Limited long-term naive CD4+ T cell reconstitution in patients experiencing viral load rebounds during HAART

Long-term (3.5 years) immune reconstitution in relation to viral load response was determined. Plasma HIV-1 RNA was suppressed in 40 patients (full responders) up to 42 months, and 17 patients achieved partial response. The measurements of CD4⁺ and CD8⁺ T lymphocyte subsets (CD45RA, CD45RACD62L, CD45RO, CD28, CD38) were carried out by flow cytometry. Full responders had a significant increase of CD4⁺ and all CD4⁺ T subsets both up to 6 and from 6 to 42 months, while the increase for partial responders was only up to 6 months. By 6 months, higher slopes were observed in full versus partial responders in the % of CD28 on CD4⁺ and the % of CD4⁺ memory subset and in both naïve and memory CD4⁺ subsets from 6 to 42 months. The percentage of CD8⁺ and its subsets was decreased significantly in full responders both up to 6 and from 6 to 42 months (except for an increase in the CD8⁺CD45RA⁺ CD62L⁺ cells), while in partial responders this decrease was only up to 6 months. Lower slopes were observed in full versus partial responders from 6 to 42 months in the percentages of CD8⁺, CD8⁺CD45RO⁺, CD8⁺CD28⁻, and CD8⁺CD38⁺ T cells. In conclusion, full responders have a stronger long-term naive CD4⁺ T cell subset reconstitution than partial responders. J. Med. Virol. 73:235–243, 2004. © 2004 Wiley-Liss, Inc.     

A prospective study on lung toxicity in patients treated with gemcitabine and carboplatin: clinical, radiological and functional assessment.

BACKGROUND: Small series and retrospective studies have suggested that treatment with gemcitabine may be associated with pulmonary toxicity. However, a prospective evaluation of cancer patients treated with gemcitabine-based chemotherapy without neoplastic involvement of the thorax and without administration of radiotherapy has not been performed. PATIENTS AND METHODS: To investigate this issue, 41 consecutive patients receiving gemcitabine and carboplatin underwent prospective evaluation of lung function, which included pulmonary symptoms, pulmonary function tests, arterial blood gases and radiographic studies. Assessment was performed before and after completion of chemotherapy in all patients. Patients with a substantial decline in diffusion capacity for carbon monoxide (DLCO), defined as a drop of > or = 20%, were reassessed 2 months later. RESULTS: After chemotherapy, there were no significant changes in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, alveolar volume or total lung capacity. In contrast, there was a significant decline in DLCO (73 +/- 22 versus 67 +/- 24% predicted; P = 0.017) and in carbon monoxide transfer coefficient (KCO) (89 +/- 24 versus 80 +/- 24% predicted; P = 0.004). Arterial blood gases did not change following treatment. Ten of the 41 patients (24%) exhibited a substantial decline in DLCO, which, however, recovered within 2 months (DLCO at baseline, immediately after therapy and at 2 months after completion of treatment, 84 +/- 14, 58 +/- 16 and 77 +/- 17% predicted, respectively; P < 0.001; baseline DLCO versus DLCO at 2 months, P > 0.05). Four of the 41 patients (10%) experienced dyspnea, which was self-limiting, with the exception of one patient who developed interstitial lung fibrosis. Among the various risk factors examined, older age, female gender and lower baseline DLCO were associated with more profound changes in DLCO post-treatment. CONCLUSIONS: This prospective analysis showed that the combination of gemcitabine and carboplatin induces a significant, but reversible, decrease in diffusion capacity, which is mostly asymptomatic. Thus, this regimen is safe as regards clinically significant lung toxicity.     

Does Adherence to the Mediterranean Diet Have a Protective Effect against Asthma and Allergies in Children? A Systematic Review

Dietary pattern may potentially impact on the pathogenesis of asthma and allergies. The Mediterranean Diet (MD) has significant health benefits due to its antioxidant and anti-inflammatory properties. The aim of this systematic review was to investigate the effectiveness of adherence to the MD against asthma and allergies in childhood. Hence, a systematic literature search was conducted on PubMed, ESBCO (Cinahl), Scopus, and the Cochrane Library databases up to 26 January 2022. The total number of articles obtained, after the initial search on the databases was conducted, was 301. Twelve studies were included, after the removal of duplicates and screening for eligibility. Our findings indicated a protective role of the MD against childhood asthma, but they also imply that the MD probably does not affect the development of allergies. Nevertheless, the heterogeneity and limitations of the studies highlight the need for randomized controlled trials that will focus on the pediatric population and hopefully provide more robust evidence.     

Inhibition of neovascularization and tumor growth, and facilitation of wound repair, by halofuginone, an inhibitor of collagen type I synthesis

Halofuginone, an inhibitor of collagen α1(I) gene expression was used for the treatment of subcutaneously implanted C6 glioma tumors. Halofuginone had no effect on the growth of C6 glioma spheroids in vitro, and these spheroids showed no collagen α1(I) expression and no collagen synthesis. However, a significant attenuation of tumor growth was observed in vivo, for spheroids implanted in CD-1 nude mice which were treated by oral or intraperitoneal (4 µg every 48 hours) administration of halofuginone. In these mice, treatment was associated with a dose-dependent reduction in collagen α1(I) expression and dose- and time-dependent inhibition of angiogenesis, as measured by MRI. Moreover, halofuginone treatment was associated with improved re-epithelialization of the chronic wounds that are associated with this experimental model. Oral administration of halofuginone was effective also in intervention in tumor growth, and here, too, the treatment was associated with reduced angiogenic activity and vessel regression. These results demonstrate the important role of collagen type I in tumor angiogenesis and tumor growth and implicate its role in chronic wounds. Inhibition of the expression of collagen type I provides an attractive new target for cancer therapy.     

Sero epidemiology of Bordetella pertussis immune responses in a healthy population in northern Greece

A seroepidemiological study was conducted on a representative sample of the northern Greek population (healthy individuals, age range=1 day to 80 years) to assess the prevalence of antibodies to pertussis toxin (PT) and filamentous hemagglutinin (FHA). Antibody concentrations were significantly elevated with age (analysis of variance (ANOVA), P<0.001). In addition, a significant increase in antibody levels was detected in subjects >50 years old compared to children aged 5-10 years (post-hoc Scheffe analysis, P=0.007). These data suggest that pertussis occurs frequently in Greek adults, and that sometimes a fifth booster vaccine dose is not given after the second year of life. Routine revaccination with the acellular vaccine for children >4 years of age, adolescents, and adults should be considered in order to ensure effective protection of the whole population.