent promoter hypermethylation and subsequent loss of protein expression has also been demonstrated in HCC at tumor suppressor gene (TSG), p16, p14, p15, SOCS1, RIZ1, E-cadherin and 14-3-3 sigma. An interesting observation emerging from these studies is the presence of a methylator phenotype in hepatocarcinogenesis, although it does not seem advantageous to have high levels of microsatellite instability. Methylation also appears to be an early event, suggesting that this may precede cirrhosis. However, these genes have been studied in isolation and global studies of methylator phenotype are required to assess the significance of epigenetic silencing in hepatocarcinogenesis. Based on previous data there are obvious fundamental differences in the mechanisms of hepatic carcinogenesis, with at least two distinct mechanisms of malignant transformation in the liver, related to CIN and CpG island methylation. The reason for these differences and the relative importance of these mechanisms are not clear but likely relate to the etiopathogenesis of HCC. Defining these broad mechanisms is a necessary prelude to determine the timing of events in malignant transformation of the liver and to investigate the role of known risk factors for HCC.

Is Coronary Artery Calcification Associated with Vertebral Bone Density in Nondialyzed Chronic Kidney Disease Patients?

Background and objectives Low bone mineral density and coronary artery calcification (CAC) are highly prevalent among chronic kidney disease (CKD) patients, and both conditions are strongly associated with higher mortality. The study presented here aimed to investigate whether reduced vertebral bone density (VBD) was associated with the presence of CAC in the earlier stages of CKD. Design, setting, participants, & measurements Seventy-two nondialyzed CKD patients (age 52 +/- 11.7 years, 70% male, 42% diabetics, creatinine clearance 40.4 +/- 18.2 ml/min per 1.73 m(2)) were studied. VBD and CAC were quantified by computed tomography. Results CAC > 10 Agatston units (AU) was observed in 50% of the patients (median 120 AU [interquartile range 32 to 584 AU]), and a calcification score >= 400 AU was found in 19% (736 [527 to 1012] AU). VBD (190 +/- 52 Hounsfield units) correlated inversely with age (r = -0.41, P < 0.001) and calcium score (r = -0.31, P = 0.01), and no correlation was found with gender, creatinine clearance, proteinuria, lipid profile, mineral parameters, body mass index, and diabetes. Patients in the lowest tertile of VBD had expressively increased calcium score in comparison to the middle and highest tertile groups. In the multiple logistic regression analysis adjusting for confounding variables, low VBD was independently associated with the presence of CAC. Conclusions Low VBD was associated with CAC in nondialyzed CKD patients. The authors suggest that low VBD might constitute another nontraditional risk factor for cardiovascular disease in CKD. Clin J Am Soc Nephrol 6: 1456-1462, 2011. doi: 10.2215/CJN.10061110

Phase I trial of DNA-hsp65 immunotherapy for advanced squamous cell carcinoma of the head and neck

Considering that mycobacterial heat-shock protein 65 (hsp65) gene transfer can elicit a profound antitumoral effect, this study aimed to establish the safety, maximum-tolerated dose (MTD) and preliminary efficacy of DNA-hsp65 immunotherapy in patients with advanced head and neck squamous cell carcinoma (HNSCC). For this purpose, 21 patients with unresectable and recurrent HNSCC were studied. Each patient received three ultrasound-guided injections at 21-day intervals of: 150, 600 or 400 mu g of DNA-hsp65. Toxicity was graded according to CTCAE directions. Tumor volume was measured before and after treatment using computed tomography scan. The evaluation included tumor mass variation, delayed-type hypersensitivity response and spontaneous peripheral blood mononuclear cell proliferation before and after treatment. The MTD was 400 mg per dose. DNA-hsp65 immunotherapy was well tolerated with moderate pain, edema and infections as the most frequent adverse effects. None of the patients showed clinical or laboratory alterations compatible with autoimmune reactions. Partial response was observed in 4 out of 14 patients who completed treatment, 2 of which are still alive more than 3 years after the completion of the trial. Therefore, DNA-hsp65 immunotherapy is a feasible and safe approach at the dose of 400 mg per injection in patients with HNSCC refractory to standard treatment. Further studies in a larger number of patients are needed to confirm the efficacy of this novel strategy.

Local immunological factors associated with recurrence of mucosal leishmaniasis

Recurrence of mucosal leishmaniasis (ML) is frequent, but the causative mechanisms are unknown. Our aim was to compare cellular and cytokine patterns of lesions from ML that evolved to recurrence or cure in order to determine the risk factor associated with recurrence. Lesions were evaluated by immunohistochemistry before and after therapy, and patients were followed-up for five years. Higher levels of CD4(+) T and IFN-gamma-producing cells were detected in active lesions and decreased after therapy. Macrophages and IL-10 were markedly increased in cured patients. Conversely, CD8(+) T and NK cells were higher in relapsed than in cured cases. Notably, a decrease in these cells in addition to decreased IL-10 and IFN-gamma was also observed after therapy. These data suggest that exacerbated CD8(+) activity, in addition to a poor regulatory response, could underlie an unfavorable fate with regard to ML. These markers may be useful for predicting the prognosis of ML in lesion studies. (C) 2008 Elsevier Inc. All rights reserved.

Copper-mediated amyloid-beta toxicity is associated with an intermolecular histidine bridge

Amyloid-beta peptide (A beta) is pivotal to the pathogenesis of Alzheimer disease. Here we report the formation of a toxic A beta-Cu2+ complex formed via a histidine-bridged dimer, as observed at Cu2+/ peptide ratios of > 0.6:1 by EPR spectroscopy. The toxicity of the A beta-Cu2+ complex to cultured primary cortical neurons was attenuated when either the pi- or tau-nitrogen of the imidazole side chains of His were methylated, thereby inhibiting formation of the His bridge. Toxicity did not correlate with the ability to form amyloid or perturb the acyl-chain region of a lipid membrane as measured by diphenyl- 1,3,5-hexatriene anisotropy, but did correlate with lipid peroxidation and dityrosine formation. P-31 magic angle spinning solid-state NMR showed that A beta and A beta-Cu2+ complexes interacted at the surface of a lipid membrane. These findings indicate that the generation of the A beta toxic species is modulated by the Cu2+ concentration and the ability to form an intermolecular His bridge.

The assessment of oral cytology utilizing ploidy analysis and virtual microscopy for the early detection of epithelial dysplasia and neoplasia in oral mucosal lesions

Oral squamous cell carcinoma (OSCC) is associated with high morbidity and mortality which is due, at least in part, to late detection. Precancerous and cancerous oral lesions may mimic any number of benign oral lesions, and as such may be left without investigation and treatment until they are well advanced. Over the past several years there has been renewed interest in oral cytology as an adjuvant clinical tool in the investigation of oral mucosal lesions. The purpose of the present study was to compare the usefulness of ploidy analysis after Feulgen stained cytological thin-prep specimens with traditional incisional biopsy and routine histopathological examination for the assessment of the pre-malignant potential of oral mucosal lesions. An analysis of the cytological specimens was undertaken with virtual microscopy which allowed for rapid and thorough analysis of the complete cytological specimen. 100 healthy individuals between 30 and 70 years of age, who were non-smokers, non-drinkers and not taking any medication, had cytological specimens collected from both the buccal mucosa and lateral margin of tongue to establish normal cytology parameters within a control population. Patients with a presumptive clinical diagnosis of lichen planus, leukoplakia or OSCC had lesional cytological samples taken prior to their diagnostic biopsy. Standardised thin preparations were prepared and each specimen stained by both Feuglen and Papanicolau methods. High speed scanning of the complete slide at 40X magnification was undertaken using the Aperio Scanscope TM and the green channel of the resultant image was analysed after threshold segmentation to isolate only nuclei and the integrated optical density of each nucleus taken as a gross measure of the DNA content (ploidy). Preliminary results reveal that ploidy assessment of oral cytology holds great promise as an adjunctive prognostic factor in the analysis of the malignant potential of oral mucosal lesions.

Pathogens associated with nursery plants imported into Western Australia

A small survey of the potting mix taken from 15 consignments of nursery grown plants imported into Western Australia from other states in Australia found that Phytophthora spp. were present in 10% of the samples and Pythium spp. were present in 25% of the samples. Plant pathogenic nematodes were isolated from 12 of 13 consignments. Potting mix appears to be an important route by which plant pathogens can be passively introduced into Western Australia.

Surgical Treatment of Morbid Obesity: Mid-term Outcomes of the Laparoscopic Ileal Interposition Associated to a Sleeve Gastrectomy in 120 Patients

The aim of this study was to evaluate the mid-term outcomes of the laparoscopic ileal interposition associated to a sleeve gastrectomy (LII-SG) for the treatment of morbid obesity. The procedure was performed in 120 patients: 71 women and 49 men with mean age of 41.4 years. Mean body mass index (BMI) was 43.4 +/- 4.2 kg/m(2). Patients had to meet requirements of the 1991 NIH conference criteria for bariatric operations. Associated comorbidities were observed in all patients, including dyslipidemia in 51.7%, hypertension in 35.8%, type 2 diabetes in 15.8%, degenerative joint disease in 55%, gastroesophageal reflux disease in 36.7%, sleep apnea in 10%, and cardiovascular problems in 5.8%. Mean follow-up was 38.4 +/- 10.2 months, range 25.2-61.1. There was no conversion to open surgery nor operative mortality. Early major complications were diagnosed in five patients (4.2%). Postoperatively, 118 patients were evaluated. Late major complications were observed in seven patients (5.9%). Reoperations were performed in six (5.1%). Mean postoperative BMI was 25.7 +/- 3.17 kg/m(2), and 86.4% were no longer obese. Mean %EWL was 84.5 +/- 19.5%. Hypertension was resolved in 88.4% of the patients, dyslipidemia in 82.3%, and T2DM in 84.2%. The LII-SG provided an adequate weight loss and resolution of associated diseases during mid-term outcomes evaluation. There was an acceptable morbidity with no operative mortality. It seems that chronic ileal brake activation determined sustained reduced food intake and increased satiety over time. LII-SG could be regularly used as a surgical alternative for the treatment of morbid obesity.

Increased Transactivation Associated with SOX3 Polyalanine Tract Deletion in a Patient with Hypopituitarism

Backgound and Aims: Correct gene dosage of SOX3 is critical for the development of the hypothalamo-pituitary axis. Both overdosage of SOX3, as a result of gene duplication, and loss of function resulting from expansion of the first polyalanine (PA) tract are associated with variable degrees of hypopituitarism, with or without mental retardation. The aim of this study was to further investigate the contribution of SOX3 in the etiology of hypopituitarism and the mechanisms involved in the phenotypic variability. Methods: We screened 154 patients with congenital hypopituitarism and an undescended posterior pituitary for mutations in SOX3 and variability in the length of the first PA tract. In addition, 300 patients with variable septooptic dysplasia were screened for variability of the PA tract. Results: We report a novel 18-base pair deletion (p.A243_A248del6, del6PA) in a female patient with hypopituitarism resulting in a 2-fold increase in transcriptional activation in vitro, compared with wild-type SOX3. We also identified a previously reported seven-alanine expansion (p.A240_A241ins7, +7PA) in two male siblings with isolated GH deficiency and a distinct phenotype, in addition to the nonsynonymous variant p.R5Q in an unrelated individual; this appears to have no functional effect on the protein. In contrast to +7PA, del6PA maintained its ability to repress beta-catenin mediated transcription in vitro. Conclusion: This is the first study to report that PA tract deletions associated with hypopituitarism have functional consequences in vitro, possibly due to increased activation of SOX3 target genes. In addition, we have expanded the phenotypic spectrum associated with PA tract expansion (+7PA) mutations to include panhypopituitarism or isolated GH deficiency, with or without mental retardation. (J Clin Endocrinol Metab 96: E685-E690, 2011)

Infection rate and risk factors associated with infections related to external ventricular drain

To describe incidence rates and risk factors associated with external ventricular drain (EVD)-related infections at a tertiary Brazilian teaching hospital. The patient cohort consisted of all patients at a major teaching hospital in Brazil with an EVD during the period 1 April 2007 to 30 June 2008 (15 months). Patients were followed up for 30 days after catheter removal. According to the Center for Diseases Control and Prevention criteria for meningitis/ventriculitis, all of the central nervous system (CNS) infections that occurred during this period could be considered to be meningitis or ventriculitis related to EVD placement. Infection rates were calculated using different denominators, such as (1) per patient (incidence), (2) per procedure, and (3) per 1,000 catheter-days (drain-associated infection rate). Patient demographic data, medical history of underlying diseases, antibiotic prophylaxis usage, American Society of Anesthesiologists Score classification, duration of surgery and hospitalization, length of time the EVD was in place, and overall mortality were evaluated during the study period. A logistic regression model was developed to identify factors associated with infection. A total of 119 patients, 130 EVD procedures, and 839 catheter-days were evaluated. The incidence of infection was 18.3%, the infection rate was 16.9% per procedure, and the drain-associated infection rate was 22.4 per 1,000 catheter-days; 77% of the infections were caused by Gram-negative micro-organisms. Only 75% of patients received antibiotic prophylaxis. The infection rate increased with length of the hospital stay. The length of time the catheter was in place was the only independent risk factor associated with infection (p = 0.0369). The incidence of EVD-related infections is high in our hospital, Gram-negative micro-organisms were the most frequent causal agents identified and length of time that the catheter was in place contributed to the infection rate.

Tobacco Smoke Induces Ventricular Remodeling Associated with an Increase in NADPH Oxidase Activity

Background: Recent studies have assessed the direct effects of smoking on cardiac remodeling and function. However, the mechanisms of these alterations remain unknown. The aim of this study was to investigate de role of cardiac NADPH oxidase and antioxidant enzyme system on ventricular remodeling induced by tobacco smoke. Methods: Male Wistar rats that weighed 200-230 g were divided into a control group (C) and an experimental group that was exposed to tobacco smoke for a period of two months (ETS). After the two-month exposure period, morphological, biochemical and functional analyses were performed. Results: The myocyte cross-sectional area and left ventricle end-diastolic dimension was increased 16.2% and 33.7%, respectively, in the ETS group. The interstitial collagen volume fraction was also higher in ETS group compared to the controls. In addition to these morphological changes, the ejection fraction and fractional shortening were decreased in the ETS group. Importantly, these alterations were related to augmented heart oxidative stress, which was characterized by an increase in NADPH oxidase activity, increased levels of lipid hydroperoxide and depletion of antioxidant enzymes (e.g., catalase, superoxide dismutase and glutathione peroxidase). In addition, cardiac levels of IFN-gamma, TNF-alpha and IL-10 were not different between the groups. Conclusion: Cardiac alterations that are induced by smoking are associated with increased NADPH oxidase activity, suggesting that this pathway plays a role in the ventricular remodeling induced by exposure to tobacco smoke. Copyright (C) 2011 S. Karger AG, Basel