Circulating Fibronectin Controls Tumor Growth

Fibronectin is ubiquitously expressed in the extracellular matrix, and experimental evidence has shown that it modulates blood vessel formation. The relative contribution of local and circulating fibronectin to blood vessel formation in vivo remains unknown despite evidence for unexpected roles of circulating fibronectin in various diseases. Using transgenic mouse models, we established that circulating fibronectin facilitates the growth of bone metastases by enhancing blood vessel formation and maturation. This effect is more relevant than that of fibronectin produced by endothelial cells and pericytes, which only exert a small additive effect on vessel maturation. Circulating fibronectin enhances its local production in tumors through a positive feedback loop and increases the amount of vascular endothelial growth factor (VEGF) retained in the matrix. Both fibronectin and VEGF then cooperate to stimulate blood vessel formation. Fibronectin content in the tumor correlates with the number of blood vessels and tumor growth in the mouse models. Consistent with these results, examination of three separate arrays from patients with breast and prostate cancers revealed that a high staining intensity for fibronectin in tumors is associated with increased mortality. These results establish that circulating fibronectin modulates blood vessel formation and tumor growth by modifying the amount of and the response to VEGF. Furthermore, determination of the fibronectin content can serve as a prognostic biomarker for breast and prostate cancers and possibly other cancers.     

Pitfalls in the diagnosis of intestinal tuberculosis: a case report

An 18-year-old long-term Norwegian resident of Somali origin was submitted to hospital with bloody diarrhoea, fever, weight loss and abdominal pain. On initial colonoscopy, colitis with segmental appearance was seen. Apart from a single polymerase chain reaction (PCR) from gastric aspirate staining, PCR and culture for acid-fast bacilli revealed negative results from the multiple samples taken including sputum, gastric fluid, stool, urine and intestinal mucosa. On physical examination and CT scan, there was no evidence of ascites, lymph node enlargement or pathologic pulmonary findings. Although the diagnosis was uncertain, tuberculostatic therapy was initiated. As the conformational testing of the PCR and the microbiological work-up remained negative and the patient's condition did not improve, tuberculostatic treatment was stopped and Crohn's disease was stated as the most likely diagnosis. Although the patient improved clinically under therapy with prednisolone, newly appearing fistulas deriving from the ascending colon were noted on follow-up. Thus tuberculostatic treatment was restarted. However, signs of an acute abdomen appeared and laparotomy was performed, thereby revealing a peritoneal spread of nodules. Resection of the ileum and ascending colon was performed. Diagnosis of intestinal tuberculosis with peritoneal spread was made by histology from resected bowel specimens showing caseating granulomas and a positive PCR result. The patient's condition improved after resection of the highly inflamed bowel segments and tuberculostatic therapy. Our case report shows the difficulty of proving intestinal tuberculosis by microbiological testing, macroscopic features on colonoscopy, histology, imaging such as CT scan and by empirical therapy. Therefore, in cases of colonic inflammation, where intestinal tuberculosis is an important differential diagnosis, a more aggressive diagnostic approach such as explorative laparoscopy should be considered.     

Rescue therapy with tacrolimus in a patient with toxic megacolon

BACKGROUND: Toxic megacolon is a life-threatening complication most commonly observed in patients with ulcerative colitis or Crohn's disease that is characterized by total or segmental nonobstructive colonic dilatation of at least 6 cm on plain abdominal films associated with systemic toxicity. CASE REPORT: We report an unusual case of fulminant steroid-refractory ulcerative colitis complicated by toxic megacolon treated successfully with the immunosuppressant tacrolimus. CONCLUSION: Tacrolimus administration induced clinical remission and bridged the time interval, until the standard immunosuppressant azathioprine could maintain clinical remission, thereby avoiding eminent emergency colectomy.     

Plasma lidocaine concentrations after local anesthesia of the groin for cardiac catheterization.

This study aimed to investigate serum lidocaine concentrations after subcutaneous infiltration of the groin for cardiac catheterization. One hundred twenty-six patients for planned heart catheterization received five different dosages (5-25 ml) of lidocaine 2% for local anesthesia of the groin in a randomized manner. All of them received an arterial sheath and 13 received both an arterial sheath and a venous sheath for right heart catheterization. Blood samples were taken before as well as 15, 30, and 120 min after subcutaneous application of the drug. Although in 33 patients with an arterial sheath (no venous sheath) excessive doses of lidocaine 2% (20-25 ml) were used, neither symptoms of intoxication nor toxic plasma levels were observed. However, in patients receiving an additional venous sheath, toxic plasma levels were obtained in a third of the cases. One of them showed symptoms of intoxication.