Enhanced Mucosal Imaging and the Esophagus—Ready for Prime Time?

Innovation of endoscopic technology has recently been introduced to improve real-time visualization of mucosal architecture and subepithelial vascular structures. Since the esophagus is easily accessible using endoscopy and the length of required observation is limited, many different types of new imaging modalities have been reported and showing promising data. Early detection of neoplastic changes in the esophagus is devoted to the treatment in early stage cancer and theoretically leads to better prognosis. This review will focus on the emerging endoscopic technologies for the management of esophageal cancer.     

Role for cytoplasmic nucleotide hydrolysis in hepatic function and protein synthesis

Nucleotide hydrolysis is essential for many aspects of cellular function. In the case of 3′,5′-bisphosphorylated nucleotides, mammals possess two related 3′-nucleotidases, Golgi-resident 3′-phosphoadenosine 5′-phosphate (PAP) phosphatase (gPAPP) and Bisphosphate 3′-nucleotidase 1 (Bpnt1). gPAPP and Bpnt1 localize to distinct subcellular compartments and are members of a conserved family of metal-dependent lithium-sensitive enzymes. Although recent studies have demonstrated the importance of gPAPP for proper skeletal development in mice and humans, the role of Bpnt1 in mammals remains largely unknown. Here we report that mice deficient for Bpnt1 do not exhibit skeletal defects but instead develop severe liver pathologies, including hypoproteinemia, hepatocellular damage, and in severe cases, frank whole-body edema and death. Accompanying these phenotypes, we observed tissue-specific elevations of the substrate PAP, up to 50-fold in liver, repressed translation, and aberrant nucleolar architecture. Remarkably, the phenotypes of the Bpnt1 knockout are rescued by generating a double mutant mouse deficient for both PAP synthesis and hydrolysis, consistent with a mechanism in which PAP accumulation is toxic to tissue function independent of sulfation. Overall, our study defines a role for Bpnt1 in mammalian physiology and provides mechanistic insights into the importance of sulfur assimilation and cytoplasmic PAP hydrolysis to normal liver function.     

Acute mesenteric infarction: an important cause of abdominal pain in ulcerative colitis

We present four cases of acute mesenteric infarction in patients with active ulcerative colitis: one presenting prior to the diagnosis of ulcerative colitis, two at the time of diagnosis, and one many years after the diagnosis had been made. Intestinal ischaemia is an important part of the differential diagnosis in patients with ulcerative colitis presenting with abdominal pain. Conversely, in patients presenting with bloody diarrhoea after mesenteric ischaemia, ulcerative colitis should be considered.     

Ten year follow up of patients referred for coronary artery bypass grafting from a single district general hospital

Objective—To determine the status of patients 10 years after referral for coronary artery bypass graft (CABG) surgery.
Design—Retrospective analysis of case notes from all patients referred between 1 April 1981 and 31 March 1985. Full information gathered from hospital notes, GP records, and Registrar General for Scotland.
Setting—District General Hospital, West Lothian, Scotland.
Patients—102 patients referred for CABG during study period. Cardiac surgery was undertaken in Brompton Hospital, London, Royal Infirmary, Edinburgh, and Western Infirmary, Glasgow.
Results—At 10 years after operation 32 patients had died (27 cardiac, five non-cardiac causes). Full data were not available for five patients. Of the 65 remaining patients 24 had no angina, 13 had had a repeat procedure (CABG or angioplasty), and 28 had angina.
Conclusions—Long term benefits of CABG surgery is disappointing. Further steps are required to reduce progression of disease in this population.

Keywords: coronary artery bypass surgery;  repeat procedure;  survival;  audit     

A clinical trial of 7 alpha-methyl-19-nortestosterone implants for possible use as a long-acting contraceptive for men

Several preparations of testosterone and its esters are being investigated alone or in combination with other gonadotropin-suppressing agents as possible antifertility agents for men. We studied the effectiveness of 7 alpha-methyl-19-nortestosterone (MENT) as an antispermatogenic agent in men. MENT has been shown to be more potent than testosterone and to be resistant to 5 alpha-reduction. For sustained delivery of MENT, we used a system consisting of ethylene vinyl acetate implants containing MENT acetate (Ac), administered subdermally. Thirty-five normal volunteers were recruited in 3 clinics and were randomly assigned to 1 of 3 doses: 1 (12 men), 2 (11 men), or 4 (12 men) MENT Ac implants. The initial average in vitro release rate of MENT Ac from each implant was approximately 400 micro g/day. Implants were inserted subdermally in the medial aspect of the upper arm under local anesthesia. The duration of treatment was initially designed to be 6 months. However, in 2 clinics the duration of treatment was extended to 9 months for the 2-implant group and to 12 months for the 4-implant group. Dose-related increases in serum MENT levels and decreases in testosterone, LH, and FSH levels were observed. Effects on sperm counts were also dose related. None of the subjects in the 1-implant group exhibited oligozoospermia (sperm count, <3 million/ml). Four subjects in the 2-implant group became oligozoospermic, 2 of whom reached azoospermia. Eight subjects in the 4-implant group reached azoospermia, with 1 exhibiting oligozoospermia, whereas 2 were nonresponders. Side effects generally seen with androgen administration, such as increases in erythrocyte count, hematocrit, and hemoglobin and a decrease in SHBG, were also seen in this study and were reversible. Changes in lipid parameters were moderate and transient. Liver enzymes showed small changes. This study demonstrates that MENT Ac, when administered in a sustained release fashion via subdermal implants, can inhibit spermatogenesis over a prolonged period after a single administration and has the potential to be used as a male contraceptive.