Ricardo Drut

Human Papillomavirus Is Present in Some Cases of Childhood Penile Lichen Sclerosus: An In Situ Hybridization and SP‐PCR Study

Abstract: Lichen sclerosus (LS) is a skin disease that may affect both sexes at all ages and at any site. Its etiology remains unknown. The observation of focal koilocytotic‐like changes in the stratum malpighii in prepuce samples of LS in children prompted us to investigate the presence of HPV‐DNA. Twenty‐three paraffin‐embedded samples of LS lesions from children aged 4 to 14 years were studied using nested‐PCR and in situ hybridization (ISH). Twelve out of 23 cases amplified HPV‐DNA (8 cases corresponded to HPV‐DNA type 6; 2 cases each to HPV‐DNA types 16 and 18). ISH detected HPV sequences in the nuclei of koilocytotic and some parakeratotic cells in 13 cases (9/13 also HPV‐DNA positive by PCR). Our results demonstrated the presence of HPV‐DNA in roughly 70% of cases of LS of the prepuce in children. We highlight the observation of koilocytotic‐like changes in the prepuce and its association with HPV. The possible pathogenetic significance between the virus and the lesion is not settled.

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.

Fox‐Fordyce Disease in Two Prepubertal Girls: Histopathologic Demonstration of Eecrine Sweat Gland Involvement

Abstract: This report presents two prepubertal girls with Fox‐Fordyce disease, The pruritic papules extensively affected the areas where apocrine glands are distributed (axillae, periareolar and Jntermammary zones, pubes, Infraumbilical midline), and also extended to the neck and face near the external angle of the eyes in one child. Analyses of several biopsy specimens showed that the main lesion was a spongiotic vesicle containing inflammatory ceils and keratlnocytes affecting the hair in‐fundibuia and acrosyringia, together, with hyperkeratosis of both adnexa, The cause of the disease remains elusive, but the microscopic findings may explain the good results obtained with keratolytic agents.

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-β1, 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-β1, 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.

Disseminated Cutaneous Eruption after BCG Vaccination

Abstract: We present nine infants (3 to 10 months of age) with numerous small, papular, papular‐lichenoid, and papulo‐pustular lesions predominantly on the upper and lower limbs associated with local (axillary) lymphadenopathy which appeared after BCG vaccination. Histopathology of the lesions showed small tuberculoid granulomas mainly in the papillary dermis. The presence of BCG bacillus was demonstrated in five out of seven samples from the lymph nodes after culture and in one skin biopsy specimen. All cases, whether treated or not, evolved to complete resolution of the skin lesions. We believe that this peculiar association results from hematogenous spread of the bacillus, which regresses after an adequate immune system reaction.

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.

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.

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.

Multiple pyogenic granuloma of the duodenum. A case report in a child

Summary An unusual location for pyogenic granuloma is reported. The lesions were found during endoscopy in the duodenum of a 13 year old boy with a history of acute myeloid leukaemia and portal hypertension who had undergone a bone marrow transplant. 4 red, raised, polypoid masses measuring 0.7cm were seen in the second and third portions of the duodenum and were resected endoscopically. Histological findings were typical of pyogenic granuloma. To our knowledge, this is the first case report of this condition occurring in the duodenal mucosa of a child.

Gliofibroma: Report of Four Cases and Review of the Literature

Abstract 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.