Vasoactive effects of stable aqueous suspensions of single walled carbon nanotubes in hamsters and mice

Single-walled carbon nanotubes synthesized with iron (Fe-SWCNT) or gadolinium (Gd-SWCNT) show promise as high performance multimodal contrast and drug-delivery agents. Our purpose was to evaluate potential vasoactive effects of SWCNT. Stable aqueous solutions of Fe-SWCNTs or Gd-SWCNTs were made using the biocompatible amphiphilic polymer N-(carbonyl-methoxypolyethyleneglycol 2000)-1,2-distearoylsn-glycero-3- phosphoethanolamine (PEG-DSPE). Both aggregated and non-aggregated (sonicated) formulations were tested. The initial vasoactivity of the formulations and their potential for inducing pro-inflammatory endothelial dysfunction were investigated in the hamster cheek pouch and murine cremaster muscle intravital microscopy models. These models provide an assay to test several formulations/dosages in a paired fashion. Abluminal exposure to small arterioles exposes both endothelial and vascular smooth muscle cells. Using abluminal exposures of dosages that would approximate the first pass of an i.v. bolus injection, both Fe-SWCNTs and Gd-SWCNTs were immediately vasoactive. Aggregated formulations induced dilation and non-aggregated formulations induced constriction in both hamsters and mice. Endothelial dysfunction was evident after exposure to either aggregated or non-aggregated forms. General loss of dilator capability was seen after exposure to non-aggregated but not aggregated forms. Thus concentrations mimicking bolus dosing of PEG-DSPE coated SWCNT induce both acute and chronic vascular responses.     

Efficacy of Duloxetine in Patients with Chronic Pain Conditions

The primary objective of this study is to review the efficacy of duloxetine in treating chronic pain using the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) recommendations for clinical significance across chronic pain states. These include pain intensity, patient ratings of overall improvement, physical functioning, and mental functioning. This review comprised the side-by-side analyses of 12 double-blind, placebo-controlled trials of duloxetine in patients with chronic pain (diabetic peripheral neuropathic pain, fibromyalgia, chronic pain due to osteoarthritis, and chronic low back pain). Patients received duloxetine (60 to 120 mg/day) or placebo. Average pain reduction was assessed over 3 months as the primary efficacy outcome. Other measures used were physical function and Patient Global Impression of Improvement. In 10 of the 12 studies, statistically significant greater pain reduction was observed for duloxetine- compared with placebo-treated patients. The response rates based on average pain reduction, improvement of physical function, and global impression were comparable across all 4 chronic pain states. Compared with patients on placebo, significantly more patients treated with duloxetine reported a moderately important pain reduction (≥30% reduction) in 9 of the 12 studies, a minimally important improvement in physical function in 8 of the 12 studies, and a moderately important to substantial improvement in Patient Global Impression of Improvement rating in 11 of the 12 studies. The analyses reported here show that duloxetine is efficacious in treating chronic pain as demonstrated by significant improvement in pain intensity, physical functioning, and patient ratings of overall improvement.     

Reye''s Syndrome-Like Illness in a Patient Receiving Amiodarone

A 16-yr-old boy who was receiving amiodarone for ventricular arrhythmias developed a Reye's syndrome-like illness several days after an upper respiratory infection. Liver biopsy revealed microvesicular fat and spotty hepatocellular necrosis, typical of Reye's syndrome. Recovery was complete. This case report suggests that medications other than aspirin may predispose to Reye's syndrome, and that children receiving amiodarone should receive prophylaxis against influenza B and chicken pox.     

Psychiatric morbidity

We studied 285 children (aged 1–15 yrs) attending a psychiatric and child guidance clinic over the period of one year (Jan 1985 to Feb 1986). Majority of children belonged to lower social class III & IV (73.4%) and unitary family (65.6%). There was male predominance (72.3%). Maximum psychiatric morbidity was observed in age group 5–9 years. Main psychiatric problems noted were neurosis (21.1%) and eating disorders (23.2%). Amongst neurosis, the commonests was hysteria (61.7%),followed by phobia (31.7%) and anxiety neurosis (6.6%). Aches and pains (51.4%) and school phobia (47.4%) were the main presenting feature of hysteria and phobia respectively. Stress of examination and failure (16.1%) and quarrels with peers, siblings or parents (13.0%) were observed to be the main precipitating factors.     

Shared Decision Making in Common Chronic Conditions: Impact of a Resident Training Workshop

Problem: Physicians must be competent in several different kinds of communication skills in order to implement shared decision making; however, these skills are not part of routine medical student education, nor are they formally taught during residency training. Intervention: We developed a 1- and 2-hour workshop curriculum for internal medicine residents to promote shared decision making in treatment decisions for four common chronic conditions: diabetes, depression, hypertension, and hyperlipidemia. The workshops included a written case exercise, a short didactic presentation on shared decision-making concepts and strategies for risk communication, and two role-playing exercises focused on decision making for depression and hyperlipidemia treatment. Context: We delivered the workshop as a required component of the resident curriculum in ambulatory medicine. To evaluate the impact of the workshop, we used written course evaluations, tracked the use of the newly introduced Decision Worksheets, and asked preceptors to perform direct observation of treatment decision conversations. Outcome: Residents were involved in the development of the workshop and helped identify key content, suggested framing for difficult topics, and confirmed the need for the skills workshop. One hundred thirty internal medicine and medicine-pediatrics residents attended 8 workshops over a 4-month period. In written cases completed before the workshop, the majority of residents indicated that they would discuss medications, but few mentioned other treatment options or documented patients’ goals and preferences in a sample encounter note with a patient with new depression symptoms. Overall, most participants (89.7%) rated the workshop as excellent or very good, and 93.5% said that they would change their practice based on what they learned. Decision Worksheets addressing diabetes, depression, hyperlipidemia, and hypertension were available on a primary care-focused intranet site and were downloaded almost 1,200 times in the first 8 months following the workshops. Preceptors were able to observe only one consult during which one of the four topics was discussed. Lessons Learned: Internal medicine residents had considerable gaps in shared decision-making skills as measured in a baseline written exercise. Residents provided valuable contributions to the development of a Decision Worksheet to be used at the point of care. Participants rated the skills workshop highly, though interns rated the exercise more useful than PGY-2 and PGY-3 residents did. The Decision Worksheets were accessed often following the sessions; however, observing the Decision Worksheets in use in real time was a challenge in the resident-faculty clinic. Additional studies are warranted to examine whether the workshop was successful in increasing residents’ ability to implement skills in practice.