Assessment of renal toxicity and osteonecrosis of the jaws in patients receiving zoledronic acid for bone metastasis.

BACKGROUND: Bisphosphonates (BP) decrease the incidence of skeletal related events among cancer patients with bone metastases from solid tumors and multiple myeloma. Renal safety and osteonecrosis of the jaws (ONJ) are two major concerns of toxicity. Information about safety of using BP beyond 2 years is scarce. Materials and methods: Patients receiving zoledronic acid (ZA) at the time of the study were reviewed. Serum creatinine levels (SCL) were collected at three different moments: before the start of BP (baseline), at the time of analysis (final), and the highest SCL during the treatment (highest). Oral examination was carried out in every patient. Separated analysis was made for patients on BP for >2 years. Concomitant risk factors for both renal toxicity and ONJ were evaluated. RESULTS: Sixty-seven patients were included. Median time of BP was 22 months, with 22 patients receiving BP for >2 years. Median baseline and final values of SCL were 0.71 mg/dl and 0.70 mg/dl, respectively (P = 0.121). Median highest SCL during treatment was 0.82 mg/dl (P <0.0001). A notable increase in the SCL was observed in six of the 67 patients (9%), four of them receiving BP for >2 years (P = 0.085). ONJ was also diagnosed in six patients, four of them in the group of prolonged BP treatment. CONCLUSION: ZA showed to be safe with a low rate of reversible renal toxicity. Patients receiving BP should be monitored carefully for renal toxicity and ONJ, especially those with exposure to BP beyond 2 years.     

Prevalence of and factors associated with current asthma symptoms in school children aged 6–7 and 13–14 yr old in Bogotá, Colombia

This cross‐sectional study of children aged 6–7 years and adolescents aged 13–14 years in Bogotá, Colombia, assessed the prevalence of asthma symptoms and their associations with dietary, health, and behavioral habits. This study is part of the International Study of Asthma and Allergies in Childhood (ISAAC)‐phase III. Asthma prevalence among the children was assessed using a parental self‐administered written questionnaire (WQ), and among adolescents using a WQ together with a video questionnaire (VQ). Associations were estimated with bivariate and multivariate analysis. The study found that the 6–7 year age‐group were more likely to report current asthma symptoms than the 13–14 year age‐group (10.4% [WQ] vs. 8.6% [WQ] and 8.0% [VQ], respectively). Factors associated with current asthma symptoms among the 6–7 year age‐group included higher maternal education (OR = 1.7, [95% CI 1.2–2.6], p = 0.007), a cat in the home during the last year (OR = 1.5, [95% CI 1.0–2.3], p = 0.036), watching TV 1–2 hours/day (OR = 2.1, [95% CI 1.2–3.9], p = 0.013), and medication with acetaminophen in the first and most recent year of life (OR = 1.8, [95% CI 1.3–2.4], p < 0.001; OR = 2.2, [95% CI 1.7–2.8], p < 0.001, respectively) or antibiotics in the first year of life (OR = 1.9, [95% CI 1.4–2.5], p < 0.001). Among the 13–14 year age‐group, factors associated with current asthma symptoms included medication with acetaminophen during the last year (OR = 1.8, [95% CI 1.4–2.3], p < 0.001); cereal, milk, and fruit consumption 3 or more times weekly (OR = 1.5, [95% CI 1.1–1.9], p = 0.010; OR = 0.8, [95% CI 0.6–1.0], p = 0.046; OR = 0.6, [95% CI 0.4–1.0], p = 0.031, respectively). Overall, compared with that in other Latin American centers, asthma prevalence in Bogotá is close the lower estimates. However, associations with dietary, health, and behavioral habits need further study to assess their complex relationship with asthma.     

Comparison of the stability of press-fit hip prosthesis femoral stems using a synthetic model femur

The motion of three different press-fit hip prosthesis femoral components was compared with that of a cemented stem and an Austin Moore noncemented hemiarthroplasty. Synthetic composite femurs were used as an experimental model to reduce the variations in shape and quality typical among cadaver femurs. Motion was measured under axial and rotational loading approximating a walking load. On the initial application of load, axial subsidence was as much as several millimeters for the noncemented stems. Considerable tightening occurred during the 5,000 walking cycles, such that the motion of the noncemented stems in some directions eventually was as small as that of the cemented stem, on the order of tens of microns.     

Statistical modeling of prognostic indices for evaluation of critically ill patients

OBJECTIVE: To identify the most predictive association of variables from the usual indices of severity of illness by statistical objective analysis. DESIGN: Logistic regression analysis of the different variables of the most important indices. SETTING: A general critical care medicine group practice in a university hospital. PATIENTS: A total of 630 critical care patients age 12 to 87 yrs were evaluated. The most important indices of severity of illness and the corresponding variables were recorded and the patient's course was followed for 3 months after ICU admission. MEASUREMENTS AND MAIN RESULTS: One of our hypotheses was that the inclusion of an excessive number of variables to obtain the most common prognostic indices of mortality in critical care patients results in an underestimation of mortality and a redundancy of prognostic information. We performed a logistic regression analysis using the variables of the currently used indices of critical care prognosis: Acute Physiology Score, Simplified Acute Physiology Score, Acute Physiology Score-II, and Mortality Prediction Model. This mathematical approach resulted in a model of five variables: organ system failure, blood glucose, serum calcium, serum prothrombin activity, and serum osmolality. The score obtained from this model gave accurate prognostic criteria:sensitivity 91.2% and specificity 90%, using a cutoff point of 0.7; sensitivity 86% and, specificity 94%, using a cutoff point of 0.5. CONCLUSIONS: Our results show that suitable statistical management of the discriminant prognostic variables allows reduction of the number of variables of the severity indices currently used, obtaining five more predictive variables.     

3H]BAY K 8644, a 1,4-dihydropyridine Ca++ channel activator: characteristics of binding to high and low affinity sites in cardiac membranes

The binding of [3H]BAY K 8644 [methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)- pyridine-5-carboxylate] to high and low affinity sites in rabbit ventricular membranes was characterized. Binding affinities were 0.66 and 138 nM at 15 degrees C and 9.1 and 72 nM at 37 degrees C, for the high and low affinity sites, respectively, and binding site densities were 0.3 and 14 pmol/mg at 15 degrees C and 0.41 and 1.4 pmol/mg at 37 degrees C, for the respective sites. The modification of high affinity [3H]BAY K 8644 binding by verapamil, diltiazem, tiapamil, Ca++ and EDTA appeared to be the same as that for nitrendipine binding, consistent with the hypothesis that the high affinity binding site for [3H]BAY K 8644 on isolated membranes is the same as the 1,4-dihydropyridine antagonist binding site. The binding of [3H]BAY K 8644 to a low affinity binding site was modified by temperature, Ca++ and diltiazem, but the lack of stereoselectivity, lack of denaturation by heat and the large number of sites indicated that most of the low affinity binding sites were not associated with Ca++ channels. It is concluded that the high affinity binding site for BAY K 8644 is associated with Ca++ channels, and is modified by at least some of the factors that modify the binding site for Ca++ channel antagonists, whereas many or all of the low affinity binding sites detected are not related to Ca++ channels.     

Immune monitoring of anti cytomegalovirus antibodies and risk of cytomegalovirus disease in heart transplantation

We sought to determine whether quantitative assessment of anti-cytomegalovirus (CMV) antibodies could be useful to identify patients at risk of cytomegalovirus (CMV) disease after heart transplantation (HT). 75 patients who underwent HT at a single health care center were prospectively studied. Induction therapy included 2 doses of daclizumab and maintenance tacrolimus (n=42) or cyclosporine (n=29), mycophenolate mofetil and prednisone. All patients received prophylaxis with gancyclovir or valganciclovir. Anti-CMV intravenous immunoglobulin (CMV-IG) was added in high risk patients (CMV D+/R- serostatus). Serial determinations of anti-CMV antibodies, immunoglobulins (IgG, IgA, IgM) and IgG-subclasses were analysed. CMV infection was based on detection of the virus by antigenemia. CMV disease consisted of detection of signs or symptoms attributable to this microorganism. Ten patients (13.3%) developed CMV disease. Mean time of development of CMV disease was 3.4+/-1.6 months. In Cox regression analysis, patients with low baseline anti-CMV titers (<4.26 natural logarithm of titer, RH: 8.1, 95%CI: 1.93-34.1, p=0.004) and recipients with 1-month post-HT IgG hypogammaglobulinemia (IgG<500 mg/dl, RH: 4.49, 95%CI: 1.26-15.94, p=0.02) were at higher risk of having CMV disease. Despite use of prophylactic CMV-IG, D+/R- patients showed significantly lower titers of anti-CMV antibodies at 7 d, 30 d and 90 d post HT as compared with HT recipients without infections. Four out of 6 of these patients developed late CMV disease. Monitoring of specific anti-CMV antibodies on the bedside warrants further evaluation as a potential tool to identify heart transplant recipients at higher risk of CMV disease.     

Hypocomplementemia in the absence of autoantibodies in women with recurrent pregnancy loss

BackgroundAccumulating data suggest an immunopathogenic role for the complement system as a causative element in pregnancy loss (PL). Formation of pathogenic antibodies with activation of the classical pathway may have a role, but this mechanism fails to characterize the majority of cases with recurrent PL. We established the prevalence of hypocomplementemia without circulating autoantibodies in women with recurrent PL.MethodsIn a retrospective case control study, 201 women with recurrent PL (two or more PL) and 30 healthy women who had normal pregnancies but no PL were studied. Serum levels of C3, C4, and factor B were determined by nephelometry. Total hemolytic activity of the complement system (CH100) was investigated by radial immunodiffusion test.ResultsThe prevalence of hypocomplementemia [low levels of C3, C4, FB or CH100 (with normal concentrations of C3, C4 and FB)] was significantly higher in women with recurrent PL (22,4 %) in comparison with controls (6.6 %; p = 0.019). C3, C4, FB hypocomplementemia or low CH100 were observed in 13 (6,5 %), 19 (9,4 %), 13 (6.5 %) and 7 (3,5 %) women with recurrent PL, respectively. Among patients with C3, C4, FB or CH100 hypocomplementemia, 10, 18, 12 and 5 patients had no circulating autoantibodies [antinuclear antibodies, anticardiolipin antibodies or antithyroid antibodies], respectively. In all, hypocomplementemia, in the absence of autoantibodies, was observed in 38 (18,9 %) women with recurrent PL in a significantly higher frequency than controls (n = 2, p = 0.049).ConclusionsHypocomplementemia, in the absence of autoantibodies was observed in a group of women with recurrent PL which might suggest a role of the complement system in the pathogenesis of PL in these patients.