Elimination and penetration of amikacin into urine in patients with decreased glomerular filtration rate.

Background: Amikacin monotherapy is recommended for urinary tract infection (UTI) treatment with multi-resistant pathogens. Even though amikacin efficacy in the treatment of UTIs is dependent on its urinary concentration, there are no robust data proving that sufficiently high urinary concentration is reached in patients with reduced glomerular filtration rate (GFR). Methods: A prospective study to monitor amikacin penetration into urine of 70 patients [40 males, median (interquartile range) age 70 (65-79) years] with different levels of glomerular filtration decline, including patients treated by dialysis, was conducted. The bactericidal efficacy of amikacin in urine samples has been evaluated. Results: Patients with estimated GFR (eGFR) <30 mL/min had significantly lower median amikacin urinary concentration than patients with eGFR >30 mL/min (89.75 vs 186.0 mg/L, P < .0001; 200.5 vs 830.0 mg/L, P < .0001; and 126.0 vs 408.0 mg/L, P < .0001 for minimal, maximal and minimal together with maximal concentrations, respectively). The amount of amikacin eliminated in the first 10-13 h after dose administration was dependent on eGFR (r2 = 0.6144, P < .0001). The urinary concentration of amikacin in patients treated by dialysis was indirectly proportional to pH of urine. The plasma concentrations of amikacin did not correlate with urinary levels in patients in either of the GFR categories. Microbiological evaluation showed that the critical urinary concentration for efficacy of amikacin during UTI monotherapy in patients treated by dialysis is 100 mg/L. We found that 4 out of 11 patients treated by dialysis did not reach this level during the treatment. Conclusion: Systemic administration of amikacin monotherapy in patients treated by dialysis is questionable as the concentrations of amikacin in their urine are often below the threshold of effectivity. Amikacin plasma concentrations are not a major determinant of amikacin concentration in urine, therefore pulse dosing is neither necessary nor safe in patients treated by dialysis, and may cause undesirable toxicity.

Dissociative symptoms reflect levels of tumor necrosis factor alpha in patients with unipolar depression.

Recent evidence indicates that the nature of interactions between the nervous system and immune system is important in the pathogenesis of depression. Specifically, alterations in pro-inflammatory cytokines have been related to the development of several psychological and neurobiological manifestations of depressive disorder, as well as to stress exposure. A number of findings point to tumor necrosis factor alpha (TNF-α) as one of the central factors in these processes. Accordingly, in the present study, we test the hypothesis that specific influences of chronic stressors related to traumatic stress and dissociation are related to alterations in TNF-α levels. We performed psychometric measurement of depression (Beck Depression Inventory [BDI]-II), traumatic stress symptoms (Trauma Symptom Checklist [TSC]-40), and psychological and somatoform dissociation (Dissociative Experiences Scale [DES] and Somatoform Dissociation Questionnaire [SDQ]-20, respectively), and immunochemical measure of serum TNF-α in 66 inpatients with unipolar depression (mean age 43.1 ± 7.3 years). The results show that TNF-α is significantly related to DES (Spearman R=-0.42, P<0.01), SDQ-20 (Spearman R=-0.38, P<0.01), and TSC-40 (Spearman R=-0.41, P<0.01), but not to BDI-II. Results of the present study suggest that TNF-α levels are related to dissociative symptoms and stress exposure in depressed patients.

Increased uric acid and glucose concentrations in vitreous and serum of patients with diabetic macular oedema.

BACKGROUND: Diabetic retinopathy (DR) is characterized by blood-retina barrier breakdown induced by local changes in the retina and systemic factors. We investigated vitreous and serum levels of glucose and uric acid (UA) in patients with DR and aimed to describe their correlation with the grade of DR. METHODS: Prospective study of 81 patients with DR and 48 non-diabetic controls. Biochemical analysis of vitreous and serum samples was performed. RESULTS: UA and glucose concentrations in vitreous and serum were significantly higher in diabetic patients than in controls. Absolute ratios (vitreous level/serum level) of UA and glucose were higher in proliferative compared with non-proliferative DR. CONCLUSIONS: The results suggest that, apart from glucose, increased levels of UA in diabetic patients may also be involved in the pathogenesis and progression of DR.

Interlaboratory study of free monoclonal immunoglobulin light chain quantification.

BACKGROUND: Quantification of monoclonal immunoglobulin free light chains (FLCs) in serum is used increasingly in clinical practice for the diagnosis, prognostic assessment, and treatment monitoring of monoclonal gammopathies. It is used as an adjunct to standard serum protein electrophoresis and immunofixation. However, methods for FLC quantification need further standardization and validation. METHODS: The Czech Myeloma Group and the Czech Society of Clinical Biochemistry have initiated an interlaboratory study where six laboratories collaborating with the primary myeloma treatment centres measured FLC concentrations in 12 serum samples from patients with monoclonal gammopathies. RESULTS: Repeatability of the measurements in five laboratories was calculated based on differences between the results of duplicate measurements. We found that repeatability depended more on the laboratory than on the device used for measurement. CONCLUSIONS: The study revealed several weak points in the methodology, including the need for a uniform sample dilution procedure. Interlaboratory reproducibility was comparable with values achieved in the NEQAS programme. Because the κ/λ ratio cannot be measured with high precision, κ and λ FLC concentrations should be used where possible. Due to its impact on the clinical management of patients with gammopathy, FLC quantification needs to become a part of the regular quality control cycle in myeloma centres.

Depression, traumatic stress and interleukin-6.

BACKGROUND: Recent evidence indicates that various types of interactions between nervous and immune system are important in pathogenesis of depression. These findings show that a significant role in developing depression play pro-inflammatory cytokines that may mediate its psychological, and neurobiological manifestations. Great importance among these cytokine molecules plays interleukin-6 (IL-6). There is growing evidence that this inflammatory process related to depression may be influenced by psychological stress as well as organic inflammatory conditions. These findings suggest that specific influences related to traumatic stress and dissociation could be found in close relationship to increased level of cytokine IL-6. METHODS: In the present study we have performed psychometric measurement of depression (BDI-II), traumatic stress symptoms (TSC-40) and dissociation (DES, SDQ-20), and immunochemical measure of serum IL-6 in 40 inpatients with unipolar depression (mean age 42.3+/-6.8). RESULTS: The results show that IL-6 is significantly correlated to BDI-II (Spearman R=0.47, p<0.01), TSC-40 (Spearman R=0.32, p<0.05), SDQ-20 (Spearman R=0.34, p<0.05) but not to DES (Spearman R=0.25, p=0.11). CONCLUSION: The findings of the present study indicate that increased level of IL-6 in depression could be directly related to symptoms of traumatic stress and somatoform dissociation.

Asbestos exposure and antineutrophil cytoplasmic Antibody (ANCA) positivity.

The authors used indirect immunofluorescence to examine the association of antineutrophil cytoplasmic antibodies (ANCAs) with exposure to asbestos among 61 asbestos-exposed patients (mean exposure = 24.6 yr) and 39 nonexposed controls. ANCA positivity was detected significantly more frequently (p = 0.034) in the asbestos-exposed group (21.3%) than in the control group (5.1%). ANCA-associated diseases did not occur more frequently among subjects exposed previously to asbestos than among unexposed controls. These findings confirmed that exposure to asbestos is another occupational factor, as is silica exposure, that is associated with ANCA positivity. The influence of asbestos appears stronger than that of silica because ANCA positivity was found among subjects who had histories of exposure to asbestos but who did not exhibit typical radiographic signs of asbestosis on their chest x-rays. Additional stimuli may be necessary to induce systemic vasculitis in asbestos-exposed persons.