Kamil Obideen

Liver-infiltrating lymphocytes in chronic human hepatitis C virus infection display an exhausted phenotype with high levels of PD-1 and low levels of CD127 expression.

ABSTRACT The majority of people infected with hepatitis C virus (HCV) fail to generate or maintain a T-cell response effective for viral clearance. Evidence from murine chronic viral infections shows that expression of the coinhibitory molecule PD-1 predicts CD8+ antiviral T-cell exhaustion and may contribute to inadequate pathogen control. To investigate whether human CD8+ T cells express PD-1 and demonstrate a dysfunctional phenotype during chronic HCV infection, peripheral and intrahepatic HCV-specific CD8+ T cells were examined. We found that in chronic HCV infection, peripheral HCV-specific T cells express high levels of PD-1 and that blockade of the PD-1/PD-L1 interaction led to an enhanced proliferative capacity. Importantly, intrahepatic HCV-specific T cells, in contrast to those in the periphery, express not only high levels of PD-1 but also decreased interleukin-7 receptor alpha (CD127), an exhausted phenotype that was HCV antigen specific and compartmentalized to the liver, the site of viral replication.

Impaired Hepatitis C Virus (HCV)-Specific Effector CD8+ T Cells Undergo Massive Apoptosis in the Peripheral Blood during Acute HCV Infection and in the Liver during the Chronic Phase of Infection

ABSTRACT A majority of patients infected with hepatitis C virus (HCV) do not sustain an effective T-cell response, and viremia persists. The mechanism leading to failure of the HCV-specific CD8+ T-cell response in patients developing chronic infection is unclear. We investigated apoptosis susceptibility of HCV-specific CD8+ T cells during the acute and chronic stages of infection. Although HCV-specific CD8+ T cells in the blood during the acute phase of infection and in the liver during the chronic phase were highly activated and expressed an effector phenotype, the majority was undergoing apoptosis. In contrast, peripheral blood HCV-specific CD8+ T cells during the chronic phase expressed a resting memory phenotype. Apoptosis susceptibility of HCV-specific CD8+ T cells was associated with very high levels of programmed death-1 (PD-1) and low CD127 expression and with significant functional T-cell deficits. Further evaluation of the “death phase” of HCV-specific CD8+ T cells during acute HCV infection showed that the majority of cells were dying by a process of cytokine withdrawal, mediated by activated caspase 9. Contraction during the acute phase occurred rapidly via this process despite the persistence of the virus. Remarkably, in the chronic phase of HCV infection, at the site of infection in the liver, a substantial frequency of caspase 9-mediated T-cell death was also present. This study highlights the importance of cytokine deprivation-mediated apoptosis with consequent down-modulation of the immune response to HCV during acute and chronic infections.

Carcinoid tumors: what should increase our suspicion?

Carcinoid tumors are neuroendocrine neoplasms, primarily of the gastrointestinal tract. Their incidence has been increasing over the last 2 to 3 decades. Patients often present with vague, nonspecific symptoms. Thus, primary care physicians should keep this diagnosis in mind and start appropriate diagnostic testing if they suspect it on a clinical basis. Patients with carcinoid tumors are also at increased risk of developing other malignancies, so close follow-up by their primary care physician is necessary. Patients often present with vague, nonspecific symptoms, and unless the primary care physician suspects that the patient has a carcinoid tumor, the appropriate testing is seldom ordered.

Intraduodenal Hydrochloric Acid Infusion for Facilitation of Cannulation of the Dorsal Pancreatic Duct at ERCP in Patients With Pancreas Divisum: A Preliminary Study

Intraduodenal Hydrochloric Acid Infusion for Facilitation of Cannulation of the Dorsal Pancreatic Duct at ERCP in Patients With Pancreas Divisum: A Preliminary Study

Nocturnal hydration--an effective modality to reduce recurrent abdominal pain and recurrent pancreatitis in patients with adult-onset cystic fibrosis.

Recurrent abdominal pain and recurrent pancreatitis are common problems associated with some patients with cystic fibrosis (CF). There is no known effective method to prevent recurrent abdominal pain and recurrent pancreatitis in such patients. The objective of this study was to determine whether nocturnal hydration (NH) prevents recurrent abdominal pain and recurrent acute pancreatitis in patients with adult-onset CF. Adult CF patients who were referred to our Pancreatic Diseases Clinic for recurrent abdominal pain and pancreatitis were enrolled in the study. Each patient was encouraged to drink plenty of water during the night and established a 6-month diary (3 months before and 3 months after NH was initiated), recording the frequency and severity of their abdominal pain, the amount of pain medication taken, and the volume of their water intake. We also reviewed the number of doctors clinic visits, emergency room visits, and hospitalizations for about 1 year before and 1 year after the initiation of the NH. The frequency and the severity of abdominal pain in this group of patients were significantly reduced. The amount of pain medication and the number of emergency room visits and hospitalizations for abdominal pain and acute pancreatitis were reduced. NH is a simple and cost-effective method to prevent recurrent abdominal pain and pancreatitis in patients with adult-onset CF.

Fluoroscopy Time During Endoscopic Retrograde Cholangiopancreatography

Fluoroscopy Time During Endoscopic Retrograde Cholangiopancreatography Kamil Obideen, Maarouf Hoteit, John Affronti, Qiang Cai Background: Endoscopic Retrograde Cholangiopancreatography (ERCP) is a gastrointestinal endoscopic procedure that requires fluoroscopy. The radiation dose of fluoroscopy is much higher than that of routine X-ray examinations, such as a chest X-ray. A few studies regarding radiation exposure of patients and ERCP staff during ERCP have been published in recent years. However, information about radiation exposure during each step of the procedure is not well known.AIMS: This study aimed to provide data regarding radiation exposure during specific components of ERCP, such as during the deep cannulation of the common bile duct (CBD). Methods: In the last several months, patients referred to us for their first ERCP were enrolled in this study. The fluoroscopy time before, during and post deep cannulation of the CBD in each ERCP were recorded. Results: We analyzed 46 successful ERCP procedures during the study period. Those procedures can be divided into two groups: 18 were diagnostic ERCPs and 28 were therapeutic ERCPs. The latter included obtaining cytology, performing sphincterotomy, balloon extraction, and stent insertion, etc. The mean FT before deep cannulation of the CBD was minimal, less than 0.1 minutes for each procedure in both groups. The mean FTs during the deep cannulation of the CBD were 4.5G4.1 minutes and 6.4G7.9 minutes for the diagnostic group and the therapeutic group respectively. The mean FTs for the whole procedure were 6.1G5.0 minutes and 16.2G11.0 minutes for the diagnostic group and the therapeutic groups respectively. The FT during deep cannulation of the CBD accounted for a significant portion of the whole FT in both the diagnostic group (4.5/6.1, about 74%) and the therapeutic group (6.4/16.2, about 40%). Conclusions: The radiation dose of one-minute FT is approximately 15 mGy at skin entrance which is equal to almost 100 routine chest X-rays. If the cannulation time can be reduced thereby shortening the FT during deep cannulation of the CBD, it will significantly reduce the radiation exposure during ERCP.