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Biomedical subjects

R Ziegler

Publications and source records attributed to R Ziegler.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effect of alpha-lipoic acid on the progression of endothelial cell damage and albuminuria in patients with diabetes mellitus: an exploratory study.

Oxidative stress plays a central role in the pathogenesis and progression of late microangiopathic complications (diabetic nephropathy) in diabetes mellitus. Previous studies suggested that treatment of diabetic patients with the antioxidant alpha-lipoic acid reduce oxidative stress and urinary albumin excretion. In this prospective, open and non-randomized study, the effect of alpha-lipoic acid on the progression of endothelial cell damage and the course of diabetic nephropathy, as assessed by measurement of plasma thrombomodulin and urinary albumin concentration (UAC), was evaluated in 84 patients with diabetes mellitus over 18 months. Forty-nine patients (34 with Type 1 diabetes, 15 with Type 2 diabetes) had no antioxidant treatment and served as a control group. Thirty-five patients (20 with Type 1 diabetes, 15 with Type 2 diabetes) were treated with 600 mg alpha-lipoic acid per day. Only patients with an urinary albumin concentration <200 mg/l were included into the study. After 18 months of follow up, the plasma thrombomodulin level increased from 35.9+/-9.5 to 39.7+/-9.9 ng/ml (P<0.05) in the control group. In the alpha-lipoic acid treated group the plasma thrombomodulin level decreased from 37.5+/-16.2 to 30.9+/-14.5 ng/ml (P<0.01). The UAC increased in patients without alpha-lipoic acid treatment from 21.2+/-29.5 to 36.9+/-60.6 ng/l (P<0.05), but was unchanged with alpha-lipoic acid. It is postulated that the significant decrease in plasma thrombomodulin and failure of UAC to increase observed in the alpha-lipoic acid treated group is due to antioxidative effects of alpha-lipoic acid, and if so that oxidative stress plays a central role in the pathogenesis of diabetic nephropathy. Furthermore, progression of the disease might be inhibited by antioxidant drugs. A placebo-controlled study is needed.

Albuminuria↗
PubMed2001

Changing serine-485 to alanine in the opossum parathyroid hormone (PTH)/PTH-related peptide receptor enhances PTH stimulation of phospholipase C in a stably transfected human kidney cell line: a useful model for PTH-analog screening?

Using site-directed mutagenesis, we have introduced a serine-485-to-alanine mutation in the opossum parathyroid hormone (PTH) receptor. This amino acid is considered to be phosphorylated by protein kinase A upon ligand binding. Both wild-type (WT) and mutant receptor were stably expressed in 293-EBNA HEK cells. The mutant receptor showed comparable binding characteristics and only a slight increase in cAMP production compared with WT. However, the PTH dose-dependent increase in inositol phosphate production was 24-fold for the mutant receptor vs. 6-fold for the WT receptor. This mutant might prove useful in the sensitive detection of phospholipase C activation through various ligands, as the PTH receptor becomes a target of therapeutic intervention in osteoporosis.

Alanine↗
PubMed2001

A case of neuroendocrine oncogenic osteomalacia associated with a PHEX and fibroblast growth factor-23 expressing sinusidal malignant schwannoma.

Oncogenic osteomalacia is a rare paraneoplastic syndrome that is characterized biochemically by hypophosphatemia and low plasma 1,25-dihydroxyvitamin D3, and clinically by osteomalacia, pseudofractures, bone pain, fatigue, and muscle weakness. We present a patient with a malignant schwannoma as the underlying cause of this disorder. A permanent cell line (HMS-97) derived from this tumor showed evidence of neuroendocrine differentiation by immunohistochemistry and of neurosecretory activity by electron microscopy. The cell line did express PHEX (phosphate-regulating gene with homologies to endopeptidases located on the X-chromosome) and FGF-23 (fibroblast growth factor-23) transcripts on northern hybridization; however, none of the known mutations from the related mendelian disorders of X-linked hypophosphatemic rickets or autosomal-dominant hypophosphatemic rickets could be detected. Tumor cell (HMS-97)-derived conditioned medium did not inhibit phosphate transport in a standard opossum kidney cell assay and in animal experiments. The medium also showed no PTH1- or PTH2-receptor-stimulating bioactivity. HMS-97 cells might be useful for further studies that aim to determine the genetic mechanism that leads to the observed PHEX and FGF-23 expression, both of which might have a direct role in the pathogenesis of oncogenic osteomalacia. In addition, these cells might be a useful tool for the investigation of neuroendocrine Schwann cell function and autoimmune peripheral nerve disease.

Female↗
PubMed2001

Effects of triiodothyronine on the insulin-like growth factor system in primary human osteoblastic cells in vitro.

Thyroid hormone plays a major role in the regulation of bone metabolism but the mechanism by which this is accomplished is not clear. Interactions of thyroid hormone with the growth hormone/insulin-like growth factors (IGFs) axis suggest an alternate pathway of action for triiodothyronine (T(3)) on bone formation, besides direct effects. The present study investigates the influence of T(3) on IGF-1, IGF-2, IGF-1 receptor (IGF-1R), and IGF binding protein (IGFBP) transcripts, and on IGF-1 action in human osteoblastic cells (hOB) under serum-free culture conditions. No influence of T(3) on IGF-1, IGF-2, IGFBP-3, or IGFBP-4 mRNA levels in hOB was observed. However, T(3) at concentrations of 10(-8) mol/L and 10(-7) mol/L increased IGF-1R mRNA levels in a dose-dependent manner (p < 0.01) and enhanced IGFBP-5 mRNA levels at a concentration of 10(-7) mol/L (p < 0.05), as assessed by reverse transcriptase-polymerase chain reaction. Correspondingly, Scatchard analysis of [(125)I]-IGF-1 binding revealed that T(3) at 10(-7) mol/L increased the number of IGF-1 binding sites in hOB, with small changes in receptor affinity. In addition, a synergistic effect of T(3) and IGF-1 on hOB proliferation was found (p < 0.05). We conclude that IGF-1R and IGFBP-5 are thyroid hormone target genes in human osteoblasts, whereas IGF-1 mRNA expression itself appears not to be regulated by T(3) in hOB. However, T(3) stimulates IGF-1R mRNA expression as well as IGF-1 binding and IGF-1 induced cell proliferation in osteoblasts, thus suggesting thyroid hormone may potentiate the effect of IGF-1 at the receptor level. This may contribute to the positive effects of thyroid hormone on bone formation, which, in addition, may be modulated by increased IGFBP-5 expression.

Base Sequence↗
PubMed2001

Low serum concentrations of insulin-like growth factor I are associated with femoral bone loss in a population-based sample of postmenopausal women.

OBJECTIVE: Cross-sectional studies suggest that the decline in insulin-like growth factor-I (IGF-1) levels with age may contribute to age-associated bone loss. However, prospective data on the relation between circulating IGF-I and bone loss in old age have not yet been reported. DESIGN: A longitudinal study (follow-up time 3.3 years) of the change of bone mineral density (BMD) at the lumbar spine and femoral neck in relation to serum IGF-I. PATIENTS: A population-based sample of 173 elderly men and 107 postmenopausal women without medical conditions or medication known to significantly affect BMD or serum IGF-I levels. MEASUREMENTS: BMD at the lumbar spine and femoral neck at baseline and after a mean follow-up-time of 3.3 years, serum-IGF-I, insulin-like growth factor binding protein 3 (IGFBP-3), sex hormone-binding globulin (SHBG) and biologically available testosterone (BAT). RESULTS: In women, there was a graded negative relationship between quartiles of serum IGF-I and bone loss at the proximal femur (P = 0.04), which persisted after adjustment for potential covariables of bone loss and serum IGF-I. In subgroup analysis the association between serum IGF-I and change in BMD was only apparent in women more than 10 years past menopause (r = + 0,38, P = 0.01). No association between serum IGF-I levels and changes in BMD was observed in men. IGF-I levels were not associated with changes in spinal BMD. CONCLUSIONS: Our data suggest that low circulating levels of IGF-I in elderly women are associated with greater femoral bone loss, and support previous findings of gender differences in the relation between serum IGF-I and BMD in older age.

Aged↗
PubMed2001

Effects of 6 years of growth hormone (GH) treatment on bone mineral density in GH-deficient adults.

OBJECTIVE: Adults with growth hormone (GH) deficiency are often osteopenic. Short-term GH replacement therapy has been shown to improve bone mineral density (BMD). However, whether the increases in BMD are progressive with time is still unclear. We therefore examined long-term changes in BMD with GH treatment in GH-deficient adults over a period of 6 years. DESIGN: Open prospective GH therapeutic study. PATIENTS: Twelve GH-deficient patients (four women, eight men) with a mean age of 42.5 years (range 24-61 years) at the beginning of GH replacement. Eleven patients suffered in addition from LH/FSH insufficiency, eight from TSH insufficiency and eight from ACTH insufficiency. Before the start of GH substitution, the insufficient anterior pituitary axes were fully substituted for an average of 9.8 years (range 2-22 years). Average daily GH dose was 2.4 IU (SD 0.86). MEASUREMENTS: BMD and bone area were measured at annual intervals at the lumbar spine and at the proximal femur using dual-X-ray absorptiometry. RESULTS: Under GH substitution, serum insulin-like growth factor I concentrations increased by 140 microg/l compared to pretherapeutic values (P = 0.0003). BMD at the lumbar spine increased by 0.16 g/cm2 (P = 0.0005), corresponding to a mean increase of 15.9% or an increase of the BMD Z-score by 1.53 SD. Increases in BMD were independently observed from years 3 to 6 by a mean of 5.8% (P = 0.0087). This increase was paralleled by an increase in the area of the lumbar vertebrae. Bone area also increased at selected sites of the proximal femur, but there was no consistent increase in BMD at the proximal femur. CONCLUSION: GH therapy in GH-deficient adults is able to progressively increase BMD and bone area at the lumbar spine over a period of at least 6 years. However, our study has several limitations, making it necessary to confirm these findings in further long-term studies.

Absorptiometry, Photon↗
PubMed2001

Diabetes mellitus a risk for osteoporosis?

Localized lesions at the foot skeleton are a serious and well recognized complication of diabetes mellitus which may impair the clinical outcome of the patients remarkably. In contrast, the presence of a generalized bone disease or osteoporosis related to diabetes mellitus is less acknowledged and its clinical relevance is less obvious. This paper is a clinically focused review of the literature on osteoporosis related to diabetes mellitus. Due to the different pathogenesis of diabetes mellitus type 1 and type 2 it is not surprising that there is no uniform entity of diabetic osteopathy. The majority of clinical studies in subjects with diabetes mellitus type 1 showed a moderately decreased bone mass at the forearm, while bone mass at the femur or lumbar spine was either decreased or not different from non-diabetic controls. In patients with diabetes mellitus type 2 the risk of osteopenia is not as clear as in type 1 diabetes. Bone mineral density at the forearm in patients with type 2 diabetes mellitus was decreased, unchanged or even increased in comparison to controls, while bone mineral density at the vertebrae or femoral neck was either not significantly different or increased, but rarely decreased. The underlying mechanisms triggering changes in bone mass in patients with diabetes mellitus type 1 and type 2 are not well known. In most studies there was no consistent relationship between the metabolic control of diabetes and bone mineral density. Biochemical parameters of the calcium and bone metabolism showed no clear relationship to the bone mineral density measurements. From few bone histology studies in humans and experimental studies there is evidence that a decreased bone formation is one major mechanism leading to reduced bone mass in diabetics. Microangiopathy at the bone tissue was also discussed as a possible reason for diabetic osteopenia. It was shown that insulin and insulin like growth factors (IGF-1, IGF-2) have an influence on bone metabolism itself and other growth factors, cytokines and hormones may determine changes in diabetic bone metabolism. Recent findings suggest that leptin is involved in the regulation of osteoblast function and bone mass, which is of special interest in diabetes mellitus type 2. The clinical relevance of osteoporosis or osteopenia is determined by the increased risk for insufficiency fractures. Few studies found an increased fracture risk, especially in older women with type 1 diabetes mellitus, while others did not show an increased risk for fractures or even found a decreased rate of fractures in women with diabetes mellitus type 2. There is a need for further longitudinal studies, including the incidence and risk factors for osteoporotic fractures. In clinical routine the extent of diagnostic and therapeutic activities in patients with type 1 or type 2 diabetes mellitus in respect to generalized bone disease or diabetic osteopenia should be based on individual conditions and risk profile for osteoporosis.

Animals↗
PubMed2001

Impact of modified radical neck dissection on biochemical cure in medullary thyroid carcinomas.

BACKGROUND: This study evaluated the outcome of total thyroidectomy and modified radical neck dissection in primary treatment of patients with medullary thyroid carcinoma (MTC). METHODS: Thirty-six patients with sporadic (n = 16) and hereditary (n = 20) MTC underwent thyroidectomy and systematic central and lateral lymph node dissection (unilateral, 23; bilateral, 13) between 1994 and 2000. Postoperative serum calcitonin levels were correlated with immediate or delayed surgery, tumor categories, and lymph node metastases. RESULTS: Sixteen of 36 (44%) patients with clinically evident MTC treated with central and lateral neck dissection exhibited normal basal and stimulated calcitonin levels at a median follow-up of 3.7 years. Lymph node involvement was detected in 75% of these patients and correlated with the TNM stages. Biochemical cure was achieved according to the T categories in 83% of the patients in stage T1, 42% in stage T2, and none of the patients in stage T4 (P = .011). Basal and stimulated calcitonin levels were found to be normal in 89% of the patients without lymph node involvement and in 30% of the patients with lymph node metastases (P = .005). CONCLUSIONS: Screening for MTC and primary treatment with total thyroidectomy and modified radical neck dissection are essential for biochemical cure of MTC.

Adolescent↗
PubMed2001

A double-blind, placebo-controlled crossover study investigating the effect of porcine secretin in children with autism.

OBJECTIVES: A recent patient series reported the incidental findings of improved social and language skills in 3 children with autistic spectrum disorders after the administration of secretin, a peptide hormone. However, a subsequent study did not find evidence for a drug effect. Parents are seeking treatment with secretin despite the absence of empirical investigations demonstrating amelioration in autism symptomology. In order to more precisely measure the effects of secretin, this study investigated the effect of a single intravenous dose of porcine secretin on 12 autistic children through a randomized, double-blind, placebo-controlled, crossover study. Children were assessed on objective language and on social, neuropsychological, and gastrointestinal measures to evaluate drug effects. The study was conducted over a 16-week trial. The results indicated that significant differences were not observed on the majority of the dependent variables. Statistically significant differences were observed on measures of positive affect and activity level following secretin infusion. In general, the autistic children did not demonstrate the improvements described in the initial retrospective report.

Affect↗
PubMed2001

Alteration of the activity of the 11beta-hydroxysteroid dehydrogenase in pregnancy: relevance for the development of pregnancy-induced hypertension?

In this study we evaluated the activity of renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) in patients with pregnancy-induced hypertension (PIH). A reduction of the activity of 11beta-HSD2 leads to pseudohyperaldosteronism due to insufficient interconversion of cortisol to its inactive 11-oxo-metabolite cortisone in the renal tubulus cell. We measured urinary free cortisol and cortisone in patients with and without PIH and calculated the urinary free cortisol to free cortisone ratio, which is well accepted as a correlate of the activity of renal 11beta-HSD2. One hundred twenty-six pregnant women were included. Fifty-nine patients had PIH (mean age 31.5 +/- 4.4 yr, blood pressure 158.7 +/- 16.0/100.8 +/- 9.5 mm Hg), and 67 were normotensive (mean age 29.4 +/- 4.6, blood pressure 112.6 +/- 8.9/68.8 +/- 8.6 mm Hg). The excretion rate of cortisol was increased in the PIH group (138.8 +/- 93.0 vs. 106.5 +/- 65.4 nmol/d, P = 0.027), whereas excretion rate of cortisone was similar (362.9 +/- 254.1 vs. 366.5 +/- 221.7 nmol/d, P = 0.933). The free cortisol to free cortisone ratio was significantly higher in the PIH group (0.47 +/- 0.25 vs. 0.31 +/- 0.12, P < 0.00002). Within this group, the patients with blood pressure in the uppermost quartile had a significantly higher free cortisol to free cortisone ratio than those in the lowest quartile [0.61 +/- 0.31 vs. 0.38 +/- 0.15 (P = 0.019) for diastolic, 0.60 +/- 0.29 vs. 0.35 +/- 0.13 (P = 0.012) for systolic, and 0.62 +/- 0.32 vs. 0.39 +/- 0.16 (P = 0.023) for mean blood pressure, respectively]. We conclude that a reduction of the activity of the 11beta-HSD2 is a relevant factor for the development of PIH. Whether the ratio of urinary free cortisol to free cortisone is a useful risk factor for the development of PIH must be investigated in further prospective studies.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2001

Serum interleukin 6 is a major predictor of bone loss in women specific to the first decade past menopause.

The role of serum interleukin 6 (IL-6) as a predictor of bone loss was examined in a population-based, longitudinal study of 137 postmenopausal German women, 52-80 yr old at baseline. Serum IL-6 and other biochemical parameters were measured in baseline blood or urine specimens. Repeat standardized measures of bone mineral density (BMD) at the femur (total hip) and the lumbar spine (L2-L4) were taken by dual x-ray absorptiometry an average of 3.3 yr apart. Medical history and anthropometric measures were obtained from standardized interview and examination. Crude and age-adjusted mean serum IL-6 levels were significantly lower in postmenopausal women with than without hormone replacement therapy at baseline. Among nonusers of hormone replacement therapy, serum IL-6 concentrations were highly predictive of femoral bone loss, independently of potential confounders and plasma sex hormones. Statistical interaction between serum IL-6 and menopausal age or menopausal age group (>10 vs. < or =10 yr) indicated that the effect of IL-6 on bone loss weakened with increasing distance from menopause and was no longer significant in women more than 10 yr after menopause. Among women up to 10 yr past menopause (n = 39), serum IL-6 was the single most important predictor of femoral bone loss, accounting for up to 34% of the total variability of change in BMD. The unadjusted linear model predicted an annual 1.34% (95% confidence interval, 0.67-2.01) decrease in total hip BMD per log unit increase in serum IL-6. A similar, although nonsignificant, effect of serum IL-6 on vertebral bone loss was restricted to women within the first 6 yr after menopause (n = 18). These epidemiological data show that serum IL-6 is a predictor of postmenopausal bone loss, and that the effect appears to be most relevant through the first postmenopausal decade. Whether these findings reflect pathogenetic differences between early and postmenopausal bone loss, and whether serum IL-6 also predicts fracture risk need further elucidation.

Age Factors↗
PubMed2001

Identification of a deletion variant in the gene encoding the human alpha(2A)-adrenergic receptor.

OBJECTIVE: The alpha(2)-adrenergic receptors are involved in the effects of catecholamines on energy metabolism. Of three known subtypes with differential expression, alpha(2A)-adrenergic receptors are also localized in adipose tissue where they counteract the lipolytic activity of beta-adrenergic receptors. This study was undertaken to assess whether variants in the alpha(2A)-adrenergic receptor gene are associated with body weight. DESIGN AND METHODS: Single strand conformation polymorphism (SSCP) screening and subsequent sequencing were applied to determine genetic variants in DNA samples from individuals with obesity, those of normal weight and those underweight. RESULTS: Analysis of the coding region resulted in the identification of an 18 bp deletion, with no other mutation found. Of 429 genotyped subjects, 7 carried the deletion, with no significant differences between lean and obese subjects. A previously identified polymorphism in the promoter of the alpha(2A)-adrenergic receptor gene also did not show an association with any of the tested body weight categories. CONCLUSION: Our data suggest that variants in the alpha(2A)-adrenergic receptor gene are unlikely to contribute to the predisposition for the lean or obese state.

Adolescent↗
PubMed2001

Serum parathyroid hormone, but not menopausal status, is associated with the expression of osteoprotegerin and RANKL mRNA in human bone samples.

OBJECTIVE: Osteoprotegerin (OPG) and its ligand 'receptor activator of NF-kB ligand' (RANKL) are important regulators of bone metabolism. RANKL, expressed in osteoblasts, activates osteoclast differentiation and osteoclast function by binding the 'receptor activator of NF-kB' (RANK), expressed in ostoclast precursors and mature osteoclasts. The effect is prevented by OPG, a soluble receptor of RANKL. In vitro studies have suggested that estrogen stimulates OPG, whereas parathyroid hormone (PTH) inhibits OPG expression and stimulates the expression of RANKL. DESIGN: In the present study, we examined the relationship between the menopause, serum PTH and the expression of OPG and RANKL in human bone tissue in vivo. METHODS: To address this question, we established a 5'-nuclease assay to quantify the mRNA copies of human OPG and RANKL, normalized to the number of copies of beta-actin mRNA in 169 women (mean age: 52.4+/-11.6 years), who underwent surgery for early breast cancer. Intact serum PTH was measured by chemoluminescence in 61 women. RESULTS: We found no significant difference in the expression of OPG and RANKL between postmenopausal women and premenopausal women. Also, the ratio of RANKL to OPG was unchanged in relation to the menopausal status. Serum PTH was negatively associated with the expression of OPG (r=-0.33, P=0.01), but also, surprisingly, with the expression of RANKL (r=-0.28, P=0.03). CONCLUSION: We failed to observe the expected changes in the expression of OPG and RANKL in human bone samples at menopause. High in vivo levels of circulating PTH are accompanied by low levels of expression of the two transcripts in human bone tissue.

Biopsy↗
PubMed2001

Hypercalcemic crisis.

Hypercalcemia may decompensate from a more or less chronic status into a critical and life-threatening condition, hypercalcemic crisis. In the majority of cases, primary hyperparathyroidism is the cause; humoral hypercalcemia of malignancy or rarer conditions of hypercalcemia will decompensate less often. The leading symptoms that characterize the crisis are oliguria and anuria as well as somnolence and coma. After a hypercalcemic crisis is recognized, an emergency diagnostic program has to be followed either to prove or to exclude primary hyperparathyroidism. In the first case, surgical neck exploration is the only way to avoid fatal outcome. The diagnostic program should be performed within hours; during this time, serum calcium should be lowered. Treatment of choice is hemodialysis against a calcium-free dialysate. Bisphosphonates could be useful as adjuvant drugs.

Critical Illness↗
PubMed2001

[Supervision of rabbit husbandry--report of a public health veterinarian].

Rabbits are wide spread farm animals and pets, which are kept in the most diverse areas. The evaluation of rabbit husbandries in regard to animal welfare legislation is often complicated by different and contradictory recommendations of various organisations, which should partly be revised. In the following article some regulations and guidelines are discussed. In addition, some aspects for the keeping of rabbits in accordance with their behavioural needs are outlined, some frequent shortcomings regarding the keeping of rabbits are described and possibilities for taking official measures are presented.

Animal Husbandry↗
PubMed2000

[Hypercalcemia caused by generalized sarcoidosis].

HISTORY AND ADMISSION FINDINGS: A 70-year-old man with a 23-year history of recurrent nephrolithiasis was admitted for evaluation of hypercalcaemia (maximal calcium concentration 3.24 mmol/l). Physical examination on admission was unremarkable except for sensory neuropathy in the right foot. INVESTIGATIONS: Chest radiogram, subsequent transbronchial lung biopsy, gallium scintigraphy and magnetic resonance imaging (MRI) of the vertebrae indicated generalized sarcoidosis, predominantly affecting the mediastinum, lumbar vertebrae and nerves of the distal limbs. Parathormone level was reduced, while the levels of vitamin D metabolites were normal. TREATMENT AND COURSE: Serum calcium level became normal within 2 weeks of starting glucocorticoid treatment. CONCLUSION: Hypercalcaemia can occur in the course of sarcoidosis even in the absence of a elderly increased level of 1,25-dihydroxyvitamin D3. In this case the cause of the hypercalcaemia of a year's duration may have been due to lymphomacrophagocytic infiltration of the bone of several vertebrae as demonstrated by MRI of the vertebral columns but not by conventional radiography. In this case an increase in cytokine secretion by macrophages may have played an important role in addition to the level of 1,25-dihydroxyvitamin D3 at the upper limit of normal that, in view of the renal failure, could only have been caused by extrarenal production. Cytokines (e.g. interleukin-1 beta and tumour necrosis factor alpha) secreted by activated macrophages are among the most powerful stimulators of bone reabsorption.

Aged↗
PubMed2000

Long-term effect of bone-marrow transplantation for childhood-onset cerebral X-linked adrenoleukodystrophy.

BACKGROUND: The childhood-onset cerebral form of X-linked adrenoleukodystrophy, a demyelinating disorder of the central nervous system, leads to a vegetative state and death within 3-5 years once clinical symptoms are detectable. The hypothesis to be tested was whether bone-marrow transplantation can over an extended period of time halt the inexorable progressive demyelination and neurological deterioration. METHODS: 12 patients with childhood onset of cerebral X-linked adrenoleukodystrophy have been followed for 5-10 years after bone-marrow transplantation. Magnetic resonance imaging (MRI), neurological, neuropsychological, electrophysiological, and plasma very-long-chain fatty acid (VLCFA) measurements were used to evaluate the effect of this treatment. FINDINGS: MRI showed complete reversal of abnormalities in two patients and improvement in one. One patient showed no change from baseline to last follow-up. All eight patients who showed an initial period of continued demyelination stabilised and remained unchanged thereafter. Motor function remained normal or improved after bone-marrow transplantation in ten patients. Verbal intelligence remained within the normal range for 11 patients. Performance (non-verbal) abilities were improved or were stable in seven patients. Decline in performance abilities followed by stability occurred in five patients. Plasma VLCFA concentrations decreased by 55% and remained slightly above the upper limits of normal. INTERPRETATION: 5-10-year follow-up of 12 patients with childhood-onset cerebral X-linked adrenoleukodystrophy shows the long-term beneficial effect of bone marrow transplantation when the procedure is done at an early stage of the disease.

Adrenoleukodystrophy↗