Treatment of chronic pulmonary aspergillosis with voriconazole: review of a case series.

PURPOSE: Chronic pulmonary aspergillosis (CPA) is a rare disease that primarily affects subjects with moderate immunodepression and/or structural alterations in the lung. METHODS: Data for patients with probable CPA were collected over 24 months. Patients with probable CPA received oral voriconazole, and clinical, laboratory and radiological follow-up was performed at 3, 6 and 12 months. RESULTS: 21 patients (mean age 52.4 years) were evaluated. Factors predisposing to CPA were tuberculosis (n = 8), chronic obstructive pulmonary disease (n = 7), corticosteroids (n = 14), chemo- or radio-therapy (n = 6), tracheostomy or endotracheal prosthesis (n = 5), smoking (n = 4), asthma (n = 3), and chronic liver disease (n = 3). Sputum or bronchial aspirate cultures were positive for Aspergillus spp. in 14 cases (66.6 %). (1,3)-ß-D-glucan on serum was positive in 16 cases (76.2 %). Excavated pulmonary thickening was evident in 14 patients (66.6 %) and in 9 of these cases (64.2 %) aspergilloma was present. [(18)F]2-fluoro-2-deoxy-D-glucose-PET-CT was positive in 13/15 patients, and simple aspergilloma was diagnosed after surgical excision in one of the negative cases. All patients were treated with oral voriconazole. Therapy was discontinued due to skin toxicity (n = 3), liver toxicity (n = 2) and severe mental disorder (n = 1). At 12 months' follow-up, nine patients (42.9 %) were considered cured or improved. Seven patients (33.3 %) died during follow-up, mainly due to underlying disease. CONCLUSIONS: A reasonable proportion of patients achieved cure or improvement with voriconazole, but 28.5 % of treated patients had to discontinue therapy because of toxicity. The high mortality makes it difficult to fully assess the real efficacy of voriconazole and to establish the correct duration of therapy.

Comparison between low-dose dobutamine echocardiography and thallium-201 scintigraphy in the detection of myocardial viability in patients with recent myocardial infarction.

AIM: To compare the predictive value of thallium-201 single photon emission computed tomography (SPECT) scintigraphy (Sci) and low-dose dobutamine echocardiography (Dob) in predicting late recovery of dysfunctioning myocardium in patients with recent, uncomplicated myocardial infarction (MI). METHODS AND RESULTS: 19 patients (18 male, aged 58+/-8 years) with recent MI and ejection fraction <50% (35.5+/-8.3%) underwent 5-15 microg/kg per min Dob, rest-redistribution Sci and coronary angiography, respectively, 14+/-6, 16+/-7 and 17+/-5 days after MI. On an eleven-segment ventricular model devised to compare Dob and Sci segment by segment, each dysfunctioning ventricular segment was considered viable if it showed recovery of mechanical function at the echocardiographic follow-up, performed 6.3+/-1.5 months after revascularization (five PTCA, five GABG) or medical therapy. Among the 104 dysfunctioning segments, of which 26 (25%) showed recovery at follow-up, Dob and Sci gave a concordant response in 50 (48%, k = 0.13), correctly predicting the recovery (or not) of function in 42. Forty-two of 54 discordant responses were due to segments judged viable only by Sci and which had no recovery at follow-up (of these 37 were akinetic or severely hypokinetic at baseline). At the segment-by-segment analysis, the sensitivity, specificity, and accuracy in predicting recovery of function at follow-up were, respectively, 69, 88 and 84% for Dob as against 88, 36 and 49% for Sci (P<0.001 for both specificity and accuracy, P=NS for sensitivity). CONCLUSION: In patients with recent MI, the specificity of Dob in the detection of myocardium capable of late mechanical recovery is significantly higher with respect to Sci, whereas sensitivity is slightly, not significantly higher for the latter. It is conceivable that Sci detects viable myocardium even if it is transmurally limited to epicardial layers in segments with severely impaired mechanical function in which viability will not affect late recovery of function.

Effects of ACE inhibition in normotensive patients with chronic glomerular disease and normal renal function.

A double-blind, placebo-controlled study was carried out to assess the effects of a three-month treatment with a new ACE inhibitor, Benazepril (BNZ), on systemic and renal hemodynamics, and urine protein excretion, in 20 patients with chronic glomerulonephritis, normal blood pressure (130/83 +/- 16/10 mm Hg), and normal renal function (creatine clearance 106 +/- 25 ml/min). Treatments with placebo or BNZ were assigned randomly. A wide range of proteinuria lowering effect was observed in overall population (from 1 to 84%, average 34%). Following the arbitrary level of a 30% reduction, two well-matched subgroups (10 patients for each one) were obtained: "good responders" (average decrease 51%), and "poor responders" (average decrease 17%). The main distinctive feature between the two groups was a higher plasma renin activity level in good than in poor responders. A positive correlation between the fall in proteinuria and blood pressure was found. Although the decrease in blood pressure seems to represent the major factor in determining the reduction in proteinuria, a multiple correlation analysis showed that the most prominent role (71%) was attributable to the combined decrease in blood pressure and filtration fraction, and then also to the efferent arteriole dilatation. Our conclusion is that ACE inhibitors are capable of also reducing proteinuria in patients with renal disease with normal blood pressure, the effect being more pronounced in those exhibiting humoral, systemic and renal hemodynamic patterns, indicating a greater activity of circulating and renal renin angiotensin system.

Renal functional reserve in patients with essential hypertension: effect of inhibition of the renin--angiotensin system.

1. Urinary albumin excretion and the effect of an acute oral protein load (a meat meal) on glomerular filtration rate ('renal functional reserve') were evaluated in 15 essential hypertensive patients with preserved renal function and compared with 12 normal subjects. 2. Seven patients had microalbuminuria (greater than 30 mg/day) that was not correlated with blood pressure values. 3. After an oral protein load, an average increase of 20% in glomerular filtration rate (from 91 +/- 19 to 110 +/- 27 ml min-1 1.73 m-2 was found in the hypertensive patients. This change was not statistically different from that observed in normal controls (from 102 +/- 7 to 124 +/- 9 ml min-1 1.73 m-2). The glomerular response in hypertensive patients was independent of age, duration of hypertension, blood pressure, plasma renin activity, urinary albumin excretion and retinal vascular alterations. 4. All patients were re-evaluated after 6 weeks treatment with a new orally active angiotensin-converting enzyme inhibitor, benazepril. Systolic, diastolic and mean blood pressures were lowered in all the patients, but the drug did not affect the glomerular response to acute protein ingestion or the magnitude of urinary albumin excretion. 5. The findings of a normal 'renal functional reserve' and a lack of change in both urinary albumin excretion and the glomerular response after angiotensin-converting enzyme inhibition cast doubt on the existence of increased intraglomerular pressure in hypertensive patients.

Amiodarone-induced pulmonary toxicity.

A patient with atrial premature depolarizations developed pulmonary toxicity during long-term treatment with amiodarone. The clinical features were cough and dyspnea. Pulmonary function tests showed a restrictive defect and severe impairment of gas transfer. Diffuse interstitial and intra-alveolar shadows were noted on chest X-ray. Lung specimens obtained by transbronchial biopsy showed hyperplasia of pneumocytes and widening of the alveolar septa. After discontinuation of amiodarone and institution of steroid therapy the patient improved symptomatically, and after 3 weeks the chest X-ray showed clearing of the bilateral infiltrates. The patient was never given any other antiarrhythmic drugs, had no important heart disease, and received the lowest daily dose of amiodarone reported in the literature of cases of pulmonary injury.

Salazopyrin-induced eosinophilic pneumonia.

A patient with ulcerative colitis developed eosinophilic pneumonia following treatment with Salazopyrin. The pneumonia resolved following discontinuation of the drug and the start of treatment with prednisolone. When the treatment with prednisolone was stopped the patient developed eosinophilic pneumonia again. When the treatment with prednisolone was resumed all side effects disappeared definitively.