Pharmacokinetic evaluation of oral fenofibrate nanosuspensions and SLN in comparison to conventional suspensions of micronized drug.

An increasing number of newly developed drugs show bioavailability problems due to poor water solubility. Formulating the drugs as nanosuspensions may help to overcome these problems by increasing saturation solubility and dissolution velocity. In the present study the bioavailability of the poorly soluble fenofibrate following oral administration was investigated in rats. Four formulations were tested: a nanosuspension type DissoCube(R), one solid lipid nanoparticle (SLN) preparation and two suspensions of micronized fenofibrate as reference formulations, one suspension in sirupus simplex and a second in a solution of hydroxyethy-cellulose in physiological saline. Both colloidal drug delivery systems showed approximately two-fold bioavailability enhancements in terms of rate and extent compared to the reference formulations. No significant differences were found in AUC(0-22 h) as well as in C(max) and t(max) between the two colloidal delivery systems. In conclusion, nanosuspensions may be a suitable delivery system to improve the bioavailability of drugs with low water solubility.

Absence of humorally mediated damage within the central nervous system of AIDS patients.

The pathogenesis of CNS damage by human immunodeficiency virus infection is unclear. Because there is little detectable virus within the CNS, we evaluated the role of the humoral immune system in mediating CNS tissue destruction. The paucity and nonspecific nature of immunoglobulin deposition rules against significant involvement of humorally mediated injury in the pathogenesis of AIDS encephalopathy.

Bone marrow involvement in large-cell lymphoma. Prognostic implications of discordant disease.

Discordant lymphomas are those in which two different histologic subtypes of non-Hodgkin's lymphoma are present simultaneously in the same patient at two or more separate disease sites. Discordance usually involves a lower grade follicular lymphoma in one anatomic site and a higher grade diffuse lesion elsewhere. A common type of discordance is seen in patients with a primary diagnosis of diffuse large-cell lymphoma (DLCL) who demonstrate bone marrow involvement by a lower grade lesion, such as a small cleaved cell or mixed small cleaved and large cell lymphoma. This study was undertaken to assess retrospectively the clinical implications of such bone marrow involvement, as well as the possible biologic mechanisms. Of the 59 DLCL cases studied, 20 (33.9%) showed evidence of bone marrow involvement, 14 of which were discordant (70%). The most significant findings included the following: Overall treatment responses and survivals in discordant patients with predominantly small cleaved cells in the marrow were similar to those in patients with no marrow involvement (mean survivals, 47.7 and 49 months, respectively), and were significantly longer than in patients with concordant marrow involvement (mean survival, 13.1 months, P < .05). Patients with discordant marrow infiltrates composed of a mixed cell population tended to do as poorly as those with concordant involvement. No clear-cut pattern of relapse in discordant patients was found, but persistence of small cleaved cells in some was reminiscent of lower grade B-cell lesions. Other features associated with lower grade lesions included older age, less incidence of central nervous system involvement, and lesser extent and proportion of marrow infiltration. Finally, in approximately half the cases with discordant involvement, lymphoma was present unilaterally, emphasizing the need to perform bilateral biopsies for staging.

Primary small-cell carcinoma of the stomach.

Primary small cell carcinoma of the stomach is an extremely rare tumor with only nine previously reported cases in the literature. Clinical behavior and prognosis are similar to small cell carcinomas of pulmonary origin. An additional case of a BI-year-old man with a gastric small cell carcinoma confined to the stomach is reported. The patient presented with an upper gastrointestinal bleed. A five centimeter ulcerated mass in the antrum was seen endoscopically and biopsied. At surgery the tumor appeared to be confined to the stomach and a subtotal gastrectomy was performed. The patient remains disease-free at 22 months. A review of nine other cases of small cell carcinoma of gastric origin reveals that most behave like their counterparts in the lung with rapid dissemination and death. However, like this patient, the only survivors for greater than one year are those amenable to surgical resection, implying that surgery has a roll in localized disease.