Cardiovascular complications of respiratory diseases

A major burden of morbidity and mortality due to respiratory diseases can be directly related to the cardiovascular (CV) complications of these disorders. Evidence from cross-sectional and longitudinal studies link reduced lung function and cardiovascular diseases. However, the underlying pathogenic mechanisms are unclear. Hypoxia-induced increased sympathetic activity, blood viscosity, or inflammation, among other factors, may mediate the underlying pathogenesis. In addition, sleep-disordered breathing (SDB) has been implicated by association in multiple CV diseases including hypertension, ischemic heart disease, congestive heart failure, arrhythmias, and stroke. However, the exact contribution of SDB, including obstructive and central sleep apneas, to the development of cardiovascular diseases is not fully understood. In this context, the contribution of the new large, prospective, Jackson Heart Study could be significant in that it is designed to answer several of these questions, specifically in the African American population. This review examines the current evidence that links both reduced lung function and SDB to CV diseases.     

Folliculosebaceous cystic hamartoma of the nipple: a case report

Folliculosebaceous cystic hamartoma (FCH) is a relatively rare and recently described lesion of the skin. Mostly, it involves the skin of the head and neck area. It is considered by most authors as a form of non-neoplastic cutaneous hamartoma comprising follicular, sebaceous and stromal elements. However, few regard it as a sebaceous trichofolliculoma, i.e. a variant of trichofolliculoma. FCH of the nipple of female breast is a very rare lesion with only one previous case reported so far in the literature. We report a similar case with a brief review of the literature.     

Characterization of a large Lebanese family segregating IgA nephropathy.

BACKGROUND: Familial aggregation of IgA nephropathy (IgAN) suggests that genetic factors contribute to the development of this trait. Because clinical manifestations in IgAN families are often limited to episodic haematuria, large kindreds tractable to linkage analysis have been difficult to identify. METHODS: We identified a large Lebanese-Druze kindred ascertained via an index case with biopsy-documented IgAN. We performed systematic screening of 38 family members and tested linkage to reported IgAN loci. RESULTS: Screening of this family identified 16 affected individuals, including 2 individuals with biopsy-documented IgAN and 14 with chronic renal failure or abnormal urinalyses on at least three separate occasions. This kindred spanned five generations and contained five consanguineous unions. Multigenerational inheritance suggested that autosomal dominant inheritance was most likely. Phenotypic manifestations among affected individuals varied from isolated haematuria to advanced renal failure necessitating transplantation; one instance of IgAN recurrence after transplantation was also documented. Older age was associated with greater severity of disease and higher incidence of renal failure. Parametric and non-parametric analyses with 33 microsatellite markers did not reveal any evidence of linkage to reported IgAN loci on chromosomes 6q22-23, 2q36 and 4q22-31. CONCLUSIONS: We describe one of the largest multigenerational IgAN kindreds reported to date. The high incidence of renal failure among older generations suggests a significant risk of progression to renal failure. We found no evidence of linkage to known loci, suggesting that familial IgAN encompasses multiple subtypes that will require distinction based on genetic or biomarker data.     

Five-lipoxygenase products in glomerular immune injury.

Leukocyte infiltration, proliferation, and activation are central pathogenetic components of immune injury in the glomerulus. Initial cellular infiltration by polymorphonuclear leukocytes (PMN) is a consequence of the deposition of immune complexes at discreet sites in the glomerulus. This is often followed by macrophage/monocyte infiltration, as well as proliferation of resident mesangial macrophages. Activated leukocytes constitute a rich source of lipid-derived bioactive autacoids, in particular, oxygenated metabolites of arachidonic acid. Here, we assess the role of the five-lipoxygenase (5-LO) family of eicosanoids, in particular, leukotrienes D4 and B4 (LTD4 and LTB4) in mediating functional and structural deterioration during immune inflammatory reactions in the glomerulus. LTD4 and other peptidyl LT appear to play a central role in the reductions in GFR in the acute phases of injury by virtue of their potent vasoactive properties, in particular, their capacity to reduce the glomerular capillary ultrafiltration coefficient, likely through contraction of smooth muscle elements in glomerular mesangial cells. The latter cells possess specific receptors for LTD4 in both humans and rat and contract in vitro when exposed to LTD4 after receptor-mediated activation of phospholipase C. LTB4, a nonvasoconstrictor LT, is released in the early phases of immune injury, likely from leukocyte sources as well as from transcellular metabolism of its precursor, LTA4, by the enzyme LTA4-hydrolase in glomerular mesangial and endothelial cells. LTB4, a potent promoter of PMN attraction, adhesion, and activation exacerbates glomerular functional impairment and structural damage by amplifying PMN-dependent mechanisms of injury. In their totality, 5-LO products of arachidonic acid contribute to the impairment of the normal glomerular filtration and sieving functions that attend acute inflammatory injury in the renal glomerulus and to the subsequent progression of glomerular destruction. This is high-lighted by the significant degree of protection afforded by the selective inhibition of arachidonate 5-LO in vivo in acute and chronic models of experimental glomerulonephritis.     

Chrysosporium parvum keratomycosis.

PURPOSE: To report a case of corneal infection with Chrysosporium parvum, a filamentous fungus usually associated with pulmonary infections. METHODS: A 43-year-old Saudi man had a corneal stromal infiltrate and perforation of his left eye. He was treated with a therapeutic penetrating keratoplasty and topical and systemic antifungal therapy. Corneal scrapings, microbiologic evaluation, and histopathologic examination of the surgical specimen were performed to establish the diagnosis. After the development of recurrent stromal keratitis at the graft-host junction, similar diagnostic and therapeutic maneuvers were performed. RESULTS: Corneal scrapings and histopathologic examination were positive for numerous septate hyphae with endospores, consistent with a diagnosis of filamentous keratomycosis. Microbiologic isolation confirmed the diagnosis of Chrysosporium parvum. Similar diagnostic maneuvers for recurrent keratitis produced identical results. CONCLUSION: To our knowledge, this is the first case of Chrysosporium parvum keratomycosis.     

A role for atrial natriuretic peptide in endothelin-induced natriuresis.

Systemic administration of low-dose endothelin increases urinary sodium excretion rate despite mild to moderate reductions in renal plasma flow and glomerular filtration rates. The role of atrial natriuretic peptide in endothelin-induced natriuresis was investigated. Administration of 2.50 pmol/min of endothelin to euvolemic rats resulted in increases in plasma atrial natriuretic peptide levels from 127 +/- 18 to 169 +/- 23 pg/mL. However, a lower dose of endothelin (0.63 pmol/min) or saline did not increase plasma levels of atrial natriuretic peptide. Mean arterial pressure was unchanged at the lower dose of endothelin and increased only slightly in rats receiving 2.5 pmol/min. To assess functional significance, renal responses to endothelin (2.5 pmol/min) in the absence and presence of a specific anti-rat atrial natriuretic peptide antibody were compared. Equivalent reductions in renal blood flow were observed. Urinary sodium excretion rates increased significantly in non-ANP-antibody-treated rats by 33 +/- 7 and 82 +/- 20% at 10 and 30 min, respectively. Atrial natriuretic peptide antibody blunted markedly endothelin-induced natriuresis: urinary sodium excretion rates changed insignificantly by 18 +/- 10 and 30 +/- 14%, respectively. Thus, endothelin infusion results in increases in plasma atrial natriuretic peptide levels, which may contribute to endothelin-induced natriuresis, providing evidence for potentially significant interactions between these peptide hormones in the regulation of sodium balance and renal vascular tone.