Familial intracranial aneurysm, the relationship of the aortic diameter.

OBJECTIVES: Familial predisposition appears as an identified risk factor for cerebrovascular disease. The primary objective of our study was to assess intracranial aneurysm (IA) recurrence rate in a population of familial IA. Secondary objectives were first to analyse the inheritance categorisation/pattern of these families and second to assess the correlation between the aortic diameter on MRI and the aneurysmal characteristics. PATIENTS AND METHODS: Over a period of 20 years (1990-2010), 26 patients from 23 families, identified from a regional register, accepted to participate in this prospective trial in order to determine, the inheritance pattern, the screening of de novo aneurysms by CT angioscan, and the aortic mensuration by MRI. The transmission pattern was categorised into autosomal dominant inheritance, autosomal recessive and autosomal dominance with incomplete penetrance. The aortic diameter was measured: anatomic coverage in the caudo-cranial direction from the iliac arteries to the ventriculo-aortic junction. RESULTS: All 26 patients [from 55.4 ± 11.2 years, sex ratio female/male: 1.36] were reviewed after a mean follow-up of 7.9 ± 6.6 years after the diagnosis of a cerebral aneurysm. The characteristics of this population were the diagnostic circumstances such as a subarachnoid hemorrhage (SAH) in 14 (53.8%), the multiple locations in 10 (38.5%) and a giant aneurysm in 4 (15.4%). Four de novo aneurysms were diagnosed in 3 patients (11.5%) after a mean follow-up of 22.3 ± 4 years, which corresponds to an annual incidence of 1.9 (95% CI 1.4-2.6%). The transmission pattern was autosomal dominant in 16 (61.5%), recessive in 3 (11.5%) and not defined in 7 (26.9%). As regards the aortic diameter, a significant decrease in the aortic diameter was observed in patients with an aneurysmal diameter superior to 10mm. CONCLUSION: The rate of de novo aneurysm justifies prolonged monitoring by imaging of these patients with familial intracranial aneurysm. The narrowing of the terminal part of the aorta could be a hemodynamic factor involved into the IA development.

Relationship between renal function and disposition of oral cefixime.

The pharmacokinetics of cefixime following a single oral dose of 200 mg have been investigated in 6 normal subjects and in 22 patients with various degrees of renal insufficiency. Serum and urine samples were collected between 0 and 72 h and were subjected to two methods of analysis: bioassay and HPLC. There was a linear relationship between the two sets of results from 228 samples. This result suggests that none of the metabolites, which may accumulate in uraemic patients, has antibacterial activity. In normal subjects, the peak serum level (Cmax) was 2.50 micrograms.ml-1 at 2.83 h (tmax); the apparent elimination half-life (t1/2) was 3.73 h; the apparent total body clearance (CL.f-1) was 154 ml.min-1, the mean renal clearance (CLR) was 39.1 ml.min-1 and the apparent fraction of the dose recovered in 24 h urine was 0.22. In uraemic patients, Cmax and tmax were slightly increased and t1/2 was increased to 12-14 h in patients with an endogenous creatinine clearance below 20 ml.min-1. The apparent volume of distribution was decreased. Apparent total and renal clearances were lower in proportion to the degree of renal insufficiency. Linear relationships were found between CL/f, CLR and creatinine clearance (CLCR). The findings suggest that the dose of cefixime needs to be reduced only in patients with severe renal failure.