Assessment of ocular neurotoxicity in patients treated with systemic cancer chemotherapeutics

Purpose: Cisplatin and Paclitaxel are two chemotherapeutic agents known to produce neurotoxicity when used for cumulative dose regimens. In this study we aim to assess their toxicity in the optic nerve, and to evaluate the retinal nerve fibre layer (RNFL) thickness and visual field changes in lung cancer patients treated with Cisplatin and Paclitaxel.

Methods: Fifteen patients who were treated intravenously with 75?mg/m² cisplatin and 175?mg/m² paclitaxel every 3 weeks, up to a maximum of six courses, were enrolled in this prospective clinical trial. All patients underwent complete ophthalmological assessments before their treatments began, as well as three months after the completion of their treatments. The RNFL thickness measurements were performed using optical coherence tomography (OCT). Functional testing included the use of frequency-doubling technology (FDT) perimetry and the Humphrey visual field analyser (HFA). The main outcome measurements included the average RNFL thicknesses and visual field indices (mean deviation [MD] and pattern standard deviation [PSD]).

Results: The median age of the 15 patients (nine male and six female) was 63.49 years old (range: 53–77). The average RNFL thickness measurement during the baseline examination was 103.73?μm (range: 97–111). Three months after the cessation of treatment the RNFL thickness declined to 97.4?μm (range: 91–102). Statistical analysis showed a significant thinning between the two measurements (p?=?0.032). The MD and PSD values recorded by the HFA demonstrated no statistically significant changes 3 months after the cessation of treatment (p?>?0.207 and p?>?0.186, respectively). There were statistically significant decreases in both the MD (0.48 to ?1.13?dB) and PSD (2.13 to 0.65?dB) indices measured by the FDT perimetry (p?=?0.041 and p?=?0.025, respectively).

Conclusions: In our study, the systemic administration of Cisplatin and Paclitaxel affected the peripapillary RNFL thicknesses and visual field indices as revealed by FDT perimetry. OCT and FDT perimetry may be adjunctive tools for the screening of ocular toxicity in patients treated with these agents.     

In vitro functional interactions of acetylcholine esterase inhibitors and muscarinic receptor antagonists in the urinary bladder of the rat

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High tea and vegetable consumption is associated with low ADMA generation in older healthy subjects

Asymmetric dimethylarginine (ADMA) has been recognized as a marker of cardiovascular risk. We sought to investigate whether consumption of tea, coffee, fruit or vegetables is associated with ADMA. In 148 consecutive apparently healthy subjects (104 men and 44 women aged 40 to 70), daily tea, coffee, fruit and vegetable consumption was ascertained by questionnaire. Plasma ADMA, symmetric dimethylarginine (SDMA), and l-arginine levels were measured by high-performance liquid chromatography. Median tea and coffee consumption was 2 cups/d, while vegetable and fruit intake was 152 (120-179)g/d and 120 (108-134)g/d, respectively. Median plasma ADMA, SDMA and arginine were 0.47 (0.43-0.53)μmol/L, 0.59 (0.54-0.66)μmol/L and 86 (68-101)μmol/L, respectively. ADMA correlated inversely with tea (r = -0.70, P < .0001) and vegetable consumption (r = -0.50, P < .0001) even after adjustment for age, sex, body mass index, smoking status, and potential dietary and biochemical parameters. No association between ADMA and fruit consumption was found. ADMA correlated positively with coffee intake (r = 0.37, P < .0001), although these associations were less potent after adjustment for dietary factors. Higher tea and vegetable intake is associated with lower plasma ADMA levels in healthy middle-aged subjects.     

Seven years of external control of fluoride levels in the public water supply in Bauru,S?o Paulo,Brazil

Fluoridation of the public water supplies is recognized as among the top ten public health achievements of the twentieth century. However, the positive aspects of this measure depend on the maintenance of fluoride concentrations within adequate levels.

Objective:

To report the results of seven years of external control of the fluoride (F) concentrations in the public water supply in Bauru, SP, Brazil in an attempt to verify, on the basis of risk/benefit balance, whether the levels are appropriate.

Material and Methods:

From March 2004 to February 2011, 60 samples were collected every month from the 19 supply sectors of the city, totaling 4,641 samples. F concentrations in water samples were determined in duplicate, using an ion-specific electrode (Orion 9609) coupled to a potentiometer after buffering with TISAB II. After the analysis, the samples were classified according to the best risk-benefit adjustment.

Results:

Means (±standard deviation) of F concentrations ranged between 0.73±0.06 and 0.81±0.10 mg/L for the different sectors during the seven years. The individual values ranged between 0.03 and 2.63 mg/L. The percentages of the samples considered "low risk" for dental fluorosis development and of "maximum benefit" for dental caries prevention (0.55-0.84 mg F/L) in the first, second, third, fourth, fifth, sixth, and seventh years of the study were 82.0, 58.5, 37.4, 61.0, 89.9, 77.3, and 72.4%, respectively, and 69.0% for the entire period.

Conclusions:

Fluctuations of F levels were found in the public water supply in Bauru during the seven years of evaluation. These results suggest that external monitoring of water fluoridation by an independent assessor should be implemented in cities where there is adjusted fluoridation. This measure should be continued in order to verify that fluoride levels are suitable and, if not, to provide support for the appropriate adjustments.     

Renal transplantation in patients with familial Mediterranean fever

Amyloidosis is the most common and devastating complication of familial Mediterranean fever (FMF). Renal transplantation is the choice of treatment of in most end-stage renal disease (ESRD). We report our experience on the outcomes in eight patients who underwent renal transplantation for ESRD due to FMF secondary to amyloidosis, and we provide a discussion on the current evidence on this topic of study. The clinical charts of eight renal transplant patients (seven male, one female) who underwent ESRD due to FMF-related amyloidosis were investigated. Five patients underwent living-donor renal transplantation and three patients underwent deceased-donor renal transplant. The mean follow-up period was 35 months (range 3-72). All patients were on triple immunosuppressive treatment and received colchicine. All allografts are currently functioning well with a mean serum creatinine level of 1.4 (range 0.7-2.6) mg/dL. Posttransplantation complications included acute rejection (n = 4), chronic rejection (n = 1), severe gastroenteritis (n = 2), and erythrocytosis (n = 5). None of the patients had proteinuria. During follow-up, we did not observe clinically severe FMF attack, septicemia, rhabdomylosis, symptoms related to vasculitis, and clinical neuropathy. The clinical outcome of the patients in this cohort was similar to that of other renal transplant patients with ESRD due to other causes. This study shows favorable prognosis of eight ESRD patients due to amyloidosis caused by FMF after renal transplantation. Renal transplantation is a safe procedure for ESRD patients having amyloidosis due to FMF. Regular use of colchicine after transplantation should be mentioned.     

Randomized trial of a comparison of the efficacy of TVT-O and single-incision tape TVT SECUR systems in the treatment of stress urinary incontinent women—2-year follow-up

Introduction and hypothesis

The aim of this study was to compare the efficacy of the use of tension-free vaginal tape obturator (TVT-O) and single-incision TVT SECUR, hammock and U approach (TVT-S, H and U), in the treatment of urodynamic stress urinary incontinence (SUI).

Methods

This single-center randomized three-arm trial compared the objective and subjective efficacy and early failure rate of the TVT-O and TVT-S H and U approach by objective criteria (cough test) and subjective criteria using the International Consultation on Incontinence Questionnaire—Short Form (ICIQ-UI SF). The objective efficacy rate was defined as the number of patients with a negative cough stress test. Subjective cure was defined by no stress leakage of urine after surgery based on the evaluation of ICIQ-UI SH (when patients ticked “Never”/“Urine does not leak” in answer to question 6: When does urine leak?). Objective and subjective efficacy were evaluated using Last Failure Carried Forward analysis, i.e., final analysis also included patients with early failure. To describe outcome at different time points, the Last Observation Carried Forward method was also implemented.

Results

One hundred ninety-seven women with proven SUI were randomized into three groups—TVT-O (n?=?68), TVT-S H (n?=?64), and TVT-S U (n?=?65). Each patient allocated to a treatment group received the planned surgery. There were no differences in each group in preoperative characteristics. Median follow-up after surgery was 2?years (SD, 0.8; range, 0.1 to 3.8?years). Of the subjects, 92.6% in the TVT-O group, 68.8% in the TVT-S H group, and 69.2% in the TVT-S U group had negative stress test (p?<?0.001). Of the subjects, 85.3 % in the TVT-O group, 68.8% in the TVT-S H group, and 61.5% in the TVT-S U group were subjectively continent (p?=?0.02).

Conclusions

Our study demonstrated a significantly lower subjective and objective cure rate in the single-incision TVT group compared to the TVT-O group.     

A Peripheral Blood Diagnostic Test for Acute Rejection in Renal Transplantation

Monitoring of renal graft status through peripheral blood (PB) rather than invasive biopsy is important as it will lessen the risk of infection and other stresses, while reducing the costs of rejection diagnosis. Blood gene biomarker panels were discovered by microarrays at a single center and subsequently validated and cross‐validated by QPCR in the NIH SNSO1 randomized study from 12 US pediatric transplant programs. A total of 367 unique human PB samples, each paired with a graft biopsy for centralized, blinded phenotype classification, were analyzed (115 acute rejection (AR), 180 stable and 72 other causes of graft injury). Of the differentially expressed genes by microarray, Q‐PCR analysis of a five gene‐set (DUSP1, PBEF1, PSEN1, MAPK9 and NKTR) classified AR with high accuracy. A logistic regression model was built on independent training‐set (n = 47) and validated on independent test‐set (n = 198)samples, discriminating AR from STA with 91% sensitivity and 94% specificity and AR from all other non‐AR phenotypes with 91% sensitivity and 90% specificity. The 5‐gene set can diagnose AR potentially avoiding the need for invasive renal biopsy. These data support the conduct of a prospective study to validate the clinical predictive utility of this diagnostic tool.