Biliary dyskinesia: a potentially unrecognized cause of abdominal pain in children

Biliary dyskinesia is defined as symptomatic biliary colic without cholelithiasis, and is diagnosed during cholescintigraphy by assessing gallbladder emptying with cholecystokinin (CCK) stimulation. Unfortunately, gallbladder emptying is not routinely assessed during cholescintigraphy in pediatric patients. The purpose of this review is to assess the effectiveness of cholecystectomy in patients with chronic abdominal pain and delayed gallbladder emptying and to assess whether these findings correlate with the histologic evidence of chronic cholecystitis. We retrospectively reviewed the medical records of all patients (n=16) at our institution from October 1997 to August 2001 who underwent quantitative cholescintigraphy with CCK stimulation that demonstrated delayed gallbladder emptying (<35% at 60 min) and who subsequently underwent cholecystectomy. Laparoscopic cholecystectomy was performed in 16 patients with chronic abdominal pain. All 16 patients had delayed gallbladder emptying (mean ejection fraction: 15±8%, range: 3–32%). The mean age was 12±2 years (range: 8–17 years). Presenting symptoms included abdominal pain (86%), fatty food intolerance (27%), emesis (13%), and diarrhea (13%). Mean duration of abdominal pain before operation was 11±19 months (range: 2 weeks–6 years). One patients symptoms persisted postoperatively, but abdominal pain resolved in all other patients. Histologic evidence of chronic cholecystitis was demonstrated in 86% of surgical specimens. Five patients underwent concurrent appendectomy, and all had normal appendiceal histology. Our experience suggests that children with chronic abdominal pain and delayed gallbladder emptying on CCK-stimulated cholescintigraphy are likely to benefit from cholecystectomy and to have histologic evidence of chronic cholecystitis.     

Development of drug resistance to gallium nitrate through modulation of cellular iron uptake

We have shown that transferrin-gallium (Tf-Ga) blocks DNA synthesis through inhibition of cellular iron incorporation and a diminution in the activity of the iron-dependent M2 subunit of ribonucleotide reductase. To examine the mechanisms of drug resistance to gallium, we developed a subline of HL60 cells (R cells) which is 29-fold more resistant to growth inhibition by gallium nitrate than the parent line (S cells). R cells displayed a 2.5-fold increase in transferrin (Tf) receptor expression, without a change in receptor affinity for Tf. The uptake and release of 67Ga were similar for both S and R cells. The uptake of 59Fe-Tf by S cells was inhibited by gallium nitrate over 24-48 h of incubation. In contrast, 59Fe-Tf uptake by R cells, although initially inhibited by gallium nitrate at 24 h, was no longer inhibited at 48 h of incubation. 59FeCl3 uptake by R cells was significantly greater than that of S cells, regardless of the time in culture. Despite the increase in 59Fe uptake by R cells, the ferritin content of these cells was lower than that of S cells. The ribonucleotide reductase electron spin resonance signal of R cells was comparable to that of S cells. R cells were not cross-resistant to Adriamycin, vincristine, cis-platinum or hydroxyurea. Resistance to gallium nitrate in this subline of HL60 cells results primarily from the ability of cells to overcome the gallium-induced block in iron incorporation. In addition, intracellular iron in R cells appears to traffic preferentially to a non-ferritin compartment.     

PI3K regulates pleckstrin-2 in T-cell cytoskeletal reorganization

Pleckstrin-2 is composed of 2 pleckstrin homology (PH) domains and a disheveled-Egl-10-pleckstrin (DEP) domain. A lipid-binding assay revealed that pleckstrin-2 binds with greatest affinity to D3 and D5 phosphoinositides. Pleckstrin-2 expressed in Jurkat T cells bound to the cellular membrane and enhanced actin-dependent spreading only after stimulation of the T-cell antigen receptor or the integrin alpha4beta1. A pleckstrin-2 variant containing point mutations in both PH domains failed to associate with the Jurkat membrane and had no effect on spreading under the same conditions. Although still membrane bound, a pleckstrin-2 variant containing point mutations in the DEP domain demonstrated a decreased ability to induce membrane ruffles and spread. Pleckstrin-2 also colocalized with actin at the immune synapse and integrin clusters via its PH domains. Although pleckstrin-2 can bind to purified D3 and D5 phosphoinositides, the intracellular membrane association of pleckstrin-2 and cell spreading are dependent on D3 phosphoinositides, because these effects were disrupted by pharmacologic inhibition of phosphatidylinositol 3-kinase (PI3K). Our results indicate that pleckstrin-2 uses its modular domains to bind to membrane-associated phosphatidylinositols generated by PI3K, whereby it coordinates with the actin cytoskeleton in lymphocyte spreading and immune synapse formation.     

Renal corticomedullary metabolite gradients during graded arterial occlusion: a localized 31P magnetic resonance spectroscopy study

In order to investigate the role of the outer medulla in acute ischemic renal failure (Epstein FH, Balaban RS, Ross BD: Redox state of cytochrome aa3 in isolated perfused rat kidney. Am J Physiol 1982;243: F356-F363), the distribution of ATP in the in vivo porcine kidney and its relationship to Na transport and to ischemia was examined by using localized 31P magnetic resonance spectroscopy. Renal cortex (ATP) was higher than medulla. Reduction in Na transport produced by partial renal arterial occlusion ("hypofiltration"), resulted in a 13% increase in the ATP/Pi ratio of the whole kidney (from 2.61 +/- 0.26 to 2.96 +/- 0.27; P less than 0.03). This increase was accounted for by a statistically significant increase in (ATP) in the cortex, with medulla contributing to an insignificant extent. Further occlusion of the renal artery to reduce GFR to zero ("hypoperfusion") resulted in a 70% fall in ATP/Pi ratio. (ATP) was reduced most in the cortex, but pH fell equally in cortex and medulla. After release of arterial occlusion, cortical ATP recovered less completely than medulla ATP. Intracellular pH and Pi were restored in both cortex and medulla. It was concluded that cortex and medulla contribute equally to the pattern of disordered energy metabolism in acute renal failure. Sparing of ATP during hypofiltration may reflect the reduced energy requirements of active Na transport.     

Cochlear sequestrum — An uncommon complication of a common disease

Sequestration of the inner ear is an unusual complication of chronic suppurative otitis media. More so when not associated with a cholesteatoma. We report a rare case of tubotympanic disease producing multiple complications including a cochlear sequestrum.