Pregnancy and childbirth after treatment with autologous hematopoietic stem cell transplantation for severe systemic sclerosis requiring parenteral nutrition. Ethical issues.

We report a pregnancy in a patient who had undergone autologous hematopoietic stem cell transplantation (AHSCT) for diffuse cutaneous systemic sclerosis (SSc). SSc onset was at age 25, with Raynaud phenomenon and evolved to include diffuse cutaneous, arthritis, pulmonary fibrosis and extensive gastrointestinal involvement. AHSCT (cyclophosphamide/ATG for conditioning) was performed four years later with improvement of all features apart from the gastrointestinal symptoms requiring parenteral nutrition (PN). Forty months after AHSCT, she had a spontaneous miscarriage necessitating curettage. Despite advice to avoid pregnancy because of poor nutritional status and recurring catheter infections from her PN, she fell pregnant one year later. The pregnancy proceeded normally and she delivered at 34 weeks, under cesarean section. The baby girl, (1990g and 4 APGAR score) after initial respiratory distress, is now 4 years old with normal growth and development. Unfortunately, the patient died early in 2008 due to severe disease progression terminating with gastrointestinal obstruction and pericarditis. This first report of a successful pregnancy in a patient with diffuse SSc treated by AHSCT illustrates that despite the possibility for a normal pregnancy, the decision to do so includes aspects of maternal prognosis.

Guidelines for autologous blood and marrow stem cell transplantation in multiple sclerosis: a consensus report written on behalf of the European Group for Blood and Marrow Transplantation and the European Charcot Foundation. BMT-MS Study Group.

Recent reports suggest the possible beneficial effects of haemopoietic stem cell transplantation (HSCT) in autoimmune diseases such as multiple sclerosis (MS). The definition of the risk/benefit ratio for such a treatment is perceived as a major issue for the neurological community worldwide. The First Consensus Conference on Bone Marrow Transplantation in Patients with Multiple Sclerosis was held in Milan, Italy on 21 February 1998. Participants from 16 European, North American, and South American countries discussed the guidelines for performing HSCT in MS. This conference was organized in order to: (a) define criteria for patient selection; (b) define transplantation procedures to maximize efficacy of the treatment and minimize its toxicity; (c) standardize patient outcome evaluation; and (d) establish an international working group to evaluate the efficacy and safety of HSCT in MS and to study the immunological changes related to HSCT in MS patients. During the meeting in Milan agreement was reached on: (a) the preparation and distribution of a consensus report on HSCT in MS and (b) the design of an open trial for an initial assessment of the safety and efficacy of HSCT in MS. The consensus reached during the meeting and the design of the clinical trial are summarized in this contribution.

Relationship between muscle strength and vitamin D metabolites: are there therapeutic possibilities in the elderly?

To test the hypothesis that muscle weakness associated with aging is in part due to low serum levels of vitamin D, we investigated the relationship between muscle strength and serum levels of vitamin D metabolites in ambulatory elderly people who were not receiving vitamin D supplementation. We enrolled 319 ambulatory elderly subjects (103 women: mean age 74.2, age range 65-86; 216 men: mean age 76.6, age range 66-95) between April and August 1995. The study design was cross-sectional. Muscle strength was measured as leg extension power in watts (LEP). Mean 25-hydroxyvitamin D serum concentrations were higher in male participants at 36.2 ng/ml (range 3.0-85.0) versus 27.4 ng/ml (range 5.0-88.0) in female subjects (p = 0.008). We found 12 percent of female and 18 percent of male subjects with 25-hydroxyvitamin D values below the lower threshold (< 12 ng/ml). Mean 1,25-dihydroxyvitamin D levels were similar in both sexes: 39.8 pg/ml (range 15.0-73.0) in women and 37.9 pg/ml (range 13.0-69.0) in men. LEP declined with age in women and men (f: r = -0.35, p = 0.001; m: r = -0.48, p < 0.0001). Men were significantly stronger than women (p < 0.0001). In men both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D showed pairwise correlation with LEP (r = 0.24; p = 0.0004/r = 0.14; p = 0.045). In women only 1,25-hydroxyvitamin D was significantly correlated with LEP (r = 0.22; p = 0.03). In ANCOVA, including all participants, explaining LEP by sex (p < 0.0001), age (p < 0.0001), BMI (p = 0.013), 1,25-dihydroxyvitamin D (p = 0.02), 25-hydroxyvitamin D (p = 0.18) and iPTH (p = 0.82), all factors showed significant effects except 25-hydoxyvitamin D and iPTH (r2 of the whole model: 0.41). In conclusion our results support the view that, in concert with other factors, deficiency of both 25-hydroxyvitamin D and 1,25-hydroxyvitamin D contributes to the age-related decline in muscle strength. Modest, but significant relationships between 1,25-dihydroxyvitamin D and muscle strength in both sexes, and 25-hydroxyvitamin D in male participants could be documented. Whether the impact of vitamin D on calcium homeostasis and bone mineral density or directly on the muscle tissue level is more important for prevention of hip fractures remains unclear. Further prospective and comparative treatment studies should be performed, in order to evaluate whether and in which dose requirements, vitamin D supplementation can improve muscle strength in the elderly.

Muscle strength in the elderly: its relation to vitamin D metabolites.

OBJECTIVE: To identify a relation between loss of muscle strength and vitamin D deficiency in ambulatory elderly persons not receiving vitamin D supplementation. DESIGN: Cross-sectional study. SETTING: All measurements were taken at the Department of Geriatrics, University Hospital, Basel, Switzerland. SUBJECTS: Three hundred nineteen patients (103 women, 216 men) selected by random sampling from participants in an ongoing interdisciplinary study on aging (mean age for women, 74.2 yrs; for men, 76.7 yrs). OUTCOME MEASURES: Leg extension power (LEP) and body mass index (BMI); serum values of 25-hydroxyvitamin D [calcidiol, 25(OH)D], 1,25-hydroxyvitamin D [calcitriol, 1,25(OH)2D], and intact parathyroid hormone (iPHT). RESULTS: Twelve percent of women and 18% of men had 25(OH)D values below the normal range (<12 ng/mL). Muscle strength was lower in older subjects (female: r = -.35; p = .0005/male: r = -.48; p < .0001) and was lower in women than in men (p < .0001). In men both 25(OH)D and 1,25(OH)2D was significantly correlated with LEP (r = 0.24; p = .0004/r = .14; p = .045). In women, only 1,25(OH)2D was significantly correlated with LEP (r = 0.22; p = .034). In an ANCOVA including all participants and explaining LEP by sex, age, BMI, 1,25(OH)2D, 25(OH)D, and iPTH, all factors showed significant effects except 25(OH)D and iPTH (r2 = .41). CONCLUSION: Muscle strength declined with age in ambulatory elderly people and showed modest, but significant, positive correlation with 1,25(OH)2 vitamin D in both sexes and with 25(OH)D in male subjects. Therefore vitamin D deficiency appears to contribute to the age-related loss of muscle strength, which might be more pronounced in institutionalized elderly people with a high prevalence of vitamin D deficiency.

Elevated PTH levels in hypovitaminosis D are more rapidly suppressed by the administration of 1,25-dihydroxy-vitamin D3 than by vitamin D3.

OBJECTIVE: To assess markers of bone metabolism in two groups of inpatients with hypovitaminosis D and elevated PTH levels receiving two different vitamin D medications. METHODS: 26 patients with secondary hyperparathyroidism (2 degrees HP) were treated either with 800 IU cholecalciferol and 1000 mg calcium or 0.5 microgram calcitriol plus 500 mg calcium daily for 6 months. 25-OH-vitamin D3, 1,25-dihydroxy-vitamin D3, intact PTH, calcium and urinary N-telopeptides of bone collagen I were measured at baseline, 3 and 6 months. RESULTS: PTH levels decreased earlier in the calcitriol group than in the cholecalciferol group. After six month no difference could be documented. Lowering of urinary N-telopeptides excretion was observed in both groups. CONCLUSION: The use of both forms of vitamin D supplementation appears to be useful for patients with hypovitaminosis D, elevated PTH levels and high telopeptide excretion.