Dose comparison trial of sustained-release fampridine in multiple sclerosis.

OBJECTIVE: To examine the efficacy and safety of three different doses of sustained-release fampridine in people with multiple sclerosis (MS). METHOD: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study recruited 206 participants at 24 centers in the United States and Canada. After a single-blind, 2-week placebo run-in, participants were randomly assigned to receive fampridine (10, 15, or 20 mg twice daily) or placebo for 15 weeks. The primary efficacy variable was percent change in walking speed based on the timed 25-foot walk. RESULTS: Trends for increased walking speed were consistent across dose groups vs placebo, but not significant, on the prospective analysis. An increase from baseline in lower extremity strength during the 12-week stable-dose period was seen in the groups receiving 10- and 15-mg doses, compared with placebo (p = 0.018 and 0.003). There were no significant changes in other secondary assessments. Post hoc analysis revealed subsets of participants in each dose group with walking speeds during the treatment period that were consistently faster than during the nontreatment period. There were significantly more "consistent responders" in the drug-treated groups than in the placebo group (36.7% compared with 8.5%). Consistent responders showed significantly greater improvement in self-assessed ambulation on the 12-Item MS Walking Scale than did nonresponders. Fampridine was generally well tolerated. Severe and serious adverse events were more frequent at the highest dose. CONCLUSIONS: This phase 2 study suggests that a subgroup of patients, when treated with fampridine, experiences a clinically relevant improvement in walking ability, which is sustained for at least 14 weeks.

Single-operator duodenoscope-assisted cholangioscopy is an effective alternative in the management of choledocholithiasis not removed by conventional methods, including mechanical lithotripsy.

BACKGROUND AND STUDY AIMS: The widespread use of cholangioscopy in the management of difficult choledocholithiasis has been limited by the need for two expert operators. This report describes the use of a technique of single-operator duodenoscope-assisted cholangioscopy (SODAC) in the successful management of 75 patients with choledocholithiasis. PATIENTS AND METHODS: The single-operator technique, allowing simultaneous control of both the duodenoscope and cholangioscope, was prospectively studied between June 1999 and June 2001 in the diagnosis and treatment of choledocholithiasis. RESULTS: A total of 109 SODAC procedures were conducted in 75 patients to manage choledocholithiasis. The indications were: firstly, SODAC-guided electrohydraulic lithotripsy (EHL) of stones in which conventional methods, including mechanical lithotripsy, had not been successful (52 SODAC procedures in 26 patients); and secondly, direct visualization of the biliary tree after cholangiography to assess the presence of stones (57 SODAC procedures in 49 patients). The locations and numbers of the stones, but not their size, were predictive of the number of SODAC-guided lithotripsy sessions required. All of the patients were free of stones at the end of the study period, and no complications were recorded. CONCLUSIONS: Single-operator SODAC-guided electrohydraulic lithotripsy was effective in the treatment of difficult cases of choledocholithiasis in which conventional methods had previously failed. The technique may allow increased use of cholangioscopy in the management of choledocholithiasis.

Management of spasticity, pain, and paroxysmal phenomena in multiple sclerosis.

Multiple sclerosis (MS) is a disease with tremendous variability and innumerable symptoms. Among the more common symptoms is spasticity. Despite a lack of full knowledge of the physiology causing this phenomenon, successful treatments have been developed. Many of these have had a recent introduction. Pain and paroxysmal phenomena are surprisingly common in MS, but have not had the recognition their frequency deserves. It is not unusual to hear that they are rare in MS, but surprisingly they are all too common. Their management is changing as newer treatments are developed.

Methotrexate in Crohn's disease: results of a randomized, double-blind, placebo-controlled trial.

BACKGROUND/AIMS: Immunosuppression with methotrexate may be useful in the treatment of Crohn's disease. We tested the efficacy of methotrexate in refractory Crohn's disease in a randomized, controlled trial. METHODOLOGY: Randomized, double-blind placebo-controlled trial of methotrexate in 33 patients with steroid-dependent Crohn's disease, 33% of whom had previously failed therapy with 6-mercaptopurine. Patients were given placebo or oral methotrexate 15 mg/week, or adjusted up to 22.5 mg/week, for up to 1 year or until treatment failure. Outcome was assessed by reduction in prednisone dosage, Crohn's Disease Activity Index, hospital admission, and laboratory parameters. RESULTS: Four patients were dropped from the study for non-compliance and one because of intercurrent illness, and 28 patients could be evaluated. Fewer methotrexate-treated patients (6/13 or 46%) had flares of Crohn's disease as compared to placebo-treated patients (12/15 or 80%), but this did not achieve statistical significance (p<0.1). There was a non-significant trend toward an increased number of significant side effects in the methotrexate-treated patients (3/13 or 23%) as compared to the placebo-treated patients (0/15 or 0%) (p<0.2). Laboratory indices of inflammation did not differ between the two groups. CONCLUSIONS: The methotrexate-treated group showed a trend toward fewer Crohn's disease flares, balanced by an increased number of significant side effects.

Medications used in the treatment of multiple sclerosis.

Recently, there have been numerous advances in the treatment of multiple sclerosis. This article focuses on reviewing the various forms of MS, managing its various symptoms, and possibly altering the course of the disease in an overall attempt to improve the quality of life of the patient.

The hospitalist: new boon for internal medicine or retreat from primary care?

The growing reliance on hospitalists in the United States has implications for several areas of internal medicine, including patient care, administration, clinical practice, and medical education. This paper discusses some of the potential advantages and disadvantages of the use of hospitalists in each of these areas. The new hospitalist practice mode highlights long-standing tensions about the role and direction of internal medicine, tensions that affect generalist and specialty care in both outpatient and hospital settings. The career trajectory of hospitalists will depend on whether burnout is a problem and on whether hospitalists will be able to compete effectively with sub-specialists, such as cardiologists and physicians specializing in AIDS. Clearly, hospitalism meets a clinical need and expands opportunities for internists, but it is important that it not overreach, forfeiting primary care turf and distorting medical education. This new field warrants close monitoring because of its potential effects and because-unlike related fields, such as emergency medicine and intensive care--its birth was strongly influenced by system-wide financial considerations.

Extended outpatient rehabilitation: its influence on symptom frequency, fatigue, and functional status for persons with progressive multiple sclerosis.

OBJECTIVE: To determine the influence of an extended outpatient rehabilitation program on symptom frequency, fatigue, and functional status for persons with multiple sclerosis (MS). DESIGN: Nonequivalent pretest/posttest control-group design, with posttest 1 year after initial assessment. Multiple regression analysis and analysis of covariance were used to control for symptom severity at the initial assessment and comorbid factors including depression, cognitive function, and social interaction. Effect sizes (ES) provided a descriptive measure of the change in outcomes. SETTING: Outpatient multidisciplinary rehabilitation clinic. PATIENTS: Forty-six patients with definite chronic progressive MS; 20 received treatment and 26 were in a nontreatment comparison group ("waiting list"). INTERVENTION: Rehabilitation services for 5 hours, 1 day per week, over 1 year. MAIN OUTCOME MEASURES: The MS-Related Symptom Checklist composite score, fatigue frequency, and selected items from the Rehabilitation Institute of Chicago Functional Assessment Scale. RESULTS: Receiving treatment was a significant predictor of reduced symptom frequency (partial r2 = .26) at the 1-year follow-up. The ES adjusted for baseline values indicated substantial reductions in symptom frequency for the treatment group (EStreatment = .27 vs ESwaitlist = -.32). Fatigue was significantly reduced at the time of follow-up for the treatment group compared with the waiting list group (EStreatment = .46 vs ESwaitlist = -.20). There were no statistically significant differences among groups regarding functional status, but there appeared to be less loss of functional status in the treatment group compared with the waiting list group (EStreatment = -.07 vs ESwaitlist = -.70). CONCLUSIONS: An extended outpatient rehabilitation program for persons with definite progressive MS appears to effectively reduce fatigue and the severity of other symptoms associated with MS.

Relationship of the antispasticity effect of tizanidine to plasma concentration in patients with multiple sclerosis.

BACKGROUND: Spasticity is a serious problem in multiple sclerosis (MS) and many patients do not achieve a satisfactory response to currently available oral antispasticity drugs. Tizanidine hydrochloride, an alpha 2-noradrenergic agonist, has been shown to have an antispasticity effect in single center trials of patients with MS. OBJECTIVE: To compare plasma concentrations of tizanidine with objective measures of muscle tone in patients with MS with moderate to severe spasticity. SETTING: Ten centers, all tertiary referral centers for the specialized treatment of patients with MS, in the United States and Canada. DESIGN: A randomized, double-blind, placebo-controlled, dose-response study of tizanidine hydrochloride (8 or 16 mg). PATIENTS: One hundred forty-two patients with spastic MS who were not taking any interfering medication, such as an antispasticity drug or other alpha-noradrenergic agonist, entered the trial. RESULTS: Tizanidine treatment reduced muscle tone significantly, as shown by improved Ashworth scores and increased knee swing amplitude recorded by the pendulum test, both of which correlated significantly with plasma concentration. Placebo had no significant effect on muscle tone. Dizziness, drowsiness, dry mouth, and fatigue were reported most often in the group treated with tizanidine at peak plasma concentration. CONCLUSIONS: Tizanidine reduces spasticity in MS, and both therapeutic effects and side effects are related to the plasma drug levels.

Prospective multicenter trial of esophageal Z-stent placement for malignant dysphagia and tracheoesophageal fistula.

BACKGROUND: Conventional esophageal prosthesis placement has been associated with a 6% to 8% perforation rate and numerous postplacement complications. Expandable esophageal stents have been developed to preclude the above but there are few studies that have prospectively defined clinical results and subsequent stent-related complications. METHODS: All patients who underwent esophageal Z-stent placement at nine university or referral hospitals were prospectively assessed. Data collected included patient demographics, acute and subacute placement problems, the ability to occlude airway fistulas, prestent and poststent dysphagia scores, and patient survival. RESULTS: Fifty-four of 56 patients (96%) with refractory dysphagia or malignant esophagoairway fistulae had 73 Z-stents successfully inserted. Initial distal deployment occurred in 13% of the patients and an additional 17% required balloon dilation to achieve maximal diameter. Acute placement complications occurred in 11% of patients and included severe pain (3), bleeding from necrotic tumor (2), and hiatal hernia intussusception (1). No perforations occurred. Eight of 11 patients (73%) had complete tracheoesophageal fistula occlusion and mean dysphagia score (+/- SD) improved from 2.6 (0.7) to 1.1 (1.2) (p < 0.01). Fifteen stents (27%) had delayed migration at a mean of 1 month and 3 required surgery for retrieval. Three patients had ultimate stent erosion resulting in bleeding in 2 (exsanguination 1) or fistula (treated with a conventional stent). CONCLUSIONS: The authors conclude that esophageal Z-stents can be placed safely and successfully in the majority of patients. The tendency of distal deployment during placement and subsequent migration problems at a time distant from placement in a patient subset deserve attention and are currently being addressed.

The use of EUS to diagnose malignant portal venous system invasion by pancreatic cancer.

BACKGROUND: CT scanning and mesenteric angiography are insensitive tests diagnosing vascular invasion by pancreatic cancer. Endoscopic ultrasound (EUS) has been proposed as an alternative. The sensitivity, specificity, and accuracy of specific EUS criteria for diagnosing malignant invasion of the branches of the portal venous system have not been determined. METHODS: This is a prospective blinded evaluation of EUS and angiography to diagnose malignant invasion of the portal venous system by pancreatic cancer in 45 patients, 28 of whom underwent surgery. Surgical staging was used as the gold standard for determining the accuracy of EUS and angiography. RESULTS: Four EUS criteria were studied and the overall accuracy rates were as follows: irregular venous wall (87%), loss of interface (78%), proximity of mass (73%), and size (39%). Although "irregular venous wall" was the most accurate, it suffered from a low sensitivity rate (47%) because of its relative inability to detect superior mesenteric vein invasion (sensitivity of 17%). The angiographic criteria had accuracy rates of 73% to 90% with low sensitivity rates (20% to 77%). The clean resection rate was 86% when all tests were used, 78% if EUS was used without angiography, and 60% if only angiography was used. CONCLUSION: EUS is highly sensitive for detecting portal and splenic vein invasion by pancreatic cancer, but may be insensitive for superior mesenteric vein involvement.

Endoscopic retrograde pancreatography: imaging findings.

Endoscopic retrograde pancreatography (ERP) is commonly used in the diagnosis and management of pancreatic disorders. The aim of this pictorial essay is to provide an overview of the common appearances of normal anatomy, anatomic variants, and pancreatic diseases at ERP.

Symptomatic therapy of multiple sclerosis.

Despite decades of aggressive research into the cause and cure of multiple sclerosis (MS), a direct management strategy remains lacking. As research continues, patients who strive for an improved quality of life may attain it through the improved management of symptoms. Symptoms occur in MS as a consequence of loss of myelin (primary symptoms), as the result of primary symptoms (secondary symptoms), and because of psychological dysfunction associated with MS (tertiary symptoms). This paper emphasizes the recent developments in the management of primary symptoms including visual loss, weakness, spasticity, urinary and sexual dysfunction, and fatigue. The adjective multiple emphasizes the numerous potential symptoms of MS. It is through their management that people with MS may lead happier, more productive lives until a cause and cure are found.

Symptom management in multiple sclerosis.

Presently, the course of multiple sclerosis (MS) can be altered little, if at all. Appropriate symptom management, however, can change the course of lives and allow for more comfortable, healthier living despite significant disease. Symptoms in MS are divided into three broad categories. Those that result from actual demyelination include decreased vision, weakness, spasticity, bladder problems, ataxia, numbness, and decreased cognition. Secondary symptoms spring from the primary; these symptoms include contractures, urinary tract infections, megacolon, decubiti, decreased bony calcification, and muscle atrophy. Tertiary symptoms are the unavoidable psychological, vocational, and social problems that occur with chronic disease. This article reviews standard therapies, but the emphasis is on newer management solutions that may not have reached their full potential, though they add to the development of an appropriate life-management plan for persons with MS. The pharmacological approach to symptom management is emphasized, while understanding that rehabilitation and medications cannot be separated in the real life alleviation of MS symptoms.

New advances in symptom management in multiple sclerosis.

Even with exciting new advances in the immunology of multiple sclerosis (MS), a definitive, etiologically aimed management strategy remains elusive. New advances in symptom management provide the clinician the means of improving the quality of life of individuals with MS. Symptoms can be divided into three broad categories: those which stem from demyelination (primary), those coming from the complications of demyelination (secondary), and those which develop from the psychological aspects of chronic disease (tertiary). The modern clinician must be able to develop a life management plan involving symptom management in MS. This article develops some strategies based on newer advances in this area.

Intraluminal pancreatic candidiasis presenting as recurrent pancreatitis.

An 88-year-old man with closely spaced attacks of acute pancreatitis who was found to have ductal changes of chronic pancreatitis with multiple noncalcified intraluminal filling defects during endoscopic retrograde pancreatography is presented. These defects proved to be fungus balls made up of Candida albicans. He was treated with longitudinal pancreaticojejunostomy and oral fluconazole and has since remained recurrence free (30 months). It is suggested that Candida superinfection may occur in a chronically dilated pancreatic duct and may contribute to symptomatic recurrent inflammation of the pancreas.