Hemodynamic effect of hydralazine in interstitial lung disease patients with cor pulmonale. Immediate and short-term evaluation at rest and during exercise

Hydralazine was administered short-term to 13 patients who had stable interstitial lung disease (ILD), pulmonary arterial hypertension (PAH); mean pulmonary arterial pressure ( [PAP]=26 +/- 9 mm Hg), and cor pulmonale (CP). All patients were studied at rest and during exercise. After intravenous hydralazine at rest, there were statistically significant increases in cardiac index (CI) (p less than 0.001), arterial oxygen saturation (SaO2) (p less than 0.01), and mixed venous saturation (S-vO2) (p less than 0.01). Pulmonary vascular resistance (Rp) (p less than 0.005) and systemic resistance (Rs) decreased (p less than 0.001), and PAP did not change. During exercise, PAP did not change; however, CI (p less than 0.01), PaO2 (p less than 0.001), and S-vO2 (p less than 0.01) increased further. The increase in Rp was significantly reduced (p less than 0.01). After continuation of oral hydralazine therapy in 12 patients for 7 days, PAP at rest was not statistically different from control; Rp and Rs remained decreased (p less than 0.001). The same results were found for CI, PaO2, S-vO2, and Rs during exercise. Although PAP did not change from control values, the drug significantly reduced the increase in Rp (p less than 0.005). Vasodilator therapy with hydralazine could be useful in patients with stable ILD who have inflammation with minimal to moderate fibrosis and PAH and might be used as an adjunct to conventional therapy for ILD and CP.     

Hypermethylation of the calcitonin gene in acute lymphoblastic leukaemia is associated with unfavourable clinical outcome

We analysed calcitonin (CALC1) gene hypermethylation using semiquantitative differential polymerase chain reaction in 105 patients with adult (n = 49) and childhood (n = 56) acute lymphoblastic leukaemia (ALL), and studied the association of CALC1 hypermethylation with clinical presentation features and disease outcome. We also investigated the possible relationship between CALC1 methylation status and expression of the cell cycle inhibitor gene p57KIP2. We observed CALC1 hypermethylation in bone marrow cells from 43% (45 out of 105) of ALL patients. Clinical, molecular and laboratory features did not differ significantly between hypermethylated and hypomethylated patients, only T-cell lineage was associated with hypermethylation (14% vs. 47%, P = 0025). Complete remission rate was similar in both groups although hypermethylated patients had a higher relapse rate (68% vs. 19%, P < 0.00001) and mortality rate (55% vs. 36%, P = 0.06) than hypomethylated patients. Estimated disease-free survival (DFS) at 6 years was 66.1% for hypomethylated patients and 5.3% for hypermethylated patients (P < 0,00001). Multivariate analysis from potential prognostic factors demonstrated that CALC1 methylation status was an independent prognostic factor in predicting DFS (P = 0.0001). Separate analysis of adult and childhood ALL patients showed similar results to the whole series. In addition, hypermethylated patients showed downregulation of p57KIP2 expression. Our results suggest that CALC1 gene hypermethylation is associated with an enhanced risk of relapse independently of known poor-prognostic factors and we describe, for the first time, a possible implication of the p57KIP2 gene in the genesis and prognosis of ALL.     

Renal implications of the renin-angiotensin-aldosterone system blockade in heart failure

The renin-angiotensin-aldosterone system actively participates in the derangement of renal function since the early stages of heart failure (HF). A diminished capacity to excrete sodium secondary to increased proximal tubular re-absorption and loss of the renal functional reserve are the two most relevant initial alterations of renal function in which angiotensin II has been proven to act directly. Meanwhile, the octapeptide contributes to maintain glomerular filtration rate (GFR) within normal limits through efferent arteriole vasoconstriction. Administration of angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor antagonists (ARA) may thus be accompanied by a functional fall in that parameter. Advanced age, higher initial serum creatinine, history of hypertension, diabetes and atrial fibrillation predict the onset of GFR impairment associated with blockade of the renin-angiotensin system. Concomitant administration of betablockers may help to protect renal function, and preliminary data indicate that the combination of ACEi and ARA is not accompanied by a higher renal risk. The good prognostic effects of aldosterone antagonists in HF does not seem to be related to intrarenal effects of these compounds with the exception of preventing potassium loss and hypokalemia. The systematic therapeutic use of drug(s) provided with beneficial renal effects, to treat arterial hypertension or myocardial ischemia, may contribute to delay of, or prevent the development of HF.     

Ultrasound-guided infraclavicular axillary vein cannulation

Background and objectivePercutaneous central venous cannulation is a challenging procedure. Traditionally, an external landmark technique has been used to identify puncture site. We wanted to evaluate an ultrasound-guided technique for the axillary vein cannulation, looking specifically at the ease of use, success rate and decreased complications.MethodsSixty consecutive surgical patients scheduled for central venous catheter placement were registered. An ultrasound scanner made for guiding an in plane puncture of axillary vein was used. After locating the vessels, an echo-guided sterile procedure was performed to cannulate the vein.ResultsCannulation was successful in all patients, and there were no complications during insertion of the catheters. Both axillary veins were cannulated, and the vein was punctured successfully at first attempt in 95% of the patients. The median time from the start of the first puncture (of the skin) until the aspiration of blood was 15 (7– 135) seconds.ConclusionThis ultrasound-guided technique for inserting central venous catheters in axillary vein was easy to apply. This procedure could increase precision and safety in patients undergoing axillary vein cannulation.