Functional consequences of ROMK mutants linked to antenatal Bartter's syndrome and implications for treatment

The antenatal variant of Bartter's syndrome is an autosomal recessive kidney disease characterized by polyhydramnios, premature delivery, hypokalemic alkalosis and hypercalciuria. It is genetically heterogeneous, having been linked recently to mutations in an ATP- sensitive, renal outer medullary K+channel, ROMK, and earlier to mutations in the Na-K-2Cl co-transporter, NKCC2. We characterized four of the mutations reported in three heterozygous ROMK variants of antenatal Bartter's and found that each expressed a distinct phenotype in Sf9 cells. One mutation expressed normal function and appears to be an allelic polymorphism. The other three mutations produced channels with significantly reduced K+fluxes. However, the mechanisms in each case were different and reflected abnormalities in phosphorylation, proteolytic processing or protein trafficking. The different mechanisms may be important in the design of appropriate therapy for patients with this disease.      

Bile reflux in benign and malignant barrett’s esophagus: Effect of medical acid suppression and nissen fundoplication

Bile reflux has been implicated in the pathogenesis and malignant degeneration of Barrett’s esophagus, but clinical studies in patients with adenocareinoma arising in Barrett’s esophagus are lacking. Ambulatory esophageal measurement of acid and bile reflux was performed with the previously validated fiberoptic bilirubin monitoring system (Bilitec) combined with a pH probe in 20 asymptomatie volunteers, 19 patients with gastroesophageal reflux disease (GERD) but no mucosal injury, 45 patients with GERD and erosive esophagitis, 33 patients with GERD and Barrett’s esophagus, and 14 patients with early adenocarcinoma arising in Barrett’s esophagus. Repeat studies were done in 15 patients under medical acid suppression and 16 patients after laparoscopie Nissen fundoplication. The mean esophageal bile exposure time showed an exponential increase from GERD patients without esophagitis to those with erosive esophagitis and benign Barrett’s esophagus and was highest in patients with early carcinoma in Barrett’s esophagus (P <0.01). Pathologic esophageal bile exposure was documented in 18 (54.5%) of 33 patients with benign Barrett’s esophagus and 11 (78.6%) of 14 patients with early adenoearcinoma in Barrett’s esophagus. Nissen fundoplieation but not medical acid suppression resulted in complete suppression of bile reflux. Bile reflux into the esophagus is particularly prevalent in patients with Barrett’s esophagus and early cancer. Bile reflux into the esophagus can be completely suppressed by Nissen fundoplication but not medical acid suppression alone. (J GASTROINTEST SURG 1998;2:333-341.) Presented at the Thirty-Eighth Annual Meeting of The Society for Surgery of the Alimentary Tract, Washington, D.C., May 11–14, 1997     

Impact of clinical history on fracture detection with radiography

The effect of knowledge of localizing symptoms and signs in the detection of fractures was studied. Forty radiographs of the extremities were examined twice by seven radiologists; the sessions were separated by 4 months. In 26 cases, a subtle fracture was present; 14 cases were normal. In half of the cases at each session, the precise location of pain, tenderness, or swelling was provided. The observer was asked to determine if the case was normal or abnormal (provide the exact location of the fracture) and to indicate the degree of confidence in the diagnosis. Responses were converted to a numeric scale for analysis. Analysis of receiver operator characteristic parameters indicates that clues regarding location of trauma facilitate detection of fractures. The improvement is based largely on an increased true-positive rate without an increased false-positive rate, regardless of the decision criteria of the radiologist (overall willingness to "overread" or "underread"). This has direct clinical applicability and reinforces the plea of radiologists for precise clinical information.