Macrophages and Galectin 3 Control Bacterial Burden in Acute and Subacute Murine Leptospirosis That Determines Chronic Kidney Fibrosis.

Previous studies have suggested that macrophages may contribute to acute Leptospira dissemination, as well as having a major role in kidney fibrosis. Our aim was to characterize the role of macrophages and galectin 3 (Gal-3) on the survival, clinical course, bacterial burden, interstitial nephritis, and chronic kidney fibrosis in Leptospira interrogans serovar Copenhageni (LIC)-induced experimental murine leptospirosis. C57BL/6J mice depleted of macrophages by liposome-encapsulated clodronate treatment and infected with LIC presented a higher bacterial burden, had reduced subacute nephritis and enhanced chronic kidney fibrosis relative to untreated, infected mice. Moreover, LIC infection in mice whose Gal-3 was disrupted (Lgals3-/-) had a higher bacterial burden and enhanced subacute nephritis and chronic kidney fibrosis when compared to C57BL/6J wild-type mice. Chronic fibrosis did not correlate with higher transcription levels of TGF-ß1 or IL-13 in the kidneys. Kidney fibrosis was found in chronically infected rats as well as in wild infected rats. On the other hand, human fibroblast cultures exhibited enhanced differentiation to myofibroblasts after treatment with LIC. Our results demonstrate that macrophages and Gal-3 play a critical role in controlling the LIC burden but has a minor role in subsequent fibrosis. Instead, kidney fibrosis was better correlated with bacterial burden. Taken together, our results do not support a role for macrophages to disseminate leptospires during acute infection, nor in chronic kidney fibrosis.

Gliofibroma: Report of Four Cases and Review of the Literature.

Gliofibroma is a relatively rare variant of a mixed glial-fibrous tumor more frequent in children than in adults. It has been reported to appear all along the neuraxis, with predilection for the midline. Its evolution is usually benign, although few examples have shown either multiple sites of involvement or leptomeningeal dissemination. Some authors regard it as part of the desmoplastic astrocytoma spectrum. We report here four examples of this rare condition which exemplify its histological patterns and biological behavior, and provide a review of the literature. Even though this tumor is commonly regarded as heterogeneous and with variable course, our literature review points to a set of clinical and pathological traits that are constant, such as age, location and gross and histological characteristics, as well as a predictable evolution. Currently, this tumor is not included in the WHO Classification of CNS tumors.

Neutrophil Extracellular Traps are Involved in the Innate Immune Response to Infection with Leptospira.

NETosis is a process by which neutrophils extrude their DNA together with bactericidal proteins that trap and/or kill pathogens. In the present study, we evaluated the ability of Leptospira spp. to induce NETosis using human ex vivo and murine in vivo models. Microscopy and fluorometric studies showed that incubation of human neutrophils with Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130 (LIC) resulted in the release of DNA extracellular traps (NETs). The bacteria number, pathogenicity and viability were relevant factors for induction of NETs, but bacteria motility was not. Entrapment of LIC in the NETs resulted in LIC death; however, pathogenic but not saprophytic Leptospira sp. exerted nuclease activity and degraded DNA. Mice infected with LIC showed circulating NETs after 2 days post-infection (dpi). Depletion of neutrophils with mAb1A8 significantly reduced the amount of intravascular NETs in LIC-infected mice, increasing bacteremia at 3 dpi. Although there was a low bacterial burden, scarce neutrophils and an absence of inflammation in the early stages of infection in the kidney and liver, at the beginning of the leptospiruric phase, the bacterial burden was significantly higher in kidneys of neutrophil-depleted-mice compared to non-depleted and infected mice. Surprisingly, interstitial nephritis was of similar intensity in both groups of infected mice. Taken together, these data suggest that LIC triggers NETs, and that the intravascular formation of these DNA traps appears to be critical not only to prevent early leptospiral dissemination but also to preclude further bacterial burden.

Decay-accelerating factor 1 deficiency exacerbates leptospiral-induced murine chronic nephritis and renal fibrosis.

Leptospirosis is a global zoonosis caused by pathogenic Leptospira, which can colonize the proximal renal tubules and persist for long periods in the kidneys of infected hosts. Here, we characterized the infection of C57BL/6J wild-type and Daf1-/- mice, which have an enhanced host response, with a virulent Leptospira interrogans strain at 14 days post-infection, its persistence in the kidney, and its link to kidney fibrosis at 90 days post-infection. We found that Leptospira interrogans can induce acute moderate nephritis in wild-type mice and is able to persist in some animals, inducing fibrosis in the absence of mortality. In contrast, Daf1-/- mice showed acute mortality, with a higher bacterial burden. At the chronic stage, Daf1-/- mice showed greater inflammation and fibrosis than at 14 days post-infection and higher levels at all times than the wild-type counterpart. Compared with uninfected mice, infected wild-type mice showed higher levels of IL-4, IL-10 and IL-13, with similar levels of α-smooth muscle actin, galectin-3, TGF-ß1, IL-17, IFN-γ, and lower IL-12 levels at 90 days post-infection. In contrast, fibrosis in Daf1-/- mice was accompanied by high expression of α-smooth muscle actin, galectin-3, IL-10, IL-13, and IFN-γ, similar levels of TGF-ß1, IL-12, and IL-17 and lower IL-4 levels. This study demonstrates the link between Leptospira-induced murine chronic nephritis with renal fibrosis and shows a protective role of Daf1.

[Cerebral sparganosis in a child: case report]. / Esparganosis cerebral. Presentación de un caso pediátrico.

We are reporting the case of an 8-year-old boy with history of seizures in whom the pathology exam of 2.5 by 3 cm surgical specimen obtained from a cortical-subcortical area of the de right occipital lobe showed a chronic granulomatous inflammatory process with a Spirometras pp larva. The patient was born and lived several years at a rural area of Tarija (Bolivia). This appears to represent the first reported case of this parasitic infection localized to the brain of a child in Argentina.

Esparganosis cerebral: Presentación de un caso pediátrico / Cerebral sparganosis in a child: Case report

Se presenta el caso de un niño de 8 años con antecedentes de epilepsia en quien el examen anatomopatológico del material extraído de una lesión de 2,5 por 3 cm localizada en la zona corticosubcortical del lóbulo occipital derecho reveló la presencia de un proceso inflamatorio crónico granulomatoso con una larva de Spirometras pp. El paciente nació y vivió varios años en una zona rural de Tarija (Bolivia). Es el primer ejemplo pediátrico de esta infestación parasitaria a nivel cerebral reconocido en la Argentina.

We are reporting the case of an 8-year-old boy with history of seizures in whom the pathology exam of 2.5 by 3 cm surgical specimen obtained from a cortical-subcortical area of the de right occipital lobe showed a chronic granulomatous inflammatory process with a Spirometras pp larva. The patient was born and lived several years at a rural area of Tarija (Bolivia). This appears to represent the first reported case of this parasitic infection localized to the brain of a child in Argentina.

Esparganosis cerebral: Presentación de un caso pediátrico / Cerebral sparganosis in a child: Case report

Se presenta el caso de un niño de 8 años con antecedentes de epilepsia en quien el examen anatomopatológico del material extraído de una lesión de 2,5 por 3 cm localizada en la zona corticosubcortical del lóbulo occipital derecho reveló la presencia de un proceso inflamatorio crónico granulomatoso con una larva de Spirometras pp. El paciente nació y vivió varios años en una zona rural de Tarija (Bolivia). Es el primer ejemplo pediátrico de esta infestación parasitaria a nivel cerebral reconocido en la Argentina.(AU)

We are reporting the case of an 8-year-old boy with history of seizures in whom the pathology exam of 2.5 by 3 cm surgical specimen obtained from a cortical-subcortical area of the de right occipital lobe showed a chronic granulomatous inflammatory process with a Spirometras pp larva. The patient was born and lived several years at a rural area of Tarija (Bolivia). This appears to represent the first reported case of this parasitic infection localized to the brain of a child in Argentina.(AU)

Esparganosis cerebral. Presentación de un caso pediátrico. / [Cerebral sparganosis in a child: case report].

We are reporting the case of an 8-year-old boy with history of seizures in whom the pathology exam of 2.5 by 3 cm surgical specimen obtained from a cortical-subcortical area of the de right occipital lobe showed a chronic granulomatous inflammatory process with a Spirometras pp larva. The patient was born and lived several years at a rural area of Tarija (Bolivia). This appears to represent the first reported case of this parasitic infection localized to the brain of a child in Argentina.

Experimental infection with Cryptosporidium parvum IIaA21G1R1 subtype in immunosuppressed mice.

Cryptosporidium parvum subtype IIaA21G1R1 oocysts were used to infect dexamethasone immunosuppressed N: NIH Swiss mice. This is the first Cryptosporidium mouse model in which the relationship between infection and apoptosis has been histologically studied at each portion of the gut in order to observe this dynamic in chronic cryptosporidiosis. Histology showed developmental stages in the duodenum, proximal and distal jejunum, ileum, cecum and colon, with the small intestine remaining infected until day 35 post infection. At proximal jejunum an inverse correlation between infection and apoptosis was observed at days 28 and 35 p.i. Data suggests that jejunum could be an interesting place to carry out further studies on the dynamics of Cryptosporidium infection and apoptosis. Based on these findings, this mouse model was useful to evaluate clinical, parasitological and histological aspects of C. parvum subtype IIaA21G1R1 infection, and it will be an appropriate tool to investigate different aspects of Cryptosporidium infection.

Hemorrhagic colitis in postdiarrheal hemolytic uremic syndrome: retrospective analysis of 54 children.

Hemorrhagic colitis (HC) is a severe manifestation of the hemolytic uremic syndrome (HUS). We performed a retrospective analysis of patients with HC with the following aims: (1) to characterize the clinicopathologic features; (2) to evaluate mortality rate; (3) to analyze severity of renal and central nervous system (CNS) disease. Patients with HC assisted between 1981-2009 were evaluated and compared with a control group of 137 patients without HC. Among 987 patients with diarrheal prodrome (D) + HUS, 54 (5.5%) presented HC. Clinical findings included abdominal pain (96%), distension (93%), hematochezia (44%), and abdominal mass (11%). Surgery was indicated in 35 patients (65%), and 17 (48.5%) required bowel resection. Transverse and ascending colon were most frequently affected. Macroscopic evaluation showed bowel necrosis (18) and perforation (12). Histologic evaluation (29) showed that 25 (86.2%) had necrosis of the affected segment (transmural in 21). A leukocyte count >20,000/mm(3) and hematocrit >30% were more common in HC patients than in controls (p < 0.001 and p < 0.0001, respectively). Mortality rate was higher in HC patients (33.3%) than in controls (1.4%; p < 0.0001). Dialysis >10 days, seizures, and coma were more frequent in HC patients than in controls (p < 0.0001). In summary, most patients had prominent abdominal findings, and almost 2/3 patients required surgery. Transverse/ascending colon was most affected, and the main histologic finding was transmural necrosis. Higher hematocrit and leukocytosis were frequent. Mortality rate was extremely high, and most had long-lasting anuria and severe neurologic involvement.

The mucosa beyond the polyps in juvenile polyposis.

Little is known of early histologic changes in the mucosa of the colon aside from the polyps in Juvenile Polyposis. Provided with a surgical specimen of a total colectomy of a 6-year-old boy with this condition, this report describes those changes. The mucosa depicted a peculiar serrated profile of the uppermost part of the crypts due to elongation of them, dilated openings, and scant stroma. Also present were frequent aberrant crypts. Early juvenile polyps presented associated with lympho-glandular sites as distorted and microcystically dilated crypts containing granular and filamentous mucoid material. The findings possibly represent the abnormal cytologic potential of this genetic condition.

Dermatosis congénita vesicular y erosiva con cicatrices reticuladas. Presentación de un caso y revisión de la literatura / Congenital erosive and vesicular dermatosis healing with reticulated supple scarring. A case report and review of the literature

La dermatosis congénita vesicular y erosiva con cicatrices reticuladas es un raro desorden cutáneo de etiología desconocida con lesiones evidentes al nacimiento. Presentamos una niña con esta condición, la cual representa el primer caso diagnosticado en la Argentina, junto a una revisión dela literatura.

Congenital erosive and vesicular dermatosis healing with reticulated, supple scarring is a rare cutaneouscondition of unknown etiology. It presents with patchy or generalized erosion and vesiclesrecognizable at birth, that heal with reticulated scarring. We report a female child with thiscondition, the first recognized in Argentina, together with a review of the literature.

Dermatosis pustular erosiva en el cuero cabelludo de una niña / Erosive pustular dermatosis of the scalp of a girl

La dermatosis pustular erosiva del cuero cabelludo es una erupción pustular idiopática que se ha asociado al trauma físico, quirúrgico o a tratamientos médicos. Se presenta una niña que desarrolla este cuadro como consecuencia del trauma quirúrgico provocado por el drenaje de múltiples abscesos en el cuero cabelludo

Erosive pustular dermatosis of the scalp is characterized by idiopathic pustular eruption often triggered by physical, medical or surgical trauma. We present a girl of 6 years of age that developed this disease as a consequence of surgical trauma after multiple scalp abscesses drainage

Langerhans cell hyperplasia of the skin mimicking Langerhans cell histiocytosis: a report of two cases in children not associated with scabies.

Langerhans cells histiocytosis (LCH) affecting the skin most commonly has clinical and histopathologic diagnostic features. We are reporting two examples of Langerhans cell (LC) hyperplasia recognized in the skin biopsies of two children initially interpreted as LCH. The first was an 8-year-old boy finally interpreted as having an atypical type of contact dermatitis, while the second, an 8-year-old girl, was assumed to have Pytiriasis lichenoides et varioliformis acuta. None showed evidences of scabies. Both presented spongiotic dermatitis with numerous CD1a+ cells. As more cases of LC hyperplasia are recognized, new details emerge helping in the differential diagnosis. Strict clinical-pathologic correlation is suggested in order to avoid misdiagnosis.

Arrhythmogenic cardiomyopathy in a patient with Noonan syndrome.

Arrhythmogenic ventricular cardiomyopathy (AVC) presents with fat replacement of the myocardium, most commonly of the right ventricle, and ventricular arrhythmias. We report an 11-year-old boy with Noonan syndrome, ventricular arrhythmias, and an ultrasound depicting hypertrophy of the ventricular septum with subaortic stenosis. A surgical resection of the left side of the ventricular septum revealed a thick fibroelastotic endocardium covering a broad band of mature adipose tissue focally containing myocardial cells, fibrosis and chronic inflammatory infiltrates. The two layers covered a band of hypertrophic myocardiocytes with mild interstitial fibrosis. Arrhythmogenic ventricular cardiomyopathy has not been previously reported in the Noonan syndrome.

Urticaria vasculitis en una niña de cinco años / Urticarial vasculitis in a girl of five years

La urticaria-vasculitis es una forma de vasculitis que se presenta en forma de habones eritematosos clínicamente semejantes a la urticaria hemorrágica de tipo alérgica, pero que histológicamente muestra cambios de vasculitis leucocitoclástica. Puede acompañarse de normocomplementemia o hipocomplementemia. En ambas situaciones puede estar asociada a síntomas sistémicos (como por ejemplo, angioedema, artralgias, dolor abdominal, fiebre, enfermedad pulmonar o renal, epiescleritis y uveitis), aunque en los casos en que se acompaña de hipocomplementemia ha sido vinculada con mayor frecuencia a enfermedades del tejido conectivo. El estudio histopatológico permite diferenciar la urticaria hemorrágica alérgica de la urticaria-vasculitis. Presentamos una niña de 5 años con urticaria-vasculitis y normocomplementemia, con lesiones cutáneas típicas asociadas a artralgias y dolor abdominal.

Urticarial vasculitis is an eruption of erythematous wheals that clinically resemble urticaria but histollogicaly shows leukocytoclastic vasculitis. Urticarial vasculitis may be divided into normocomplementemic and hypocomplementemic variants. Both subsets can be associated with systemic symptoms (for example, angioedema, arthralgias, abdominal or chest pain, fever, pulmonary or renal disease, epiescleritis and uveitis), more often the second variant which has been linked to connective-tissue disease. Histopathological evaluation allows to differentiate between hemorrhagic allergic urticaria and urticarial vasculitis. We report the case of a 5-year-old girl presenting with normocomplementemic uticarial vasculitis, with typical cutaneous lesions associated to arthralgias and abdominal pain.

Neuroblastoma in a patient with Coffin-Siris syndrome.

We report the case of an 8-year-old boy with the phenotypic features of Coffin-Siris syndrome diffuse hypertrichosis, flat occiput, scant scalp hair, flat supraorbital arch, triangular eyebrows, horizontal palpebral fissure, anteverted nares, triangular philtrum, coarse lips, high-arched palate, micrognathia, low set and dorsaly rotated ears, short neck, wide thorax, widely set nipples, transverse palmar crease, psychomotor delay, urinary malformations (paraurethral diverticulum, hypoplasia of left kidney associated with vesicoureteral reflux grade 3-4), bilateral inguinal hernia, and dorsolumbar kyphoscoliosis. In the follow-up he presented a retroperitoneal neuroblastoma. Although this type of tumor has been referred to develop in several genetic and mutimalformative syndromes, it seems that present association has not been previously reported.

Papillary carcinoma of the thyroid developed in congenital dyshormonogenetic hypothyroidism without goiter: Diagnosis by FNAB.

A 5-year-old girl known to have congenital dyshormonogenetic hypothyroidism since birth and under appropriate treatment (without goiter) developed a thyroid nodule which was found in the clinical follow-up. Fine-needle aspiration biopsy of the nodule allowed to diagnose a papillary thyroid carcinoma, a diagnosis which was certified by the surgical specimen exam. Dyshormonogenetic goiter may rarely associate with thyroid carcinoma. The present case appears unique since goiter was not present.

Thigh-leg skin tube pedicle and amniotic band syndrome.

We are reporting the case of a young infant presenting with a cutaneous tubular bridge running from the dorsal aspect of the middle third of the thigh to the middle third of the leg resulting in a permanent flexion position of the limb. This finding was associated with another related to the amniotic band syndrome. Surgical resection showed a tube formed exclusively by normal skin tissue. The case appears unique although related lesions have been reported in the literature.