Calciphylaxis – a topical overview

'Calciphylaxis', a calcification syndrome associated with ischaemic cutaneous necrosis, is acquired naturally in humans in disease states. It is a life and limb-threatening complication, usually observed in patients with renal disease and secondary hyperparathyroidism, but known to occur in the absence of renal or parathyroid disease. The reported mortality rate, which ranges from 60-80%, relates to wound infection, sepsis and organ failure. It is a small-vessel vasculopathy, which is estimated to occur in about 4% of haemodialysis patients. Clinically, violaceous, reticulate areas of cutaneous necrosis and eschar may be evident, particularly in the extremities. In addition to the clinical picture, a raised calcium phosphorous product, an elevated parathyroid hormone level, radiographic evidence of vessel and soft-tissue calcification and the finding of mural calcification affecting small arteries and arterioles on histopathology help to confirm the diagnosis of this entity which generally has a poor prognosis. A high index of suspicion and an active multidisciplinary management approach, with rigorous attention to wound care and prevention of sepsis, are vital in the management of these patients. In this overview, we discuss the pathophysiology, clinical features and associations, risk factors, diagnosis and management issues relating to calciphylaxis.     

Impact of antibiotic-resistant pathogens colonizing the respiratory secretions of patients in an extended-care area of the emergency department.

OBJECTIVE: To determine the incidence of acquired infection, and the incidence, risk factors, and molecular typing of multidrug-resistant bacterial organisms (MROs) colonizing respiratory secretions or the oropharynx of patients in an extended-care area of the emergency department (ED) in a tertiary-care university hospital. METHODS: A case-control study was conducted regarding risk factors for colonization with MROs in ED patients from July 1996 to August 1998. The most prevalent MRO strains were determined using plasmid and genomic analysis with PFGE. RESULTS: MROs colonized 59 (25.4%) of 232 ED patients and 173 controls. The mean ED length of stay for the 59 cases was 13.9 days versus 9.8 days for the 173 controls. The mean length of stay prior to the first isolation of MROs was 9.9 days. MRO species included Acinetobacter baumannii, Staphylococcus aureus, and Pseudomonas aeruginosa. The rate of hospital-acquired infection was 32.7 per 1,000 ED patient-days. The case fatality rate was significantly higher for cases. Univariate analysis identified mechanical ventilation, nebulization, nasogastric intubation, urinary catheterization, antibiotic therapy, and number of antibiotics as risk factors for MRO colonization. Multivariate regression analysis found that mechanical ventilation and nasogastric intubation independently predicted MRO colonization. Endemic clones were identified by PFGE in ED patients and were also found in patients in other parts of the hospital. CONCLUSIONS: Prolonged stay in the ED posed a risk for colonization with MROs and for contracting nosocomial infections, both of which were associated with increased mortality. Patients colonized with antibiotic-resistant A. baumannii may serve as a reservoir for spread in this hospital.     

Alpha-SM actin expression as prognostic indicator in IgA nephropathy (Berger's disease)

Recent studies have demonstrated that α-Smooth Muscle actin expression in glomerular and tubulointerstitial compartments of renal tissue could represent a prognostic marker in several renal diseases. Our objective was to identify the prognostic value of α-SM actin actin expression on the evolution of renal damage in Primary IgA nephropathy (Berger’s Disease). 43 patients followed up from 1988 to 1999 at the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil, was studied. Clinical-laboratory data were obtained from the medical records of the patients using a protocol containing name, race, gender, origin, profession, age at clinical presentation of the disease and personal and family history. The parameters assessed in the approach to IgA nephropathy were serum creatinine, creatinine clearance, serum albumin, total serum protein, 24 hours proteinuria, glycaemia, serum sodium, potassium, calcium and phosphorus ions, analysis of urinary sediment, serum complement profile, blood count, and renal biopsy. Morphological evaluation was performed by renal biopsy using common light and immunofluorescence microscopy. Immunohistochemical studies were performed using a murine monoclonal antibody to α-SM actin. Our data showed that α-SM actin expression in the glomerular and tubulointerstitial compartments are not correlated with unfavorable clinical course of primary IgA nephropathy.     

Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy

The dominant cone-rod dystrophy gene CORD6 has previously been mapped to within an 8 cM interval on chromosome 17p12-p13. The retinal- specific guanylate cyclase gene (RETGC-1), which maps to within this genetic interval and previously was implicated in Leber's congenital amaurosis, was screened for mutations within this family and in a panel of small families and individuals with various cone and cone- rod dystrophy phenotypes. A missense mutation (E837D) was identified in affected members of the CORD6 family, as well as a second missense mutation (R838C) in three other families with dominant cone-rod dystrophy. RETGC-1 is only the fourth gene to be implicated in cone-rod dystrophy and this is the first report of dominant mutations in this gene.      

Recombinant cysteine proteinase from Leishmania (Leishmania) chagasi implicated in human and dog T-cell responses

High in vitro lymphoproliferative responses were induced in humans and dogs by a recombinant Leishmania (Leishmania) chagasi cysteine proteinase, with secretion of IFN-gamma in asymptomatic subjects or of IFN-gamma, interleukin 4 (IL-4), and IL-10 in oligosymptomatic subjects. In contrast, responses of symptomatic patients and dogs were lower, with production of IL-4 and IL-10.