Multiple granular cell tumors are an associated feature of LEOPARD syndrome caused by mutation in PTPN11

We report a patient with a clinical and molecular diagnosis of LEOPARD syndrome (LS) associated with multiple granular cell tumors (MGCT). Bidirectional sequencing of exons 7, 12, and 13 of the PTPN11 gene revealed the T468M missense mutation in exon 12. This mutation has been previously reported in patients with LS. To our knowledge, this is the first report of MGCT associated with molecularly characterized LS and provides the first molecular evidence linking granular cell tumors (GCT) to the Ras/mitogen-activated protein (MAP) kinase pathway. We propose that MGCT can be associated with LS. Analysis of GCT from this case tested negatively for loss of heterozygosity (LOH) at the PTPN11 and NF1 loci and did not show deletions of the PTEN gene. The absence of LOH of PTPN11 supports published functional data that T468M is a dominant-negative mutation.     

Evaluation of pain experienced during breast ductal endoscopy

PURPOSE: Ductal endoscopy is valuable for the differential diagnosis of bloody nipple discharge; however, the pain associated with this procedure has not been evaluated. This study aims to assess the pain experienced by patients during ductal endoscopy. METHODS: We studied a consecutive series of women who underwent ductal endoscopy, to investigate the cause of bloody nipple discharge. The procedure was performed using standard local anesthesia (lidocaine 1% 10 ml without epinephrine, involving nipple block and periaureolar administration). Patients were asked to score the level of pain with a visual analog scale, 1, 4, 7, 12, 17, 22, 27, and 32 min after the procedure, and describe their overall and maximum pain. RESULTS: This series comprised 20 women aged from 27 to 68 years old. The overall pain (mean +/- SE) score was equal to 5.8 +/-0.3, and the maximum pain score was 8.3 +/- 0.2. The peak of pain corresponded with when the dilator was inserted through the sphincter. The group in which the dilator was inserted after 4 min experienced more intense maximum and overall pain after 7, 12, 17 and 22 min. CONCLUSIONS: Pain is an important factor in ductal endoscopy, and peaks relatively early. A standard, baseline local lidocaine dose of greater than 10 ml may be necessary at the beginning of the procedure. Late insertion of the dilator seems to be an indicator of the force of the procedure.     

MHB4 Comparison of Standard Gamble, Time Trade-Off, and Visual Analog Scale Scores for Hypothetical Stroke Health States Using a Computer-Based Program

The most frequently used techniques for conducting utility assessments are the Standard Gamble (SG), the Time Trade-Off (TTO), and the Visual Analog Scale (VAS).
OBJECTIVES: The objectives of this study were to compare scores obtained on the SG, TTO, and VAS for hypothetical stroke health states; to determine the effect of age and gender on utility scores; to identify any ceiling or floor effects, and to determine the presence of interviewer effects.
METHODS: Forty-nine PharmD students from the College of Pharmacy at the University of Iowa were selected as the sample, and utility assessments were conducted by two interviewers, for hypothetical stroke scenarios adapted from the Glasgow Outcomes Sale. The health states evaluated were Good Recovery, Moderate Disability, Severe Disability, and a Vegetative State. Two rounds of interviews were separated by a period of 4 months. Regresion analysis was used to identify the factors influencing utility scores.
RESULTS: Mean SG scores for the four health states were 82.2, 62.7, 26.3, and 3.3, respectively. TTO scores for the four health states were 79.9, 57.3, 24.6, and 2.9, respectively. However, VAS scores were found to be higher than both TTO and SG scores. Neither age nor gender were found to be statistically significant determinants of reported utility scores. Interviewer effects were found for one out of 12 assessments in round 1, while none were observed in round 2. Floor effects were observed for all three techniques for the vegetative state.
CONCLUSION: Further research using larger, more representative samples from the general population is required to establish the validity of computer-based programs for utility assessments.     

Multiple symptoms in patients with chronic obstructive pulmonary disease in Norway

This paper examines the prevalence of multiple symptoms and the relationships between future expectations and multiple symptoms in a cross‐sectional study of 100 patients with chronic obstructive pulmonary disease. A questionnaire was used to examine the patients’ symptoms of breathlessness, anxiety, depression, sleeplessness, fatigue, and pain, and their outlook for the future. All patients reported breathlessness, 64% anxiety, 69% depression, 28% sleeplessness, 72% fatigue, and 45% pain. Those with anxiety reported significant depression (P < 0.001), and those with fatigue reported significant depression (P = 0.004). Patients who reported pain also reported significant sleeplessness (P = 0.022). A negative outlook for the future was reported by 42% of patients who also reported significantly more anxiety, depression, sleeplessness, fatigue, and pain (P ≤ 0.049). Multiple symptoms are common in chronic obstructive pulmonary disease, and patients with a pessimistic view of the future reported more symptoms. Those with multiple symptoms and a negative outlook toward the future may benefit from interventions to help them achieve a more positive outlook for the future, which may relieve symptom burden.     

Assessment of the steady-state pharmacokinetic interaction between etravirine administered as two different formulations and tenofovir disoproxil fumarate in healthy volunteers

Objective

Two open‐label, randomized, cross‐over trials in healthy volunteers were conducted to investigate the pharmacokinetic interaction between etravirine and tenofovir disoproxil fumarate.

Methods

Etravirine was administered as either 800 mg twice a day (bid) (phase II formulation in Study 1) or 200 mg bid (phase III formulation in Study 2) for 8 days followed by a 12 h pharmacokinetic evaluation. After a minimum of 14 days washout, tenofovir disoproxil fumarate 300 mg once a day was administered for 16 days. Volunteers were randomized to receive co‐administration of etravirine with tenofovir disoproxil fumarate on either days 1–8 or days 9–16 followed by a 12 h pharmacokinetic evaluation for etravirine on day 8 or 16, respectively. Plasma and urine tenofovir concentrations were determined on days 8 and 16 over 24 h.

Results

The least square mean (LSM) ratio [90% confidence interval (CI)] for the area under the plasma concentration–time curve from 0 to 12 h (AUC_{12 h}) for etravirine co‐administered with tenofovir disoproxil fumarate vs. etravirine alone was 0.69 (0.61–0.79) and 0.81 (0.75–0.88) in Studies 1 and 2, respectively. The LSM ratio (90% CI) for the effect of etravirine on tenofovir AUC_{24 h} was 1.16 (1.09–1.23) in Study 1 and 1.15 (1.09–1.21) in Study 2.

Conclusions

These alterations are not considered clinically relevant for either drug and no dose adjustment is necessary when etravirine and tenofovir disoproxil fumarate are co‐administered.