Modulation of all-trans retinoid acid pharmacokinetics in acute promyelocytic leukaemia by prolonged interferon-α therapy

Summary. Continuous treatment with all-trans retinoid acid (ATRA) induces accelerated drag catabolism which is considered responsible for acquired resistance to ATRA. We studied the effect of interferon-o:2a (IFN) on ATRA pharmacokinetics in two patients with acute promyelocytic leukaemia (APL) in complete remission maintained by alternating 15d of IFN and 15 d of ATRA. Day 15 ATRA levels obtained during IFN + ATRA treatment were significantly higher than those observed in patients maintained on ATRA alone. In one patient IFN was discontinued and day 15 ATRA levels decreased to those observed in patients scheduled for maintenance with ATRA alone. In our two patients IFN substantially reduced the induction of ATRA catabolism, indicating a potential role for IFN in modulating ATRA pharmacokinetics.     

Endoscopic Resection of Squamous Papilloma of the Esophagus

Squamous papilloma is a rare, benign esophageal tumor which may be confused with verrucous carcinoma of the esophagus. The case of a 45-year old male who was found to have an esophageal squamous papilloma is presented. This case serves to demonstrate the important role of fiberoptic endoscopy for the transendoscopic resection of this tumor.     

Computed Tomography During Experimental Balloon Dilatation For Calcific Aortic Stenosis. A Look into the Mechanism of Valvuloplasty

Thin-slice contiguous computed tomographic scanning was performed in four postmortem hearts with calcific aortic valve stenosis (mean weight: 583 ± 78 g; mean age: 65 ± 10 years) before, during, and after balloon valvuloplasty. Balloons of increasing diameter (15–19 mm single balloons, and 3 × 12-mm trefoil-shaped balloon) were positioned across the aortic valve and manually inflated to pressures of 3 to 4 atmospheres. During inflation of the 3 × 12-mm balloon a larger residual orifice, potentially free for blood passage, was observed in the two cases with bicuspid valves and in one case with a fused tricuspid valve, while the reverse was noted in one case with a tricuspid valve without fusion. In most cases valvular orifice enlargement only occurred with larger diameter balloons. After valvuloplasty aortic valve area increased from 0.72 (range 0.20–0.95) cm² to 2.36 (range 0.95–3.14) cm². The smallest orifice enlargement after dilatation occurred in case 1, where valvular calcified deposits had the largest volume and the highest computed tomographic attenuation value. In each patient macroscopic changes (fracture of nodular calcifications, commissural splitting, tearing of the central raphe) were noted. No calcium dislodgement or aortic ring damage was observed. In autopsy specimens computed tomography provided accurate evaluation of aortic valve morphology, extent of valve calcification, balloon-leaflet relationship during inflation, and effects of the dilatation on valve leaflets and commissures. Advances in computed tomographic cardiovascular imaging may achieve similar results in the clinical setting, and allow a more rational, individualized approach to the valvuloplasty procedure. (J Interven Cardiol 1988:1:2)     

Low dose of clarithromycin in triple therapy for the eradication of Helicobacter pylori: One or two weeks?

The aims of this pilot study were: (i) to compare the ef?cacy of low-dose clarithromycin (250 mg twice daily) for 1 or 2 weeks; and (ii) to evaluate possible therapeutic advantages in associating the low-dose clarithromycin with an anti-secretory agent or tripotassium dicitrate bismuthate (De Nol; Yamanouchi Pharm, Corugate Milano, Italy). A prospective, randomized, open trial was carried out on consecutive outpatients with dyspeptic symptoms and Helicobacter pylori infection. We enrolled 129 patients in one of the following schedules: (A) De Nol 120 mg q.i.d., clarithromycin 250 mg b.i.d. and metronidazole 250 mg q.i.d. for 2 weeks; (B) omeprazole 20 mg b.i.d., clarithromycin 250 mg b.i.d. and metronidazole 250 mg q.i.d. for 2 weeks; or (C) omeprazole 20 mg b.i.d., clarithromycin 250 mg b.i.d. and metronidazole 250 mg q.i.d. for 1 week. Results were evaluated by Per Protocol (PP) and Intention-To-Treat analysis (ITT). Eradication rate was 100% after treatment A, 92.6% after treatment B and 86.5% after treatment C by PP and 83.3, 75.7, and 68.1%, respectively by ITT. Side effects were reported by 16 subjects: 26.6% in group A; 9.1% in group B; and 7.5% in group C; in two cases side effects led to the withdrawal of the treatment. In conclusion, 500 mg clarithromycin per day in association with omeprazole and metronidazole, for 1 week gave comparable results to the same schedule for a 2 week period. The use of clarithromycin with bismuth and metronidazole produced a therapeutic gain compared with both of the anti-secretory schedules, although this was not statistically signi?cant.     

HIGH LEVEL OF A NERVE GROWTH FACTOR IN THE SERUM OF A PATIENT WITH MEDULLARY CARCINOMA OF THE THYROID GLAND

The serum of a patient with a familial medullary thyroid carcinoma showed levels of a factor, active in the nerve growth factor (NGF) bioassay and cross-reacting immunologically with mouse NGF, 20-1000 times higher than sera from normal controls or from patients with unrelated tumours. Variations of the level of this factor in the serum closely correlated with the progression of the disease. One of the patient's sons, apparently clinically normal, also showed high levels of this factor in the serum, raising the possibility that abnormality in the production of this factor could be present at an early stage of the disease.