Bilateral periorbital ecchymoses. An often missed sign of amyloid purpura.

Immunoglobulin light chain (AL) amyloidosis is a systemic disease caused by a plasma cell clone synthesizing an unstable light chain, which forms amyloid fibrils. Deposition of amyloid fibrils affects primarily kidney, heart, nervous system, spleen, liver, gastrointestinal tract and the skin. Skin bleeding in these patients is called amyloid purpura. Classically, it occurs spontaneously and bilaterally in the periorbital region. Vessel wall fragility and damage by amyloid are the principal causes of periorbital and gastrointestinal bleeding. Additionally, coagulation factor inhibitory circulating paraprotein, hyperfibrinolysis, platelet dysfunction or isolated acquired factor X deficiency may contribute to even more severe, diffuse bleedings. Early diagnosis remains essential for improving prognosis of patients with AL amyloidosis. Although pictures of amyloid purpura have been often reported in the literature, the clinical diagnosis may be delayed. We report a case of cutaneous manifestation of AL amyloidosis diagnosed not until one year after the appearance of the first symptoms. Diagnostic work-up revealed that the patient suffered from multiple myeloma with secondary AL amyloidosis. Atraumatic ecchymoses at the face, particularly the eyelids as well as in the neck should raise the suspicion of AL amyloidosis.

A young man with a renal colic

We report the case of a 35-year-old man with no cardiovascular morbidity, presenting with acute flank pain, microscopic haematuria and normal blood pressure. Initially diagnosed as a ureteral colic, the patient was recovered 6 weeks later with severe hypertensive crisis. Further investigations revealed a massive renal infarction secondary to medial fibromuscular dysplasia (FMD). Several aspects of this presentation are intriguing. Renal infarcts are usually seen in older patients having cardiac problems and/or major atheromatous plaques. In addition, FMD is mainly observed in young females and rarely progresses to renal artery occlusion. Furthermore, in this case, FMD remained silent until the acute renal infarction occurred, despite a significant kidney size reduction at the time of diagnosis. Finally, the observation of a delayed hypertensive response to a major renovascular insult provides incentives to discuss possible pathophysiological mechanisms involved in renovascular hypertension.

Unilateral ureteropelvic junction obstruction in children: long-term followup after unilateral pyeloplasty.

PURPOSE: The benefit of surgery on renal function in unilateral ureteropelvic junction stenosis (UPJS) is still debated. We evaluated renal function outcome after unilateral pyeloplasty in 53 children. MATERIALS AND METHODS: We retrospectively reviewed 123I-hippuran renography performed at diagnosis and 5 to 15 years (mean +/- SD 7 +/- 3 years) after successful pyeloplasty. UPJS was prenatally detected in 26 children because of urinary tract infection in 17 and miscellaneous reasons in 10. Relative function (RF) and absolute function were measured on background corrected renograms. Absolute function of the affected and contralateral kidneys was determined by an accumulation index (AI), representing the percent injected dose extracted by each kidney 30 to 90 seconds after the heart peak. RESULTS: Preoperatively 33 of the 53 UPJS kidneys had a decreased AI but only 8 had a RF of less than 40%, which was improved in 7 at followup. In addition, the AI improved in 29 kidneys, of which 19 (36%) normalized. Of the UPJS kidneys 14 had an initially decreased AI that remained abnormal at followup. In these kidneys preoperative RF was less than 40% in all. At followup RF was greater than 40% in 4 children, in whom the AI of the UPJS kidney did not improve but the AI of the contralateral one decreased from supranormal to normal. Seven contralateral kidneys had a supranormal AI, whereas the AI remained normal in 3, of which the RF in the UPJS kidney remained at less than 40%. The AI and RF were normal in 20 UPJS kidneys and remained normal. CONCLUSIONS: When normal, the AI and RF reflected renal function outcome similarly. The AI added relevant information in UPJS kidneys with impaired function, showing compensation of the contralateral kidney.

Uroradiological screening for upper and lower urinary tract anomalies in patients with hypospadias: a systematic literature review.

INTRODUCTION: Hypospadias is associated with anomalies of the urinary tract, but the exact prevalence and significance of these anomalies are still controversial. OBJECTIVES: To assess the percentage of patients with hypospadias and associated urological anomalies, either requiring or not requiring medical or surgical attention. MATERIAL AND METHODS: We searched several databases using the following Mesh terms: hypospadias AND urination, ultrasonography, urinary tract/abnormalities, urinary bladder/radiography, ureteral obstruction, hydronephrosis or vesico-ureteral reflux. Type of uroradiological studies performed, type of urological anomalies, medical or surgical interventions, number of patients available, enrolled and undergoing uroradiological studies and number of patients with abnormal uroradiological exams were recorded. RESULTS: We found 24 studies. Four studies included 100% of available patients. In the other ones, the percentage of patients undergoing uroradiological screening varied from 12 to 82%. Frequency of anomalies varied from 0 to 56%. The most common anomalies were kidney position anomalies, vesico-ureteral reflux and hydronephrosis. CONCLUSIONS: The data published about screening patients with hypospadias for associated anomalies of their urinary tract are of poor quality. The clinical significance of the anomalies found is difficult to evaluate. We found no relationship between the severity of the hypospadias and associated anomalies of the upper or lower urinary tract.

Fungus ball in the urinary tract: A rare entity.

A fungal mass in the urinary tract (fungus ball), mainly occurring in compromised patients, is a rare and dangerous complication of candiduria. We report 2 cases of fungus ball associated with hydronephrosis and sepsis. As reported in the literature, we treated the first patient by prompt relief of obstruction by nephrostomy and local and systemic antifungal agent. The second patient failed to respond to this treatment due to a distal ureteral stenosis and required open surgery with fungus ball removal and ureteral reimplantation. Despite a large success in urinary tract drainage with antifungal treatments, some cases need a modified approach due to anatomical modification.

Evidence-based recommendations for genetic diagnosis of familial Mediterranean fever.

Familial Mediterranean fever (FMF) is a disease of early onset which can lead to significant morbidity. In 2012, Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) was launched with the aim of optimising and disseminating diagnostic and management regimens for children and young adults with rheumatic diseases. The objective was to establish recommendations for FMF focusing on provision of diagnostic tools for inexperienced clinicians particularly regarding interpretation of MEFV mutations. Evidence-based recommendations were developed using the European League against Rheumatism standard operating procedure. An expert committee of paediatric rheumatologists defined search terms for the systematic literature review. Two independent experts scored articles for validity and level of evidence. Recommendations derived from the literature were evaluated by an online survey and statements with less than 80% agreement were reformulated. Subsequently, all recommendations were discussed at a consensus meeting using the nominal group technique and were accepted if more than 80% agreement was reached. The literature search yielded 3386 articles, of which 25 were considered relevant and scored for validity and level of evidence. In total, 17 articles were scored valid and used to formulate the recommendations. Eight recommendations were accepted with 100% agreement after the consensus meeting. Topics covered were clinical versus genetic diagnosis of FMF, genotype-phenotype correlation, genotype-age at onset correlation, silent carriers and risk of amyloid A (AA) amyloidosis, and role of the specialist in FMF diagnosis. The SHARE initiative provides recommendations for diagnosing FMF aimed at facilitating improved and uniform care throughout Europe.

O valor da tomografia computadorizada helicoidal sem contraste na avaliação de pacientes com dor no flanco

Os nossos objetivos foram estabelecer a eficácia da tomografia computadorizada sem contraste em diagnosticar a ureterolitíase, calcular a freqüência dos principais sinais tomográficos e medir a concordância interobservador, comparando-a com os resultados obtidos na urografia excretora, realizando estudo prospectivo duplo-cego em 25 pacientes com cólica nefrética. Em ambos os procedimentos avaliamos a existência de aumento renal, hidronefrose e cálculo ureteral. Deste último, descrevemos a sua localização e dimensão. Nos exames de tomografia computadorizada sem contraste procuramos também por estrias perirrenais, edema periureteral e o sinal do halo. Em 23 dos 25 exames de tomografia computadorizada sem contraste (92%) e em 17 das 25 urografias excretoras (68%) houve concordância dos resultados entre os dois observadores. Em 21 dos 25 pacientes os resultados dos dois métodos foram concordantes. Concluímos que a tomografia computadorizada sem contraste apresenta eficácia superponível à urografia excretora na avaliação de pacientes com cólica nefrética, sendo um método reprodutível e sem promover o desconforto do uso do contraste endovenoso.

Tumor de pequenas células redondas desmoplásico intra-abdominal: relato de caso

Os autores relatam um caso de tumor de pequenas células redondas desmoplásico intra-abdominal acometendo paciente do sexo masculino, de 21 anos de idade, atendido com quadro de dor abdominal, trombose do membro inferior direito e perda da função renal, de causa obstrutiva. A investigação demonstrou volumosa lesão abdominopélvica, sólida, bocelada, com áreas císticas internas, situada posteriormente à bexiga, causando obstrução ureteral, compressão da veia ilíaca direita e oclusão parcial do reto, além de acometimento de linfonodos intra e retroperitoneais. São descritos os achados cirúrgicos, de ultra-sonografia, tomografia computadorizada e ressonância magnética, bem como aqueles do estudo macroscópico, microscopia e imuno-histoquímica.

Sinais de uretelolitíase na tomografia computadorizada helicoidal sem contraste: ensaio iconográfico e revisão de literatura

O principal sinal diagnóstico de ureterolitíase na tomografia computadorizada é a visualização direta do cálculo no interior do ureter. Todavia, a sua caracterização pode ser prejudicada devido a suas pequenas dimensões, variação da respiração entre a aquisição dos cortes tomográficos, escassez de gordura retroperitoneal ou eliminação recente do cálculo. Neste contexto, foram descritos diversos sinais secundários de obstrução ureteral, observados na tomografia computadorizada, que podem auxiliar no diagnóstico de casos duvidosos, além de quantificar o grau de obstrução urinária.

Avaliação da concordância interobservador na análise da tomografia computadorizada sem contraste no diagnóstico da urolitíase em pacientes com cólica renal aguda

OBJETIVO: Avaliar a reprodutibilidade da tomografia computadorizada sem contraste na avaliação da litíase ureteral e os sinais secundários de obstrução do sistema coletor em pacientes com cólica renal aguda. MATERIAIS E MÉTODOS: Estudo prospectivo de 52 pacientes com diagnóstico clínico de cólica renal aguda submetidos a exame de tomografia computadorizada de abdome sem contraste. Os exames foram realizados com técnica helicoidal e posteriormente analisados por três observadores independentes, com a concordância interobservador avaliada pelo método estatístico kappa (kapa). Foram analisados os parâmetros: a) presença, localização e mensuração dos cálculos ureterais; b) dilatação do sistema coletor intra-renal; c) heterogeneidade da gordura perirrenal; d) dilatação ureteral; e) edema da parede ureteral (sinal do halo). RESULTADOS: Foram encontrados 40 cálculos ureterais na tomografia computadorizada (77%). A concordância interobservador para a identificação do cálculo ureteral e da dilatação ureteral foi quase perfeita (kapa = 0,89 e kapa = 0,87, respectivamente), substancial para dilatação do sistema coletor intra-renal (kapa = 0,77) e moderada para heterogeneidade da gordura perirrenal e para edema da parede ureteral (kapa = 0,55 e kapa = 0,56, respectivamente). CONCLUSÃO: A tomografia computadorizada de abdome sem contraste apresenta elevada reprodutibilidade na avaliação da litíase ureteral e dos sinais secundários de obstrução do sistema coletor.

Definição do nível da junção ureterovesical pela tomografia computadorizada

OBJETIVO: Definir o nível da implantação ureteral na bexiga através da tomografia computadorizada. MATERIAIS E MÉTODOS: Através de tomografia computadorizada da pelve com contraste endovenoso de 46 pacientes (31 homens e 15 mulheres) com idade entre 18 e 45 anos, com pelo menos um dos ureteres contrastado pelo contraste excretado, medimos as distâncias do meato ureteral até o teto acetabular e a borda superior da sínfise púbica, além do volume da bexiga. Utilizamos o teste t de Student para avaliar se houve diferenças estatísticas entre grupos. RESULTADOS: O nível da implantação ureteral na bexiga foi, em média, 10,6 ± 8,1 mm abaixo do teto acetabular e, em média, 29,7 ± 9,5 mm acima da borda superior da sínfise púbica. Nos pacientes com volume de repleção vesical menor que 200 ml e maior ou igual a 200 ml os níveis da implantação ureteral na bexiga foram, em média, 11,6 ± 7,3 mm e 10,2 ± 8,4 mm abaixo do teto acetabular (p = 0,61) e, em média, 28,3 ± 7,3 mm e 30,3 ± 10,2 mm acima da borda superior da sínfise púbica (p = 0,52), respectivamente, e nos pacientes do sexo masculino e feminino foram, em média, 11,8 ± 8,0 mm e 8,3 ± 8,0 mm abaixo do teto acetabular (p = 0,17) e, em média, 27,7 ± 9,2 mm e 33,9 ± 8,8 mm acima da borda superior da sínfise púbica (p = 0,34), respectivamente. CONCLUSÃO: Calcificações localizadas abaixo de 3 cm do teto acetabular e abaixo de 1,5 cm acima da borda superior da sínfise púbica provavelmente não representam cálculos ureterais. O grau de repleção vesical e o sexo não interferem significativamente na posição do meato ureteral.

Estudo do jato urinário intravesical com Doppler colorido em pacientes com e sem refluxo vesicoureteral

OBJETIVO: O presente estudo teve como objetivo comparar os achados da uretrocistografia miccional com o ultra-som Doppler duplex colorido, em pacientes com suspeita de refluxo vesicoureteral. MATERIAIS E MÉTODOS: A pesquisa foi realizada através do estudo dos ângulos dos jatos urinários intravesicais, nos planos axial e longitudinal. Foi analisada, também, a distância (em centímetros) entre os meatos ureterais. RESULTADOS: Do total de 32 pacientes estudados (com média de idade de 5 anos e 2 meses), 18 pacientes apresentaram refluxo vesicoureteral (10 com refluxo unilateral, sendo 4 no lado direito e 6 no lado esquerdo, e 8 com refluxo bilateral) e 14 pacientes não apresentaram refluxo. Os valores angulares dos jatos urinários intravesicais e as distâncias entre os meatos ureterais foram obtidos para todos os pacientes e foram calculados a média, o desvio-padrão e o coeficiente de variação. CONCLUSÃO: Os dados evidenciaram tendência de que a lateralização do meato ureteral seja sinal de predisposição ao refluxo vesicoureteral. A análise estatística não-paramétrica de Mann-Whitney não evidenciou diferenças significativas (p > 0,05) entre os grupos (ângulos de inclinação dos jatos urinários intravesicais e distância entre os meatos ureterais).

The nitric oxide pathway in pig isolated calyceal smooth muscle.

In pig and humans, whose kidneys have a multi-calyceal collecting system, the initiation of ureteral peristalsis takes place in the renal calyces. In the pig and human ureter, recent evidence suggests that nitric oxide (NO) is an inhibitory mediator that may be involved in the regulation of peristalsis. This study was designed to assess whether the NO synthase/NO/cyclic GMP pathway modulates the motility of pig isolated calyceal smooth muscle. Immunohistochemistry revealed a moderate overall innervation of the smooth muscle layer, and no neuronal or inducible NO synthase (NOS) immunoreactivities. Endothelial NOS immunoreactivities were observed in the urothelium and vascular endothelium, and numerous cyclic GMP-immunoreactive (-IR) calyceal smooth muscle cells were found. As measured by monitoring the conversion of L-arginine to L-citrulline, Ca(2+)-dependent NOS activity was moderate. Assessment of functional effects was performed in tissue baths and showed that NO and SIN-1 decreased spontaneous and induced contractions of isolated preparations in a concentration-dependent manner. In strips exposed to NO, there was a 10-fold increase of the cyclic GMP levels compared with control preparations (P < 0.01). It is concluded that a non-neuronal NOS/NO/cyclic GMP pathway is present in pig calyces, where it may influence motility. The demonstration of cyclic GMP-IR smooth muscle cells suggests that NO acts directly on these cells. This NOS/NO/cyclic GMP pathway may be a target for drugs inhibiting peristalsis of mammalian upper urinary tract. Neurourol. Urodynam. 18:673-685, 1999.

Thioflavin-S staining of bacterial inclusion bodies for the fast, simple, and inexpensive screening of amyloid aggregation inhibitors

Amyloid aggregation is linked to a large number of human disorders, from neurodegenerative diseases as Alzheimer"s disease (AD) or spongiform encephalopathies to non-neuropathic localized diseases as type II diabetes and cataracts. Because the formation of insoluble inclusion bodies (IBs) during recombinant protein production in bacteria has been recently shown to share mechanistic features with amyloid self-assembly, bacteria have emerged as a tool to study amyloid aggregation. Herein we present a fast, simple, inexpensive and quantitative method for the screening of potential anti-aggregating drugs. This method is based on monitoring the changes in the binding of thioflavin-S to intracellular IBs in intact Eschericchia coli cells in the presence of small chemical compounds. This in vivo technique fairly recapitulates previous in vitro data. Here we mainly use the Alzheimer"s related beta-amyloid peptide as a model system, but the technique can be easily implemented for screening inhibitors relevant for other conformational diseases simply by changing the recombinant amyloid protein target. Indeed, we show that this methodology can be also applied to the evaluation of inhibitors of the aggregation of tau protein, another amyloidogenic protein with a key role in AD.

Dual inhibitors of beta-amyloid aggregation and acetylcholinesterase as multi-target anti-Alzheimer drug candidates

Notwithstanding the functional role that the aggregates of some amyloidogenic proteins can play in different organisms, protein aggregation plays a pivotal role in the pathogenesis of a large number of human diseases. One of such diseases is Alzheimer"s disease (AD), where the overproduction and aggregation of the β-amyloid peptide (Aβ) are regarded as early critical factors. Another protein that seems to occupy a prominent position within the complex pathological network of AD is the enzyme acetylcholinesterase (AChE), with classical and non-classical activities involved at the late (cholinergic deficit) and early (Aβ aggregation) phases of the disease. Dual inhibitors of Aβ aggregation and AChE are thus emerging as promising multi-target agents with potential to efficiently modify the natural course of AD. In the initial phases of the drug discovery process of such compounds, in vitro evaluation of the inhibition of Aβ aggregation is rather troublesome, as it is very sensitive to experimental assay conditions, and requires expensive synthetic Aβ peptides, which makes cost-prohibitive the screening of large compound libraries. Herein, we review recently developed multi-target anti-Alzheimer compounds that exhibit both Aβ aggregation and AChE inhibitory activities, and, in some cases also additional valuable activities such as BACE-1 inhibition or antioxidant properties. We also discuss the development of simplified in vivo methods for the rapid, simple, reliable, unexpensive, and high-throughput amenable screening of Aβ aggregation inhibitors that rely on the overexpression of Aβ42 alone or fused with reporter proteins in Escherichia coli.