Kenneth Manas

TNF-α induced endothelial MAdCAM-1 expression is regulated by exogenous, not endogenous nitric oxide

BackgroundMAdCAM-1 is an adhesion molecule expressed in Peyers patches and lymphoid tissues which is mobilized by cytokines like TNF-α and is a major determinant of lymphocyte trafficking to the gut in human inflammatory bowel disease (IBD). It has been suggested that both reactive oxygen and nitrogen metabolites participate in regulating adhesion molecule expression in response to TNF-α.MethodsTo examine how exogenous and endogenous sources of NO modulate MAdCAM-1 induction by TNF-α, we pre-treated mouse lymphatic endothelial cells with either long or short acting NO donors prior to TNF-α-stimulation, and measured MAdCAM-1 induction at 24 h.Results and DiscussionDETA-NO, a long-acting NO donor, and SperNO, a rapid releasing NO donor both inhibited TNF-α-stimulated MAdCAM-1 expression in a concentration dependent manner. Both NO donors also reduced a4b7-dependent lymphocyte endothelial adhesion. Inhibition of endogenous NO production by either L-NAME, a non-selective NOS inhibitor, or by 1400 w, a selective iNOS inhibitor failed to induce, or potentiate TNF-α regulated MAdCAM-1 expression.ConclusionsExogenous NO donors may be beneficial in the treatment of IBD, while endogenous nitric oxide synthases may be less effective in controlling adhesion molecule expression in response to cytokines.

Laboratory Markers as Predictors of Mortality in Patients With Clostridium difficile Infection

Previous studies have identified laboratory markers for severe Clostridium difficile infection (CDI). The most consistent of these markers is the presence of marked leukocytosis. We examined the validity of these markers as predictors of mortality in patients with CDI. We excluded patients with preexisting hematologic conditions that would be expected to impair their ability to demonstrate leukocytosis. On univariate analysis, marked leukocytosis (P = 0.02), thrombocytopenia (P = 0.008), and increased blood urea nitrogen (P < 0.001) and creatinine (P = 0.001) levels were found to be significantly associated with mortality in patients with CDI. However, on logistic regression analysis, only renal impairment was found to be an independent predictor (odds ratio, 5.07). Importantly, in our study, leukocytosis was not an independent predictor after adjustment for other variables, which may be due to our selection criteria when adjusting for confounding variables. We are therefore of the opinion that in immunocompromised hosts who are leukopenic at the time of CDI diagnosis, other laboratory markers should be identified to serve as indicators for severe disease.

Eosinophilic gastroenteritis of the pancreas : An unusual cause of obstructive jaundice

Eosinophilic gastroenteritis (EG) is a rare gastrointestinal disorder of undetermined etiology and is manifest by eosinophilic infiltration of any area of gastrointestinal tract, most frequently stomach and small intestine. Peripheral eosinophilia is present in about 80% of patients. Definitive diagnosis requires histologic evidence of eosinophilic infiltration; which is usually patchy in distribution. Steroids are the mainstay of treatment. We present a case of 47-year-old man with abdominal pain, jaundice, and marked eosinophilia. Endoscopic retrograde cholangio-pancreatogram revealed a dilated common bile duct. There was biopsy proven eosinophilic infiltration in stomach, duodenum, gall bladder, and pancreas. Obstructive jaundice is an extremely rare manifestation of EG. This unusual case illustrates the wide variety of gastrointestinal manifestations caused by EG and emphasizes the importance of clinical suspicion and endoscopic mucosal biopsies in diagnosis of EG. This entity should be considered in the patients with chronic and relapsing gastrointestinal symptoms.

Diabetic Ketoacidosis-induced Hypertriglyceridemic Acute Pancreatitis Treated with Plasmapheresis—Recipe for Biochemical Disaster Management

Diabetic ketoacidosis (DKA)-induced hypertriglyceridemia causing pancreatitis is an interesting phenomenon that has rarely been reported in literature. Plasmapharesis is a well known treatment modality for hypertriglyceridemia-induced pancreatitis. We report a patient with DKA-induced hypertriglyceridemic acute pancreatitis treated successfully with plasmapharesis.

Substitution with Alternative Anti-TNFα Therapy (SAVANT)—Outcomes of a Crohnʼs Disease Cohort Undergoing Substitution Therapy with Certolizumab

Background:Biological therapy targeting tumor necrosis factor-alfa has revolutionized the treatment of Crohns disease (CD). Our study retrospectively reviewed clinical outcomes of 60 patients administratively substituted from Infliximab or Adalimumab to Certolizumab. Maintenance of disease and failure rates after substitution of anti–tumor necrosis factor-alfa agents in CD patients were monitored over 1 year, and this is the first outcomes study of patients maintained on Infliximab or Adalimumab substituted to Certolizumab. Methods:A hospital pharmacy directive required all patients on biological therapy to be administratively substituted to Certolizumab therapy. This single-center retrospective analysis initially included 68 CD patients presenting at Louisiana State University Health Sciences Center-Shreveport. Clinical, endoscopic, and serologic data were compared at baseline and at 4 intervals over 1 year. Results:Of 60 enrolled CD patients, 45 (75%) successfully transitioned to Certolizumab and had stable disease at 1 year. Of the 15 (25%) patients who “failed” substitution at 1 year, 5 were returned to Adalimumab and 7 to Infliximab; 3 were maintained on steroids awaiting subsequent therapy. Importantly, when patients were segregated on the basis of initial disease control, it was found that 3 (12.5%) previously well-controlled patients failed therapy, whereas 12 (33.3%) who initially had active disease failed Certolizumab substitution. Conclusions:Our study found that 25% of CD patients substituted to Cimzia failed substitution, whereas 75% still exhibited a good clinical response with stable disease at 1 year. Our findings indicate that disease status and behavior at the time of biological substitution may predict therapeutic responsiveness.

Harbingers for Clostridium difficile-Associated Diarrhea

Purpose Recent research has recognized surrogate markers for Clostridium difficile-associated diarrhea (CDAD). Among the most consistently identified markers are the leukocyte count, platelet count, and albumin level. Previous investigators failed to exclude patients with hematologic disorders that may have confounded their results. Therefore, the exclusion of this subset from our study lends it a unique perspective. Methods We undertook a retrospective review of inpatients at our institution that were diagnosed with nosocomial diarrhea and subsequently had a stool sample sent for C. difficile toxins A and B. Patients with major hematologic disorders were excluded. Results A total of 77 C. difficile-positive patients and 91 C. difficile-negative patients were studied. Patients with CDAD had a significantly higher leukocyte and platelet count but a lower albumin level compared with patients without CDAD. Conclusion Our results support the conclusion of preceding studies that leukocytosis, thrombocytosis, and hypoalbuminemia are reliable clinical predictors for CDAD even after careful exclusion of confounding factors.

Synthetic Cannabinoid Abuse and a Rare Alpha-1-Antitrypsin Mutant Causing Acute Fulminant Hepatitis: A Case Report and Review of the Literature

Synthetic cannabinoids (SCs) abuse is on the rise because they are easily obtained over the counter; they are potent psychoactive compounds and routine drug testing does not detect them. As their abuse is on the rise, so are their detrimental side effects; however, the occurrence of acute hepatitis due to SCs abuse has been reported only once before. In this case, testing revealed that the patient was also heterozygous for alpha-1-antitrypsin (A-1-AT) with the phenotype of PI⁎EM. This mutant phenotype has never been reported as a cause of A-1-AT disease and the abuse of SCs in a patient with this phenotype has also never been reported. This case illustrates the possible need to expand routine drug testing for SCs and consider A-1-AT phenotyping in certain clinical scenarios.