For the initial treatment of AIDS-associated cryptococcal meningitis, the use of higher-dose amphotericin B plus flucytosine is associated with an increased rate of cerebrospinal fluid sterilization and decreased mortality at two weeks, as compared with regimens used in previous studies. Although consolidation therapy with fluconazole is associated with a higher rate of cerebrospinal fluid sterilization, itraconazole may be a suitable alternative for patients unable to take fluconazole.

Aims/hypothesisIndividuals with type 2 diabetes mellitus have increased rates of macrovascular disease (MVD). Endothelial progenitor cells (EPCs), circulating angiogenic cells (CACs) and smooth muscle progenitor cells (SMPCs) are suggested to play a role in the pathogenesis of MVD. The relationship between vasoregenerative EPCs or CACs and damaging SMPCs and the development of accelerated MVD in diabetes is still unknown. We tried to elucidate whether EPC, CAC and SMPC numbers and differentiation capacities in vitro differ in patients with and without diabetes or MVD.MethodsPeripheral blood was obtained from insdividuals with and without diabetes and MVD (coronary or peripheral artery disease). EPC and SMPC numbers were determined with flow cytometry. Furthermore, CAC and SMPC numbers were quantified after in vitro culture. Their in vitro differentiation capacity was investigated with real-time RT-PCR and quantitative immunofluorescence.ResultsIn diabetic patients both EPC and CAC levels were reduced (1.3-fold [p < 0.05] and 1.5-fold [p < 0.05], respectively). CAC outgrowth from diabetic patients with MVD was reduced 1.5-fold compared with diabetic patients without MVD (p < 0.05). SMPC levels were similar between diabetic patients and healthy controls. The CAC/SMPC ratio of in vitro cultured progenitor cells was reduced 2.3-fold in samples from diabetic patients (p < 0.001). The differentiation capacity of CACs and SMPCs in vitro remained similar independently of diabetes or MVD.Conclusions/interpretationThe ratio between EPCs or CACs and SMPCs is disturbed in type 2 diabetes in favour of SMPCs. This may translate into reduced vascular repair capacity, thereby promoting MVD in type 2 diabetes.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-012-2590-5) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

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