Zamir S. Brelvi

A System for Monocytic Differentiation of Leukemic Cells HL 60 by a Short Exposure to 1,25-Dihydroxycholecalciferol

Abstract The human promyelocytic cell line HL 60 can be induced to differentiate toward more mature myeloid or monocytic forms by a variety of agents. This process is thought to require several days of exposure to the inducer, thus making it difficult to identify the early cellular changes which are fundamental to the differentiation program, and to relate the induction to phases of the cell cycle. In order to study the kinetics of leukemic cell differentiation we have developed a system for the induction of rapid monocytic maturation in a subpopulation of HL 60 cells. The cells are exposed to 10-7 M 1,25-dihydroxycholecalciferol for 4 hr in serum-free medium. Subsequent incubation in a complete medium results in cellular differentiation recognizable by several criteria (phagocytosis, nonspecific esterase reaction, adherence to substratum, cell morphology) beginning at 10 hr from the exposure to the inducer. Approximately 20 hr later 30-40% of the cells in culture show the differentiated phenotype and are capable of phagocytosis. The proportion of differentiated cells in culture decreases thereafter. This system has been utilized to study the expression of c-myc oncogene in relation to the kinetics of maturation, and it was found that the inhibition of the expression of this gene precedes the onset of phenotypic differentiation by approximately 8 hr, is transient, and is accompanied by a brief retardation of cell proliferation, which resumes the normal rate within 24 hr of the exposure to the inducer.

Hemobilia Secondary to Transjugular Intrahepatic Portosystemic Shunt Procedure: A Case Report

A 59 year-old woman with liver cirrhosis due to hepatitis C, complicated by refractory hepatic hydrothorax was treated with a TIPS (transjugular intrahepatic portosystemic shunt) procedure. The procedure was complicated by substantial gastrointestinal hemorrhage. EGD (esophagogastroduodenoscopy) was performed and revealed hemobilia. A hepatic angiogram was then performed revealing a fistulous tract between a branch of the hepatic artery and biliary tree. Bleeding was successfully stopped by embolization of the bleeding branch of the right hepatic artery. Hemobilia is a rare cause of upper gastrointestinal bleeding with an increasing incidence due to the widespread use of invasive hepatobiliary procedures. Hemobilia is an especially uncommon complication of TIPS procedures. We recommend that in cases of hemobilia after TIPS placement, a physician should immediately evaluate the bleeding to exclude an arterio-biliary fistula.

Metastatic Gastric MALT Lymphoma Masquerading as Pulmonary Infiltrates, with a Dramatic Response to Chemotherapy

In 1983, Isaacson and Wright described the entity mucosaassociated lymphoid tissue lymphoma [1]. It is a type of nonHodgkin’s lymphoma, now classified as an extranodal marginal zone B cell lymphoma [2]. By definition, a low-grade lymphoma, mucosa-associated lymphoid tissue (MALT) lymphoma is thought to develop as a result of chronic antigenic stimulation. Epidemiologic models indicate that over 90 % of gastric MALT lymphomas arise in the presence of Helicobacter pylori infection and that eradication of H. pylori infection leads to endoscopic and histologic remissions in the majority of those cases [3, 4]. Autoimmune diseases may also create a setting of chronic inflammation and antigenic stimulation leading to MALT lymphoma [5]. It is also postulated that elements of the innate immune system play a role in the defense against lymphoproliferative diseases, and particularly, natural killer cell dysfunction is seen in high-grade nonHodgkin’s lymphomas [6]. Genetic abnormalities, notably certain high-risk chromosomal translocations such as t(11;18), t(1;14), and t(14;18), to name a few, have also been implicated as a cause of antigenindependent proliferation, particularly in cases not associated with or not responsive to H. pylori eradication [7]. On immunophenotype analysis, MALT lymphoma demonstrates B cell markers, CD19, CD20, and CD45 [8]. Predominantly found in gastric tissue, it can virtually arise in any epithelial tissue. Some sites worth mentioning include the lung, eye, skin, salivary glands, and breast. Systemic screening is therefore essential when MALT lymphoma is suspected. A good history and physical exam are key, followed by definitive histopathologic diagnosis via biopsies. Endoscopic biopsies for gastric MALT lymphoma are diagnostic in more than 75 % of the patients and should include evaluation for H. pylori infection [9]. Here, we report a case of metastatic gastric MALT lymphoma with a dramatic response to treatment.

Intravenous Glucagon Beneficial During Colonoscopy in Patient with IBS

Background and Aim: Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by abdominal pain or discomfort and altered bowel habits. Patients with IBS requiring colonoscopy take longer time to cecum with higher need for medications used for conscious sedation. Glucagon is routinely used during endoscopic procedures to reduce peristalsis that interfere with the procedure. However, randomized controlled data using glucagon during endoscopic procedures are lacking. We designed a prospective randomized placebo-controlled trial to study the effect of intravenous glucagon given during colonoscopy. Materials and Methods: We received approval from the FDA for this off-label use of glucagon during colonoscopy. This is a double-blind randomized placebo-controlled study. Patients were selected based on ROME III criteria for IBS; patients who met Rome III criteria and had an indication for colonoscopy for age-specific colon cancer screening or for work up of any alarm signs. We selected 34 patients meeting the Rome III for IBS and randomized into Group A and Group B. Both the performing endoscopist and patients were blinded. These patients in both groups initially received a standard dose of conscious sedation, up to 100 mcg of fentanyl and up to 5 mg of midazolam intravenously. In Group A, 17 patients, in addition to conscious sedation, received 1 ml saline as placebo. In Group B, 17 patients, in addition to conscious sedation, received 1 mg of intravenous glucagon. Parameters evaluated were as follows: 1) Total time required for colonoscopy 2) Completion of colonoscopy as documented by cecal intubation or visualization of appendicular orifice 3) Level of comfort in patient concerned to postprocedure spasmodic pain, which was based on Wong-Baker FACES pain rating scale and 4) Calculate the amount of sedation required in both groups of patients and also at what extent glucagon helped to decrease the requirement of sedatives. Data was analyzed using the student t-test.

Reprogramming of gastric motility with "pulse therapy" (metoclopramide and erythromycin) in severe gastroparesis

Gastroparesis is a very common condition, however many times it becomes difficult to manage even after long-term treatment due to multiple etiologies or improper therapy. Patients with severe gastroparesis are considered candidates for gastric electrical stimulants. The “Pulse Therapy” using metoclopramide and erythromycin to reprogram gastric motility can delay or even avoid the need for gastric electrical stimulants. This case report focuses on a patient with severe gastroparesis, who was considered for a gastric pacemaker implantation and was instead treated successfully with “Pulse Therapy.” As a part of this regimen, he was given metoclopramide continuously for 3 months along with pulses of erythromycin for 10 days a month for 3 months. Patient recovered dramatically that he no longer remained a candidate for gastric pacemaker implantation. This case study emphasizes on how the proper use of prokinetic agents based on symptoms and gastric emptying study can reprogram the stomach motility in these patients with severe gastroparesis.