Morphology of the cloaca in the estuarine crocodile, Crocodylus porosus, and its plastic response to salinity

The cloacal complex of Crocodylus porosus is composed of three chambers (proctodaeum, urodaeum, and coprodaeum) separated by tight, muscular sphincters. The proctodaeum is proximal to the cloacal vent and houses the genitalia. The urodaeum is the largest chamber, is capable of storing large quantities of urine, and is lined with an epithelium with the capacity for transepithelial water and ion exchange. The coprodaeum, the most orad cloacal chamber, is a small, only marginally expandable chamber that has an epithelium composed almost entirely of mucus-secreting cells. The coprodaeum and lower intestine are reported to be the site(s) for urine modification in birds and bladderless lizards. A radiographic trace of urine storage in C. porosus kept for 2 months under hyperosmotic conditions showed no signs of retrograde movement of urine into the coprodaeum or rectum. Instead, urine was stored in the urodaeum of C. porosus. Examination of the mucosal surface of the urodaeum by SEM showed a plastic response to environmental salinity, with a possible increase in surface area in animals kept in hyperosmotic water compared with animals from fresh water. We propose the urodaeum as the primary site for postrenal modification of urine in C, porosus. (C) 2000 Wiley-Liss, Inc.

Glutamate-mediated transmission, alcohol, and alcoholism

Glutamate-mediated neurotransmission may be involved in the range of adaptive changes in brain which occur after ethanol administration in laboratory animals, and in chronic alcoholism in human cases. Excitatory amino acid transmission is modulated by a complex system of receptors and other effecters, the efficacy of which can be profoundly affected by altered gene or protein expression. Local variations in receptor composition may underlie intrinsic regional variations in susceptibility to pathological change. Equally, ethanol use and abuse may bring about alterations in receptor subunit expression as the essence of the adaptive response. Such considerations may underlie the regional localization characteristic of the pathogenesis of alcoholic brain damage, or they may form part of the homeostatic change that constitutes the neural substrate for alcohol dependence. (C) 2000 Elsevier Science Ltd. All rights reserved.

Magnetic resonance imaging (MRI) and diseases of the liver and biliary tract. Part 1. Basic principles, MRI in the assessment of diffuse and focal hepatic disease

Magnetic resonance imaging (MRI) relies on the physical properties of unpaired protons in tissues to generate images. Unpaired protons behave like tiny bar magnets and will align themselves in a magnetic field. Radiofrequency pulses will excite these aligned protons to higher energy states. As they return to their original state, they will release this energy as radio waves. The frequency of the radio waves depends on the local magnetic field and by varying this over a subject, it is possible to build the images we are familiar with. In general, MRI has not been sufficiently sensitive or specific in the assessment of diffuse liver disease for clinical use. However, because of the specific characteristics of fat and iron, it may be useful in the assessment of hepatic steatosis and iron overload. Magnetic resonance imaging is useful in the assessment of focal liver disease, particularly in conjunction with contrast agents. Haemangiomas have a characteristic bright appearance on T-2 weighted images because of the slow flowing blood in dilated sinusoids. Focal nodular hyperplasia (FNH) has a homogenous appearance, and enhances early in the arterial phase after gadolinium injection, while the central scar typically enhances late. Hepatic adenomas have a more heterogenous appearance and also enhance in the arterial phase, but less briskly than FNH. Hepatocellular carcinoma is similar to an adenoma, but typically occurs in a cirrhotic liver and has earlier washout of contrast. The appearance of metastases depends on the underlying primary malignancy. Overall, MRI appears more sensitive and specific than computed tomography with contrast for the detection and evaluation of malignant lesions. (C) 2000 Blackwell Science Asia Pty Ltd.

Is there a role for axillary dissection for patients with operable breast cancer in this era of conservatism?

Background: The trend in breast cancer surgery is toward more conservative operative procedures. The new staging technique of sentinel node biopsy facilitates the identification of pathological node-negative patients in whom axillary dissection may be avoided. However, patients with a positive sentinel node biopsy would require a thorough examination of their nodal status. An axillary dissection provides good local control, and accurate staging and prognostic information to inform decisions about adjuvant therapy. In addition, the survival benefit of axillary treatment is still debated. The objectives of the present study were to examine the pattern of lymph node metastases in the axilla, and evaluate the merits of a level III axillary dissection. Methods : Between June 1997 and May 2000, 308 patients underwent a total of 320 level III dissections as part of their treatment for operable invasive breast cancer. The three axillary levels were marked intraoperatively, and the contents in each level were submitted and examined separately. The patterns of axillary lymph node (ALN) metastases were examined, and factors associated with 4 positive nodes, and level III ALN metastases were evaluated by univariate and multivariate analyses. Results: An average of 25 lymph nodes were examined per case (range: 8-54), and using strict anatomical criteria, the mean numbers of ALN found in levels I, II and III were 18 (range: 2-43), 4 (range: 0 19), and 3 ( range: 0-11), respectively. Axillary lymph node involvement was found in 45% of the cases (143/320). Of the 143 cases, 78% (n = 111) had involvement of level I nodes only, and 21% (n = 30) had positive ALN in levels II and, or, III, in addition to level I. Involvement of lymph nodes in level II or III without a level I metastasis was found in two cases only (0.6%). By including level II, in addition to level I, in the dissection, four cases (1%) were converted from one to three positive nodes to 4 positive nodes (P = 0.64). By the inclusion of level III to a level I and II dissection, three cases (1%) were converted from one to three positive nodes to 4 positive nodes (P = 0.74). Involvement of lymph nodes in level III was found in 22 cases (7%), and 51 cases (16%) had 4 positive nodes. Palpability of ALN, pathological tumour size, and lymphovascular invasion (LVI), were significantly associated with level III involvement and 4 positive nodes by univariate and multivariate analyses. The frequencies of level III involvement and 4 positive nodes in patients with palpable ALN were 22% and 42%, respectively. The corresponding frequencies in patients with a clinically negative axilla, and a primary tumour which was >20 mm and LVI positive, were over 14% and 31%, respectively. Conclusion: Level III axillary dissection is appropriate for patients with palpable ALN, and in those with a tumour which is >20 mm and LVI positive, principally to reduce the risk of axillary recurrence. Staging accuracy is achieved with a level II dissection, or even a level I dissection alone based on strict anatomical criteria. Sentinel node biopsy is a promising technique in identifying pathological node-positive patients in whom an axillary clearance provides optimal local control and staging information.

Identification of "pathologs" (disease-related genes) from the RIKEN mouse cDNA dataset using human curation plus FACTS, a new biological information extraction system

Background: A major goal in the post-genomic era is to identify and characterise disease susceptibility genes and to apply this knowledge to disease prevention and treatment. Rodents and humans have remarkably similar genomes and share closely related biochemical, physiological and pathological pathways. In this work we utilised the latest information on the mouse transcriptome as revealed by the RIKEN FANTOM2 project to identify novel human disease-related candidate genes. We define a new term patholog to mean a homolog of a human disease-related gene encoding a product ( transcript, anti-sense or protein) potentially relevant to disease. Rather than just focus on Mendelian inheritance, we applied the analysis to all potential pathologs regardless of their inheritance pattern. Results: Bioinformatic analysis and human curation of 60,770 RIKEN full-length mouse cDNA clones produced 2,578 sequences that showed similarity ( 70 - 85% identity) to known human-disease genes. Using a newly developed biological information extraction and annotation tool ( FACTS) in parallel with human expert analysis of 17,051 MEDLINE scientific abstracts we identified 182 novel potential pathologs. Of these, 36 were identified by computational tools only, 49 by human expert analysis only and 97 by both methods. These pathologs were related to neoplastic ( 53%), hereditary ( 24%), immunological ( 5%), cardio-vascular (4%), or other (14%), disorders. Conclusions: Large scale genome projects continue to produce a vast amount of data with potential application to the study of human disease. For this potential to be realised we need intelligent strategies for data categorisation and the ability to link sequence data with relevant literature. This paper demonstrates the power of combining human expert annotation with FACTS, a newly developed bioinformatics tool, to identify novel pathologs from within large-scale mouse transcript datasets.

Neuroprotective Effects of Diazepam, Carbamazepine, Phenytoin and Ketamine after Pilocarpine-induced Status Epilepticus

Cell damage and spatial localization deficits are often reported as long-term consequences of pilocarpine-induced status epilepticus. In this study, we investigated the neuroprotective effects of repeated drug administration after long-lasting status epilepticus. Groups of six to eight Wistar rats received microinjections of pilocarpine (2.4 mg/mu l, 1 mu l) in the right dorsal hippocampus to induce a status epilepticus, which was attenuated by thiopental injection (35 mg/kg, i.p.) 3 hrs after onset. Treatments consisted of i.p. administration of diazepam, ketamine, carbamazepine, or phenytoin at 4, 28, 52, and 76 hr after the onset of status epilepticus. Two days after the treatments, rats were tested in the Morris water maze and 1 week after the cognitive tests, their brains were submitted to histology to perform haematoxylin and eosin staining and glial fibrillary acidic protein (GFAP) immunofluorescence detection. Post-status epilepticus rats exhibited extensive gliosis and cell loss in the hippocampal CA1, CA3 (70% cell loss for both areas) and dentate gyrus (60%). Administration of all drugs reduced cell loss in the hippocampus, with best effects observed in brains slices of diazepam-treated animals, which showed less than 30% of loss in the three areas and decreased GFAP immunolabelling. Treatments improved spatial navigation during training trials and probe trial, with exception of ketamine. Interestingly, in the probe trial, only diazepam-treated animals showed preference for the goal quadrant. Our data point to significant neuroprotective effects of repeated administration of diazepam against status epilepticus-induced cell damage and cognitive disturbances.

Mycobacterium chelonae valve endocarditis resulting from contaminated biological prostheses

Objectives: A rapid-growing mycobacteria biological prosthetic valve (BPV) endocarditis related to prosthetic manufacturing process is described in Brazil. Methods: From 1999 to 2008, thirty-nine patients underwent BPV replacement due to culture-negative suspected endocarditis. All these cases had histological sections stained by Ziehl-Neelsen method. Clinical and microbiological data were reviewed in all acid-fast bacilli (AFB) positive cases. The 16S-23S internal transcribed sequence (ITS) was amplified using DNA extracted from paraffin-embedded samples, digested with restrictions enzymes and/or sequenced. Results: Eighteen AFB positive BPV (18/39)(46%) were implanted in 13 patients and were from the same manufacturer. Four of them were implanted in other hospitals. Thirteen BPV were histologically proven endocarditis and five showed a colonization pattern. The examination of six non-implanted ""sterile"" BPV from this manufacturer resulted in 5 AFB positive. Mycobacterium chelonae was the AFB identified by ITS restriction analysis and sequencing. Conclusions: Rapid-growing mycobacteria infections must be suspected and Ziehl-Neelsen stain always performed on histology of either early or late BPV endocarditis, particularly when blood cultures are negative. (C) 2010 The British Infection Society. Published by Elsevier Ltd. All rights reserved.

Attentional modulation of visual cortex activity following right parietal damage in humans

Pathological inattention following parietal damage causes perceptual impairments for visual stimuli in the contralesional hemifield. Here we used functional magnetic resonance imaging (fMRI) to examine visual cortex activity in parietal patients as they performed a spatial attention task. Righthemisphere patients and healthy controls viewed counterphasing checkerboards in which coloured targets appeared briefly within the contralesional and ipsilesional hemifields. In separate fMRI runs participants focused their attention covertiy on the left or right hemifield, or on both hemifields concurrentiy. They were required to detect coloured targets that appeared briefly within the attended hemifield(s), and to withhold responses to distractor stimuli. Neural activit}' was significantly attenuated in early visual areas within the damaged hemisphere. Crucially, although attention significantiy modulated early visual activit}' within the intact (left) hemisphere, there was relatively littie modulation of activity within the affected hemisphere. Our findings suggest that parietal lesions alter early cortical responses to contralesional visual inputs.

Acute Toxic Leukoencephalopathy: Potential for Reversibility Clinically and on MRI With Diffusion-Weighted and FLAIR Imaging

OBJECTIVE. Toxic leukoencephalopathy may present acutely or subacutely with symmetrically reduced diffusion in the periventricular and supraventricular white matter, hereafter referred to as periventricular white matter. This entity may reverse both on imaging and clinically. However, a gathering together of the heterogeneous causes of this disorder as seen on MRI with diffusion-weighted imaging (DWI) and an analysis of their likelihood to reverse has not yet been performed. Our goals were to gather causes of acute or subacute toxic leukoencephalopathy that can present with reduced diffusion of periventricular white matter in order to promote recognition of this entity, to evaluate whether DWI with apparent diffusion coefficient (ADC) values can predict the extent of chronic FLAIR abnormality ( imaging reversibility), and to evaluate whether DWI can predict the clinical outcome ( clinical reversibility). MATERIALS AND METHODS. Two neuroradiologists retrospectively reviewed the MRI examinations of 39 patients with acute symptoms and reduced diffusion of periventricular white matter. The reviewers then scored the extent of abnormality on DWI and FLAIR. ADC ratios of affected white matter versus the unaffected periventricular white matter were obtained. Each patient`s clinical records were reviewed to determine the cause and clinical outcome. Histology findings were available in three patients. Correlations were calculated between the initial MRI markers and both the clinical course and the follow-up extent on FLAIR using Spearman`s correlation coefficient. RESULTS. Of the initial 39 patients, seven were excluded because of a nontoxic cause (hypoxic-ischemic encephalopathy [HIE] or congenital genetic disorders) or because of technical errors. In the remaining 32 patients, no correlation was noted between any of the initial MRI markers (percentage of ADC reduction, DWI extent, or FLAIR extent) with the clinical outcome. Three patients had histologic correlation. However, moderate correlation was seen between the extent of abnormality on initial FLAIR and the extent on follow-up FLAIR (r = 0.441, p = 0.047). Of the 13 patients who underwent repeat MRI at 21 days or longer, the reduced diffusion resolved in all but one. Significant differences were noted between ADC values in affected white matter versus unaffected periventricular white matter on initial (p < 0.0001) but not on follow-up MRI (p = 0.13), and in affected white matter on initial versus follow-up (p = 0.0014) in those individuals who underwent repeat imaging on the same magnet (n = 9), confirming resolution of the DWI abnormalities. CONCLUSION. Acute toxic leukoencephalopathy with reduced diffusion may be clinically reversible and radiologically reversible on DWI, and may also be reversible, but to a lesser degree, on FLAIR MRI. None of the imaging markers measured in this study appears to correlate with clinical outcome, which underscores the necessity for prompt recognition of this entity. Alerting the clinician to this potentially reversible syndrome can facilitate treatment and removal of the offending agent in the early stages.

Immune response to vaccination with DNA-hsp65 in a phase I clinical trial with head and neck cancer patients

DNA-hsp65, a DNA vaccine encoding the 65-kDa heat-shock protein of Mycobacterium leprae (Hsp65) is capable of inducing the reduction of established tumors in mouse models. We conducted a phase I clinical trial of DNA-hsp65 in patients with advanced head and neck carcinoma. In this article, we report on the vaccine`s potential to induce immune responses to Hsp65 and to its human homologue, Hsp60, in these patients. Twenty-one patients with unresectable squamous cell carcinoma of the head and neck received three doses of 150, 400 or 600 mu g naked DNA-hsp65 plasmid by ultrasound-guided intratumoral injection. Vaccination did not increase levels of circulating anti-hsp65 IgG or IgM antibody, or lead to detectable Hsp65-specific cell proliferation or interferon-gamma (IFN-gamma) production by blood mononuclear cells. Frequency of antigen-induced IL-10-producing cells increased after vaccination in 4 of 13 patients analyzed. Five patients showed disease stability or regression following immunization; however, we were unable to detect significant differences between these patients and those with disease progression using these parameters. There was also no increase in antibody or IFN-gamma responses to human Hsp60 in these patients. Our results suggest that although DNA-hsp65 was able to induce some degree of immunostimulation with no evidence of pathological autoimmunity, we were unable to differentiate between patients with different clinical outcomes based on the parameters measured. Future studies should focus on characterizing more reliable correlations between immune response parameters and clinical outcome that may be used as predictors of vaccine success in immunosuppressed individuals. Cancer Gene Therapy (2009) 16, 598-608; doi:10.1038/cgt.2009.9; published online 6 February 2009

Ion and urea regulation in elasmobranch fish

In recent years our understanding of the control of ion and urea metabolism in elasmobranch fish has increased with many more species being investigated. This has demonstrated that many species regarded as stenohaline marine are at least, partially euryhaline and may survive in environments less concentrated than full seawater. This presentation will review these recent findings and then compare the osmoregulatory strategies of a partially euryhaline species, Scyliorhinus canicula, with a fully euryhaline migratory species Carcharinus leucas. This will include new data for both species and will generate new models for the control of ion and urea metabolism in elasmobranchs on which to base future research.

Heart Transplantation in Arrhythmogenic Right Ventricular Dysplasia: Case Reports

Objective. Arrhythmogenic right ventricular dysplasia (ARVD) is a myocardial disease of familiar, origin where the myocardium is replaced by fibrofatty tissue predominantly in the right ventricle. Herein we have presented the clinical courses of 4 patients with ARVD who underwent orthotopic heart transplantation. Patients and Methods. Among 358 adult patients undergoing heart transplantation, 4 (1.1%) displayed ARVD. The main indication for transplantation was the progression to heart failure associated with arrhythmias. All 4 patients displayed rapid, severe courses leading to heart failure with left ventricular involvement and uncontrolled arrhythmias. Results. In all cases the transplantation was performed using a bicaval technique with prophylactic tricuspid valve annuloplasty. One patient developed hyperacute rejection and infection, leading to death on the 7th day after surgery. The other 3 cases showed a good evolution with clinical remission of the symptoms. Pathological study of the explanted hearts confirmed the presence of the disease. Conclusions. ARVD is a serious cardiomyopathy that can develop malignant arrhythmias, severe ventricular dysfunction with right ventricular predominance, and sudden cardiac death. Orthotopic heart transplantation must always be considered in advanced cases of ARVD with malignant arrhythmias or refractory congestive heart failure with or without uncontrolled arrhythmias, because it is the only way to remit the symptoms and the disease.

Phosphate Binder Impact on Bone Remodeling and Coronary Calcification - Results from the BRiC Study

Background and Aims: Calcium-containing phosphate binders have been shown to increase the progression of vascular calcification in hemodialysis patients. This is a prospective study that compares the effects of calcium acetate and sevelamer on coronary calcification (CAC) and bone histology. Methods: 101 hemodialysis patients were randomized for each phosphate binder and submitted to multislice coronary tomographies and bone biopsies at entry and 12 months. Results: The 71 patients who concluded the study had similar baseline characteristics. On follow-up, the sevelamer group had higher levels of intact parathyroid hormone (498 +/- 352 vs. 326 +/- 236 pg/ml, p = 0.017), bone alkaline phosphatase (38 +/- 24 vs. 28 +/- 15 U/l, p = 0.03) and deoxypyridinoline (135 +/- 107 vs. 89 +/- 71 nmol/l, p = 0.03) and lower LDL cholesterol (74 +/- 21 vs. 91 +/- 28 mg/dl, p = 0.015). Phosphorus (5.8 +/- 1.0 vs. 6 +/- 1.0 mg/dl, p = 0.47) and calcium (1.27 +/- 0.07 vs. 1.23 +/- 0.08 mmol/l, p = 0.68) levels did not differ between groups. CAC progression (35 vs. 24%, p = 0.94) and bone histological diagnosis at baseline and 12 months were similar in both groups. Patients of the sevelamer group with a high turnover at baseline had an increase in bone resorption (eroded surface, ES/BS = 9.0 +/- 5.9 vs. 13.1 +/- 9.5%, p = 0.05), whereas patients of both groups with low turnover at baseline had an improvement in bone formation rate (BFR/BS = 0.015 +/- 0.016 vs. 0.062 +/- 0.078, p = 0.003 for calcium and 0.017 +/- 0.016 vs. 0.071 +/- 0.084 mu m(3)/mu m(2)/day, p = 0.010 for sevelamer). Conclusions: There was no difference in CAC progression or changes in bone remodeling between the calcium and the sevelamer groups. Copyright (C) 2008 S. Karger AG, Basel

The interaction between N-category and N-ratio as a new tool to improve lymph node metastasis staging in gastric cancer: Results of a single cancer center in Brazil

Background: Depth of tumor invasion (T-category) and the number of metastatic lymph nodes (N-category) are the most important prognostic factors in patients with gastric cancer. Recently, the ratio between metastatic and dissected lymph nodes (N-ratio) has been established as one. The aim of this study is to evaluate the impact of N-ratio and its interaction with N-category as a prognostic factor in gastric cancer. Methods: This was a retrospective study in which we reviewed clinical and pathological data of 165 patients who had undergone curative surgery at our institution through a 9-year period. The exclusion criteria included metastases, gastric stump tumors and gastrectomy with less than 15 lymph nodes dissected. Results: The median age of the patients was 63 years and most of them were male. Total gastrectomy was the most common procedure and 92.1% of the patients had a D2-lymphadenectomy. Their 5-year overall survival was 57.7%. T-category, N-category, extended gastrectomy, and N-ratio were prognostic factors in overall and disease-free survival in accordance with univariate analysis. In accordance with TNM staging, N1 patients who have had NR1 had 5-year survival in 75.5% whereas in the NR2 group only 33% of the cases had 5-year survival. In the multivariate analysis, the interaction between N-category and N-ratio was an independent prognostic factor. Conclusion: Our findings confirmed the role of N-ratio as prognostic factor of survival in patients with gastric cancer surgically treated with at least 15 lymph nodes dissected. The relationship between N-category and N-ratio is a better predictor than lymph node metastasis staging. (C) 2010 Elsevier Ltd. All rights reserved.