This European multicenter study compares the efficacy and tolerance of the combination of pyrimethamine-clindamycin (Pyr-Cm) with the standard therapy pyrimethamine-sulfadiazine (PyrSdz) for the ...treatment of toxoplasmic encephalitis (TE) in patients with AIDS. Two hundred ninety-nine human immunodeficiency virus-infected patients with TE were randomly assigned to receive 50 mg of pyrimethamine daily combined with either 2,400 mg of clindamycin or 4 g of sulfadiazine for 6 weeks followed by maintenance therapy with 25 mg of pyrimethamine daily with either 1,200 mg of clindamycin or 2 g of sulfadiazine. An intent-to-treat analysis showed that Pyr-Cm was less effective than Pyr-Sdz; the overall risk of progression of TE was 1.84 times higher for patients receiving Pyr-Cm therapy. There was no statistically significant difference in efficacy during acute therapy, although the rate of crossover motivated by a lack of response was higher among Pyr-Cm recipients. The difference in efficacy was evidenced during the maintenance phase of treatment; the relapse rate was twice as high among patients in the Pyr-Cm group (P = .02). The rate of side effects due to both regimens was similar, although the toxic effects of Pyr-Cm led to fewer discontinuations of therapy than did those of Pyr-Sdz (11% vs. 30%, respectively; P = .001). Pyr-Sdz appears to be the most effective treatment of TE. Pyr-Cm is a valuable alternative but is less effective for long-term prevention of relapses.
In human diabetes, degenerative and functional disorders of the central nervous system, including depression, are common findings. Defective dentate gyrus (DG) neurogenesis is associated with ...affective-related disorders and depression. We previously demonstrated reduced DG neurogenesis in a pharmacological type 1 diabetes model, the streptozotocin (STZ)-treated mouse. Here, we explored DG neurogenesis in a spontaneous T1D model, the nonobese diabetic (NOD) mouse, at prediabetic and diabetic stages.
Cell proliferation was assessed in the DG of 5, 8 and 12-week-old control C57BL/6 and BALB/c strains and NOD mice, killed 2 h after bromodeoxyuridine (BrdU) administration. Survival of the newly generated cells was studied in 15-week-old animals that were killed 21 days after BrdU injection. The number of proliferative BrdU-positive cells in the DG was, regardless of age, constantly and significantly lower in NOD than in control strains, showing the presence of hippocampal alterations far before clinical diabetes onset in NOD mice. Diabetes also strongly decreased cell survival in NOD DG. However, cell phenotype proportion, as assessed by co-localization with neuronal or glial markers and confocal microscopy, was not modified.
Hippocampal neurogenesis is strongly diminished in the spontaneous NOD model, like in the STZ model. Notably, NOD hippocampal DG cell proliferation defect takes place during the prediabetic stage. Whether this early alteration might result, in this autoimmune strain, from hypothalamo-pituitary adrenal axis alterations and/or ongoing brain inflammatory process sharing many characteristics of aging is discussed and deserves further investigation.
To measure the prevalence and analyse the characteristics of malnutrition among subjects attending an AIDS outpatient clinic and a day care center, to improve the nutritional management of ...HIV-infected subjects.
Prospective cross-sectional study.
AIDS clinic in a University Hospital in Paris.
124 HIV-seropositive adults attending the clinic.
Evaluation of nutritional status using anthropometry, impedancemetry, plasma albumin and pre-albumin assays. Degree of malnutrition, defined by the percentage of body weight loss (BWL), calculated by reference to the usual body weight.
Among the 124 subjects recruited (M:F sex ratio: 3.3, mean age: 36.3 +/- 7.2 y), 77 (62.1%, 95%CI: 53.9-70.3) had normal nutrition status (BWL < or = 5%), 16 (12.9%, 95%CI: 7.0-18.2) moderate malnutrition (5% < BWL < or = 10%), 21 (16.9% 95%CI: 10.3-23.5) intermediate malnutrition (10% < BWL < or = 20%), and 10 (8.1%, 95%CI: 3.3-12.9) severe malnutrition (BWL > 20%). BWL was related to the CDC class (variance analysis, P < 9 x 10(-5)) and CD4 cell count (P < 3 x 10(-5)). Malnutrition was observed even among CDC class A subjects (14.9%). BWL was also related to the body mass index (P < 3 x 10(-6)), lean body mass (P < 3 x 10(-5)), body fat (P < 7 x 10(-6)), and as assessed by impedancemetry, body cell mass (P < 10(-5)) an the extra/intra cellular water ratio (P < 2 x 10(-4)). The decrease in lean body mass was related to the decrease in body cell mass.
Given its high frequency, malnutrition should be prevented, detected, monitored and treated from the early stages of HIV infection among patients attending AIDS clinics in order to improve survival and quality of life.
Manifestations of cytomegalovirus (CMV) disease in patients with AIDS include retinitis, gastrointestinal tract infection, neuropathy, encephalitis, pneumonitis, and disseminated infection. We ...describe a patient whose first manifestation of CMV infection was CMV-related bronchitis. A 44-year-old heterosexual HIV-seropositive woman had had recurrent fever and sinusitis for 8 months and stomatitis for 4 months. Her symptoms persisted despite multiple courses of therapy with oral antibiotics. The patient was treated with 90 mg/kg of foscarnet twice daily until her retinitis stabilized and then with 120 mg/kg of foscarnet daily. The stomatitis and sinusitis quickly resolved.
The results of a study on onychomycosis in AIDS related complex and AIDS patients presenting for dermatology consultation at an infectious diseases department are reported. The clinical results ...showed that most patients presented a proximal white superficial onychomycosis. The association with a clinical interdigital involvement was rare, but the association with a mycotic plantar keratoderma was more frequent. The laboratory results showed that dermatophytes were the most frequent etiologic agents, especially Trichophyton rubrum (58%). Although most of these patients presented an oral candidiasis, Candida albicans was isolated only in seven patients' nails. Surprisingly, Pityrosporum ovale was the only etiologic organism that was found in two patients. This result was confirmed with a histologic examination.
The multipole-to-local (M2L) operator is the most time-consuming part of the far field computation in the fast multipole method for Laplace equation. Its natural expression, though commonly used, ...does not respect a sharp error bound: we here first prove the correctness of a second expression. We then propose a matrix formulation implemented with basic linear algebra subprograms (BLAS) routines in order to speed up its computation for these two expressions. We also introduce special data storages in memory to gain greater computational efficiency. This BLAS scheme is finally compared, for uniform distributions, to other M2L improvements such as block FFT, FFT with polynomial scaling, rotations and plane wave expansions. When considering runtime, extra memory storage, numerical stability and common precisions for Laplace equation, the BLAS version appears as the best one.
The files of 45 human immunodeficiency virus-infected patients with ocular toxoplasmosis were reviewed, with a median follow-up of eight months. The condition was unilateral in 37 of the 45 patients ...(82%) and was bilateral in eight (18%). Inflammation of the anterior chamber and the vitreous was present in 32 of 53 eyes (60%) and 38 of 53 eyes (72%), respectively. Cytomegalovirus retinitis developed during the follow-up period in nine patients (20%). Cerebral toxoplasmosis was concurrently diagnosed with the ocular toxoplasmosis in 13 patients (29%). The efficacy of the combination of pyrimethamine and sulfadiazine or clindamycin was assessed in 42 patients for the induction therapy and in 38 patients for the maintenance therapy. Induction therapy was always effective within a median period of six weeks. During maintenance treatment, the 24-month relapse rates were 0.20 and 0.18 for the 50-mg/day and 25-mg/day dosage of pyrimethamine, respectively. The overall 12-month survival rate was 0.72. Our results suggested that ocular toxoplasmosis has a better ocular prognosis than cytomegalovirus retinitis, but that it requires appropriate treatment because life-threatening cerebral involvement is often associated.
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