Mediators of asthma: nitric oxide

Endogenous nitric oxide is an ubiquitous gaseous molecule that regulates many aspects of human airway biology including the modulation of airway and vascular smooth muscle tone. It is generated from the three different enzymes nitric oxide synthases (NOS) -1, -2 and -3 which are all expressed in pulmonary cells. NOS-1 is localised primarily to neuronal structures, where NO is a mediator of the inhibitory Non-Adrenergic Non-Cholinergic System and NOS-3 is present in endothelial cells. While these enzymes are constitutively expressed, NOS-2 is an inducible enzyme independent of calcium and highly induced in inflammatory diseases such as allergic asthma, where NO may act beneficial or deleterious depending on the site of and amount of generation. The use of NO-donor compounds or classical unselective NOS inhibitors did not lead to significant therapeutical effects in asthmatic patients. Insights on the precise role of NO in asthma can only be achieved by targeting NO generation selectively. More potent and selective NOS-2 inhibitors have to clarify a role of NOS-modification based therapy in clinical routine. NO can also be detected in the exhaled air. Increased levels of exhaled NO in asthmatic patients may be useful for a non-invasive determination of airway inflammation.     

Percutaneous transradial coronary palmaz-schatz stent implantation,guided by intravascular ultrasound

Intravascular ultrasound (IVUS) allows accurate assessment of stent deployment, its use being confined to the use of 8 French (F) guiding catheters. We evaluated the feasibility of combining transradial artery Palmaz-Schatz stent implantation through 6F guiding catheters with IVUS for assessment of stent diameter after delivery at moderate inflation pressures (10-12 atmospheres [atm]) with compliant balloons and after high pressure dilatations with balloons of intermediate compliance. In 8 consecutive patients, 12 stents were delivered with Scimed® Express^TM balloon catheters at 10-12 atm followed by IVUS (EndoSonics® CathScanner; Visions® FX 3.5F 20 MHz transducer). An ultrasound study was repeated after high pressure dilatations (16-20 atm) with Schneider® Magical Speedy^TM balloon catheters. The balloon diameters were derived from manufacturer provided specifications. In all patients the transducer could easily be advanced through the guiding catheters. Reference diameter of the stented segment was 3.7 ± 0.5 mm (2.7-4.5) and the diameter of Scimed® Express^TM balloons during inflation was 4.0 ± 0.3 mm (3.6-4.7). Stent diameter was 3.0 ± 0.1 mm (2.8-3.2) (P < 0.001 compared to the reference and the balloon diameter). The diameter of the Schneide® Magical Speedy^TM balloons at secondary dilatations with 16 ± 3 atm (14-20) was 4.1 ± 0.4 mm (3.3-4.5) (P = 0.50 compared to the initial balloon diameter). Final stent diameter was 3.3 ± 0.4 mm (2.9-4.1) (P = 0.02 compared to the initial stent diameter). All stents were symmetrically deployed and well apposed. No damage to vessel or stents was detected after passage of the transducer. Thus ultrasound guided stenting via 6F guiding catheters is feasible, and high pressure dilatations with balloons of intermediate compliance results in better stent expansion than after 10-12 atm inflations with compliant balloon catheters.     

A CASE OF HEPATOCELLULAR ADKNOMATOSIS WITH A FOLLOW-UP OF 11 YEARS

Hepatoccllular adenomatosis is characterized by the presence of numerous (arbitrarily > 10) adenomas within an otherwise normal liver without a history of glycogen storage disease or steroid hormone therapy. Although the disease is rare, its importance lies in its tendency to produce symptoms such as abdominal pain and its potential for abdominal hemorrhages. However, the prognosis of hepatocellular adenomatosis remains uncertain. Here we describe the ease of a -40-yr-old female with hepatoccllular adenomatosis without evidence of serious complications, who was observed over a period of 11 yr.     

Clinical efficacy and survival with first-line inhaled iloprost therapy in patients with idiopathic pulmonary arterial hypertension.

AIMS: To describe the long-term clinical efficacy of inhaled iloprost as first-line vasodilator mono-therapy in patients with idiopathic pulmonary arterial hypertension (IPAH). METHODS AND RESULTS: Seventy-six IPAH patients were prospectively identified and treated with inhaled iloprost. Clinical, haemodynamic, and exercise parameters were obtained at baseline, after 3 and 12 months of therapy and yearly thereafter. Four endpoints were prospectively defined as follows: (i) death, (ii) transplantation, (iii) switch to intravenous (i.v.) therapy, or (iv) addition of or switch to other active oral therapy. During follow-up (535+/-61 days), 11 patients died, six were transplanted, 25 were switched to i.v. prostanoids, 16 received additional or other oral therapy, and 12 patients discontinued iloprost inhalation for other reasons. Event-free survival at 3, 12, 24, 36, 48, and 60 months was 81, 53, 29, 20, 17 and 13%, respectively. Among haemodynamic and exercise parameters, mixed venous oxygen saturation (P<0.001), right atrial pressure (P<0.001), and peak oxygen uptake (P=0.002) were associated with event-free survival. CONCLUSION: In this study, only a minority of patients could be stabilized with inhaled iloprost mono-therapy during a follow-up period of up to 5 years. In the presence of multiple treatment options, chronic iloprost inhalation as mono-therapy appears to have a limited role.