Biomedical subjects

Robert Burakoff

Publications and source records attributed to Robert Burakoff.

7 recordsLinked to original sources

PubMed2006

A phase 1/2A trial of STA 5326, an oral interleukin-12/23 inhibitor, in patients with active moderate to severe Crohn's disease.

BACKGROUND: Intestinal inflammation associated with Crohn's disease is characterized by a type 1 helper T cell response and elevated levels of interleukin (IL)-12. We report our clinical experience with a novel oral IL-12/IL-23 inhibitor (STA 5326) for the treatment of active Crohn's disease. MATERIALS AND METHODS: We conducted an open-label, dose-escalating trial of the orally delivered small molecule immunomodulator STA 5326 in 73 patients with active Crohn's disease (Crohn's disease activity index [CDAI] 220-450, inclusive). Five cohorts of patients were treated for up to 4 weeks with 14 mg twice a day (bid), 35 mg daily (qd), 28 mg bid, 35 mg bid, or 70 mg qd. The endpoints of the study included safety and improvement in clinical activity measured by the CDAI and the Crohn's disease endoscopic index of severity. RESULTS: STA 5326 was well tolerated. Reported adverse events were similar across dose cohorts. The most common (>15%) drug-related adverse events observed were dizziness, nausea, headache, and fatigue. Clinical activity at day 28/29 was observed at qd doses of 28 mg and above for the clinical endpoints of response and remission: 70 points or greater decrease in CDAI (range 42%-82% of patients); 100 points or greater decrease in CDAI (range 38%-64% of patients), and CDAI <150 (range 15%-36%). CONCLUSIONS: Oral qd dosing of STA 5326 for 4 weeks was well tolerated in doses up to 70 mg qd in patients with active moderate to severe Crohn's disease. Clinical activity was observed at qd doses of 28 mg and above.

Administration, Oral↗

PubMed2006

5-aminosalicylate therapy is associated with higher 6-thioguanine levels in adults and children with inflammatory bowel disease in remission on 6-mercaptopurine or azathioprine.

BACKGROUND: Small uncontrolled trials have suggested that 5-aminosalicylate (5-ASA) medications increase 6-thioguanine nucleotide (6-TGn) levels in adults with Crohn's disease (CD) on azathioprine (AZA) or 6-mercaptopurine (6-MP), presumably through the inhibition of thiopurine methyltransferase (TPMT). We tested the theory that coadministration of 5-ASA agents with AZA/6-MP results in higher 6-TGn levels in a large cohort of children and adults with CD or ulcerative colitis (UC). METHODS: A retrospective cohort study identified all children and adults treated for IBD with AZA/6-MP at 2 tertiary medical centers. Patients were included if their TPMT genotype was known and 6-TGn and 6-methymercaptopurine (6-MMP) levels had been obtained after 3 months of clinical remission at a stable dose of AZA/6-MP. 6-TGn and 6-MMP levels were compared between patients taking and those not taking 5-ASA medications through the use of linear regression models to identify and adjust for potentially confounding variables. RESULTS: Of the 126 patients included, 88 were taking 5-ASA medications. Patients on 5-ASA agents had higher mean 6-TGn levels after adjustment for confounding variables (Delta6-TGn, 47.6 +/- 21.8 pmol/8 x 10 red blood cells; P = 0.03). CD and TPMT heterozygosity was independently associated with higher 6-TGn levels (P = 0.01 and P = 0.03, respectively). 5-ASA exposure was not associated with a change in 6-MMP levels. CONCLUSIONS: We found that 5-ASA therapy is associated with higher 6-TGn levels in children and adults with IBD on 6-MP/AZA. TPMT inhibition may not explain this effect because 5-ASA exposure did not affect 6-MMP levels. The observed association of CD with higher 6-TGn levels is novel and needs to be verified in prospective studies.

Adolescent↗

PubMed2006

Use of antibiotics in the treatment of inflammatory bowel disease.

An increasing amount of evidence suggests that enteric flora may have a role in the pathogenesis of inflammatory bowel disease (IBD). Patients with IBD appear to have an altered composition of luminal bacteria that may provide the stimulus for the chronic inflammation characterizing IBD. The suspected role of bacteria in the pathogenesis of IBD provides the rationale for using agents, such as antibiotics, that alter the intestinal flora. However, there remains much uncertainty about the optimal use of antibiotics in the treatment of Crohn's disease, ulcerative colitis, and pouchitis. This article reviews the literature and presents a clinical model for the use of antibiotics in IBD.

Anti-Bacterial Agents↗

PubMed2003

Inflammatory bowel disease in African Americans.

Ulcerative colitis (UC) and Crohn's disease (CD) are idiopathic inflammatory disorders of the gastrointestinal tract. The two disorders encompass a wide spectrum of clinical presentations and are diagnosed on the basis of their clinical, endoscopic, radiologic, and histologic features. Combined, the two disorders affect approximately 800,000 patients in the United States. An assessment of the epidemiology of these disorders is complicated by a wide range of factors including the absence of population based registries in ethnically diverse regions, the use of retrospective data, and highly variable clinical presentations which may delay or obscure the diagnosis. In this paper we review the available data regarding the epidemiology, clinical presentation, and clinical course of inflammatory bowel disease in African Americans.

Black or African American↗

PubMed2003

The percutaneous endoscopic gastrostomy tube. medical and ethical issues in placement.

OBJECTIVE: Offering and recommending PEG tube placement to patients has been a topic of considerable interest in the medical literature. The role of individual health care professionals in the decision making process is poorly defined. PEG tubes are often placed inappropriately because of unrealistic and inaccurate expectations of what they can accomplish in patients unable to tolerate adequate oral intake. We have developed an algorithm for PEG placement for the geriatric, oncology, and neurology patients based on a critical review of current literature. METHODS: An extensive review of the literature was performed focusing on PEG tube placement in oncology, neurology, and geriatric patients. This algorithm was developed to provide both the primary care provider and the specialist with appropriate indications for PEG placement in these patient populations. RESULTS: Appropriate indications for PEG placement are 1) Esophageal obstruction (e.g., esophageal cancer), 2) Neurologic etiology of dysphagia without obstruction (e.g., status post cerebrovascular accident, pseudobulbar palsy), 3) Prolonged refusal to swallow without evidence of concomitant terminal illness (e.g., protracted pseudodementia due to severe depression), 4) Supplemental nutrition for patients undergoing chemotherapy or radiation therapy. CONCLUSIONS: If no physiologic benefit is expected with PEG placement (anorexia-cachexia syndrome), the health care team has no obligation to offer or perform an intervention. This same principle would apply if intervention improves physiologic states but has no effect on quality of life (e.g., permanent vegetative state). Small-bore feeding tubes are cost effective and relatively safe for enteral feedings of up to 6-8 weeks. This is especially pertinent in the population with acute neurological deficits, in which prognostication on extent of impairment is best estimated by communication with neurologist. In the geriatric population there is no proved benefit in weight gain or markers of nutrition (albumin, prealbumin) in patients with malnutrition due to impaired oral intake.

Aged↗

PubMedDate not supplied

Indeterminate colitis.

Explore the source record for details and available documents.

Antibodies, Antineutrophil Cytoplasmic↗

PubMedDate not supplied

Indeterminate colitis: clinical spectrum of disease.

A diagnosis of indeterminate colitis (IC) is based on endoscopic, histologic, and radiologic findings when the criteria for either Crohn's colitis or ulcerative colitis (UC) cannot be definitively established. Population-based studies have demonstrated that the average annual incidence of IC ranges 1.6 to 2.4/100,000 versus 7.3 to 13.6/100,000 for UC. At the time of initial diagnosis of inflammatory bowel disease, up to 10% to 15% of patients will be diagnosed as having IC. Over time, greater than 50% of patients with IC will be given a diagnosis of UC or Crohn's, with the majority being diagnosed with UC. Therefore, approximately 4% to 5% of all patients with inflammatory bowel disease will be left with the diagnosis of IC. Clinically, patients with IC seem to have a more severe course with a greater chance of colectomy and pouch failure. No studies have been undertaken to determine the optimum treatment regimen for IC. Recent studies have shown that patients with IC are still appropriate candidates for ileal pouch anal anastomosis. In conclusion, the current data support the premise that IC may be a separate entity, but future studies will have to focus on the genotypic and phenotypic characterization of these patients.

Colitis↗