Phase I study of mitonafide in solid tumors

Summary Mitonafide was the first synthetized compound of a new series of 3-nitronaphthalimides with intercalative properties. A phase I study with a conventional escalation scheme was developed. The schedule of drug administration was a daily ×5 days by short (1h) intravenous (i.v.) infusion, every 21 days. Thirty evaluable patients were treated at doses from 15.4 mg/m²/d×5 days to 138.6 mg/m²/d×5 days. The study was interrupted due to appearance of central nervous system toxicity in 5 patients treated at doses above 118 mg/m²×5 days. This toxicity consisted firstly of loss of memory in all patients. It was irreversible and progressed in 3 patients to disorientation and confusion, leading to dementia in one of them. This was considered to be dose-limiting toxicity, and since it appeared to be related to the administration schedule, no further studies with short i.v. infusions of mitonafide are recommended. A phase I study utilizing a more desirable administration schedule over longer periods of time is ongoing in other centers.     

Synthesis and bioacceptability of fluorinated surfactants derived from F-alkylated tertiary amines

Two methods for synthesizing tertiary F-alkylated amines are reported. The more general method allows the access in 56–87% yields to various N,N-dialkyl F-alkyl amines. These amines are key intermediates leading in 52–96% yields to several families of surfactants, including zwitterionic and cationic derivatives and amine oxides, potentially useful in the formulation of fluorocarbon emulsions for diagnostic and therapeutic uses. The toxicity of the new surfactants and the influence of the polar head were assessed: the long chain compounds (8, 9 and 10) were found to be toxic for cell cultures and the zwitterionic compounds (7b and 8) have a LD₅₀ < 250 mg·kg bw⁻¹ in mice. The hemolysis test highlights the influence of the polar head: the zwitterionic compounds (7 and 8) were found to be non-hemolytic even at remarkably high concentrations (100 g l⁻¹ for 8), whereas the cationic compounds 9 are highly hemolytic even at very low concentrations (0.05 g l⁻¹).     

The double-orifice mitral valve. An evaluation by two-dimensional echocardiography and color echo-Doppler

Double-orifice mitral valve is an uncommon congenital heart defect. The isolated occurrence of this anomaly is exceptional and, more often, is encountered in association with other congenital cardiac abnormalities. Principal among these are the partial and complete forms of the atrioventricular canal. In this paper, we present two cases of double-orifice mitral valve. Our first case is associated with subaortic stenosis and coarctation of aorta. The second case is an isolated one resembling a severe mitral stenosis. As we know, the diagnosis of this rare anomaly by color-Doppler technique has not been previously reported. We believe this technique provides definite anatomical and functional information about double-orifice mitral valve.     

Mesenteric adenitis and acute terminal ileitis: US evaluation using graded compression

One hundred seventy consecutive patients with clinical suggestion of acute appendicitis were studied by ultrasound (US) with the examiner using the graded compression technique. In 14 patients, the only US findings consisted of enlarged mesenteric lymph nodes in combination with mural thickening of the terminal ileum. This was consistent with the findings at surgery in four patients and with the results of barium studies in seven patients. In nine of 14 patients, stool cultures were performed, eight of which were positive for Yersinia enterocolitica. None of these 14 patients finally proved to have appendicitis. In a patient with acute pain in the right lower quadrant whose appendix cannot be visualized sonographically and whose US findings consist of enlarged mesenteric lymph nodes and mural thickening of the terminal ileum, the diagnosis is probably mesenteric adenitis and acute terminal ileitis. Appendectomy should be avoided in this condition.