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PubMedDate not supplied

Longitudinal analysis of the 90K glycoprotein in the Italian HIV-seroconversion study: temporal trend and predictability of the maturity of HIV infection.

OBJECTIVES: To evaluate the level of 90K as a predictor of AIDS; to describe 90K levels over time after HIV serconversion; and to evaluate the 90K level as a marker of the maturity of infection. DESIGN: Prospective incident cohort of HIV-infected individuals with documented dates of seroconversion. METHODS: Cox models were applied to estimate the crude and adjusted relative hazards (RH) of AIDS by level of 90K. Regression models were applied to describe the temporal trend and the correlates of the level of 90K over time after HIV-seroconversion. Logistic models were applied to evaluate the probability of a sample of 90K having been taken within a certain time period after HIV-seroconversion. RESULTS: The study population consisted of 150 participants of the Italian Seroconversion Study. A total of 429 measurements of 90K were taken. Both early and later measurements of 90K were highly predictive of AIDS, also when adjusting for CD4 lymphocyte count and HIV load. The 90K level (U/ml) increased by 10% annually (95% CI: 7%-13%); the increase over time was linear. IDUs had higher 90K levels than heterosexuals and homosexuals over the course of HIV disease. High 90K levels were highly predictive of distant seroconversions (age-adjusted probability, 74%), whereas were poorly predictive of recent seroconversions (age-adjusted probability, 5%); the results were similar for the predictability of CD4 lymphocyte count. CONCLUSIONS: The level of 90K is a useful prognostic tool for clinical purposes. As a marker of the maturity of infection, 90K is similar to the CD4 lymphocyte count, with the advantage of being able to use serum instead of fresh whole blood. It has a good capacity to identify distant infections.

Acquired Immunodeficiency Syndrome↗
PubMed2006

A longitudinal analysis of healthcare costs after treatment optimization following genotypic antiretroviral resistance testing: does resistance testing pay off?

OBJECTIVE: To assess the impact of antiretroviral therapy optimized by genotypic antiretroviral resistance testing (GRT) on healthcare costs over a 2-year period in patients after antiretroviral treatment failure. STUDY DESIGN: Non-randomized, prospective, tertiary care, clinic-based study. PATIENTS: One-hundred and forty-two HIV patients enrolled in the 'ZIEL' study and the Swiss HIV Cohort Study who experienced virological treatment failure. METHODS: For all patients GRT was used to optimize the antiretroviral treatment regimen. All healthcare costs during 2 years following GRT were assessed using microcosting. Costs were separated into ART medication costs and healthcare costs other than ART medication (that is, non-ART medication costs, in-patient costs and ambulatory [out-patient] costs). These cost estimates were then split into four consecutive 6-month periods (period 1-4) and the accumulated cost for each period was calculated. Univariate and multivariate regression modelling techniques for repeated measurements were applied to assess the changes of healthcare costs over time and factors associated with healthcare costs following GRT. RESULTS: Overall healthcare costs after GRT decreased over time and were significantly higher in period 1 (32%; 95% confidence interval [Cl]: 18-47) compared with period 4. ART medication costs significantly increased by 1,017 (95% Cl: 22-2,014) Swiss francs (CHF) from period 1-4, whereas healthcare costs other than ART medication costs decreased substantially by a factor of 3.1 (95% Cl: 2.6-3.7) from period 1 to period 4. Factors mostly influencing healthcare costs following GRT were AIDS status, costs being 15% (95% Cl: 6-24) higher in patients with AIDS compared with patients without AIDS, and baseline viral load, costs being 12% (95% Cl: 6-17) higher in patients with each log increase in plasma RNA. CONCLUSIONS: Optimized antiretroviral treatment regimens following GRT lead to a reduction of healthcare costs in patients with treatment failure over 2 years. Patients in a worse health state (that is, a positive AIDS status and high baseline viral load) will experience higher overall costs.

Adult↗
PubMedDate not supplied

Frequent p53 mutation in relapsed acute lymphoblastic leukemia with cytogenetic instability: a longitudinal analysis.

P53 mutation, through defects in repairing DNA damages, is associated with genomic instability. In 24 adult patients with relapsed acute lymphoblastic leukemia (ALL), the status of the p53 gene at different stages was serially followed by cytogenetic and polymerase-chain reaction/single strand conformation polymorphism (PCR/SSCP) analysis. P53 mutation was detected in 6 patients (25%) and all were at relapsed stages: 3 at first relapse, 2 at second relapse and one at refractory phase. Loss of the remaining p53 allele was demonstrated in 5 of them by cytogenetic and SSCP analysis. Furthermore, all of the p53 mutations were associated with appearance of complex cytogenetic changes (CCG), suggesting of cytogenetic instability (CGI). The frequency of acquiring p53 mutation during leukemic progression is significantly higher in patients with CGI than in patients without CGI (6/11 v 0/13, p = 0.003). P53 mutation was detected either concurrently (n = 2) or after (n = 4, 2(+)-18 months) appearance of CCG. The results suggest that p53 mutation is frequently involved during ALL relapse and is closely linked with cytogenetic instability.

Adult↗
PubMed1998

[Nutrition dwarfism: longitudinal analysis of anthropometric and metabolic parameters in rats].

UNLABELLED: Nutritional dwarfing (ND) is the result of nonorganic causes reflective of a voluntary or unintentional reduction in food intake, inappropriate eating behavior, dissatisfaction with body weight or unhealthy approaches toward weight control. Patients with ND have reached an equilibrium between their genetic growth potential and their nutritional intake. This study was undertaken to compare on a growing rat model the metabolic alterations in terms of substrate utilization (SU), oxygen consumption (VO2) and growth rate velocity. Twenty male weanling Wistar rats were randomized to 3 groups: control (C), experimental 4 (E4) and 8 (E8). C was fed "ad libitum" with a stock diet, E4 and E8 were underfed by 80% of the requirements during four or eight weeks, respectively. During the depletion phase the following measurements were performed: 1a) body weight (Wt), 1b) length, 1c) Weight for Length ratio z-score, 2) Body composition (BC) by EM-SCAN Tobec Model 3 000, Springfield. USA, 3) VO2 by indirect calorimetry, ECO-OXYMAX. RESULTS: 1) wt for length was -0.70 +/- 0.43 for E4 (t = 4 weeks) and 1.44 +/- 0.32 for E8 (t = 8 weeks), 2% of fat mass was within the normal range, 3) VO2 was not significantly different between groups. Chronic suboptimal nutrition (80%) decreased growth velocity which was the sole manifestation of nutritional inadequacy.

Animals↗
PubMed1998

Longitudinal analysis of the acute Sendai virus-specific CD4+ T cell response and memory.

The development and persistence of Sendai virus-specific CD4+ T cell memory has been analyzed following respiratory infection of C57BL/6J mice by determining the prevalence of IL-2-producing Th cell precursors (Thp). Frequencies as high as 1:40 virus-specific CD4+ T cells were found in the regional lymph nodes and spleen during the acute phase of the host response and persisted at levels > or =1:500 for 2 to 3 mo. Thereafter, these CD4+ T cells tended to distribute more to the spleen than to the lymph nodes, a pattern that persisted for the life of the animals. From 3 to 12 mo after infection, virus-specific Thp were always detectable, although the numbers were diminished relative to those measured during the acute phase. Thereafter, however, in both contemporary and cumulative assays, there was a progressive increase in both the frequency and number of Thp. These increases were especially apparent for mice more than 2 years of age. This may reflect enrichment of the CD4+CD44high memory set due to the gradual diminution of the naive CD4+CD62LhighCD44low component. Analysis of DNA staining profiles for the CD4+ T cells showed high levels of cycling for the acute phase of the response, whereas the rate of T cell turnover measured for the CD4+CD44high population by bromodeoxyuridine incorporation indicated a pattern of stable, continuing proliferation throughout life. Virus-specific CD4+ T cell memory resulting from a single exposure to a readily eliminated RNA virus is thus maintained indefinitely in laboratory mice.

Acute Disease↗