Morphological changes in spiral ganglion cells after intracochlear application of brain-derived neurotrophic factor in deafened guinea pigs

When guinea pigs are deafened with ototoxic drugs spiral ganglion cells (SGCs) degenerate progressively. Application of neurotrophins can prevent this process. Morphological changes of rescued SGCs have not been quantitatively determined yet. It might be that SGCs treated with neurotrophins are more vulnerable than SGCs in cochleae of normal-hearing guinea pigs. Therefore, the mitochondria and myelinisation of type-I SGCs were studied and the perikaryal area, cell circularity and electron density were determined. Guinea pigs were deafened with a subcutaneous injection of kanamycin followed by intravenous infusion of furosemide. Brain-derived neurotrophic factor (BDNF) delivery was started two weeks after the deafening procedure and continued for four weeks. Four cohorts of cochleae were studied: (1) cochleae of normal-hearing guinea pigs; (2) of guinea pigs two weeks after deafening; (3) six weeks after deafening; (4) cochleae treated with BDNF after deafening. The deafening procedure resulted in a progressive loss of SGCs. Six weeks after deafening the size of mitochondria, perikaryal area and cell circularity of the remaining untreated SGCs were decreased and the number of layers of the myelin sheath was reduced. In the basal part of the cochlea BDNF treatment rescued SGCs from degeneration. SGCs treated with BDNF were larger than SGCs in normal-hearing guinea pigs, whereas circularity had normal values and electron density was unchanged. The number of layers in the myelin sheath of BDNF-treated SGCs was reduced as compared to the number of layers in the myelin sheath of SGCs in normal-hearing guinea pigs. The morphological changes of SGCs might be related to the rapid loss of SGCs that has been reported to occur after cessation of BDNF treatment.     

Utility of fluorodeoxyglucose-PET in patients with differentiated thyroid carcinoma

AIM: In differentiated thyroid carcinoma, persistent plasma thyroglobulin (Tg) is a specific marker for persistent or recurrent disease after thyroidectomy and radioiodine ablation. When Tg remains elevated and no substrate can be found on whole-body radioiodine imaging (131I-WBS), or even when recurrent disease is suspected with normal Tg, conventional imaging (CI) is often insufficient. As fluorodeoxyglucose (FDG)-PET has proven to be an effective modality for detecting various types of cancer, the utility of FDG-PET was analysed and compared with CI in this retrospective study in patients with differentiated thyroid cancer. PATIENTS AND METHODS: After total thyroidectomy and radioiodine ablation, 68 FDG-PET scans were performed in 39 patients with elevated Tg levels or clinical suspicion of recurrent disease. At the time of FDG-PET, 54 131I-WBS (in 30 patients) were negative, 14 (in 11 patients) were equivocal. Tg was normal at the time of 14 scans (10 patients) and elevated in 54 (in 33 patients). FDG-PET results were compared with histology, 131I-WBS and CI and clinical follow-up. Sensitivity and specificity were evaluated in various subgroups. RESULTS: Overall, there were 35 true-positive, two false-positive, 20 true-negative and three false-negative FDG-PET scans. In six of these cases (one true positive, five true negative) FDG-PET was repeated without intervention and in an additional eight FDG-PET scans no definite conformation of abnormal FDG-PET could be obtained, so these results were not used for statistical analysis. Sensitivity, specificity, PPV and NPV for the whole group were 92, 88, 94 and 83%, respectively. In 38 scans performed on 31 patients with elevated Tg levels, who were not known with recurrence, this was 84, 100, 100 and 75%, respectively. In 16 scans in 10 patients with known recurrence (all with elevated Tg), sensitivity and PPV were 100% without false-positive or false-negative results. When Tg was not detectable (14 scans in 10 patients), sensitivity, specificity, PPV and NPV were 100, 75, 60 and 100%, respectively. After 35 FDG-PET scans (51%), there was a change in patient management by avoiding ineffective 131I treatment, by guiding surgical reintervention, or avoiding futile surgery. One FP FDG-PET resulted in an unnecessary surgical procedure. In 33 cases, FDG-PET did not lead to a change in treatment policy, which retrospectively would have been beneficial in six cases. CONCLUSION: FDG-PET affected patient management in patients with differentiated thyroid cancer and negative 131I-WBS, not only when Tg is elevated, but also when Tg is not detectable and therefore the use of FDG-PET as a diagnostic tool is justified in these patients.     

Relationship between habitual refractive errors and headache complaints in schoolchildren.

PURPOSE: Refractive error (RE) is considered to be a possible cause for headaches. We aimed to gain insight into the relation between habitual RE (sphere and astigmatism) and headache complaints. METHODS: In a cross-sectional study the habitual refractive state of 487 children, aged between 11 and 13 years, was measured using an autorefractometer (Topcon, RM-8000B). Headache complaints were measured using a questionnaire. Data were analyzed using Pearson correlation coefficients, bivariate analysis, and multiple logistic regression analysis. RESULTS: For right eyes we found 15% habitual myopia < -0.50 D and 12% habitual hyperopia > +0.50 D; habitual astigmatism > 0.25 D was found in 33% of children. Pearson R between right and left eyes was 0.76 for the spherical component and 0.42 for the cylindrical. In the total group of children 70% reported the occurrence of headache in the last year. These headaches were reported as "often or frequent" by 37% of children, "severe" by 15%, "with long duration" by 45%, and "with severe burden" by 27%. In the total sample we found various associations between gender, sphere/cylinder components of habitual RE, and headache complaints. Headache was reported more in girls than in boys. Of the total variance of headache complaints in girls, the sphere component of habitual RE explained 4% of frequency, 6% of intensity, 2% of duration, and 2% of amount of burden. Of the total variance of headache complaints in boys the cylinder component of habitual RE explained 3% of frequency, and 4% in amount of burden. CONCLUSION: Habitual RE and headache complaints are relatively common conditions in schoolchildren aged between 11 and 13 years. Headache complaints showed a small but statistically significant association with the sphere component of habitual RE in girls and the cylinder component of habitual RE in boys. The associations found between habitual RE and headache complaints indicate that habitual RE might be a risk factor for headache in children.     

Costs and effects of secondary prevention with perindopril in stable coronary heart disease in Poland: an analysis of the EUROPA study including 1251 Polish patients

OBJECTIVES: To estimate the long-term impact of treatment with perindopril on costs and health effects in patients with stable coronary artery disease in Poland. METHODS: The cost-effectiveness analysis was based on data from a randomized double-blind, placebo-controlled trial. A decision-tree analysis was employed, including Monte Carlo and bootstrapping techniques. This study was a sub-study of the EUROPA (European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease) trial (n = 12 218; mean follow-up 4.2 years). Resource use was based on data from Polish EUROPA study patients (n = 1251), while effectiveness was based on the whole EUROPA study. The health gain of perindopril in life-years was based on overall EUROPA study results, and the adapted Polish life expectancy of patients not dying during the trial. Costs were calculated in new Polish zloty (PLN), year 2003 values; euro1 = PLN4.053. Only direct healthcare costs related to cardiovascular events and medication use were studied. RESULTS: When observed mortality was combined with life expectancy beyond the end of the study, perindopril use showed a gain in life expectancy of 0.182 life-years (SD +/- 0.129) at a cost of PLN1983 (SD +/- 103) with discounting of 5% per annum on costs and no discounting on effects. This resulted in an incremental cost-effectiveness ratio (ICER) of PLN10 896 per life-year gained. The probability that the ICER for perindopril was below the threshold of PLN60 000 was 88%. The overall results were insensitive to discount rates for costs and life-years. CONCLUSIONS: Perindopril leads to a reduction in the risk of coronary events among patients with stable heart disease. When the expected improvement in life expectancy is combined with associated medical costs, there is a high probability that perindopril is cost effective, given the threshold of PLN60 000 per life-year gained.     

Feasibility of withholding antibiotics in selected febrile neutropenic cancer patients.

PURPOSE: To investigate the feasibility of withholding antibiotics and early discharge for patients with chemotherapy-induced neutropenia and fever at low risk of bacterial infection by a new risk assessment model. PATIENTS AND METHODS: Outpatients with febrile neutropenia were allocated to one of three groups by a risk assessment model combining objective clinical parameters and plasma interleukin 8 level. Patients with signs of a bacterial infection and/or abnormal vital signs indicating sepsis were considered high risk. Based on their interleukin-8 level, remaining patients were allocated to low or medium risk for bacterial infection. Medium-risk and high-risk patients received standard antibiotic therapy, whereas low-risk patients did not receive antibiotics and were discharged from hospital after 12 hours of a febrile observation. End points were the feasibility of the treatment protocol. RESULTS: Of 196 assessable episodes, 76 (39%) were classified as high risk, 84 (43%) as medium risk, and 36 (18%) as low risk. There were no treatment failures in the low-risk group (95% CI, 0% to 10%). Therefore, sensitivity of our risk assessment model was 100% (95% CI, 90% to 100%), the specificity, positive, and negative predictive values were 21%, 13%, and 100%, respectively. Median duration of hospitalization was 3 days in the low-risk group versus 7 days in the medium- and high-risk groups (P < .0001). The incremental costs of the experimental treatment protocol amounted to a saving of 471 (US $572) for every potentially low-risk patient. CONCLUSION: This risk assessment model appears to identify febrile neutropenic patients at low risk for bacterial infection. Antibiotics can be withheld in well-defined neutropenic patients with fever.     

A randomized trial comparing omega-3 fatty acid plasma levels after ingestion of emulsified and non-emulsified cod liver oil formulations

Objectives: Emulsified formulations of omega-3 fatty acids may increase plasma concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) compared with non-emulsified formulations. The current study evaluated plasma concentrations of DHA?+?EPA as well as DHA and EPA individually following administration of emulsified vs non-emulsified cod liver oil formulations.

Methods: In this randomized, 2-period, crossover study (ClinicalTrials.gov NCT02428699), 47 healthy adults received single doses of an emulsified cod liver oil formulation and a non-emulsified cod liver oil formulation, each containing 10% cod liver oil plus 10% cod oil and closely matched DHA and EPA content. Blood samples were collected for 24?h after dosing to analyze DHA and EPA plasma concentrations using a validated methodology. DHA?+?EPA, DHA, and EPA pharmacokinetics were compared using an analysis of covariance model. The incremental area under the plasma concentration curve at 24?h (iAUC_0–24?h) for DHA?+?EPA was the primary endpoint.

Results: DHA?+?EPA, DHA, and EPA plasma concentrations reached higher levels in plasma following administration of the emulsified vs non-emulsified formulation. The emulsified cod liver oil formulation produced iAUC_0–24?h values for DHA?+?EPA, DHA, and EPA that were 1.66, 1.78, and 1.64 times higher, respectively, than the non-emulsified formulation; iAUC_0–10?h values were 1.84, 1.96, and 1.79 times higher, respectively (all p?<?0.01). Maximum concentrations of DHA?+?EPA, DHA, and EPA in plasma were significantly higher for the emulsified than the non-emulsified formulation (p?<?0.001).

Conclusions: DHA?+?EPA, DHA, and EPA plasma concentrations were significantly higher for the emulsified cod liver oil supplement vs the reference non-emulsified cod liver oil supplement.