Clinical Factors Associated with High Glycemic Variability Defined by Coefficient of Variation in Patients with Type 2 Diabetes.

BACKGROUND: High glycemic Variability (HGV) has become a stronger predictor of hypoglycemia. However, clinical factors associate with HGV still are unknown. OBJECTIVE: To determine clinical variables that were associated with a coefficient of variation (CV) above 36% evaluated by continuous glucose monitoring (CGM) in a group of patients with diabetes mellitus. METHODS: A cohort of patients with type 2 diabetes (T2D) was evaluated. Demographic variables, HbA1c, glomerular filtration rate (GFR) and treatment regimen were assessed. A bivariate analysis was performed, to evaluate the association between the outcome variable (CV> 36%) and each of the independent variables. A multivariate model was constructed to evaluate associations after controlling for confounding variables. RESULTS: CGM data from 274 patients were analyzed. CV> 36% was present in 56 patients (20.4%). In the bivariate analysis, demographic and clinical variables were included, such as time since diagnosis, hypoglycemia history, A1c, GFR and treatment established. In the multivariate analysis, GFR <45 mL/min (OR 2.81; CI 1.27,6.23; p:0.01), A1c > 9% (OR 2.81; CI 1.05,7.51; p:0.04) and hypoglycemia history (OR 2.09; CI 1.02,4.32; p:0.04) were associated with HGV. Treatment with iDPP4 (OR 0.39; CI 0.19,0.82; p:0.01) and AGLP1 (OR 0.08; CI 0.01,0.68; p:0.02) was inversely associated with GV. CONCLUSION: Clinical variables such as GFR <45 mL/min, HbA1C>9% and a history of hypoglycemia are associated with a high GV. Our data suggest that the use of technology and treatments able to reduce glycemic variability could be useful in this population to reduce the risk of hypoglycemia and to improve glycemic control.

Mortality among methicillin-resistant Staphylococcus aureus carriers in long-term care facilities.

INTRODUCTION: Little is known about the natural course of patients with chronic stable illnesses colonized with methicillin-resistant Staphylococcus aureus (MRSA). The aim is to determine the impact of MRSA colonization in mortality among long-term health care facility (LTHCF) residents. METHOD: A multicenter, prospective, observational study was designed. Residents in 4 LTHCFs were classified according to MRSA carriage status and followed for 12 months. Treatment consisted of 5 days of nasal mupirocin in MRSA carriers. RESULTS: Ninety-three MRSA-carriers among 413 residents were identified. Thirty-one MRSA-colonized patients died during the study period, 11 of whom from an infectious disease. Independent predictors of their higher mortality rates included heart failure, current neoplasm, MRSA carriage and COPD at 3 months and these same factors plus stroke, Bar-thel index <40, pressure ulcers, and older age at 12 months. MRSA-persistence was 35% and 62.5% at 3 and 12 months, respectively. CONCLUSIONS: MRSA colonization among frail LTHCFs residents is highly prevalent, and is associated with higher mortality. Despite treatment of MRSA carriers, many remained colonized. Factors that promote persistence of MRSA colonization, and the impact of their modification on mortality rates in these patients, need further investigation.

Prevalence and risk factors for meticillin-resistant Staphylococcus aureus in an acute care hospital and long-term care facilities located in the same geographic area.

UNLABELLED: To determine the prevalence and risk factors (RF) for methicillin-resistant Staphylococcus aureus (MRSA) during stay in 1 acute care hospital (ACH) and 4 long-term care facilities (LTCF). After obtaining the informed consent, nasal and skin ulcer swabs were taken and a survey was conducted to determine RF for MRSA. Six hundred and ninety nine patients were included, 413 LTCF and 286 ACH patients and MRSA prevalence were 22.5% and 7.3% respectively. MRSA was located in the nares, skin ulcers, and in both in 61.4%, 21.1%, and 17.5%. Among MRSA carriers, 81% of the ACH and 66.7% of the LTCF patients were only colonized. The multivariate analysis for the ACH revealed the following factors to be associated with MRSA: referral from an LTCF (OR 4.84), pressure ulcers (OR 4.32), a Barthel score < 60 (OR 2.60), and being male (OR 5.21). For the LTCF: urinary catheterisation (OR 3.53), pressure ulcers (OR 2.44), other skin lesions (OR 2.64), antibiotic treatment in ≤ 6 months, (OR 2.23), previous MRSA colonization (OR 2.15), and a Barthel score <20 (OR 1.28). Molecular typing identified 2 predominant clones Q, P, present in all centres. No relationship was found between clones and antibiotic susceptibility. IN CONCLUSION: MRSA prevalence is high in all centres but is 3 times greater in LTCF. The risk factors most strongly associated with MRSA were pressure ulcers and a stay in an LTCF. We propose preventive isolation in these cases.

Use of monoclonal antibodies in diagnosis of paracoccidioidomycosis: new strategies for detection of circulating antigens.

The precise diagnosis of paracoccidioidomycosis, in most cases, is established by direct methods and indirect immunological tests. The latter method is reliant on the identification of the host's humoral responses, which are usually impaired or absent in patients with severe juvenile forms of the disease and in immunocompromised patients. Determining disease activity or assessing treatment responses by measuring antibody levels is difficult, since antibody titer may remain elevated or persist at stationary levels, even in the presence of clinical improvement. Consequently, there is a need for alternative tests aimed at the identification of circulating antigens. A modification of the standard hybridoma production method was used to raise a panel of murine monoclonal antibodies (MAbs) against the yeast form of Paracoccidioides brasiliensis. Of these, MAb PIB, directed against an 87-kDa determinant, was used to develop an inhibition ELISA (inh-ELISA) capable of detecting as little as 5.8 ng of circulating antigen per ml of serum. Sera from 46 patients with paracoccidioidomycosis or other mycoses and sera from healthy individuals were evaluated by the inh-ELISA; overall sensitivity was 80.4% (37 of 46 paracoccidioidomycosis patients tested positive), and specificity compared with that of normal controls from areas of endemicity was 81.4%. The inh-ELISA detected circulating antigen in 100% of patients with the acute form of paracoccidioidomycosis and in 83.3 and 60% of patients with the chronic multifocal and unifocal forms of paracoccidioidomycosis according to the patients' clinical presentation. These results indicate that the inh-ELISA with MAb PIB is effective in the detection of circulating antigen and that this test may be useful for monitoring responses to treatment and establishing disease prognoses.

Development of a novel antigen detection test for histoplasmosis.

Histoplasmosis is an important systemic fungal infection, particularly among immunocompromised individuals living or travelling in areas of endemicity, who, without antifungal therapy, may develop a progressive disseminated fatal infection. For such patients, the detection of antibody responses by immunodiffusion or complement fixation test is of limited use. In contrast, the detection of Histoplasma capsulatum circulating antigens may provide a more practical approach to the rapid diagnosis of the disease. Accordingly, an inhibition enzyme-linked immunosorbent assay (ELISA) for the detection of a 69- to 70-kDa H. capsulatum-specific determinant and incorporating a species-specific murine monoclonal antibody was developed. With sera from patients with different forms of the disease (n = 35), the overall sensitivity of the test was found to be 71.4%, while the specificity was found to be 98% with normal human sera from areas of endemicity (n = 44) and 85.4% with sera from patients with other chronic fungal or bacterial infections (n = 48). This novel, highly specific ELISA provides a significant addition to the existing diagnostic tests for the detection of histoplasmosis.

The calcium-sensitive epitope of pemphigus foliaceus antigen is present on a murine tryptic fragment and constitutes a major antigenic region for human autoantibodies.

Recent findings indicate that the pemphigus foliaceus (PF) antigen is involved in epidermal cell adhesion and that characteristic PF lesions result from loss of this function as a consequence of autoantibody binding. In the present communication we present data on the epitopes involved in the human autoantibody binding to an immunologically reactive murine tryptic fragment of the PF antigen (tf-PF). Immunoprecipitation experiments showed that 39 PF sera, obtained from North American, Colombian, and Brazilian patients recognized only calcium-sensitive epitope(s) on the tf-PF. Immunofluorescence blocking experiments showed that preincubation with tf-PF completely blocked the immunofluorescence of 80% of the sera when tested on human skin substrate, and 86% of the sera when tested on murine skin substrate. These results show that the calcium-sensitive epitope(s) originally recognized on human PF complex, is (are) present on the murine tf-PF and constitute(s) a major antigenic region for the human PF autoantibodies. They also implicate this region of the PF antigen in the pathogenesis of PF as well as in epidermal cell adhesion.

Comparison of patellar resurfacing versus nonresurfacing in bilateral total knee arthroplasty.

Twenty-five patients who received bilateral total knee prostheses were studied to evaluate the advantages and disadvantages of patellar resurfacing. Only patients with advanced patellofemoral disease were included in the study. In all patients, patellar resurfacing had been done in the right knee but not in the left knee. The DePuy porous-coated implant was used in all cases. Subjective criteria were compared with objective criteria, which included range of motion, knee flexion and extension, and roentgenographic evaluation. The findings in this study suggest that patellar resurfacing can offer the patient a superior knee with regard to pain relief and strength.

Studies of the relationship of the 230-kD and 180-kD bullous pemphigoid antigens.

In bullous pemphigoid (BP), autoantibodies from most patients recognize a high molecular weight 230-kD epidermal antigen (Ag) by immunoprecipitation. By Western immunoblotting, 50-70% of sera recognize the high molecular weight Ag, but 30-50% recognize a low molecular weight, 180-kD epidermal Ag. We examined the specificities of affinity-purified antibodies against these Ag. Antibodies specific for the 230- and 180-kD Ag were prepared by immunoaffinity against Ag immobilized on nitrocellulose and released by acid glycine. IgG eluted from the 230-kD Ag band retained its specific binding to the 230-kD Ag by immunoblotting, and bound to the epidermal basement membrane zone (BMZ) by indirect immunofluorescence (IF) and to hemidesmosomes by indirect immunoelectron microscopy (EM). IgG affinity purified by the 180-kD Ag band bound only the 180-kD Ag in immunoblotting, with no cross reaction to the 230-kD Ag, bound the epidermal BMZ by indirect IF, and also bound to hemidesmosomes in immuno-EM. IgG specific for the 230-kD Ag in immunoblotting immunoprecipitated only the 230-kD Ag, with no apparent precipitation of the 180-kD Ag. Surprisingly, IgG specific for the 180-kD Ag precipitated both the 180- and the 230-kD Ag in immunoprecipitation, and the 230-kD Ag band was much more intense than the 180-kD Ag band. This study shows that apparent cross-reactivity between these Ag by BP autoantibodies can only be detected in native conditions by immunoprecipitation, and cannot be demonstrated using denatured Ag in immunoblotting. The two proteins appear to be distinct Ag, closely associated in the epidermal hemidesmosome, but the exact relationship of these Ag to each other may not be clarified until complete structural data become available.

South American pemphigus foliaceus: study of an epidemic in El Bagre and Nechi, Colombia 1982 to 1986.

Between 1982 and 1986 we have had the chance to study 21 patients with pemphigus foliaceus of the 'fogo selvagem' type. The patients came from El Bagre and Nechi, rural areas of Colombia with some gold mining. This is the first outbreak of South American pemphigus foliaceus reported in Colombia. The majority of the patients were mestizo men, who worked as farmers or miners or both, with an average age of 44. Five patients were relatives. Eleven patients (52%) had mild disease, three (14%) moderate disease and seven (33%) severe disease. During hospitalization, three patients died due to complications or as a result of immunosuppressive treatment. Of the remaining 18 patients, 10 were in remission with treatment, one was in remission without treatment, while no information was available on the remaining seven.

[Structure of the dermo-epidemic junction]. / Estructura de la unión dermoepidérmica.

The basement membranes are extracellular proteic matrixes involved mainly in cell-substrate interactions. The dermo-epidermal junction (DEJ) is defined as the region formed by the dermal pole of the basal cell layer, the intercellular spaces, the lamina densa or basal lamina and the acellular fibrous components of the papillary dermis. The functions of the DEJ are to bind the epithelia to the connective tissue, and to preserve the viability of the epidermis by means of connecting it to the dermis. which is in charge of providing the necessary nutrients for its normal proliferation. The purpose of the present communication is to provide a concise review of the recent knowledges about the ultrastructure of the DEJ, with special emphasis on its antigenic components.

Treatment of paracoccidioidomycosis with ketoconazole: a three-year experience.

The results of ketoconazole therapy in 38 patients with active paracoccidioidomycosis are described. Treatment consisted of a 200 mg tablet a day for 6 months. Evaluation was accomplished by means of a scoring system and the results were as follows: none of the patients worsened during therapy, one was found to be unchanged, five had minor improvement, 330 had major improvement, and there was complete resolution of the pretherapy conditions in 13. These findings plus the lack of toxicity of the drug and the facility for oral administration, make of ketoconazole a first line drug for the treatment of paracoccidioidomycosis.

Post-therapy status of paracoccidioidomycosis treated with ketoconazole.

Twenty-four paracoccidioidomycosis patients who completed a course of therapy with ketoconazole were followed for 12 months after treatment, and 10 of these patients were followed for 24 months. Only two of these patients relapsed; the remaining continued in remission. There were no fatalities. Immunologic tests showed decreased antibody activity and increased skin test reactivity to paracoccidioidin in comparison with the results obtained at the end of therapy. These findings indicate that ketoconazole therapy has improved the prognosis of patients with paracoccidioidomycosis.

Host defense against experimental paracoccidioidomycosis.

An experimental model for the study of paracoccidioidomycosis was established in BALB/c mice. Both normal and athymic nu/nu animals were challenged intraperitoneally and intratracheally with yeastlike cells of Paracoccidioides brasiliensis. After challenge, all immunologically intact (+/+) mice survived, whereas nu/nu mice gradually succumbed. The latter had focal peritoneal, liver, spleen, and lung lesions consisting of P. brasiliensis with inflammation, polymorphonuclear leukocytes, monocytes, and histiocytic reactions, but no granuloma formation. Thymus transplantation heightened resistance of nu/nu mice to P. brasiliensis. These studies indicate that the nu/nu mouse develops progressive lethal paracoccidioidomycosis after intraperitoneal and intratracheal challenge, and that thymus-dependent immune mechanisms mediate host defense.

Eficacia del ketoconazol en pacientes con paracoccidioidomicosis recidivante. / Efficacy of ketoconazole in patients with recurrent paracoccidioidomycosis

Se realizo un estudio para determinar si los pacientes con paracoccidioidomicosis recidivante se beneficiarian del tratamiento con ketoconazol en forma similar a aquellos recientemente diagnosticados y no tratados anteriormente. Utilizando um sistema de puntaje se comparo la respuesta de ambos grupos,no encontrandose diferencia alguna entre ellos.Seis meses de tratamiento produjeron la remision del proceso em todos los 8 pacientes estudiados. El ketoconazol parece ser efectivo para el control de las recaidas en la paracoccidioidomicosis