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Biomedical subjects

G R Lichtenstein

Publications and source records attributed to G R Lichtenstein.

At least 19 recordsLinked to original sources
PubMed2005

A randomized, double-blind, placebo-controlled trial of CDP571, a humanized monoclonal antibody to tumour necrosis factor-alpha, in patients with corticosteroid-dependent Crohn's disease.

AIM: To evaluate CDP571, a humanized monoclonal antibody to tumour necrosis factor-alpha, for the treatment of corticosteroid-dependent Crohn's disease. METHODS: Patients with corticosteroid-dependent Crohn's disease (use of prednisolone 15-40 mg/day or budesonide 9 mg/day for at least 8 weeks, a previous failed attempt to discontinue corticosteroids within 8 weeks, and Crohn's Disease Activity Index score 150 points or less) were enrolled in a 16-week, randomized, double-blind, placebo-controlled trial. The patients received intravenous CDP571 (20 mg/kg at week 0 and 10 mg/kg at week 8) or placebo. Corticosteroid therapy was decreased following a predefined schedule. The primary efficacy end-point was the percentage of patients with corticosteroid-sparing [i.e. no disease flare (Crohn's Disease Activity Index score > or =220 points) and no longer requiring corticosteroid therapy] at week 10. The major secondary efficacy end-point was corticosteroid-sparing at week 16. RESULTS: Seventy-one patients received treatment. Corticosteroid-sparing was achieved by 19 of 39 (48.7%) CDP571 patients and 13 of 42 (40.6%) placebo patients (P = 0.452) at week 10, and by 18 of 39 (46.2%) CDP571 patients and seven of 32 (21.9%) placebo patients (P = 0.032) at week 16. CDP571 therapy was well-tolerated and the incidence of serious adverse events was similar to placebo. CONCLUSIONS: The CDP571 was effective for corticosteroid-sparing at week 16 but not week 10, and was well-tolerated in patients with corticosteroid-dependent Crohn's disease.

Adult↗
PubMed2005

Review article: monitoring of immunomodulators in inflammatory bowel disease.

The armamentarium of medications for the treatment of inflammatory bowel disease is growing and becoming more complicated to use. Immunomodulators are a class of medications that have found a niche for the treatment of Crohn's disease and ulcerative colitis. Because of the mounting supporting evidence for efficacy, the most commonly-used immunomodulators are azathioprine, mercaptopurine, methotrexate and ciclosporin. These medications are being used more often due to their steroid-sparing and potentially surgery-sparing effects. Immunomodulators are also known for a significant side-effect profile and require careful monitoring. This review provides the latest information for clinicians on efficacy, side-effects, dosing and monitoring of these medications for treatment of inflammatory bowel disease.

Azathioprine↗
PubMed2001

Approach to corticosteroid-dependent and corticosteroid-refractory Crohn's disease.

Corticosteroids are considered a drug of choice for the treatment of patients with moderately to severely active Crohn's disease (CD), an inflammatory bowel disease characterized by chronic recurrent flares of disease activity. However, among patients receiving corticosteroid therapy for induction of remission, 20% have corticosteroid-refractory disease and 36% of those with an initial response develop corticosteroid dependency within 1 year. Chronic corticosteroid exposure in patients who are corticosteroid dependent increases the risk for serious drug-related adverse effects. Withdrawal or reduction of corticosteroid therapy without exacerbation of symptoms is therefore recognized as an important goal of treatment. Therapies that have been shown to facilitate "steroid sparing' include the immunomodulators azathioprine/6-mercaptopurine and methotrexate and the antitumor necrosis factor-alpha monoclonal antibody infliximab. In corticosteroid-dependent patients, budesonide may be substituted for conventional corticosteroid therapy without loss of response and with less risk for toxicity, but its long-term efficacy requires further evaluation. A preliminary controlled study suggests that the investigational anti-TNF monoclonal antibody CDP-571 may also be clinically beneficial as a corticosteroid-sparing agent. This review summarizes the clinical evidence that supports consideration of these agents as alternatives in patients with CD who are dependent on, refractory to, or intolerant of conventional corticosteroid therapy.

Anti-Inflammatory Agents↗
PubMed2001

Medical therapy for Crohn's disease: the state of the art.

Various medications are used to control the symptoms of Crohn's disease. This article reviews the traditional medical therapies of Crohn's disease, including aminosalicylates and corticosteroids, and the broad armamentarium of immune modulators and biologic agents that are becoming increasingly important in the management of Crohn's disease.

Adjuvants, Immunologic↗
PubMed2001

Cytomegalovirus colitis complicating ulcerative colitis in the steroid-naive patient.

We report a case of cytomegalovirus (CMV) presenting as acute refractory colitis in a patient with a pre-existing 14-month history of ulcerative colitis (UC) who had never previously been treated with corticosteroids or immunosuppressants. A review of existing literature and previous cases of patients with coincident CMV and UC are examined, stratifying these cases based upon absence or presence of corticosteroid use. To date, only five previous case reports of CMV colitis in patients naive to corticosteroids have been described, and only one previous case has had UC diagnosed over 4 wk before the development of CMV colitis. We further discuss the relationship between these two diseases as well as the diagnosis, treatment, patient characteristics, and outcome of CMV infection of the colon in patients with underlying UC. We discuss the need to consider the diagnosis of CMV colitis in patients with refractory UC who are not receiving corticosteroid treatment as well as those who are refractory and are being treated with immunosuppressants and/or corticosteroids.

Acute Disease↗
PubMed2001

Pediatric Crohn's disease: risk factors for postoperative recurrence.

OBJECTIVE: Postoperative recurrence of Crohn's disease in adults has been extensively studied; however, the course of Crohn's disease after surgery in children has not been well defined. The aim of this study was to examine the postoperative course of pediatric Crohn's disease and the factors that may predict early postoperative recurrence. METHODS: We identified 100 resective surgeries in 79 children with Crohn's disease seen at the Children's Hospital of Philadelphia between 1978 and 1996. A retrospective, multivariable analysis of factors potentially influencing postoperative clinical recurrence was performed. Preoperative and postoperative height measurements were compared, and z scores were computed for height-for-age. Two-tailed t test was used for the analysis. RESULTS: Clinical recurrence rates were 17% at 1 yr, 38% at 3 yr, and 60% at 5 yr. Patients with colonic Crohn's disease had a significantly shorter postoperative recurrence-free interval (median 1.2 yr) than patients with ileocecal (median 4.4 yr) or diffuse disease (median 3.0 yr) (p = 0.01). On multivariable analysis, a high Pediatric Crohn's Disease Activity Index at the time of surgery (p = 0.01) and preoperative use of 6-mercaptopurine (6-MP) (p < 0.005) were also independently associated with higher postoperative recurrence rates. There was a significant improvement in z scores for height (p = 0.04) after surgery. CONCLUSIONS: In children undergoing resective surgery for Crohn's disease, high rates of postoperative Crohn's disease recurrence are associated with severe disease at the time of surgery, colonic Crohn's disease, and the preoperative use of 6-MP. Patients who require preoperative use of 6-MP are likely to suffer from a more aggressive disease and would benefit from postoperative 6-MP prophylaxis. Height growth was improved after intestinal resection for Crohn's disease.

Adolescent↗
PubMed2001

Integrating anti-tumor necrosis factor therapy in inflammatory bowel disease: current and future perspectives.

Crohn's disease and ulcerative colitis are two idiopathic inflammatory disorders of the GI tract. Manifestations of disease can be severe and lead to long term therapy with a variety of medications and/or surgery. Standard medical therapy consists of agents that either treat suppurative complications or modulate the inflammatory cascade in a nonspecific manner. Many specific chemokine and cytokine effectors that promote intestinal inflammation have been identified. Such work has led to experimental clinical trials with a variety of cytokine antagonists. Compounds directed against one such cytokine, tumor necrosis factor alpha (TNF), have demonstrated the greatest clinical efficacy to date. This is consistent with scientific observations that suggest a central role for TNF in the inflammatory cascade. Infliximab is a chimeric monoclonal antibody against TNF that has been demonstrated to be effective for the treatment of Crohn's disease. Infliximab is Food and Drug Administration approved for the treatment of Crohn's disease. There exist several other TNF antagonists in various phases of investigation, including the monoclonal antibody CDP 571, the fusion peptide etanercept, the phosphodiesterase inhibitor oxpentifylline, and thalidomide. The clinical efficacy of these agents and the role of TNF in the pathogenesis of inflammatory bowel disease is reviewed.

Animals↗
PubMed2001

An open-label trial of the PPAR-gamma ligand rosiglitazone for active ulcerative colitis.

OBJECTIVES: Previous research has demonstrated that ligands for the gamma subtype of peroxisome proliferator-activated receptors (PPARs) reduce inflammation in two different murine models of colitis. This study was designed to examine the potential efficacy of rosiglitazone, a ligand for the gamma subtype of PPARs, as a therapy for active ulcerative colitis. METHODS: Fifteen patients with mild to moderately active ulcerative colitis despite therapy with 5-aminosalicylic acid compounds were enrolled in an open-label study of rosiglitazone (4 mg b.i.d. p.o.) for 12 wk. Thirteen of 15 patients were receiving concomitant therapy with corticosteroids and/or immunomodulator medications. Disease activity was measured with the Disease Activity Index. RESULTS: After 12 wk of therapy, four patients (27%) had achieved clinical remission, of whom three (20%) also had an endoscopic remission. Four additional patients (27%) had a clinical response without achieving remission. Two patients were hospitalized with worsened disease activity, and one patient was withdrawn for nephrotic syndrome. CONCLUSIONS: These data suggest that ligands for the gamma subtype of PPARs may represent a novel therapy for ulcerative colitis. A double blind, placebo-controlled, randomized trial is warranted.

Adult↗
PubMed2001

Management of bone loss in inflammatory bowel disease.

Decreased bone mineral density, osteoporosis, is a common disorder in the United States and elsewhere in the world. This disorder is estimated to account for more than 1.5 million bone fractures each year and is estimated to cost over 13 billion dollars annually. Inflammatory Bowel Disease is a relatively common disorder with estimates suggesting that approximately one million Americans are afflicted by these conditions. Osteoporosis is a common extraintestinal complication of inflammatory bowel disease. The importance of the many possible mechanisms contributing to the loss of bone mass in IBD is uncertain. Several of these specific factors, including the use of corticosteroids, calcium deficiency, vitamin D deficiency, chronically active inflammatory bowel disease, and malnutrition. Assessment of the bone mineral density is an important exercise since new therapeutic options exist and new options are available to combat and even prevent this costly complication.

Adrenal Cortex Hormones↗
PubMed2001

Thoracic spine spasms secondary to hemorrhagic intestinal ulcer.

A case of thoracic spine spasms secondary to a bleeding duodenal ulcer is presented. A 41-year-old male with 14-week history of thoracic spine spasm was treated with bed rest, spinal manipulation, physical therapy, medication, and a thoracolumbar brace. Subsequently, a provocative thoracic discogram performed at T9-T10 created periscapular pain and also reproduced the presenting thoracic spasms. Intradiscal electrothermal annuloplasty (IDET) was performed at the T9-T10 level, but without sustained relief. The patient presented to a spine center for evaluation. The diagnosis of thoracic discogenic disease was suspected. A second provocative thoracic discogram was performed and failed to reproduce his thoracic spasms. Three weeks after being referred to a chronic pain management physician, the patient presented to a local emergency room with hema-temesis. An endoscopic evaluation revealed a bleeding duodenal ulcer. Following medical treatment of the duodenal ulcer with a proton pump inhibitor the patient had complete resolution of his thoracic spasms. This represents the first reported case of thoracic spine spasms as an initial presenting symptom of a bleeding peptic ulcer.

Journal Article↗
PubMed2000

Fatal hyperammonemia after orthotopic lung transplantation.

BACKGROUND: A case of fatal hyperammonemia complicating orthotopic lung transplantation was previously reported. OBJECTIVE: To describe the incidence, clinical features, and treatment of hyperammonemia associated with orthotopic lung transplantation. DESIGN: Retrospective cohort analysis. SETTING: Academic medical center and lung transplantation center in Philadelphia, Pennsylvania. PATIENTS: 145 sequential adult patients who underwent orthotopic lung transplantation. MEASUREMENTS: Plasma ammonium levels. RESULTS: Six of the 145 patients who had had orthotopic lung transplantation developed hyperammonemia, all within the first 26 days after transplantation. The 30-day post-transplantation mortality rate was 67% for patients with hyperammonemia compared with 17% for those without hyperammonemia (P = 0.01). Development of major gastrointestinal complications (P = 0.03), use of total parenteral nutrition (P < 0.001), and lung transplantation for primary pulmonary hypertension (P = 0.045) were associated with hyperammonemia. CONCLUSIONS: Hyperammonemia is a potentially fatal event occurring after orthotopic lung transplantation. It is associated with high nitrogen load, concurrent medical stressors, primary pulmonary hypertension, and hepatic glutamine synthetase deficiency.

Adult↗