Gastrojejunocolic fistula--a rare complication of stomach surgery

The gastrojejunocolic fistula represents a clinical entity that occurs very rarely following gastro-jejunal anastomoses and manifests itself clinically and paraclinically by a severe malabsorption syndrome. The results of the physiopathological approach may be summed up as follows: reduced level of seric proteins, fluid and electrolytic depletion, deficiencies in the absorption of the vitamins soluble in fats and water, which may all vary from mildness to severeness, depending on the flow rate of the fistula. Most often, the diagnosis is set by performing barium enema, which is positive for all cases, whereas the barium passage is less efficient, enabling diagnosis in only 33% of the cases. The radiological image may be reduced on principle to one single sign: the abnormal fistulous trajectory (barium passes from the stomach directly into the colon or the enema fills the gastric lumen). It is recommended that surgical treatment be performed in a single stage, by resecting the entire fistula and re-establishing the gastro-jejunal and colic continuity. We report a case of gastrojejunocolic fistula in a patient that underwent 2/3 gastric resection for gastric ulcer 9 years ago.     

Can the difference in serum concentration of urea and cystatin C be used in diagnosis and prognosis of heart failure?

Changes in renal function are an important diagnostic and prognostic indicator in patients with heart failure (HF). They are caused by decreased renal perfusion and consequently decreased glomerular filtration rate (GFR), or by the effect of increased neurohormonal activity (sympathetic nervous system [SNS], rennin–angiotensin–aldosterone system [RAAS] and arginine vasopressin [AVP]). However, the increase of serum concentration of urea, creatinine and other metabolites is not specific for HF. Therefore, it is not possible to distinguish HF from renal diseases solely based on the increase of their concentration, since the increase of their concentration caused by the decrease of GFR cannot be differentiated from the increase due to neurohormonal activity. Urea and cystatin C (Cys C) have different mechanisms of renal elimination, so it can be assumed that in HF their concentrations will not be increased proportionally, what can be used for diagnostic and prognostic purposes. After glomerular filtration Cy C undergoes proximal tubular reabsorption and breakdown, without returning to the blood flow. Since it is not secreted, its serum concentration depends only on GFR. In contrast to Cys C, urea is filtered in glomerulus and subsequently reabsorbed in proximal tubules and colleting duct. Reabsorption of urea is modified by effects of SNS, RAAS and AVP. Therefore its serum concentration depends upon GFR and neurohormonal effect on the tubular function. Since the increase of serum concentration of Cys C is caused only by the effect of the decreased renal perfusion on GFR, while the increase of urea is a result from both decreased GFR and tubular effects of increased neurohormonal activity, the paper hypothesis is that in HF the increase of urea will be significantly higher than the increase of serum Cys C, while in the patients with renal diseases their increase would be mostly proportional. It can be assumed that the disproportion between the increase of Cys C and urea would indicate an increased neurohormonal activity in patients with HF and correlate with its activity. If this hypothesis is proved correct, this parameter could be used in HF diagnosis and risk stratification of such patients.     

Hypoxia-Inducible Factor 1-Alpha Release After Intracoronary Versus Intramyocardial Stem Cell Therapy in Myocardial Infarction

We have investigated the effect of stem cell delivery on the release of hypoxia-inducible factor 1 alpha (HIF-1α) in peripheral circulation and myocardium in experimental myocardial ischemia. Closed-chest, reperfused myocardial infarction (MI) was created in domestic pigs. Porcine mesenchymal stem cells (MSCs) were cultured and delivered (9.8?±?1.2?×?10⁶) either percutaneously NOGA-guided transendocardially (Group IM) or intracoronary (Group IC) 22?±?4 days post-MI. Pigs without MSC delivery served as sham control (Group S). Plasma HIF-1α was measured at baseline, immediately post- and at follow-up (FUP; 2 h or 24 h) post-MSC delivery by ELISA kit. Myocardial HIF-1α expression of infarcted, normal myocardium, or border zone was determined by Western blot. Plasma level of HIF-1α increased immediately post-MI (from 278?±?127 to 631?±?375 pg/ml, p?<?0.05). Cardiac delivery of MSCs elevated the plasma levels of HIF-1α significantly (p?<?0.05) in groups IC and IM immediately post-MSC delivery, and returned to baseline level at FUP, without difference between the groups IC and IM. The myocardial tissue HIF-1α expression in the infarcted area was higher in Group IM than in Group IC or S (1,963?±?586 vs. 1,307?±?392 vs. 271?±?110 activity per square millimeter, respectively, p?<?0.05), while the border zone contained similarly lower level of HIF-1α, but still significantly higher as compared with Group S. Trend towards increase in myocardial expression of HIF-1α was measured in Group IM at 24 h, in contrast to Group IC. In conclusion, both stem cell delivery modes increase the systemic and myocardial level of HIF-1α. Intramyocardial delivery of MSC seems to trigger the release of angiogenic HIF-1α more effectively than does intracoronary delivery.     

COAT platelets

PURPOSE OF REVIEW: COAT platelets are a recently described subpopulation of cells resulting from simultaneous activation with collagen and thrombin. The complete process by which COAT platelets are produced is still not clear, although significant recent progress has been made. RECENT FINDINGS: COAT platelets retain several procoagulant proteins on their surface by a previously unrecognized mechanism involving transglutaminase mediated conjugation of serotonin to released alpha-granule proteins. Fibrinogen and thrombospondin have been found to bind serotonin-conjugated proteins and thereby provide the requisite link for stabilization of serotonin-derivatized, procoagulant proteins on COAT platelets. SUMMARY: Multivalent interactions, resulting from traditional receptor interactions and binding of conjugated serotonin by fibrinogen and thrombospondin, result in exceptionally strong retention of procoagulant alpha-granule proteins on the surface of COAT platelets. The physiologic significance of this new subclass of platelets remains to be determined.     

Conformational disturbance in Abl kinase upon mutation and deregulation

Protein dynamics are inextricably linked to protein function but there are few techniques that allow protein dynamics to be conveniently interrogated. For example, mutations and translocations give rise to aberrant proteins such as Bcr-Abl where changes in protein conformation and dynamics are believed to result in deregulated kinase activity that provides the oncogenic signal in chronic myelogeous leukemia. Although crystal structures of the down-regulated c-Abl kinase core have been reported, the conformational impact of mutations that render Abl resistant to small-molecule kinase inhibitors are largely unknown as is the allosteric interplay of the various regulatory elements of the protein. Hydrogen exchange mass spectrometry (HX MS) was used to compare the conformations of wild-type Abl with a nonmyristoylated form and with 3 clinically relevant imatinib resistance mutants (T315I, Y253H and E255V). A HX-resistant core localized to the interface between the SH2 and kinase domains, a region known to be important for maintaining the down-regulated state. Conformational differences upon demyristoylation were consistent with the SH2 domain moving to the top of the small lobe of the kinase domain as a function of activation. There were conformational changes in the T315I mutant but, surprisingly, no major changes in conformation were detected in either the Y253H or the E255V mutants. Taken together, these results provide evidence that allosteric interactions and conformational changes play a major role in Abl kinase regulation in solution. Similar analyses could be performed on any protein to provide mechanistic details about conformational changes and protein function.     

A shorter time to the first treatment may be predicted by the absolute number of regulatory T-cells in patients with Rai stage 0 chronic lymphocytic leukemia

Regulatory T-cells (Tregs) are increased in chronic lymphocytic leukemia(CLL) and correlates with clinical and biological features of active/progressive disease. However, little is known about their ability to predict the time to first treatment (TFT). We evaluated 75 patients with Rai stage 0 CLL, in whom the absolute number of Tregs was determined at diagnosis, and correlated to main clinical and biological features, as well as to the need of receiving any specific therapy during the course of the disease. After a median follow-up of 30 months, 12 patients(16%) required therapy at some time from the diagnosis. Treated patients showed a significant higher number of peripheral white blood cells and B-lymphocytes, platelet count, cases with unmutated immunoglobulin heavy chain status, and high-risk cytogenetic abnormalities,as well as lower hemoglobin values, than patients who did not need therapy. A greater number of circulating Tregs was detected in treated patients (P < 0.001). Multivariate analysis confirmed that the absolute number of Tregs was an independent predictor of TFT in these patients, the best predictive cut-off being 41/mL. These data show that the absolute Tregs cell number is able to identify Rai stage 0 CLL patients at higher risk of requiring therapy.