Über den Einfluß der Stoffe der Digitalingruppe auf den Blutdruck von Kaninchen

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Fixed drug eruption from piroxicam

The pathogenetic mechanism of fixed drug eruption (FDE) is still unknown. One of the most common causes of FDE is the use of nonsteroidal antiinflammatory drugs (NSAIDs). Oxicams are in the NSAID group and piroxicam is one of the most used of these drugs. FDE caused by piroxicam is rare but a few cases have been reported. Patch tests are useful for diagnosing some cases of FDE; they give variable results on previously affected skin while no reaction appears on unaffected skin. Some cases of cross-sensitivity among piroxicam and other substances have been reported. We report two new cases of FDE due to piroxicam with negative patch test on normal skin and positive results on affected skin.     

Prediction of recurrence by quantification of p185neu protein in non-small-cell lung cancer tissue.

The concentration of c-erbB-2 oncogene-encoded protein (p185neu) in fresh tumour samples obtained at the time of surgery from 94 non-small-cell lung cancer patients (NSCLC) was determined by an enzyme immunoassay. The relative prognostic importance was estimated, and the influence of other predictors was assessed by means of a Cox''s proportional regression model. Median concentration of p185 in tumour tissues was 206 U mg(-1) (range 21-1050 U mg(-1)). p185 level did not differ significantly among subgroups defined by TNM classification, histological type, sex and age. Categorization of patients by p185 level, with 206 U mg(-1) and 343 U mg(-1) taken as cut-off values (corresponding to the 50th and 80th percentiles of the frequency distribution), showed that the recurrence rate, cumulative disease-free likelihood at the 36-month follow-up and median time from surgery to the diagnosis of recurrence worsened progressively as the level of p185 increased. Multivariate analysis confirmed the independent prognostic value of p185 level. Risk of recurrence increased by 1.304 for every increase of 100 units in p185 concentration (95% CI 1.141-1.490) (P<0.001). These findings encourage the inclusion of p185 concentration assay in a future predictive multifactorial prognostic index in NSCLC.     

Non-secretory multiple myeloma presenting as primary plasma cell leukaemia.

A case of non-secretory multiple myeloma presenting as primary plasma cell leukaemia in a 65 year old woman is presented. Bone pain was the initial clinical manifestation. Laboratory analysis showed 20% of circulating immature plasma cells. Despite the presence of osteolytic lesions, no M-component could be demonstrated in serum protein electrophoresis, and serum and urine immunoelectrophoresis. Bone marrow aspirate demonstrated an 83% infiltration of plasma cells showing various degrees of immaturity. Immunofluorescence with monoclonal antisera demonstrated intracytoplasmic kappa light chains in a high percentage of plasma cells. Immature plasma cells without cellular capacity to synthesize and excrete complete immunoglobulins could be more aggressive, leading to an initial leukaemic process. Previous work regarding possible pathogenetic mechanisms, clinical and laboratory features, and response to treatment of this extremely rare association are reviewed.     

Impact of syphilis infection on HIV viral load and CD4 cell counts in HIV-infected patients

OBJECTIVES: To assess the effect of early syphilis on HIV viral load (VL) and CD4 cell count in patients with HIV and to analyze factors associated with changes in HIV VL and CD4 cell count. DESIGN: Multicenter study of a series of patients with HIV who were diagnosed with early syphilis infection during 2004 through 2005. Patients who started or changed their highly active antiretroviral therapy (HAART) regimen during the analysis period were excluded. RESULTS: One hundred eighteen patients were analyzed: 95.8% were men, mean patient age was 38.2 years, 83.9% were homosexual men, 50.8% were on antiretroviral therapy at the time syphilis was diagnosed, and HIV and syphilis diagnoses were coincident in 38 (32.2%) cases. CD4 cell counts were lower during syphilis than before (590 vs. 496 cells/microL; P = 0.0001) and after syphilis treatment (509 vs. 597 cells/microL; P = 0.0001). The HIV VL increased in 27.6% of patients during syphilis. The only factor associated with an HIV VL increase was not being on HAART, and the only factor associated with a CD4 count decrease >100 cells/microL during syphilis was the prior CD4 cell count. CONCLUSIONS: Syphilis infection was associated with a decrease in the CD4 cell count and an increase in the HIV VL in almost one third of the patients. In this series, more than two thirds of the syphilis cases were diagnosed in patients who were previously known to be infected with HIV.     

Effect of adverse drug reactions on length of stay in surgical intensive care units

OBJECTIVE: To determine the frequency of adverse drug reactions in surgical intensive care units and evaluate their effect on the length of stay. DESIGN: Prospective cohort study. Between May 1997 and December 1999, while the patients were staying in the surgical intensive care unit, data were gathered regarding suspected adverse drug reactions and on different variables related to the length of stay. SETTING: Surgical intensive care units of our hospital. PATIENTS: A total of 401 patients hospitalized in the surgical intensive care unit. MAIN RESULTS: In 37 of the 401 patients seen (9.2%; 95% confidence interval, 6.6-12.5), 39 different adverse drug reactions were detected. The adverse drug reactions were most frequently caused by the following drugs: morphine hydrochloride (n = 13), meperidine hydrochloride (n = 9), and metamizole (n = 7). Five adverse drug reactions were severe, the suspected medication had to be discontinued in 14 cases, and new drugs were necessary to manage the adverse drug reaction in 28 cases. The crude estimation of the effect of adverse drug reactions performed on the length of stay with a bivariant regression model indicated that each adverse drug reaction was related to an increase of 3.39 days (95% confidence interval, 1.47-5.31) in the length of stay. This estimation was reduced to 2.31 days (95% confidence interval, 0.64-3.99) when considering other variables that might cause confusion for analysis, although it is still important. CONCLUSIONS: Adverse drug reactions are a significant clinical and economic problem in surgical intensive care units.     

Validation of a simplified medication adherence questionnaire in a large cohort of HIV-infected patients: the GEEMA Study

OBJECTIVE: To assess the effectiveness of the simplified medication adherence questionnaire (SMAQ) in identifying non-adherent patients. DESIGN: Prospective observational study of adherence. The six-item SMAQ was developed. The following aspects were evaluated: (i) criterion validity, comparison with electronic adherence monitoring; (ii) construct validity, association between adherence, as defined by the SMAQ, and virological outcomes; and (iii) reliability, internal consistency and reproducibility. PATIENTS: A group of 3004 unselected HIV patients who had initiated nelfinavir therapy combined with other antiretroviral drugs [21% naive, 15% protease inhibitor (PI)-naive, 64% PI-experienced] between January 1998 and December 1999 were enrolled in 69 hospitals in Spain. The SMAQ was administered at months 3, 6 and 12. RESULTS: The SMAQ showed 72% sensitivity, 91% specificity and a likelihood ratio of 7.94 to identified non-adherent patients, compared with the medication-event monitoring system (40 patients evaluated). At month 12, 1797 patients were evaluated, of whom 32.3% were defined as non-adherent; viral load < 500 copies/ml found in 68.3% of the adherent, and 46% of the non-adherent patients. A logistic regression analysis of PI-naive patients was performed, including age, sex, baseline viral load > 5 log10/ml, CD4 cell count < 200 x 10(6)/l, and non-adherence as independent variables. Non-adherence was the only significant risk factor in failing to achieve virological suppression. Cronbach's alpha internal consistency coefficient was 0.75, and overall inter-observer agreement was 88.2%. CONCLUSION: The SMAQ appears to be an adequate instrument with which to assess adherence in HIV-infected patients, and may be applied in most clinical settings.     

Decreasing prevalence of HCV coinfection in all risk groups for HIV infection between 2004 and 2011 in Spain

While hepatitis C virus (HCV) infection seems to be expanding among HIV‐infected men who have sex with men (MSM), the rate of coinfection in intravenous drug users (IDU) is assumed to remain constant. We evaluated the serial prevalence of HIV/HCV coinfection across all risk groups for HIV infection in Spain. We used data from 7045 subjects included in the multicentre, prospective Spanish Cohort of Adult HIV‐infected Patients (CoRIS) between 2004 and 2011. We analysed risk factors for HIV/HCV coinfection by logistic regression analyses. The prevalence of HIV/HCV coinfection decreased from 25.3% (95% CI, 23.1–27.5) in 2004–2005 to 8.2% (95% CI, 6.9–9.5) in 2010–2011. This trend was consistently observed from 2004 to 2011 among all risk groups: IDU, 92.4% to 81.4%; MSM, 4.7% to 2.6%; heterosexual men, 13.0–8.9%; and heterosexual women, 14.5–4.0% (all P < 0.05). Strongest risk factors for HIV/HCV coinfection were IDU (OR, 54.9; 95% CI, 39.4–76.4), birth decade 1961–1970 (OR, 2.1; 95% CI, 1.1–3.7) and low educational level (OR, 2.4; 95% CI, 1.6–3.5). Hence, the prevalence of HIV/HCV coinfection decreased in Spain between 2004 and 2011. This decline was observed across all risk groups and is likely to be explained by a declining burden of HCV in the general population.     

Peptidomic analysis of type 1 diabetes associated HLA‐DQ molecules and the impact of HLA‐DM on peptide repertoire editing

HLA‐DM and class II associated invariant chain (Ii) are key cofactors in the MHC class II (MHCII) antigen processing pathway. We used tandem mass spectrometry sequencing to directly interrogate the global impact of DM and Ii on the repertoire of MHCII‐bound peptides in human embryonic kidney 293T cells expressing HLA‐DQ molecules in the absence or presence of these cofactors. We found that Ii and DM have a major impact on the repertoire of peptides presented by DQ1 and DQ6, with the caveat that this technology is not quantitative. The peptide repertoires of type 1 diabetes (T1D) associated DQ8, DQ2, and DQ8/2 are altered to a lesser degree by DM expression, and these molecules share overlapping features in their peptide binding motifs that are distinct from control DQ1 and DQ6 molecules. Peptides were categorized into DM‐resistant, DM‐dependent, or DM‐sensitive groups based on the mass spectrometry data, and representative peptides were tested in competitive binding assays and peptide dissociation rate experiments with soluble DQ6. Our data support the conclusion that high intrinsic stability of DQ‐peptide complexes is necessary but not sufficient to confer resistance to DM editing, and provide candidate parameters that may be useful in predicting the sensitivity of T‐cell epitopes to DM editing.     

Modelling the effect of insulin on the disposal of meal-attributable glucose in type 1 diabetes

The management of postprandial glucose excursions in type 1 diabetes has a major impact on overall glycaemic control. In this work, we propose and evaluate various mechanistic models to characterize the disposal of meal-attributable glucose. Sixteen young volunteers with type 1 diabetes were subject to a variable-target clamp which replicated glucose profiles observed after a high-glycaemic-load (\(n=8\)) or a low-glycaemic-load (\(n=8\)) evening meal. [6,6-\(^{2}\hbox {H}_2\)] and [U-\(^{13}\hbox {C}\);1,2,3,4,5,6,6-\(^{2}\hbox {H}_{7}\)] glucose tracers were infused to, respectively, mimic: (a) the expected post-meal suppression of endogenous glucose production and (b) the appearance of glucose due to a standard meal. Six compartmental models (all a priori identifiable) were proposed to investigate the remote effect of circulating plasma insulin on the disposal of those glucose tracers from the non-accessible compartments, representing e.g. interstitium. An iterative population-based parameter fitting was employed. Models were evaluated attending to physiological plausibility, posterior identifiability of their parameter estimates, accuracy—via weighted fitting residuals—and information criteria (i.e. parsimony). The most plausible model, best representing our experimental data, comprised: (1) a remote effect x of insulin active above a threshold \(x_{C}\) = 1.74 (0.81–2.50) \(\cdot \,10^{-2}\) min\(^{-1}\) [median (inter-quartile range)], with parameter \(x_{C}\) having a satisfactory support: coefficient of variation CV = 42.33 (31.34–65.34) %, and (2) steady-state conditions at the onset of the experiment (\(t=0\)) for the compartment representing the remote effect, but not for the masses of the tracer that mimicked endogenous glucose production. Consequently, our mechanistic model suggests non-homogeneous changes in the disposal rates for meal-attributable glucose in relation to plasma insulin. The model can be applied to the in silico simulation of meals for the optimization of postprandial insulin infusion regimes in type 1 diabetes.