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The kidney responds to high levels of ANG II, as may occur during malignant hypertension, by increasing sodium and water excretion. To study whether kidney medullary transporters contribute to this response, rats were made hypertensive using ANG II. Within 3 days of being given ANG II, systolic blood pressure (BP) was increased (200 mmHg), vs control (130 mmHg), and remained high through day 14. Kidney inner medullary (IM) tip and base and outer medulla were analyzed for transporter protein abundance. There were significant decreases in UT-A1 urea transporter, aquaporin-2 (AQP2) water channel, and NKCC2/BSC1 Na(+)-K(+)-2Cl(-) cotransporter. To determine whether the decreases were a response to hypertension, ANG II, or an ANG II-induced increase in aldosterone, rats were given 1) norepinephrine (to increase BP) and 2) ANG II plus spironolactone (to block the mineralocorticoid receptor). Norepinephrine (7 days) increased BP, urine volume, sodium excretion, and decreased urine osmolality and UT-A1, AQP2, and NKCC2/BSC1 abundances, similar to ANG II. ANG II alone or with spironolactone yielded similar increases in BP, urine volume, and urine osmolality, and decreases in UT-A1 and AQP2 proteins in the IM tip. Plasma vasopressin was unaffected by treatment. Water diuresis did not change UT-A1 but decreased AQP2 and NKCC2/BSC1 abundances. We conclude that decreases in UT-A1, AQP2, and NKCC2/BSC1 proteins may contribute to the diuresis and natriuresis that occur following ANG II or norepinephrine-induced acute hypertension and do not appear to involve ANG II stimulation of aldosterone or thirst.

Background: Poor and uninsured people have increased risk of medical and psychiatric illness, but they might be more reluctant to seek care than those with higher incomes. Little information exists about the biopsychosocial problems and concerns of this population in primary care.Methods: We surveyed 500 consecutive patients (aged 18 to 64 years) in a primary care clinic serving only uninsured, low-income patients. We used self-report questions about why patients were coming to the clinic, a chronic illness questionnaire, the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire, and items from the Childhood Trauma Questionnaire. Providers completed a questionnaire naming problems elicited from patients.Results: Patients reported their most common chronic medical problems to be headaches, chronic back problems, and arthritis. The most common concerns patients wanted to discuss with providers and that providers elicited from patients were problems with mood. Compared with patients without current major mental illness, patients with a current major mental illness reported significantly (P < .001) more concerns, chronic illnesses, stressors, forms of maltreatment and physical symptoms.

Pediatric autoimmune hepatitis (AIH) is relatively common and has a characteristic but relatively nonspecific histopathology with a usually prominent lymphoplasmacytic infiltrate. Herein, we describe for the first time the presence of characteristic hyaline droplets in the cytoplasm of Kupffer cells on routine hematoxylin and eosin (H&E) sections in AIH. The medical records and pathologic material over a 20-year period (1992 to 2012) were reviewed from children with AIH (n=30), hepatitis B virus (n=30), and hepatitis C virus (n=30) from the pathology files at Boston Children's Hospital. All children had percutaneous needle liver biopsies. We reviewed sections stained with H&E, PAS, and PAS with diastase for the presence of hyaline droplets in all 90 biopsies. We also performed immunohistochemical analysis for IgG, IgA, and IgD in 6 biopsies with AIH. Hyaline droplets were identified in Kupffer cells throughout the lobules in 15 of 30 biopsies (easily found in 13 and rare in 2); conversely, no droplets were identified in 15. Droplets were identified in 10 AIH type 1 biopsies, 1 in AIH type 2, 3 in overlap syndrome, and 1 in unclassified. Serum IgG levels, when available, were correlated with biopsy findings. Seventeen patients had serum IgG levels available for review. The average IgG level in patients without droplets in their biopsies was 1364 mg/dL, in contrast to 3424 mg/dL in patients with droplets (P=0.021). Immunohistochemical analysis performed in 6 biopsies revealed that droplets were nearly always positive for IgG, occasionally for IgA, and rarely for IgD. None of the biopsies in patients with hepatitis C contained hyaline droplets. One biopsy of a patient with hepatitis B revealed hyaline droplets; this biopsy had an unusually prominent plasmacytic infiltrate, and the patient was found to have an elevated IgG serum level and antibodies to smooth muscle actin. As far as we are aware, hyaline droplets in Kupffer cells on routine H&E sections have never been described. They should be distinguished from the nonspecific granular lysosomal structures frequently found in Kupffer cells in a variety of chronic liver diseases and from erythrophagocytosis. Hyaline droplets may occur in AIH regardless of the type and correlate with a >2-fold increase in serum level of IgG as compared with patients without droplets in their biopsies. Identification of hyaline droplets in Kupffer cells provides a useful diagnostic clue to distinguish AIH from other forms of chronic hepatitis.

Our experience suggests that targeted therapy with dabrafenib and trametinib can be safely combined with antiangiogenic therapy and may improve quality of life and survival in patients with leptomeningeal disease associated with aPXA. To our knowledge, this is the first time dabrafenib, trametinib, and bevacizumab have been combined to treat a pediatric high-grade glioma.Anaplastic PXAs pose a therapeutic challenge because of their rarity and lack of consensus guidelines for treatment. The natural history of these tumors is poorly described, but a recent review of 37 patients with PXA reclassified by the 2016 WHO classification and found that 20% fulfilled criteria for aPXA. 7 All patients were treated with maximal safe resection and those with a MIB-1 of greater than 5% or with residual disease were treated with adjuvant RT. The 3-year progression-free survival (PFS) was 32% for aPXAs compared with 80% for grade II PXAs. Another retrospective series of eight patients with aPXA demonstrated a 1-year PFS of 57%. 8 In this cohort, six patients had subtotal resections and all progressed despite adjuvant radiation and chemotherapy. Among them, four patients developed disseminated disease. Few treatments have been shown to be effective in leptomeningeal carcinomatosis from gliomas, but bevacizumab can improve symptom control through its antiangiogenic effects and normalization of the blood-brain barrier. 9Mutations in the oncogene BRAF have been reported in 40-60% of PXAs. 2 A basket study of vemurafenib for nonmelanoma cancers with BRAF V600E mutations included four patients with recurrent aPXAs, three of whom had a partial response. 3 Our case report and others 4,10 suggest that BRAF-mutant aPXAs may be sensitive to targeted therapy, even if disseminated or refractory to other treatments. The growing experience with targeted therapy in rare pediatric gliomas justifies a need for a larger clinical trial. Multicenter national clinical trials for recurrent/refractory BRAF-mutant pediatric glioma are ongoing (NCT01748149) and will lead to better understanding of how to manage these challenging tumors. CONFLICT OF INTERESTThe authors declare that there is no conflict of interest. ORCID Alissa A. Thomas

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D E, boy aged 11 History: Presented in March 1965 with acute abdominal pain accompanied by vomiting. Signs of effusion found at left base pre-operatively. Gangrenous appendix removed followed by aspiration from left chest of half a pint of thick, pink, creamy fluid; aspirate showed red cells, lymphocytes and occasional endothelial cells. Appendix showed acute suppurative changes, but no evidence of tuberculosis. A subsequent chest X-ray included the left humerus which showed subcortical erosion possibly related to chest lesioiL. No other bone lesions seen on limited skeletal survey. Transferred to St George's Hospital. Past history: Born in India. Came to England July 1964. No tuberculosis in family. On examination: Thin, pale, Indian boy. Weight 4 stone 64 lb (on 10th percentile). Slightly dys