A Multicenter Study of the Predictive Value of Crescents in IgA Nephropathy.

The Oxford Classification of IgA nephropathy does not account for glomerular crescents. However, studies that reported no independent predictive role of crescents on renal outcomes excluded individuals with severe renal insufficiency. In a large IgA nephropathy cohort pooled from four retrospective studies, we addressed crescents as a predictor of renal outcomes and determined whether the fraction of crescent-containing glomeruli associates with survival from either a ≥50% decline in eGFR or ESRD (combined event) adjusting for covariates used in the original Oxford study. The 3096 subjects studied had an initial mean±SD eGFR of 78±29 ml/min per 1.73 m2 and median (interquartile range) proteinuria of 1.2 (0.7-2.3) g/d, and 36% of subjects had cellular or fibrocellular crescents. Overall, crescents predicted a higher risk of a combined event, although this remained significant only in patients not receiving immunosuppression. Having crescents in at least one sixth or one fourth of glomeruli associated with a hazard ratio (95% confidence interval) for a combined event of 1.63 (1.10 to 2.43) or 2.29 (1.35 to 3.91), respectively, in all individuals. Furthermore, having crescents in at least one fourth of glomeruli independently associated with a combined event in patients receiving and not receiving immunosuppression. We propose adding the following crescent scores to the Oxford Classification: C0 (no crescents); C1 (crescents in less than one fourth of glomeruli), identifying patients at increased risk of poor outcome without immunosuppression; and C2 (crescents in one fourth or more of glomeruli), identifying patients at even greater risk of progression, even with immunosuppression.

Department Wide Validation in Digital Pathology-Experience from an Academic Teaching Hospital Using the UK Royal College of Pathologists' Guidance.

AIM: we describe our experience of validating departmental pathologists for digital pathology reporting, based on the UK Royal College of Pathologists (RCPath) "Best Practice Recommendations for Implementing Digital Pathology (DP)," at a large academic teaching hospital that scans 100% of its surgical workload. We focus on Stage 2 of validation (prospective experience) prior to full validation sign-off. METHODS AND RESULTS: twenty histopathologists completed Stage 1 of the validation process and subsequently completed Stage 2 validation, prospectively reporting a total of 3777 cases covering eight specialities. All cases were initially viewed on digital whole slide images (WSI) with relevant parameters checked on glass slides, and discordances were reconciled before the case was signed out. Pathologists kept an electronic log of the cases, the preferred reporting modality used, and their experiences. At the end of each validation, a summary was compiled and reviewed with a mentor. This was submitted to the DP Steering Group who assessed the scope of cases and experience before sign-off for full validation. A total of 1.3% (49/3777) of the cases had a discordance between WSI and glass slides. A total of 61% (30/49) of the discordances were categorised as a minor error in a supplementary parameter without clinical impact. The most common reasons for diagnostic discordances across specialities included identification and grading of dysplasia, assessment of tumour invasion, identification of small prognostic or diagnostic objects, interpretation of immunohistochemistry/special stains, and mitotic count assessment. Pathologists showed similar mean diagnostic confidences (on Likert scale from 0 to 7) with a mean of 6.8 on digital and 6.9 on glass slide reporting. CONCLUSION: we describe one of the first real-world experiences of a department-wide effort to implement, validate, and roll out digital pathology reporting by applying the RCPath Recommendations for Implementing DP. We have shown a very low rate of discordance between WSI and glass slides.

Amitriptyline aggravates the fibrosis process in a rat model of infravesical obstruction.

Infravesical obstruction (IVO) secondary to benign prostatic hypertrophy can affect up to 50% of men over 50 years old and may cause serious and irreversible alterations throughout the urinary tract, especially in the bladder. Therapeutic approaches are currently limited. Amitriptyline has recently been described as an analgesic, anti-inflammatory and myorelaxant in some experimental models. The objective of this study was to investigate the effects of amitriptyline hydrochloride on the process of fibrosis in a bladder outlet obstruction model in rats. Male Wistar rats were subjected to IVO and studied at intervals of 1 and 14 days postprocedure. The rats were randomly divided into five groups: sham, IVO1-T, IVO1-NT, IVO14-T and IVO14-NT. Bladder tissue was processed for histopathology, immunohistochemistry and RT-PCR. The IVO14 groups presented bladder fibrosis, smooth muscle cell hypertrophy and bladder wall thickening. The IVO14-T group demonstrated a higher intensity of fibrosis, higher macrophage infiltration rate and higher gene expression of Transforming growth factor (TGF) Tgf-ß1. Thus this data shows that in this experimental mode amitriptyline had an amplifying effect on the process of fibrosis as a whole.

Electroacupuncture and moxibustion decrease renal sympathetic nerve activity and retard progression of renal disease in rats.

BACKGROUND/AIM: Chronic kidney disease (CKD) is an increasing major public health problem worldwide. The sympathetic nervous system and nitric oxide play an important role in the pathogenesis of CKD. Traditional Chinese medicine has accumulated thousands of years of therapeutic experiences. Electroacupuncture (EA) and moxibustion (MO) are two such therapeutic strategies. The aim of this study was to investigate the renal and hemodynamic effects of EA-MO in an experimental model of a CKD. METHODS: Male Wistar rats submitted to 5/6th nephrectomy (5/6 NX) were studied for 8 weeks. There were four groups: (1) control, normal rats; (2) NX, 5/6 NX only; (3) NX-AS, 5/6 NX and EA-MO session using sham points, and (4) NX-AM, 5/6 NX and EA-MO session using real acupoints. Biochemical and blood pressure studies, renal sympathetic nerve activity measurements, nitric oxide levels and the histopathological indices were assessed. RESULTS: The EA- and MO-treated group presented significant improvement in all measured functional and histopathological parameters. CONCLUSION: These findings suggest that EA-MO had beneficial effects on CKD. This effect was probably achieved by the modulation of the renal sympathetic nerve activity and nitric oxide levels, leading to decreased blood pressure, which is associated with less proteinuria.

Electroacupuncture and moxibustion attenuate the progression of renal disease in 5/6 nephrectomized rats.

BACKGROUND/AIM: Chronic kidney disease is a worldwide public health problem and the prevention of its progression is still a major challenge in nephrology. Specific therapies that inhibit or attenuate this process are neither available nor satisfactory. Traditional Chinese medicine has been increasingly recognized as an effective therapeutic approach in several fields of medicine. The aim of this study was to investigate the effects of electroacupuncture (EA) and moxibustion (MO) in an experimental model of progressive renal disease in rats. METHODS: Twenty-one male Wistar rats were submitted to 5/6th nephrectomy (NX) and assessed 8 weeks later and were divided into three groups: NX = only 5/6 NX, NX-AS = 5/6 NX and a 20-min EA-MO session in sham points, and NX-AM = 5/6 NX and a 20-min EA-MO session in three real acupuncture points. The treatment consisted of 16 sessions twice a week. Renal function, urine volume, serum creatinine, 24-hour proteinuria, direct and indirect blood pressure, glomerulosclerosis and tubulointerstitial fibrosis indices were assessed. RESULTS: The NX-AM group showed a significant decrease in all investigated parameters when compared to the control groups. CONCLUSION: Our results suggest that EA and MO attenuated the progression of renal disease in the experimental model of 5/6 NX.

IgA Nephropathy in Salvador, Brazil. Clinical and laboratory presentation at diagnosis.

INTRODUCTION: IgA nephropathy (IgAN) is the most prevalent primary glomerulopathy in the world, but great variation is reported in different countries. In Brazil, the reported prevalence is high in the Southeastern States and low in Salvador, Bahia State, Brazil. OBJECTIVES: This study investigated the clinical and histological patterns of patients with IgAN in Salvador, Brazil. METHODS: This is a descriptive study that included all patients with a diagnosis of IgAN performed in native kidney biopsies collected from referral nephrology services of public hospitals in Salvador between 2010 and 2015. Results: Thirty-two cases of IgAN were identified, corresponding to 6% of primary glomerulopathies. There was a slight male predominance (56%) and the median age was 30 [22-40] years. Hematuria was present in 79%, non-nephrotic proteinuria was present in 61%, and hypertension was present in 69% of patients. Segmental sclerosis (S1 lesions) was present in 81% of cases, and chronic tubulo-interstitial lesions (T1 and T2 lesions) were present in 44% of cases. Patients with M1 and T2 MEST-C scores exhibited higher serum urea and creatinine than other patients. CONCLUSION: The prevalence of IgAN was lower in Salvador than other regions of Brazil. Chronic histological lesions and laboratory markers of severe disease were frequent. M1 and T2 MEST-C scores were correlated with markers of renal dysfunction.

Influence of immunosuppressive drugs on the CD30 molecule in kidney transplanted patients.

BACKGROUND: Soluble CD30 (sCD30) is a suggested marker for kidney transplantation outcomes. We investigated whether sCD30 serum levels are influenced by immunosuppression and whether they correlate with findings in protocol biopsies and with CD30 gene expression in peripheral blood mononuclear cells (PBMC). METHODS: We studied 118 kidney transplant recipients that initially received tacrolimus (TAC) and, at month-3, were converted or not to sirolimus (SRL). RESULTS: sCD30 serum levels gradually declined after transplantation, being the decline more pronounced in the SRL group. CD30 gene expression in PBMC was higher in the SRL group than in the TAC group. Patients with IF/TA ≥ I in the month-24 protocol biopsy had higher sCD30 levels than patients without IF/TA, in the SRL group (P = .03) and in the TAC group (P = .07). CD30+ cells were observed in three out of 10 biopsies with inflammatory infiltrate from the SRL group. In mixed lymphocyte cultures, SRL and TAC diminished the number of CD30+ T cells and the sCD30 levels in the supernatant, but the effect of SRL was stronger. CONCLUSIONS: Overall, sCD30 levels are lower in SRL-treated patients, but the association between increased sCD30 levels and IF/TA at month-24 post-transplantation is stronger in SRL than in TAC-treated patients.

The efficiency of combined coagulant and ballast to remove harmful cyanobacterial blooms in a tropical shallow system.

We tested the hypothesis that a combination of coagulant and ballast could be efficient for removal of positively buoyant harmful cyanobacteria in shallow tropical waterbodies, and will not promote the release of cyanotoxins. This laboratory study examined the efficacy of coagulants [polyaluminium chloride (PAC) and chitosan (made of shrimp shells)] alone, and combined with ballast (lanthanum modified bentonite, red soil or gravel) to remove the natural populations of cyanobacteria collected from a shallow eutrophic urban reservoir with alternating blooms of Cylindrospermopsis and Microcystis. PAC combined with ballast was effective in settling blooms dominated by Microcystis or Cylindrospermopsis. Contrary to our expectation, chitosan combined with ballast was only effective in settling Cylindrospermopsis-dominated blooms at low pH, whereas at pH≥8 no effective flocculation and settling could be evoked. Chitosan also had a detrimental effect on Cylindrospermopsis causing the release of saxitoxins. In contrast, no detrimental effect on Microcystis was observed and all coagulant-ballast treatments were effective in not only settling the Microcystis dominated bloom, but also lowering dissolved microcystin concentrations. Our data show that the best procedure for biomass reduction also depends on the dominant species.

Current distribution pattern of biopsy-proven glomerular disease in Salvador, Brazil, 40 years after an initial assessment.

INTRODUCTION: A report on the prevalence of glomerular disease diagnosed via renal biopsy in Salvador, BA, Brazil was published in 1973 and showed a predominance of membranoproliferative glomerulonephritis, which was frequently associated with hepatosplenic schistosomiasis. OBJECTIVE: In this study, we investigate the potential changes in the distribution of glomerular diseases after a period of important epidemiological transition in Brazil. METHODS: Pathology reports of all patients subjected to kidney biopsy from 2003 to 2015 in a referral nephrology service were reviewed. Clinical, laboratorial and pathological diagnoses were collected for analysis. Histological slides of the biopsies performed between 2003 and 2006 were reviewed to examine the accuracy of the estimates based on the pathology reports. RESULTS: Among the biopsies performed during the time period, 1,312 met the inclusion criteria for the study. Focal and segmental glomerulosclerosis was the most prevalent diagnosis, followed by lupus nephritis. However, a trend toward a decrease in the prevalence of focal and segmental glomerulosclerosis was detected (p < 0.05), and an increase in lupus (p < 0.0001) and membranous glomerulonephritis (p < 0.005) was observed. CONCLUSION: The data presented herein suggest the occurrence of changes in the distribution of nephrological diseases in Salvador, Brazil. The disease that was most prevalent shifted from membranoproliferative glomerulonephritis to focal and segmental glomerulosclerosis from 1975 to 2006 and from focal and segmental glomerulosclerosis to lupus nephritis from 2006 to 2015.

An update on pathology of IgA nephropathy.

IgA Nephropathy (IgAN) is the commonest of the glomerular diseases in the world. Its progression rate of 30-40% of the cases em 20-30 years makes IgAN an important healthcare issue in Nephrology. Diagnosis of IgAN depends on biopsy findings, particularly at immunofluorescence microscopy. The frequence of IgAN diagnosis is variable in different populations and depends on screening and biopsy indication policies. IgAN pathogenesis is considered multifactorial; its primordial defect is the production of galactosis-deficient IgA molecules. This review paper discusses the most uptodate aspects of the pathogenesis, pathological classification and clinical implications of IgAN.

Frequency and clinical histological analysis of glomerular diseases in a tertiary hospital in southern Brazil.

INTRODUCTION: The glomerulopathies are the most common biopsy-proven kidney diseases. The epidemiological investigation of glomerulopathies allows the identification of their distribution and main causes and enables the development of prevention and treatment strategies. OBJECTIVE: This study aims to identify the frequency and clinical-pathological correlation of glomerular diseases diagnosed at the HC-UFPR over the period of 5 years. METHODS: 131 biopsies were performed between January 1, 2008 and December 31, 2012 and were analysed by light and immunofluorescence microscopy. Histopathological slides were reviewed by a pathologist. Clinical and laboratory data and the immunofluorescence microscopy results were extracted from medical records. The findings were tabulated and analysed. RESULTS: 128 of 131 cases were reanalysed. 46.5% were obtained from men. Patients' age averaged 43 years for men and 38 for women. In 99 cases, the indication of biopsy was identified; 49.5% cases presented nephrotic syndrome, 17.17%, acute renal failure and 15.15%, chronic renal failure; 8.08%, nephritic syndrome; 6.06%, isolated proteinuria and 4.04% isolated hematuria. In 61.21% an underlying disease related to the glomerulopathy could be identified; 33.62% corresponded to primary disease and in 5.17% of cases the nature of the glomerulopathy could not be determined. Among secondary glomerulopathies, the most frequent was Lupus Nephritis (49.29%), and among the primary, Focal Segmental Glomerulosclerosis (30.77%) and Membranous Nephropathy (25.64%). CONCLUSION: The average patient with glomerulopathy in this service is an adult with nephrotic syndrome. Unlike other reports, secondary glomerulopathies were predominant. These findings may reflect the tertiary characteristic of the assistance at HC-UFPR.

A case of renal recovery in atypical hemolytic uremic syndrome treated with eculizumab.

Atypical Hemolytic Uremic Syndrome (aHUS) is a rare, life-threatening disease that can occur at any age and be sporadic or familial. aHUS is caused by an uncontrolled activation of the complement system. Plasma Exchange (PE) has been the standard treatment for years with poor results, leading approximately 40% of patients to end-stage renal disease (ESRD) or death during the first clinical manifestation. Eculizumab, an humanized monoclonal antibody directed against complement component C5, has emerged in the last few years as a new therapheutic aproach with promising results. Our goal is to present a case of an adult patient where eculizumab was sucessfully used as upfront therapy avoiding the potential significant morbidity of PE.

BCG modulation of anaphylactic antibody response, airway inflammation and lung hyperreactivity in genetically selected mouse strains (Selection IV-A).

The effect of Bacillus Calmette-Guérin (BCG) treatment in allergic pulmonary reaction was studied in mice genetically selected accordingly to a High (H-IVA) or Low (L-IVA) antibody responsiveness. Mice were immunized with ovalbumin (OVA) or OVA plus BCG. Two days after nasal antigenic challenge, seric IgE and IgG1 anti-OVA, eosinophils in pulmonary tissue, inflammatory cells in bronchoalveolar lavage and the compliance and conductance of respiratory system were evaluated. H-IVA mice were found more susceptible than L-IVA, and BCG was able to inhibit simultaneously the production of IgE, the bronchopulmonary inflammation and bronchial hyperresponsiveness in these genetically selected mice.

Patchwork psicanalítico: costurando em tempos revoltos / Psychoanalytic patchwork: sewing on troubled times / Patchwork psicoanalítico: tejiendo en tiempos revueltos / Patchwork psychanalytique

Com a pandemia de covid-19, o mundo inteiro foi atingido de forma dramática e ameaçadora. Houve a perda da ilusão de que teríamos um lugar seguro neste planeta, de que poderiamos nos amparar, de que o mal poderia ser controlado por nós. Diante desse cenário, o trabalho de acolhimento e a possibilidade de dar voz às angústias vividas consistem no primeiro passo para promover o enfrentamento de uma experiência de vida tão difícil, o que minimiza os riscos de adoecimento mental. Assim, o presente estudo tem como objetivo refletir sobre o papel da psicanálise, do voluntariado e da escuta do psicanalista no Atendimento Humanitário em Saúde Mental da Sociedade Psicanalítica de Mato Grosso do Sul.

The whole world has been affected by Covid-19 pandemic in a dramatic and threatening way. People have lost the illusion that we would have a safe place on this planet and that we could count on each other, that bad things could be controlled by us. Given this scenario, being open to help people and the possibility of giving voice and attention to anxiety were the first steps to support facing this difficult life experience which might minimize the risks of mental illnesses. Thus, the present study aims at reflecting on the role of psychoanalysis, volunteering and psychoanalytic examination in the Humanitarian Care in Mental Health, from Mato Grosso do Sul Psychoanalytical Society

Con la pandemia de la Covid-19, el mundo entero fue afectado de forma considerable y amenazadora. Sobrevino la pérdida de la ilusión de que tendríamos un lugar seguro en este planeta, que podríamos sostenernos, que el mal podría ser controlado por nosotros. Ante este escenario, el trabajo de hospitalidad y la posibilidad de dar voz a las angustias vividas consisten en el primer paso para promover el enfrentamiento de una experiencia de vida tan difícil, lo que minimiza los riesgos de una enfermedad mental. Así, el presente estudio tiene como objetivo reflexionar sobre el papel del psicoanálisis, del voluntariado y escucha del psicoanalista en la Atención Humanitaria en Salud Mental de la Sociedad Psicoanalítica de Mato Grosso do Sul.

En raison de la pandémie du Covid-19, le monde entier a été touché de manière dramatique et menaçante. Il y a eu la perte des illusions tels qu'il y aurait un endroit sûr pour nous sur cette planète, que nous pourrions nous soutenir, que nous pourrions maîtriser le mal. Face à ce panorama, le travail d'accueil et la possibilité de donner voix aux angoisses vécues consistent en un premier pas pour promouvoir l'affrontement d'une expérience de vie si difficile, ce qui minimise les risques de contracter une maladie mentale. Ainsi, la présente étude vise à réfléchir sur le rôle de la psychanalyse, du volontariat et de l'écoute du psychanalyste aux Soins Humanitaires en Santé Mentale, de la Société Psychanalytique de l'État de Mato Grosso do Sul.

IgA nephropathy in Brazil: apropos of 600 cases.

IgA nephropathy (IgAN) is th e commonest primary glomerular disease worldwide. Studies on its prevalence in Brazil are however scarce. Databases and clinical records from 10 reference centres were retrospectively reviewed. Clinical and laboratory features at the moment of the biopsy were retrieved (age, gender, presence of hematuria, serum creatinine [mg/dL], proteinuria [g/24 h]). Renal biopsy findings were classified according to Haas single grade classification scheme and the Oxford Classification of IgAN. 600 cases of IgAN were identified, of which 568 (94.7 %) were on native kidneys. Male to female ratio was 1.24:1. Patients averaged 32.76 ± 15.12 years old (range 4-89, median 32). Proteinuria and hematuria were observed, respectively in 56.63 and 72.29 % of patients. The association of both these findings occurred in 37.95 % of the cases. Serum creatinine averaged 1.65 ± 0.67 mg/dL (median 1.5 mg/dL) at diagnosis. Segmental sclerosis and mesangial hypercellularity were the main glomerular findings (47.6 and 46.2 %) The commonest combination by Oxford Classification of IgAN, was M0 E0 S0 T0 (22.4 %). Chronic tubulo-interstitial lesions with an extension wider than 25 % of the renal cortex could be identified in 32.2 % of the cases. Tubular atrophy and interstitial fibrosis were more strongly associated with higher 24-h proteinuria and serum creatinine levels. Segmental sclerosis (S1) showed a stronger tendency of association with the presence of tubulo-interstitial lesions (T1 and T2) than other glomerular variables. To the best of our knowledge this is the largest series of IgAN in Brazil. It depicts the main biopsy findings and their possible clinical correlates. Our set of data is comparable to previous reports.

Subclinical Lesions and Donor-Specific Antibodies in Kidney Transplant Recipients Receiving Tacrolimus-Based Immunosuppressive Regimen Followed by Early Conversion to Sirolimus.

BACKGROUND: There is no evidence on the incidence of subclinical inflammation and scaring lesions in patients receiving tacrolimus (TAC) minimization and elimination immunosuppressive regimens. METHODS: This study analyzed preimplantation, 3 and 24 months protocol biopsies and anti-HLA donor-specific antibodies (DSA) in 140 low immunological risk kidney transplant recipients receiving reduced TAC exposure, prednisone, and mycophenolate, randomized at 3 months to be converted or not to sirolimus (SRL). RESULTS: Mean TAC concentrations were 6.0 ± 2.4 ng/mL and 5.8 ± 2.2 ng/mL at 3 and 24 months. The incidence of subclinical inflammation lesions at 3 months was 9.3%. The incidence of (interstitial fibrosis) IF/(tubular atrophy) TA at month 24 was 57.6%, higher in SRL compared to TAC group (68.8 vs 44.4%; P = 0.022). Patients converted to SRL showed higher incidence of acute rejection (7.3% vs 0%), proteinuria (59.6% vs 25%; P = 0.001), and DSA (17.8% vs 7.3%; P = 0.201), respectively. Biopsy-proven acute rejection (odds ratio [OR] 2.32, 95% confidence interval [95% CI], 0.979-5.518, P = 0.056), subclinical inflammation lesions at 3 months (OR, 11.75; 95% CI, 1.286-107.474; P = 0.029) and conversion to SRL (OR, 2.72; 95% CI, 1.155-6.383; P = 0.022) were associated with IF/TA at month 24. Black ethnicity (OR, 0.22; 95% CI, 0.058-0.873; P = 0.031), donor age (OR, 2.74; 95% CI, 1.329-5.649; P = 0.006), and conversion to SRL (OR, 2.34; 95% CI, 1.043-5.267; P = 0.039) were associated with inferior renal function at 24 months. CONCLUSIONS: In kidney transplant recipients receiving reduced TAC exposure, subclinical inflammation lesions at 3 months were associated with IF/TA at 24 months. Conversion from TAC to SRL was associated with inferior renal function, higher incidence of IF/TA, and trends to higher incidence of DSA at 24 months.

Experimental evidence for a direct cytotoxicity of Loxosceles intermedia (brown spider) venom in renal tissue.

Brown spider (Loxosceles genus) venom causes necrotic lesions often accompanied by fever, hemolysis, thrombocytopenia, and acute renal failure. Using mice exposed to Loxosceles intermedia venom, we aimed to show whether the venom directly induces renal damage. The experimental groups were composed of 50 mice as controls and 50 mice that received the venom. Light microscopic analysis of renal biopsy specimens showed alterations including hyalinization of proximal and distal tubules, erythrocytes in Bowman's space, glomerular collapse, tubule epithelial cell blebs and vacuoles, interstitial edema, and deposition of eosinophilic material in the tubule lumen. Electron microscopic findings indicated changes including glomerular epithelial and endothelial cell cytotoxicity as well as disorders of the basement membrane. Tubule alterations include epithelial cell cytotoxicity with cytoplasmic membrane blebs, mitochondrial changes, increase in smooth endoplasmic reticulum, presence of autophagosomes, and deposits of amorphous material in the tubules. We also found that the venom caused azotemia with elevation of blood urea levels but did not decrease C3 complement concentration or cause hemolysis in vivo. Confocal microscopy with antibodies against venom proteins showed direct binding of toxins to renal structures, confirmed by competition assays. Double-staining immunofluorescence reactions with antibodies against type IV collagen or laminin, antibodies to venom toxins, and fluorescent cytochemistry with DAPI revealed deposition of toxins in glomerular and tubule epithelial cells and in renal basement membranes. Two-dimensional electrophoresis showed venom rich in low molecular mass and cationic toxins. By immunoblotting with antibodies to venom toxins on renal extracts from venom-treated mice, we detected a renal binding toxin at 30 kD. The data provide experimental evidence that L. intermedia venom is directly involved in nephrotoxicity.

Modulation of eosinophil migration from bone marrow to lungs of allergic rats by nitric oxide.

Chronic blockade of nitric oxide (NO) synthesis attenuates the eosinophil infiltration into airways of allergic rats. This study was designed to investigate whether the inhibition of eosinophil influx to the lung of allergic rats reflects modifications in the pattern of cell mobilization from the bone marrow to peripheral blood and/or to lung. Male Wistar rats were treated with N(omega)-nitro-l-arginine methyl ester (l-NAME; 20mg/rat per day) for 4 weeks and sensitized with ovalbumin (OVA). In control rats, the pulmonary OVA-challenge promoted an early (24h) increase in the bone marrow eosinophil population that normalized at 48 h after OVA-challenge, at which time the eosinophils disappeared from the blood and reached the lungs in mass. In l-NAME-treated rats, an accumulation of eosinophils in bone marrow was observed at 24 and 48 h post-OVA-challenge. No variation in this cell type number was observed in peripheral blood and bronchoalveolar lavage throughout the time-course studied. In control rats, the adhesion of bone marrow eosinophils to fibronectin-covered wells was significantly increased at 24h after OVA-challenge, whereas in l-NAME-treated rats the increased adhesion was detected at 48 h. A 32% decrease in the expression of inducible nitric oxide synthase (iNOS) (but not endothelial nitric oxide synthase; eNOS) in eosinophils from l-NAME-treated rats was observed. The levels of IgE, IgG(1) and IgG(2a) were not affected by the l-NAME treatment. Our findings suggest that inhibition of NO synthesis upregulates the binding of eosinophils to extracellular matrix proteins such as fibronectin, producing a delayed efflux of eosinophils from bone marrow to peripheral blood and lungs.

Fine-needle aspiration cytology of pulmonary rheumatoid nodule: case report and review of the major cytologic features.

Patients with rheumatoid disease may develop extra-articular lesions, affecting viscera and soft tissues. Pulmonary rheumatoid nodules show morphologic features reminiscent of a necrotizing inflammation of rheumatoid synovitis and differ from subcutaneous rheumatoid nodules only by their location, extension, and size. Although cytologic studies on pleural effusions in rheumatoid disease have long been performed, there are no more than three reports concerning the fine-needle aspiration (FNA) diagnosis of pulmonary rheumatoid nodules. The authors report on a case of a 62-yr-old woman with rheumatoid disease in whom a FNA diagnosis of pulmonary rheumatoid nodule was successfully performed. The authors highlight the main cytologic features of the entity and emphasise the high index of clinical and pathologic suspicions needed to be able to diagnose this lesion.

Acute kidney injury in patients infected by H1N1: clinical histological correlation in a series of cases.

INTRODUCTION: Influenza A (H1N1) virus was first reported on April 2009 and, since then, several studies have reported the characteristics concerning the clinical presentation and pulmonary involvement. However, accurate information about the acute kidney injury (AKI) and kidney histopathological findings in these patients remain scarce. OBJECTIVE: To describe the kidney histopathological findings of 6 patients with H1N1 who developed AKI and underwent kidney biopsy, correlating them with clinical features. METHODS: We studied six patients admitted to Hospital de Clínicas UFPR with a PCR-confirmed diagnosis of H1N1who developed ARF and underwent kidney biopsy. We reviewed their medical file and the microscopy findings of the biopsy. RESULTS: Clinical and/or laboratory evidence of AKI was present in all cases, and only one did not present oliguria. Kidney tissues revealed glomerular lesions in two patients: one patient, with systemic lupus erythematosus, showed changes consistent with lupus nephritis class III A-C according to the ISN/RPS 2003 and focal thrombotic microangiopathy; the other one had intercapillary nodular glomerulosclerosis, but without clinical or laboratory evidence of diabetes. Vacuolar degenerative tubular changes were present in all cases, with focus of oxalosis in two cases. Mild to moderate atherosclerosis was found in two patients. CONCLUSION: In this study, varying degrees of vacuolar degenerative tubular changes were present in all patients, but there were no signs of acute tubular necrosis. It seems that in the present study a prerenal cause of acute renal failure was the main involved mechanim to explain the cause of renal failure in these patients.