Differential chemokine expression in chronic GVHD of the conjunctiva.

In chronic GVHD after BMT, the conjunctiva represents a target organ. GVHD can lead to severe inflammation and dry-eye syndrome (sicca syndrome). The molecular mechanisms are largely unknown. We examined the expression of chemokines in the conjunctiva in cases of chronic GVHD. In this study, we included 10 patients with chronic GVHD and 10 healthy controls. Clinical data were collected and tear film analysis and conjunctival cytology were carried out. Conjunctival biopsies were taken from all participants. Gene expression profiles of chemokines and their corresponding receptors were evaluated by means of quantitative real-time PCR. Chemokine protein expression was analysed by immunohistochemical analyses. Expressions of the Th1-associated chemokines, chemokine (C-X-C motif) ligand (CXCL) 9 (Mig), CXCL10 (IP-10), and their receptor chemokine (C-X-C motif) receptor 3 (CXCR3) were significantly increased in GVHD patients. Immunohistochemical analysis confirmed marked expression of the inflammatory CXCR3 ligands. A total of six patients had a moderate or severe sicca syndrome. Impression cytology revealed a mild keratinisation, moderate keratinisation or severe squamous metaplasia in three patients, respectively. Chronic GVHD of the conjunctiva is characterised by the expression of Th1-associated chemokines. Taken together, our results confirm that the conjunctiva is a target organ in this T cell-mediated process and add to molecular understanding of conjunctival GVHD.

Do different delivery systems of hormone therapy have different effects on psychological symptoms in surgically menopausal women? A randomized controlled trial.

OBJECTIVE: To compare the influence of different delivery forms of estrogen therapy on menopausal and psychological symptoms in surgically menopausal women. STUDY DESIGN: Surgically menopausal women were assigned to a 1-year-therapy with oral conjugated estrogen 0.625mg/day (n=35), intranasal 300microg/day estradiol hemihidrate (n=33), percutaneous gel 1.5mg/day estradiol hemihidrate (n=32) or no treatment (control group, n=32). Serum E(2) and FSH levels, Kupperman's Scale used to assess climacteric symptoms, Hamilton Depression Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS) scores were assessed before and after 1-year-therapy. RESULTS: After 1 year, the greatest increase in E(2) was in the oral group, followed by the transdermal gel, and then the intranasal group (oral vs transdermal gel: p=0.022: oral vs intranasal: p=0.0001; transdermal gel vs intranasal: p=0.0001). All treatment groups improved significantly in total Kupperman index score and HARS (p<0.05) with no difference between the groups. With regard to HDRS, all treatment groups improved significantly (p<0.05) with the greatest improvement in the oral group, and no difference between transdermal gel and intranasal groups (oral vs transdermal gel: p=0.015; oral vs intranasal: p=0.001; transdermal gel vs intranasal: p=0.735). Control group scored worse in all tests after study (p<0.05). All scores correlated significantly with post-treatment serum E(2) and FSH levels (p<0.001). CONCLUSION: Oral, intranasal and percutaneous gel estradiol therapies significantly improve menopausal and psychological symptoms in surgically menopausal women with oral route better than transdermal gel and intranasal modalities against depressive mood.

Efficacy of tibolone and transdermal estrogen therapy on psychological symptoms in women following surgical menopause.

OBJECTIVE: This study investigated the efficacy of tibolone and transdermal estradiol therapy on menopausal and psychological symptoms in women following surgical menopause. METHOD: Seventy-five women who had undergone surgical menopause were randomized to a 6-month double-blind interventional study treatment with oral 2.5 mg/day tibolone, transdermal 3.9 mg/week estradiol or oral placebo. The patients were assessed using Kupperman's Scale, Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS) before and at the end of the 6 months of treatment. RESULT: Sixty-five subjects completed the study: 23 on tibolone, 21 on transdermal estradiol and 21 on placebo. At the end of the 6 months of therapy, highly significant improvements in menopausal symptoms, depression and anxiety scores were observed in both groups (tibolone and transdermal estradiol groups) as compared with baseline values (p<0.001). However, in the placebo group, there were no significant differences on changes from baseline to the end of treatment (p>0.05). CONCLUSION: These results suggest that tibolone and transdermal estradiol therapy significantly improve menopausal and psychological symptoms in women following surgical menopause.