Growth hormone replacement therapy in patients with traumatic brain injury.

In patients with severe traumatic brain injury (TBI), a growth hormone deficiency (GHD) is frequent and may contribute to the cognitive sequelae and reduction in quality of life (QoL). Recent studies have suggested that GH replacement therapy (GHRT) can improve processing speed and memory. The aim of the study was to analyze the efficacy of GHRT on cognition, activities of daily living (ADL), and QoL and the factors that predicted and contributed to these effects. We included patients at least 1 year after their TBI and assessed pituitary functions (with stimulation tests), cognition (attention, memory, and executive function), participation in ADL and QoL. GHD was treated for at least 1 year in 23 patients, who were compared with 27 non-treated patients. Other deficiencies were also treated. Measurements were performed at baseline and 1 year later. An analysis of variance of the factors group and session (p ≤ 0.05) showed that most cognitive parameters had improved at 1 year (evidencing a session effect). A stronger effect of GHRT (i.e. a group x session interaction) was found for Rey Osterrieth complex figure recall and 2/6 domains in the QoL questionnaire ("personal" and "functional"). Trends (p ≤ 0.07) were also found for spatial orientation and immediate recall in the verbal memory test. Greatest improvements were associated with lower performance before treatment. The magnitude of the improvements in ADL and QoL was moderately correlated with the improvement in cognition. In conclusion, replacement therapy can improve cognition and QoL in patients with TBI who have GHD, especially in those with severe disabilities.

Lasting pituitary hormone deficiency after traumatic brain injury.

Pituitary deficiencies have been reported after traumatic brain injury (TBI) and may contribute to lasting cognitive disorders in this context. In a population of TBI patients with persistent cognitive and/or behavioral disorders, we sought to determine the prevalence of lasting pituitary deficiency and relationships with TBI severity, cognitive disorders, and impairments in activities of daily living (ADL). Fifty-five patients were included (mean age 36.1 years; 46 men) at least 1 year after TBI. They underwent a comprehensive evaluation of pituitary function (basic tests and stimulation), initial TBI severity, and long-term outcomes (cognitive performance, Glasgow Outcome Scale score, impact on ADL, and quality of life [QoL]). We used chi-squared and Mann-Whitney tests to probe for significant (p≤0.05) relationships between pituitary disorders and other parameters. Thirty-eight (69%) patients had at least one pituitary hormone deficiency. Growth hormone deficiency was more prevalent (severe: 40.0%; partial: 23.6%) than corticotropin (27.3%) or thyrotropin (21.8%) deficiencies. Other deficiencies were rare. Growth hormone deficiency was associated with attention and verbal memory disorders and reduced involvement in ADL. We did not find any relationship between pituitary deficiency and the TBI's initial severity. In a multivariate analysis, the TBI severity was introduced as a first factor, and pituitary deficits as a secondary factor for explaining the late outcome (ADL and QoL). In conclusion, TBI patients with cognitive sequelae must undergo pituitary screening because growth hormone, corticotropin, and thyrotropin deficits are particularly common and can adversely affect ADL and reduce QoL.

Differential mucin expression in colon carcinoma HT-29 clones with variable resistance to 5-fluorouracil and methotrexate.

A current challenge is to define the biological characteristics of colon tumor cells resistant to chemotherapy. Distinct sub-populations of mucus-secreting cells were previously obtained from the colon cancer cell line HT-29 after long-term treatment with the anti-cancer drugs, 5-fluorouracil (5-FU) and methotrexate (MTX). Since mucins are increasingly implicated as playing a role in carcinogenesis, we studied the pattern of mucin expression in two HT-29 clones of mucus-secreting and two clones of enterocyte-like phenotype which differ in their capacity to resist to 5-FU and/or MTX. The expression of both transmembrane (MUC1, MUC3, MUC4) and secreted gel-forming (MUC2, MUC5AC, MUC5B, MUC6) mucins in clones was studied by northern and/or western blotting. The four HT-29 clones showed three cellular phenotypes: (1) The mucus-secreting clone HT29-5F12 consists of unpolarized cells with mucus secretions that have anti-colonic mucin immunoreactivity, and mainly expresses MUC2 and is resistant to 5-FU and sensitive to MTX; (2) The mucus-secreting clone HT29-5M21 forms a monolayer of polarized cells with strong anti-gastric mucin immunoreactivity and mainly expresses MUC5AC and MUC5B and is resistant to MTX and sensitive to 5-FU; (3) The two enterocyte-like clones, HT29-5F7 and HT29-5M12 are resistant to both MTX and 5-FU and express mainly MUC1 and MUC5B, respectively. These clones which originate from a same colorectal tumour and display different patterns of mucin expression as well as differing resistance to MTX and 5-FU will make useful in vitro models for studying the potential role of mucins or other biological markers in drug resistance pathways.