Intranasal and inhaled fluticasone propionate for pollen-induced rhinitis and asthma

BACKGROUND: Studies suggest that nasal treatment might influence lower airway symptoms and function in patients with comorbid rhinitis and asthma. We investigated the effect of intranasal, inhaled corticosteroid or the combination of both in patients with both pollen-induced rhinitis and asthma. METHODS: A total of 262 patients were randomized to 6 weeks' treatment with intranasal fluticasone propionate (INFP) 200 microg o.d., inhaled fluticasone propionate (IHFP) 250 microg b.i.d., their combination, or intranasal or inhaled placebo, in a multicentre, double-blind, parallel-group study. Treatment was started 2 weeks prior to the pollen season and patients recorded their nasal and bronchial symptoms twice daily. Before and after 4 and 6 weeks' treatment, the patients were assessed for lung function, methacholine responsiveness, and induced sputum cell counts. RESULTS: Intranasal fluticasone propionate significantly increased the percentages of patients reporting no nasal blockage, sneezing, or rhinorrhoea during the pollen season, compared with IHFP or intranasal or inhaled placebo. In contrast, only IHFP significantly improved morning peak-flow, forced expiratory volume in 1 second (FEV1) and methacholine PD20, and the seasonal increase in the sputum eosinophils and methacholine responsiveness. CONCLUSIONS: In patients with pollen-induced rhinitis and asthma, the combination of intranasal and IHFP is needed to control the seasonal increase in nasal and asthmatic symptoms.     

Contribution of cellular HIV-1 DNA quantification to the efficacy analysis of antiretroviral therapy: a randomized comparison of 2 regimens, including 3 drugs from 2 or 3 classes (TRIANON, ANRS 081)

Cellular HIV-1 DNA level was sequentially measured by quantitative polymerase chain reaction in 141 patients not previously treated with highly active antiretroviral therapy (HAART), who were enrolled in a 72-week randomized trial (ANRS 081 "Trianon") comparing 2 regimens, including 3 drugs from 2 classes (indinavir + stavudine + lamivudine, group 1) or 3 classes (indinavir + stavudine + nevirapine, group 2). The median decrease from baseline to week 72 in cellular HIV-1 DNA level was not significantly different between the 2 groups (0.54 and 0.45 log10 copies/10 peripheral blood mononuclear cells [PBMCs] in groups 1 and 2, respectively), whereas a higher proportion of patients maintained a plasma HIV-1 RNA level less than 20 copies/mL at week 72 in group 1 than in group 2 (79% and 52%; P = 0.0009). Furthermore, the difference in cellular HIV-1 DNA decrease from baseline to week 72 between patients who achieved a plasma HIV-1 RNA level less than 20 copies/mL at week 72 and those who did not was not statistically significant (0.54 and 0.45 log10 copies/10 PBMCs, respectively; P = 0.14). The decay in cellular HIV-1 DNA from baseline to week 72 was higher in antiretroviral-naive patients than in pretreated patients (0.55 and 0.23 log10 copies/10 PBMCs, respectively; P = 0.0008). The cellular HIV-1 DNA level change under therapy was best fitted to a 2-phase decay model with a junction point at week 16, from which its half-life was estimated at 18 weeks during the initial phase and at 104 weeks thereafter. In conclusion, the changes under therapy in cellular HIV-1 DNA level, which were mostly coincident to those of plasma HIV-1 RNA, did not add significant information to the comparison of the viral efficacy of the 2 studied regimens.     

Three-year durability of dual-nucleoside versus triple-nucleoside therapy in a Thai population with HIV infection

We compared the long-term immunologic and virologic efficacy of the dual- and triple-nucleoside therapy for HIV infection. This was a retrospective analysis of 2 randomized clinical trials in antiretroviral-naive patients. In the dual-nucleoside group, 15 started with didanosine (ddI) monotherapy and then added stavudine (d4T) after 24 weeks, 63 started with various doses of d4T and ddI, and 53 started with zidovudine (ZDV) and lamivudine (3TC). In the triple-nucleoside group, 53 started with ZDV, 3TC, and ddI. After 48 weeks, patients who were not failing were randomized to immediate (before treatment failure) versus delayed (at the time of virologic failure) switching from ddI and d4T to ZDV and 3TC or vice versa and from ZDV, 3TC, and ddI to d4T, 3TC, and abacavir (ABC). Failure was defined as a plasma HIV-1 RNA level>or=1 log10 above nadir or >or=10,000 copies/mL when nadir was <500 copies/mL. Patients failing therapy before week 48 received the new treatment as in the immediate switching group. Hydroxyurea was added to the last treatment regimen if patients failed after week 96. CD4 count and plasma HIV-1 RNA level (branched DNA assay with a cutoff point of 50 copies/mL) at week 144 were analyzed by intention to treat. Compared with the dual-nucleoside group, the triple-nucleoside group had a higher proportion of patients with <50 copies/mL at 144 weeks (60% vs. 18%; P<0.001), higher median CD4 count (388 cells/microL vs. 346 cells/microL; P=0.018), and longer duration of response, defined as the time from onset of viral suppression (<500 copies/mL) to the time of treatment failure (the first of 2 consecutive HIV-1 RNA measurements >500 copies/mL never followed by 2 consecutive visits showing suppressible viremia to <500 copies/mL) or discontinuation from the study (144 weeks vs. 104 weeks; P=0.002). Multivariate regression analyses showed that significant predictors for treatment success, defined as a plasma viral load <50 copies/mL at week 144, were asymptomatic clinical status at enrollment, a baseline plasma viral load 相似文献   

Are house dust mite allergen levels influenced by cold winter weather?

BACKGROUND: Moisture is vitally important for house dust mites and they cannot survive in cold or hot-dry climates. AIMS OF THE STUDY: To investigate the influence of two extraordinarily cold and dry winters in 1995/1996 and 1996/1997 on house dust mite levels in German homes. METHODS: Dust samples were collected between June 1995 and December 2001 on the mattresses of 655 adults and 454 schoolchildren living in five different areas of Germany. We compared house dust mite allergen Dermatophagoides pteronyssinus (Der p 1) levels before and during the winters of 1995/1996 and 1996/1997 with levels after these winters. RESULTS: D. pteronyssinus (Der p 1) levels in samples taken after the cold winters of 1995/1996 and 1996/1997 were approximately two times lower than Der p 1 levels in dust samples collected before or during these respective winters (Geometric means: Erfurt 89 vs 33 ng/g; Hamburg 333 vs 219 ng/g; Bitterfeld, Hettstedt, and Zerbst 296 vs 180 ng/g). Except for Hamburg, the decrease in Der p 1 levels was statistically significant. D. pteronyssinus levels measured in dust samples collected in 2001 (i.e. 3 years after the two cold winters) show a statistically non-significant increase (Geometric means: Erfurt 33 vs 39 ng/g; Hamburg 219 vs 317 ng/g), suggesting that it may take a long time for mite allergen levels to increase again after a sudden decrease. CONCLUSION: We conclude that Der p 1 levels in German mattress dust samples have been approximately reduced by a factor of three to four by the two consecutive cold winters of 1995/1996 and 1996/1997.     

Risk of T-cell lymphomas in persons with AIDS

Lymphomas in persons with AIDS are mostly B-cell types, but T-cell lymphomas have also been reported. We examined T-cell lymphoma risk in the 2-year period after AIDS onset by linking 302,834 adults with AIDS to cancer registry data. Of 6,788 cases of non-Hodgkin's lymphoma (NHL) with specified histologies, 96 (1.4%) were T-cell lymphomas. Assessment was based on clinical diagnosis and histology because T-cell marker data were inadequate, but when present, marker data supported the T-cell diagnosis. The relative risk of T-cell lymphoma, estimated by standardized incidence ratio, was 15.0 (95% confidence interval: 10.0--21.7). Risks were increased for all subtypes, including mycosis fungoides, peripheral lymphomas, cutaneous lymphomas, and adult T-cell leukemia/lymphoma (ATLL). HIV-related immunodeficiency could be important, but differences between the population developing AIDS and the general population (e. g., immigration from the Caribbean region for ATLL) might independently increase T-cell lymphoma risk.     

HIV-1 induction-maintenance at the lymph node level: the "Apollo-97" Study

OBJECTIVE: To assess the effects of five-drug combination therapy on HIV-1 load in lymph nodes and subsequent maintenance with four and three drugs. METHODS: Ten pharmacotherapeutically naive patients received a combination of zidovudine, lamivudine, didanosine, ritonavir, and saquinavir for 24 weeks, then zidovudine, lamivudine, didanosine, and saquinavir for the next 24 weeks, and finally zidovudine, lamivudine, and saquinavir for the last 24 weeks. HIV-1 RNA in lymph nodes was measured using quantitative polymerase chain reaction (PCR) at baseline, after 12, 24, 48, and 78 weeks. Plasma HIV-1 RNA, proviral DNA in peripheral blood mononuclear cells (PBMCs), circulating lymphocyte subsets, and protease inhibitor levels in blood were also regularly measured. Genotypic resistance was assessed in the different compartments in 2 patients who were failed by therapy. RESULTS: HIV-1 RNA decreased in lymph nodes in 9 patients and was stable in 1 despite initial control of plasma replication <20 copies/ml in each patient. Lymph node levels rebounded in 1 patient at week 72 as a result of lack of adherence and remained stable in the 8 others despite maintenance regimens. This represents a mean drop of -3.17 log in lymph nodes for the 8 patients maintaining undetectable viremia at 72 weeks. In the patient with stable lymph node viral RNA, selection of the M184V mutation was demonstrated at this level before detection in plasma and low blood saquinavir levels were found throughout the study. Continuous improvements in immune parameters were observed in all cases, although PBMC proviral DNA levels either showed a continuous decrease or stabilized to a plateau. CONCLUSIONS: More complex regimens do not perform better in lymph nodes than classic triple therapy. The persistence of HIV-1 RNA in lymph nodes could be related with cellular resistance mechanisms rather than an insufficient potency of the regimens.     

Does the addition of recombinant LH in WHO group II anovulatory women over-responding to FSH treatment reduce the number of developing follicles? A dose-finding study

BACKGROUND: In anovulatory women undergoing ovulation induction, addition of recombinant human LH (rLH) to FSH treatment may promote the dominance of a leading follicle when administered in the late follicular phase. The objective of this study was to find the optimal dose of rLH that can maintain the growth of a dominant follicle, whilst causing atresia of secondary follicles. METHODS: Women with infertility due to anovulation and over-responding to FSH treatment were randomized to receive, in addition to 37.5 IU recombinant human FSH (rFSH), either placebo or different doses of rLH (6.8, 13.6, 30 or 60 microg) daily for a maximum of 7 days. The primary efficacy endpoint was the proportion of patients who had exactly one follicle > or = 16 mm on hCG day. RESULTS: Among 153 enrolled patients, the five treatment groups were similar in terms of baseline characteristics. The proportion of patients with exactly one follicle > or = 16 mm ranged from 13.3% in the placebo group to 32.1% in the 30 microg rLH group (P = 0.048). The pregnancy rate ranged from 10.3% in the 60 microg group to 28.6% in the 30 microg rLH group. Adverse events were similar between groups. CONCLUSIONS: In patients over-responding to FSH during ovulation induction, doses of up to 30 microg rLH/day appear to increase the proportion of patients developing a single dominant follicle (> or = 16 mm). Our data support the 'LH ceiling' concept whereby addition of rLH is able to control development of the follicular cohort.     

Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes

BACKGROUND: Psoriatic plaques are characterized by infiltration with CD4+ CD45RO+ and CD8+ CD45RO+ memory effector T lymphocytes. The recombinant protein alefacept binds to CD2 on memory effector T lymphocytes, inhibiting their activation. METHODS: In a multicenter, randomized, placebo-controlled, double-blind study, we evaluated alefacept as a treatment for psoriasis. Two hundred twenty-nine patients with chronic psoriasis received intravenous alefacept (0.025, 0.075, or 0.150 mg per kilogram of body weight) or placebo weekly for 12 weeks, with follow-up for 12 additional weeks. Before treatment, the median scores on the psoriasis area-and-severity index were between 14 and 20 in all groups (0 denotes no psoriasis and 72 the most severe disease possible). RESULTS: Alefacept was well tolerated and nonimmunogenic. The mean reduction in the score on the psoriasis area-and-severity index two weeks after treatment was greater in the alefacept groups (38, 53, and 53 percent in the groups receiving 0.025, 0.075, and 0.150 mg per kilogram, respectively) than in the placebo group (21 percent, P<0.001). Twelve weeks after treatment, 28 patients who had received alefacept alone were clear or almost clear of psoriasis. Three patients in the placebo group were clear or almost clear; all three had received additional systemic therapy for psoriasis. Alefacept reduced peripheral-blood memory effector T-lymphocyte (CD45RO+) counts, and the reduction in the number of memory-effector T lymphocytes was correlated with the improvement in psoriasis. CONCLUSIONS: Treatment with alefacept for 12 weeks is associated with improvement in chronic plaque psoriasis; some patients have a sustained clinical response after the cessation of treatment. Alefacept selectively targets CD45RO+ memory effector T lymphocytes, suggesting that they have a role in the pathogenesis of psoriasis.