Acquired brown syndrome secondary to superior oblique muscle cysticercosis.

BACKGROUND: Acquired Brown syndrome is known to occur after trauma, iatrogenic events, cysts of superior oblique muscle tendon, and inflammation. The purpose of this study is to report a large series of patients with acquired Brown syndrome secondary to superior oblique muscle cysticercosis and to discuss its management. METHODS: Retrospective analysis was performed of clinical and imaging features, management, and outcome in seven patients with cysticercosis of the superior oblique muscle presenting clinically as Brown syndrome. RESULTS: Seven patients were identified (five male and two female) ranging in age from 6 to 45 years. All patients had the ocular motility limitation, ie, limitation of elevation in adduction., characteristic of Brown syndrome. This was associated with pain and swelling in the superior nasal orbit. Diagnosis was established by observing the cysticercus cyst with scolex on imaging (ultrasound B scan, magnetic resonance imaging, and/or computed tomography). Oral albendazole (15 mg/kg) and oral prednisolone (1mg/kg) were given for 4 weeks, and the patients were followed up for 1 year. Clinical recovery with improvement of ocular motility and regression of imaging features was noted in all patients. CONCLUSIONS: Acquired Brown syndrome secondary to superior oblique muscle cysticercosis is a rare entity. Awareness of this condition, which leads to early diagnosis and institution of prompt medical treatment, results in a successful clinical outcome.     

Mast cells are an essential hematopoietic component for polyp development

It is generally agreed that most colon cancers develop from adenomatous polyps, and it is this fact on which screening strategies are based. Although there is overwhelming evidence to link intrinsic genetic lesions with the formation of these preneoplastic lesions, recent data suggest that the tumor stromal environment also plays an essential role in this disease. In particular, it has been suggested that CD34(+) immature myeloid precursor cells are required for tumor development and invasion. Here we have used mice conditional for the stabilization of beta-catenin or defective for the adenomatous polyposis coli (APC) gene to reinvestigated the identity and importance of tumor-infiltrating hematopoietic cells in polyposis. We show that, from the onset, polyps are infiltrated with proinflammatory mast cells (MC) and their precursors. Depletion of MC either pharmacologically or through the generation of chimeric mice with genetic lesions in MC development leads to a profound remission of existing polyps. Our data suggest that MC are an essential hematopoietic component for preneoplastic polyp development and are a novel target for therapeutic intervention.     

Lower whole blood ionized magnesium concentrations in hypocalcemic infants of gestational diabetic mothers.

Infants of insulin dependent (class B and above) diabetic mothers (IDM's) have a high rate of neonatal hypocalcemia (NHC) and hypomagnesemia. We carried out this study to test the hypotheses that: (1) infants of gestational diabetic (class A) mothers (IGDM's) are also at risk for NHC and (2) NHC in IGDM's relates to decreased whole blood Mg(2+) concentration. Thirty one term infants born to gestational diabetic mothers of classes A1 (diet controlled, n = 23) and A2 (requiring insulin, n = 8) of White's classification, were compared at 24 +/- 2 hours of age to 32 healthy, appropriate for gestational age controls, born after uncomplicated pregnancy, labor and delivery. Whole blood Mg(2+) and Ca(2+) were measured using an ion-specific electrode (Nova 8, Nova biomedical, Waltham, MA). The rate of NHC was higher in the IGDM group as compared to the control group (9 out of 31 [29%] vs. 1 out of 32 [3.1%] infants; p < 0.01). Whole blood Mg(2+) was lower in the IGDM group than in controls (p < 0.05). In multiple regression analysis, when Ca(2+) was used as the dependent variable and Mg(2+), diabetes class, gestational age, macrosomia and one minute Apgar scores were the independent variables, only Mg(2+) and diabetes class were significant (R2 = 0.4374; p < 0.01). Our results are consistent with the theory that Mg deficiency plays a role in NHC encountered in IGDM's, similar to what occurs in infants of insulin-dependent diabetic mothers.     

CD4+CD25+ regulatory lymphocytes induce regression of intestinal tumors in ApcMin/+ mice

Colorectal cancer in humans results from sequential genetic changes in intestinal epithelia commencing with inactivation of the APC tumor suppressor gene. Roles for host immunity in epithelial tumorigenesis are poorly understood. It has been previously shown that CD4+CD25+ lymphocytes inhibit colitis-associated epithelial tumors in Rag-deficient mice. Here we show that addition of CD4+CD25+ lymphocytes in ApcMin/+ mice reduces multiplicity of epithelial adenomas. Interleukin-10 was required in regulatory cells for therapeutic effect. Recipients of regulatory cells showed increased apoptosis and down-regulation of cyclooxygenase-2 within tumors coincident with tumor regression. These data suggest a role for regulatory lymphocytes in epithelial homeostasis in the ApcMin/+ mouse model of intestinal polyposis. Similarities with cancer of the breast, prostate, lung, and other sites raise the possibility of broader roles for regulatory lymphocytes in prevention and treatment of epithelial cancers in humans.     

CD4(+)CD25(+) regulatory lymphocytes require interleukin 10 to interrupt colon carcinogenesis in mice

Roles for host immune response in carcinogenesis are not well defined. Recent studies have shown that microbially driven inflammation can lead to colon cancer and that prior transfer of regulatory lymphocytes expressing CD4 and CD25 prevents the innate inflammatory events that lead to colon cancer in mice. To further examine the ability of regulatory lymphocytes to inhibit carcinogenesis, 129/SvEv Rag-2-deficient mice were inoculated by gastric gavage with Helicobacter hepaticus, an enteric bacterial pathogen of mice. Mice were then treated at 1, 3, or 12 months after infection with adoptive transfer of CD4(+)CD45RB(lo)CD25(+)-regulatory cells. Mice dosed with regulatory cells at 4 or 12 weeks after H. hepaticus infection had reduced severity of inflammatory bowel disease and significantly lower risk of colon cancer during the 8 month observation period, compared with infected mice that had not received cells. This suggested that regulatory cells were able to interrupt the ongoing innate immune events in the stepwise progression to cancer. Transfer of regulatory cells into chronically infected mice with established cancer reduced severity of colitis, epithelial dysplasia, and cancer, but did not eliminate all tumors. Regulatory cells lacking anti-inflammatory cytokine interleukin (IL)-10 were unable to inhibit inflammatory bowel disease, dysplasia, or cancer, showing that IL-10 was required for the protective effects of lymphocytes in this setting. Taken together, the data suggest that IL-10-mediated suppression of host innate inflammatory response was pivotal in interrupting carcinogenesis. Regulatory lymphocytes and cytokines may have implications for novel therapies for colon cancer in humans.     

Racial Disparities in Pediatric Asthma: A Review of the Literature

The burden of asthma disproportionately affects children living in economically disadvantaged urban communities. The relationships between ethnicity, genetic differences, lower socioeconomic status, poor medication adherence, greater exposure to environmental triggers, and absence of regular asthma care all contribute to this disparity. This review aims to identify and discuss recent studies on additional factors that may also impact to pediatric asthma disparity. The body of work examined in this review suggests that these disparities are the result of gene–environment interactions, vitamin D metabolism, socioeconomic status, urban environment, healthcare setting, and associated health beliefs.     

CD4+ lymphocytes modulate prostate cancer progression in mice

Chronic inflammation contributes to the development of prostate cancer in humans. Here, we show that male Apc^Min/+ mice also develop prostate carcinoma with increasing age, mimicking that seen in humans in their 5th or 6th decade of life. Proinflammatory cytokines were significantly linked with cancer and increasing age in our mouse model; however, prostate and bowel tissues lacked evidence of inflammatory cell infiltrates other than mast cells. Lymphocytes protected against cancer, and protection from prostate cancer resided in antiinflammatory CD4⁺CD25⁺ regulatory (T_REG) cells that downregulated inflammatory cytokines. Supplementation with syngeneic T_REG cells collected from wild‐type mice reduced the levels of interleukin (IL)‐6 (p < 0.05) and IL‐9 (p < 0.001) and lowered prostate cancer risk (p < 0.05). Depletion of CD25⁺ cells in 2‐month‐old animals increased the expression of IL‐6 (p < 0.005) within prostate and increased the frequency of high‐grade prostatic intraepithelial neoplasia (p < 0.05) and microinvasive prostatic carcinoma (p < 0.05) in dorsolateral prostate. Depletion of CD25⁺ cells in young animals also increased the frequency of intestinal cancer in Min mice. Taken together, chronically elevated proinflammatory cytokines promoted carcinoma in Apc^Min/+ mice. T_REG lymphocytes downregulated inflammation‐associated carcinogenic processes and contributed to immune and epithelial homeostasis. © 2009 UICC