Anti-glomerular basement membrane disease and dual positivity for antineutrophil cytoplasmic antibody in a patient with membranous nephropathy

We present the case of a 50-year-old man who underwent kidney biopsy for nephrotic syndrome. In addition to a membranous pattern, anti-glomerular basement membrane (anti-GBM) staining was noted before manifestations of anti-GBM disease. Hematuria and renal failure ensued 2 weeks later. In addition, he had simultaneous circulating levels of anti-GBM antibody and both perinuclear (P-) and cytoplasmic (C-) antineutrophil cytoplasmic antibody (ANCA).     

Bone dysplasias and mental functioning.

Fourteen patients suffering from various degrees of bone dysplasia and mental handicap with superimposed neuroses or psychotic episodes are reported. Known biochemical and chromosomal causes are noted. Mental states associated with syndromes and mental malfunctioning or impairment because of skeletal defects or other factors are briefly discussed. High IgE was noted in the three cases of bone dysplasias suffering from chromosomal anomalies. Importance of early diagnosis, treatment and genetic counselling in bone dysplasias to prevent mental disorder is emphasized.     

Endothelins Mediate Neutrophil Activation, ProMMP-9 Release and Endothelial Cell Detachment

Neutrophils isolated from human peripheral blood added to a monolayer of human endothelial cells (ECV-304 cell line) stimulated with LPS (100 ng ml⁻¹) resulted in: (a) neutrophil activation, measured by spreading and release of leukotriene B₄ (LTB₄); (b) neutrophil degranulation, measured by release of matrix pro-metalloproteinase-9 (proMMP-9) and (c) loss of the monolayer integrity due to detachment of the endothelial cells. Stimulation of endothelial cells with tumor necrosis factor-α (TNF-α 10 ng ml⁻¹) or interleukin-1 (IL-1; 10 ng ml⁻¹) induced a similar dose-dependent increase in the neutrophil activation and endothelial cell detachment. Pre-treatment of LPS-activated ECV-304 cells with [Phe22]BigET-1(19–37) (10⁻⁹ M; an inhibitor of endothelin converting enzyme (ECE)) or addition of BQ-123 (10⁻⁶ M; a selective endothelin A (ET_A) receptor antagonist) to the co-cultures, significantly reduced neutrophil spreading (50–70% inhibition) as well as the levels of LTB₄ (70–100% inhibition) and proMMP-9 (40–50% inhibition) in the co-culture supernatants. In addition, the detachment of endothelial cells was also reduced (60–75% inhibition). Moreover, the exogenous addition of ET-1 (10⁻⁹ M) to neutrophil suspensions induced neutrophil spreading and release of LTB₄ and proMMP-9. Taken together, these findings indicate that neutrophils added to stimulated endothelial cells in the co-culture system employed in this study, get activated by products of these cells and degranulate. In parallel, the detachment of endothelial cell monolayer from the culture plates, possibly by the action of neutrophil granule-derived gelatinases, is observed. Endothelins (ETs) produced by the endothelial cells are suggested to play an essential role in these phenomena.     

Management of malignant colon polyps: Current status and controversies

Colon cancer remains a significant clinical problem worldwide and in the United States it is the third most common cancer diagnosed in men and women.It is generally accepted that most malignant neoplasms of the colon arise from precursor adenomatous polyps.This stepwise progression of normal epithelium to carcinoma,often with intervening dysplasia,occurs as a result of multiple sequential,genetic mutations-some are inherited while others are acquired.Malignant polyps are defined by the presence of cancer cells invading through the muscularis mucosa into the underlying submucosa(T1).They can appear benign endoscopically but the presence of malignant invasion histologically poses a difficult and often controversial clinical scenario.Emphasis should be initially focused on the endoscopic assessment of these lesions.Suitable polyps should be resected en-bloc,if possible,to facilitate thorough evaluation by pathology.In these cases,proper attention must be given to the risks of residual cancer in the bowel wall or in the surrounding lymph nodes.If resection is not feasible endoscopically,thenthese patients should be referred for surgical resection.This review will discuss the important prognostic features of malignant polyps that will most profoundly affect this risk profile.Additionally,we will discuss effective strategies for their overall management.     

A multinational observational investigation of illness perceptions and quality of life among patients with a Fontan circulation

Objective: First, to compare QOL and illness perceptions between patients with a Fontan circulation and patients with anatomically simple defects (ie, atrial septal defects [ASD] or ventricular septal defects [VSD]). Second, to explore illness perceptions as a mediator of the association between congenital heart disease (CHD) diagnosis and QOL.
Design: Cross-sectional observational study.
Setting: Twenty-four cardiology centers from 15 countries across five continents.
Patients: Four hundred thirty-five adult patients with congenital heart disease (177 Fontan and 258 ASD/VSD) ages 18-83 years.
Outcome Measures: QOL and illness perceptions were assessed by the Satisfaction With Life Scale and the Brief Illness Perceptions Questionnaire, respectively.
Results: Patients with a Fontan circulation reported lower QOL (Wald Z = -3.59, p 5 <.001) and more negative perceptions of their CHD (Wald Z = -7.66, p < .001) compared with patients with ASD/VSD. After controlling for demographics, anxiety, depressive symptoms, and New York Heart Association functional class, path analyses revealed a significant mediation model, αβ = 0.15, p = .002, 95% CI = 0.06-0.25, such that CHD diagnosis was indirectly related to QOL through illness perceptions.
Conclusions: The Fontan sample’s more negative perceptions of CHD were likely a reflection of life with a more complex defect. Illness perceptions appear to account for unique differences in QOL between groups of varying CHD complexity. Psychosocial screening and interventions may be important treatment components for patients with CHD, particularly those with Fontan circulations.     

Influence of age on the development of immunological lung response in intrauterine undernourishment

OBJECTIVE: We investigated the effect of intrauterine undernourishment on some features of asthma using a model of allergic lung inflammation in rats. The effects of age at which the rats were challenged (5 and 9 wk) were also evaluated. METHODS: Intrauterine undernourished offspring were obtained from dams that were fed 50% of the nourished diet of counterparts and were immunized at 5 and 9 wk of age. They were tested for immunoglobulin E anti-ova titers (by passive cutaneous anaphylaxis), cell count in the bronchoalveolar fluid, leukotriene concentration, airway reactivity, mucus production, and blood corticosterone and leptin concentrations 21 d after immunologic challenge. RESULTS: Intrauterine undernourishment significantly reduced the antigen-specific immunoglobulin E production, inflammatory cell infiltration into airways, mucus secretion, and production of leukotrienes B(4)/C(4) in the lungs in both age groups compared with respective nourished rats. The increased reactivity to methacholine that follows antigen challenge was not affected by intrauterine undernourishment. Corticosterone levels increased with age in the undernourished rats' offspring, but not in the nourished rats' offspring. Undernourished offspring already presented high levels of corticosterone before inflammatory stimulus and were not modified by antigen challenge. Leptin levels increased with challenge in the nourished rats but not in the undernourished rats and could not be related to corticosterone levels in the undernourished rats. CONCLUSION: Intrauterine undernourishment has a striking and age-dependent effect on the offspring, reducing lung allergic inflammation.