CGRP peptide and regenerating sensory axons

CGRP peptide, a widely expressed constituent of sensory neurons, plays important roles in nerve function and repair when axons are severed. CGRP synthesis declines, yet peptide nonetheless accumulates in severed axon endbulbs. In this work we explore an apparent selective and ongoing expression of CGRP peptide in regenerative sensory axon sprouts. Following sural nerve crush in rats out to 14 days, regenerating and branching sensory axons had intense and selective expression of CGRP, not associated with endbulbs. Parent L4 and L5 perikarya and axons in the sural nerve proximal to crush, however, did not exhibit such heightened CGRP presence. Instead, back labeling of regenerating axons with fluorogold or diamidino yellow labeled perikarya with reduced CGRP expression. Similarly, ATF-3, a robust marker of axotomized neurons, was associated with reduced, rather than elevated expression of alphaCGRP mRNA. Unexpectedly, however, we identified an enlarged secondary population of intact uninjured neurons, frequently smaller and projecting to the dorsal horn with new and heightened intense CGRP expression but not ATF-3- or tracer-labeled. Distal regenerating sensory axons selectively express CGRP peptide despite reduced perikaryal content, a phenomenon not explained by simple accumulation. Having an injured neighbor neuron, however, may also paradoxically alter how CGRP is expressed in intact neurons.     

Development and application of a universal method for quantitation of anionic constituents in active pharmaceutical ingredients during early development using suppressed conductivity ion chromatography

A universal method for quantitation of anionic substances in active pharmaceutical ingredients (API) during early development was developed using ion chromatography (IC). The method was developed to allow rapid characterization of APIs in support of early clinical studies The method parameters were chosen to allow quantitation of monovalent, divalent, and trivalent inorganic ions as well as monvalent and divalent carboxylic acids. These parameters were also chosen to ensure appropriate performance for regulated analyses using less than 10mg of API per replicate. The method was applied to and validated for a range of anionic analytes in APIs of varying hydrophobicity to demonstrate applicability to various analyses encountered during early development of pharmaceuticals.     

Tumor necrosis factor alpha blockade with infliximab for refractory uveitis and scleritis

OBJECTIVE: To assess the efficacy and safety of the anti-tumor necrosis factor alpha agent infliximab in treatment-resistant uveitis and scleritis. DESIGN: Retrospective, noncomparative interventional case series. PARTICIPANTS: Seven patients with noninfectious ocular inflammatory disease that was refractory to alternative immunosuppression. These included one patient with idiopathic retinal vasculitis and panuveitis, one patient with intermediate uveitis, one patient with chronic juvenile anterior uveitis, three patients with scleritis, and one patient with scleritis and peripheral ulcerative keratitis. Four patients had an underlying systemic disease that was in remission in three cases. INTERVENTION: Infusions of infliximab, 200 mg, were given at 4-week to 8-week intervals, depending on the clinical response. MAIN OUTCOME MEASURES: Clinical response, including symptoms, visual acuity, degree of scleral vascular engorgement, corneal thinning, anterior chamber activity, and posterior segment inflammation, reduction in concomitant immunosuppression, and adverse effects. RESULTS: The mean patient age was 47 years (range, 24-78), and four patients were female. The mean number of infliximab infusions was seven (range, 2-19), and the mean follow-up period was 12 months (range, 4-22 months). Six patients experienced a clinical improvement, with five achieving remission and significant reduction in immunosuppression. One patient showed an initial response but developed a delayed hypersensitivity response that precluded further treatment. No other adverse effects occurred. CONCLUSIONS: Infliximab seems to be an effective and safe treatment for noninfectious uveitis and scleritis and may be indicated as rescue therapy for relapses of ocular inflammation or as maintenance therapy when conventional immunosuppression has failed. Further investigation of infliximab for treatment-resistant scleritis and uveitis is warranted.     

What impact will an increased number of teaching general practices have on patients,doctors and medical students?

BACKGROUND: Recommendations for medical training have seen a growing drive for undergraduate teaching to take place within the community - primarily in the general practice surgery. In light of the ongoing expansion of medical student numbers, many more general practices will be required to participate in undergraduate teaching. AIM: To explore the perceptions of primary care staff on the impact that increasing student numbers will have on them, on their patients and on the students themselves. DESIGN OF STUDY: Semi-structured interviews. SETTING: Three general practices presently involved in undergraduate teaching, 3 practices about to become involved in undergraduate teaching and 1 non-teaching practice, all in the Black Country area of the West Midlands. METHODS: Semi-structured interviews with prearranged prompts were undertaken with a variety of practice staff including general practitioners (GPs), practice managers and practice nurses, as well as administrative and reception staff. RESULTS: Eleven GPs, 6 practice managers, 4 practice nurses and 6 receptionists/administrators took part in the interviews. Three main themes emerged relating to the effects on students and reflecting attitudes towards the Black Country, the experience of working among deprived populations and issues around access to the new training locations. The majority of interviewees were of the opinion that patients both enjoy taking part in undergraduate teaching and are able to benefit from the process. Positive impacts on practice infrastructure were also elicited, but when asked about the resource implications for the practice of undergraduate teaching, there was a dichotomy of opinion. CONCLUSION: For many practices, involvement in undergraduate teaching is a double-edged sword.     

Continued parental attendance at a clinic for adult survivors of childhood cancer

PURPOSE: Adult survivors of childhood cancer have been an underserved and understudied population. Few clinics are available to take care of them, unlike the numerous ones that exist for children. The authors established a clinic that would take care of all survivors diagnosed before the age of 25 years, ensuring the participation of a significant number of adults. The authors observed that many adult patients came to their annual visits accompanied by one or both of their parents. The rate was almost three times as high compared with parents in either a primary care or subspecialty internal medicine clinic. METHODS: The authors investigated this phenomenon by asking parents of adult survivors to fill out a questionnaire that collected demographic information as well as reasons for parents accompanying their adult children to doctors' appointments. Open-ended comments were also solicited. RESULTS: Most parents who came with their adult survivor children did not accompany their other children to doctor visits and commented that they felt there was a unique bond created by the cancer experience that did not diminish with increasing age of their children. The rate of parental attendance was independent of diagnosis or demographic indicators. Many parents stated that they continued to be concerned about their child's diagnosis, overall health, and risk for cancer recurrence. DISCUSSION: Parents of adult survivors of childhood cancer may harbor deep feelings of protectiveness that continue well beyond the initial treatment and off-treatment periods when the threat of primary cancer recurrence is a realistic concern. This can be manifested in them by accompanying their adult children to doctors' appointments and deserves further study.     

Treatment of vulvar intraepithelial neoplasia 2/3 with imiquimod

OBJECTIVE: To retrospectively review the charts of 13 women diagnosed with vulvar intraepithelial neoplasia (VIN) 2/3 treated with imiquimod and to evaluate the efficacy of this treatment. STUDY DESIGN: Retrospective review. All 13 women were treated and evaluated by a single gynecologist. The extent of the lesions prior to treatment and the extent and degree of improvement were documented. Biopsy confirmation of disease was obtained for each individual. Response to treatment was categorized as complete regression, at least 75% regression or not improved. RESULTS: The mean duration of treatment was 3.3 months, and follow-up after completion of therapy was 5.5 months. Eight of the 13 women had complete regression of the VIN. Four patients demonstrated 75% regression of disease, and in one diabetic woman no improvement was seen. In two women demonstrating 75% lesion regression, invasive carcinoma of the vulva was found in the area of residual disease. In one instance this was determined to be superficially invasive squamous cell carcinoma (1 mm of invasion), and in the second an anal tag was found to have invasive squamous cell carcinoma. CONCLUSION: Medical management of VIN 2/3 with imiquimod is worth considering. However, careful evaluation of the patient must be carried out prior to the institution of therapy to exclude the presence of invasive squamous cell carcinoma.