Vascular complications of sickle cell disease.

Sickle cell disease (SCD) is a monogenetic disorder caused by a mutation in the ß-globin gene HBB leading to polymerization of red blood cells causing damage to cell membranes, increasing its rigidity and intravascular hemolysis. Multiple lines of evidence suggest that SCD can be viewed as pan-vasculopathy associated with multiple mechanisms but driven by hemoglobin S polymerization. Here we review the pathophysiology, clinical manifestations and management strategies for cerebrovascular disease, pulmonary hypertension and renal disease associated with SCD. These "vascular phenotypes" reflect the systemic nature of the complications of SCD and are a major threat to the well-being of patients with the disorder.

Dieulafoy's lesion: a rare cause of lower gastrointestinal bleeding.

The most common etiologies of lower gastrointestinal bleeding include ischemia, diverticulosis, and angiodysplasia. A Dieulafoy's lesion, an uncommon cause of upper gastrointestinal bleeding, is even more rare as an etiology of lower gastrointestinal bleeding. We report a case of an elderly patient with abrupt hematochezia requiring stabilization and blood transfusions. The presumptive diagnosis was diverticulosis or an arteriovenous malformation, but colonoscopy revealed that the source of bleeding was a Dieulafoy's lesion in the ascending colon. The lesion was injected with epinephrine, followed by placement of clips to achieve hemostasis. There were no subsequent interventions and the patient was safely discharged.

A novel protein kinase D inhibitor attenuates early events of experimental pancreatitis in isolated rat acini.

Novel protein kinase C isoforms (PKC δ and ε) mediate early events in acute pancreatitis. Protein kinase D (PKD/PKD1) is a convergent point of PKC δ and ε in the signaling pathways triggered through CCK or cholinergic receptors and has been shown to activate the transcription factor NF-κB in acute pancreatitis. For the present study we hypothesized that a newly developed PKD/PKD1 inhibitor, CRT0066101, would prevent the initial events leading to pancreatitis. We pretreated isolated rat pancreatic acinar cells with CRT0066101 and a commercially available inhibitor Gö6976 (10 µM). This was followed by stimulation for 60 min with high concentrations of cholecystokinin (CCK, 0.1 µM), carbachol (CCh, 1 mM), or bombesin (10 µM) to induce initial events of pancreatitis. PKD/PKD1 phosphorylation and activity were measured as well as zymogen activation, amylase secretion, cell injury and NF-κB activation. CRT0066101 dose dependently inhibited secretagogue-induced PKD/PKD1 activation and autophosphorylation at Ser-916 with an IC(50) ∼3.75-5 µM but had no effect on PKC-dependent phosphorylation of the PKD/PKD1 activation loop (Ser-744/748). Furthermore, CRT0066101 reduced secretagogue-induced zymogen activation and amylase secretion. Gö6976 reduced zymogen activation but not amylase secretion. Neither inhibitor affected basal zymogen activation or secretion. CRT0066101 did not affect secretagogue-induced cell injury or changes in cell morphology, but it reduced NF-κB activation by 75% of maximal for CCK- and CCh-stimulated acinar cells. In conclusion, CRT0066101 is a potent and specific PKD family inhibitor. Furthermore, PKD/PKD1 is a potential mediator of zymogen activation, amylase secretion, and NF-κB activation induced by a range of secretagogues in pancreatic acinar cells.

A case of idiopathic retroperitoneal fibrosis.

Retroperitoneal fibrosis is the presence of a fibrotic plaque in the prelumbar or presacral area. It can occur as a result of certain medications, fluid collections, inflammatory disease of various intra-abdominal organs, previous surgery or radiation therapy and various metastatic neoplasms. Most cases of retroperitoneal fibrosis are considered idiopathic. We report an interesting case of idiopathic retroperitoneal fibrosis with the emphasis on the importance of pathology to establish the diagnosis.

A comparison of the consensus and clinical definitions of pancreatitis with a proposal to redefine post-endoscopic retrograde cholangiopancreatography pancreatitis.

OBJECTIVES: We evaluated the correlation between the consensus and clinical definitions of pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP), with the objective of updating and revising the definition of post-ERCP pancreatitis (PEP). METHODS: Three hundred patients were subjected to serial serum amylase & lipase levels testing and abdominal computed tomography scan for abdominal pain after ERCP. Main outcome measures included the correlation between consensus and clinical definitions. RESULTS: Using consensus criteria, 25 patients had acute pancreatitis (11 of mild and 14 of moderate severity). Forty-three patients had acute pancreatitis using the clinical definitions (18 of mild and 25 of moderate severity). At 4 hours, serum hyperamylasemia of under 1.5-fold and at 12 hours a serum hyperamylasemia of under 2-fold had a negative predictive value of 0.94 for development of PEP. Serum hyperamylasemia following ERCP had a poor positive predictive value for PEP. CONCLUSIONS: Clinical and consensus definitions are poorly correlated; use of the latter leads to significant underrecognition of PEP. The adoption of clinical definition results in uniformity of diagnosis of pancreatitis for clinical care and research. Serum amylase levels at 4 and 12 hours after ERCP have a high negative predictive value for PEP.