A dose finding study with 0.1%, 0.2%, and 0.4% glyceryl trinitrate ointment in patients with chronic anal fissures

BACKGROUND: Anal fissure is a common painful condition affecting the anal canal. The majority of acute fissures heal spontaneously. However, some of these acute fissures do not resolve but become chronic. Chronic anal fissures were traditionally treated by anal dilation or by lateral sphincterotomy. However, both of these surgical treatments may cause a degree of incontinence in up to 30% of patients. Several recent trials have shown that nitric oxide donors such as glyceryl trinitrate (GTN) can reduce sphincter pressure and heal up to 70% of chronic fissures. AIM: This study addressed the dose-response to three different concentrations of GTN ointment compared with placebo in a double blind randomised controlled trial. METHOD: A double blind, multicentre, randomised controlled trial was set up to compare placebo ointment against three active treatment arms (0.1%, 0.2%, and 0.4% GTN ointment applied at a dose of 220 mg twice daily) in chronic anal fissures. The primary end point was complete healing of the fissure. RESULTS: Two hundred patients were recruited over an eight month period from 18 centres. After eight weeks of treatment the healing rate in the placebo group was 37.5% compared with 46.9% for 0.1%, 40.4% for 0.2%, and 54.1% for 0.4% GTN. None was significantly better than the placebo response. A secondary analysis excluded fissures without secondary criteria for chronicity. Healing rates were then found to be 24% in the placebo group compared with 50% in the 0.1% GTN group, 36% in the 0.2% group, and 57% in the 0.4% GTN group. These values were statistically significantly different for the placebo group compared with 0.1% GTN, 0.4% GTN, and for the GTN treated group as a whole. CONCLUSIONS: The results of this study have demonstrated the significant benefit of topical GTN when applied to patients suffering from chronic anal fissures but acute fissures showed a tendency to resolve spontaneously. The high proportion of fissures which healed in the placebo group suggests that the definition of "chronicity" needs to be reassessed. Further studies are required to confirm the optimal therapeutic strategy.     

Assessing functional status: exploring the relationship between the multiple sclerosis functional composite and driving

OBJECTIVE: To explore the relationship between the Multiple Sclerosis Functional Composite (MSFC), which is comprised of 3 clinical dimensions (arm and hand function, leg function and ambulation, cognition), and an everyday functional skill, driving performance. DESIGN: Cohort study. SETTING: Medical rehabilitation research organization. PARTICIPANTS: Twenty-nine individuals with documented multiple sclerosis (MS) and limited motor decrements. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Driving-related skills were measured by using the overall category rating from the Useful Field of View (UFOV) Test, its 3 subtests, the error and latency scores from the Neurocognitive Driving Test (NDT), subjective (self-report) and objective (Department of Motor Vehicles [DMV] reports) reported driving experience, and number of motor vehicle crashes. Within the group, differences were explored between participants rated as low risk versus moderate-high risk on the UFOV overall score and between participants who reported a change in driving habits after MS versus those who reported no change. RESULTS: The overall MSFC score correlated significantly with the UFOV overall score, the visual-information processing and selective attention subtests of the UFOV, the NDT latency score, as well as with the number of days a week the individual drove and the number of crashes reported by the DMV. An examination of the MSFC components revealed that the cognition component was significantly related to the UFOV overall score, all 3 subtests of the UFOV, and the NDT latency score. The arm and hand function component correlated significantly with NDT latency and the selective attention subtest of the UFOV. Individuals classified as low risk on the UFOV overall had more education, better MSFC scores, and lower NDT latency scores. Only the overall MSFC score distinguished those who reported a change in driving habits after onset of MS. CONCLUSIONS: Problems with everyday functional skills such as driving are accurately identified through the use of the overall MSFC and its components.     

Collaborative drug therapy management by pharmacists--2003

Since publication of the initial ACCP position statement on CDTM by pharmacists in 1997, the public, government, and much of the health care community at large have come to better appreciate the growing complexity of providing effective and safe drug therapy in today's health care environment. Increased interest in the issues of cost and quality of drug use is evident in the increasing coverage of the issue in the lay press and professional literature. This represents real progress, as well as real opportunity, for pharmacists. It also heightens the potential for a better understanding of the vital role that pharmacists can play in addressing these concerns. The percentage of patients who take several drugs for chronic diseases will continue to increase. Based on current trends, the number of patients who lack adequate access to care, or who receive either suboptimal, inappropriate, or unnecessarily expensive drug therapy for their acute and chronic diseases, will increase. Even as financial and human resources are increasingly strained within the current health care system, costs will continue to rise unless changes are made. Fortunately, qualified pharmacists are prepared, capable, and willing to help address a significant portion of these challenges. The public, many health care providers, some legislators, and a few insurers now recognize that pharmacists, because of their education and training in drug therapy, are well positioned both to accept additional responsibility for patient care and to provide services that make a real difference in health care quality and outcomes. The health care programs administered by the U.S. Public Health Service, the armed forces, and the Veterans Health Administration, as well as 38 states, now support pharmacist participation in CDTM. Pharmacists, working in an interdisciplinary structure with physicians and other health care providers, have demonstrated that they can improve the effectiveness, efficiency, and safety of drug therapy by providing CDTM. It is time to incorporate this valuable professional skill of the contemporary pharmacist as a core component of the delivery of health care services.     

Compared with control subjects,the systemic sympathetic nervous system is activated in patients with mitral regurgitation

Background

Whether the systemic sympathetic nervous system is activated as a compensatory mechanism in response to mitral regurgitation (MR) in humans is unknown. We tested the hypotheses that the systemic sympathetic nervous system would be activated in patients with MR in comparison with control subjects and that this activation would occur early in the disease process as a compensatory mechanism for chronic left ventricular (LV) volume overload.

Methods

We studied 37 patients with MR who underwent right heart catheterization and biplane cineventriculography to obtain LV end-diastolic and end-systolic volumes, ejection fractions, and regurgitant volumes. In these 37 patients with MR and in 23 control subjects, an [³H]-norepinephrine ([³H]-NE) infusion and multiple arterial blood samples provided data for a 2-compartment modeling analysis to calculate extravascular NE release rates (NE₂).

Results

The mean NE₂ (2.05 ± 0.76 μg/min/m²) in the patients with MR was greater than that in the control subjects (1.48 ± 0.75 μg/min/m², P = .007). Furthermore, the mean NE₂ values were also greater in the patients with MR who were in clinical class I (P = .05), with a pulmonary capillary wedge pressure <12 mm Hg (P = .05) or a LV ejection fraction ≥0.60 (P = .06) compared with the control subjects. The mean NE₂ values were increased further in patients with MR who had a LV ejection fraction <0.60 (P = .02).

Conclusions

The systemic sympathetic nervous system is activated in patients with MR in comparison with control subjects, and this activation appears to occur early in the disease process as a compensatory mechanism for LV volume overload.     

Expression of alpha2a-2b neuregulin-1 is associated with early peripheral nerve repair along muscle-enriched tubes

Using RT-PCR, we have investigated expression of isoforms beta1 (the axonal isoform) and alpha2a-2b (the mesenchymal isoform) of neuregulin-1, one of the most important known trophic factors for Schwann cells, in the rat sciatic nerve repaired by muscle-enriched non-nervous conduits (made by a vein filled with fresh skeletal muscle). Repaired nerves were harvested 2, 6 and 13 days post-operatively. Results showed that while muscle-vein combined grafts were enriched in mRNA coding for alpha2a-2b since the very early regeneration stages, isoform beta1 mRNA was not detectable inside the tubes at day 2 and 6 post-operatively while its expression at day 13 was very slight. These results suggest that Schwann cell survival and activity inside a fresh muscle-enriched non-nervous conduit graft (a key factor for successful nerve regeneration along the graft) may be supported by the mesenchymal isoform of neuregulin-1 during very early repair phases, i.e. when axons are still not present along the tube.