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At least 631 records · Page 35Linked to original sources
PubMed1999

Bone marrow effects of anagrelide therapy in patients with myelofibrosis with myeloid metaplasia.

In a prospective study investigating the therapeutic role of anagrelide in myelofibrosis with myeloid metaplasia, 20 patients received anagrelide in daily oral doses of 0.5-3 mg. 17 patients were evaluable and received anagrelide for a median of 2 years (range 0.5-4 years). No patient had a clinically appreciable benefit. Bone marrow (BM) examinations at baseline and after 6 and 12 months of treatment were available for 17, 17 and 12 patients, respectively. In all evaluable cases, BM megakaryocyte number increased after 6 months of anagrelide treatment. Also, Ulex europaeus agglutinin-1 staining of megakaryocytes revealed a left-shifted maturation pattern in most patients with a platelet response to anagrelide. However, megakaryocyte staining intensity for transforming (TGF-beta) and platelet-derived (PDGF) growth factors was not affected consistently by treatment. No patient had a >/=2 grade change in either BM fibrosis or osteosclerosis. These in-vivo data support our previous in-vitro observations that anagrelide interferes with megakaryocyte maturation rather than proliferation. Lack of a positive treatment effect is consistent with the finding that anagrelide did not significantly alter megakaryocyte expression of TGF-beta and PDGF.

Aged↗
PubMed1999

Renal bone disease: radiological investigation.

The bone disease associated with chronic renal impairment is complex and multifactorial, and has changed over past decades. Whereas originally features of vitamin D deficiency (rickets/osteomalacia) and secondary hyperparathroidism (erosions, osteosclerosis, brown cysts) predominated, improvement in management and therapy have resulted in such readiographic features being present in a minority of patients. Metastatic calcification and "adynamic" bone develop as a complication of disease (phosphate retention) and treatment (phosphate binders). New complications (amyloid deposition, noninfective spondyloarthropathy, osteonecrosis) are now seen complicating long-term hemodialysis and/or renal transplantation. Radiographs remain the most important imaging technique, but occasionally other imaging and quantitative techniques (CT, MRI, bone densitometry) are relevant to diagnosis and management.

Aluminum↗
PubMedDate not supplied

Dialysis bone disease.

The bone disease associated with end-stage renal failure (ESRD) and treatment are complex and multifactorial, and has changed in both clinical and imaging features over the past three decades. Whereas previously features of vitamin D deficiency (rickets/osteomalacia) and intense, and prolonged, secondary hyperparathyroidism (bone resorption, osteosclerosis, metastatic calcification) predominated, these features are now rarely evident radiologically. This has occurred through the better understanding of vitamin D metabolism and improvements in therapeutic management. However, metastatic calcification in soft tissues and 'adynamic" bone continue to be problematic. New complications have developed as a consequence of treatment (dialysis and transplantation), including amyloid deposition, noninfective sponyloarthropathy, osteonecrosis, and osteopenia/osteoporosis). Radiographs remain the most widely used imaging technique in examining for skeletal disease in patients with ESRD on maintenance dialysis. Occasionally, more sophisticated imaging (CT, MRI, nuclear medicine scanning) are helpful (parathyroid tumor localization, differentiation between infection and amyloid deposition). Developments in quantitative methods to assess bone density enable the effects of ESRD and treatment to be studied and monitored. Technical developments in computed tomography (rapid, multislice scanning) allow quantitation and monitoring of metastatic cardiac calcification in patients on hemodialysis, which has relevance to prognosis.

Bone Density↗
PubMed2005

Pathogenesis of myelofibrosis with myeloid metaplasia: lessons from mouse models of the disease.

The primary genetic lesion(s), as well as the biological processes responsible for the typical structural changes of the bone marrow microenvironment in idiopathic myelofibrosis, are still poorly understood, although a central role in disease pathogenesis has been attributed to the clonal proliferation and defective maturation of megakaryocytes. Two animal models of the disease have been described, that in the last few years significantly contributed to the elucidation of some of the pathogenetic steps of the human disease; these are represented by mice genetically modified to overexpress thrombopoietin and by knock-down mice with defective GATA-1 expression in megakaryocytes (GATA-1(low) mice). This review will outline these murine models, both characterized by extensive accumulation of megakaryocytes in hematopoietic tissues, and illustrate how they provided insights into the identification of some of the molecules and mechanisms responsible for the development of fibrosis and osteosclerosis that present major similarities with those observed in patients with idiopathic myelofibrosis.

Animals↗
PubMed2003

Treatment approaches in myelofibrosis with myeloid metaplasia: the old and the new.

Myelofibrosis with myeloid metaplasia (MMM) is currently classified as a chronic myeloproliferative disorder (CMPD) and is characterized by prominent bone marrow stromal reaction including collagen fibrosis, osteosclerosis, and angiogenesis. Among the CMPD, MMM carries the worst prognosis with an overall median survival of 5 years; the clinical course is marred by profound constitutional symptoms, progressive anemia, and symptomatic splenomegaly. Causes of death include leukemic transformation, which occurs in approximately 10% of patients in the first decade of the disease. At present, allogeneic hematopoietic stem cell transplantation (HSCT) is the only treatment modality that has the potential to either cure the disease or prolong survival. Both drug therapy and autologous HSCT are currently palliative. Conventional treatment agents in MMM include androgen preparations, corticosteroids, erythropoietin (EPO), and hydroxyurea. In addition, both splenectomy and radiation therapy have defined therapeutic roles. Thalidomide is the most effective investigational agent at the present time. Optimal therapy for an individual patient requires a sound understanding of disease risk factors, as well as a full appreciation of the risk to benefit ratio for a specific treatment modality.

Angiogenesis Inhibitors↗
PubMed2002

MR imaging characteristics of osteoradionecrosis of the pelvis after radiation therapy on gynecological tumors.

PURPOSE: To describe MR imaging characteristics of osteoradionecrosis (ORN) of the pelvis as a result of radiation therapy (RT) on gynecological tumors. MATERIAL AND METHODS: Radiography, computed tomography (CT) and magnetic resonance imaging (MRI) were performed on 9 women (mean age 67.5 years) with gynecological tumors to identify ORN. T1- and T2-weighted sequences and contrast-enhanced t1-weighted sequences with and without fat saturation were used. The patients began developing pain after the completion of RT indicating a possible ORN a which time MRI was performed. MR images were correlated with the results of clinical examinations. RESULTS: Depending on the time elapsed after RT, ORN presented with different signal intensities. The acquired images suggested that signal changes in T2-weighted images as well as the different enhancement behaviour of ORN could be dependent on the time elapsed after RT. Visualisation of the affected regions was best achieved with fat-saturated T1-weighted sequences. CT showed increased density in the affected regions corresponding to osteosclerosis. In all cases the sacroiliac joint was affected, some times bilaterally. CONCLUSION: MRI is helpful in detecting and characterizing ORN. Changes in signal intensity, based on histopathological tissue changes could make a chronological classification possible.

Aged↗
PubMed2004

[Erdheim-Chester disease as differential diagnosis in bilateral exophthalmos].

This report describes the case of a patient who had symmetrical exophthalmos, periorbital xanthelasmas and reduced vision. Next to Wegener's granulomatosis the differential diagnosis of Erdheim-Chester disease is discussed. It concerns a rare systemic histiocytosis of unknown etiology. Above all, the skeleton system with symmetrical long bone osteosclerosis is affected. Manifestations in the area of the orbit have seldom been reported with bilateral retrobulbar infiltrations, exophthalmos, diplopia, compression of the optic nerve and periorbital xanthelasmas.

Adult↗
PubMed2005

[Permanent hypoparathyroidism due to thyroid cancer surgical procedures in patients exposed to radiation in the Chernobyl, Ukraine, nuclear reactor accident].

BACKGROUND AND OBJECTIVE: Postoperative hypoparathyroidism is a rare, but complex endocrine disorder. The purpose of this case series study was to evaluate the symptoms, signs and sequelae of the disease in a major homogeneous patient group after the Chernobyl accident in the Ukraine. PATIENTS AND METHODS: This study is based on a random sample of 25 patients with symptomatic permanent hypoparathyroidism after surgical procedures on the thyroid for carcinoma following the Chernobyl accident in May 1986. They underwent physical examination and their parathyroid hormone and calcium levels in serum were determined. The signs, symptoms and sequelae of their disease were systematically assessed by a validated specific questionnaire. The extent of individual distress by the symptoms and signs were analysed by using a Likert scale (points between 1 = no and 5 = maximal distress). RESULTS: In 14 patients (56%) (age at time of operation: 18.24 +/- 4.26 years) paresthesias occurred at least every third day. Very frequent general symptoms were joint pains and hair loss (in 17 patients / 68%). 19 patients (76%) had enamel defects, 17 (68%) increasingly dry skin since the operation. Psychical symptoms like excitability (20 patients / 80%) and depressed mood since the operation (16 patients / 64%) were strikingly frequent. The patients were affected more by dry skin (2,76 on the Likert scale) than by paraesthesias (2,56) or joint pains (2,68) and most of all by depressive mood (2.96) and excitability (3.38). 4 patients (16%) had kidney stones, while osteoporosis and osteosclerosis occurred in 7 (28%) respectively 3 persons (12%). 6 patients (24%) had cataracts and 3 (12%) had basal ganglia calcification. Interestingly, 1/3 of all patients had only non-characteristic symptoms of the disease consistent with a latent form of hypoparathyroidism. CONCLUSIONS: Our data partly show a severe form of hypoparathyroidism of very young persons in the Chernobyl region, a finding which strongly supports the need of exact diagnosis and interdisciplinary treatment options of this postoperative disorder.

Adolescent↗
PubMed2003

An unusual tonsillolith.

A case of a large tonsillolith of the left palatine is presented. The lesion was detected incidentally during radiographic examination of a patient presenting with right mandibular pericoronitis. The patient had no symptoms referable to the left tonsillar region. Superimposition of the tonsillolith on the left mandibular ramus on panoramic radiographic examination created the false impression of an intraosseous radiopaque lesion. Many radiopaque structures and lesions occur in the soft tissues close to the jaws and are often observed on panoramic radiographs produced by imaging units with broad focal troughs. Such radiopacities in the mandibular molar-ramus region include sialolith, phlebolith, cysticercosis and calcified lymph node, carotid artery arteriosclerosis, stylohyoid ligament mineralization, and dystrophic calcification in acne scars. Tonsilloliths may present on panoramic radiograph as radiopaque objects superimposed on the midportion of the ascending mandibular ramus, and may be initially misinterpreted as intraosseous lesions of the mandible, such as foreign body, odontoma, sclerosing osteitis, Garre osteomyelitis, fibrous dysplasia, idiopathic osteosclerosis, and osteoma.

Adult↗
PubMed2001

Linking osteopetrosis and pycnodysostosis: regulation of cathepsin K expression by the microphthalmia transcription factor family.

Various genetic conditions produce dysfunctional osteoclasts resulting in osteopetrosis or osteosclerosis. These include human pycnodysostosis, an autosomal recessive syndrome caused by cathepsin K mutation, cathepsin K-deficient mice, and mitf mutant rodent strains. Cathepsin K is a highly expressed cysteine protease in osteoclasts that plays an essential role in the degradation of protein components of bone matrix. Cathepsin K also is expressed in a significant fraction of human breast cancers where it could contribute to tumor invasiveness. Mitf is a member of a helix-loop-helix transcription factor subfamily, which contains the potential dimerization partners TFE3, TFEB, and TFEC. In mice, dominant negative, but not recessive, mutations of mitf, produce osteopetrosis, suggesting a functional requirement for other family members. Mitf also has been found-and TFE3 has been suggested-to modulate age-dependent changes in osteoclast function. This study identifies cathepsin K as a transcriptional target of Mitf and TFE3 via three consensus elements in the cathepsin K promoter. Additionally, cathepsin K mRNA and protein were found to be deficient in mitf mutant osteoclasts, and overexpression of wild-type Mitf dramatically up-regulated expression of endogenous cathepsin K in cultured human osteoclasts. Cathepsin K promoter activity was disrupted by dominant negative, but not recessive, mouse alleles of mitf in a pattern that closely matches their osteopetrotic phenotypes. This relationship between cathepsin K and the Mitf family helps explain the phenotypic overlap of their corresponding deficiencies in pycnodysostosis and osteopetrosis and identifies likely regulators of cathepsin K expression in bone homeostasis and human malignancy.

Alleles↗
PubMed1998

Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice.

Cathepsin K is a recently identified lysosomal cysteine proteinase. It is abundant in osteoclasts, where it is believed to play a vital role in the resorption and remodeling of bone. Pycnodysostosis is a rare inherited osteochondrodysplasia that is caused by mutations of the cathepsin-K gene, characterized by osteosclerosis, short stature, and acroosteolysis of the distal phalanges. With a view to delineating the role of cathepsin K in bone resorption, we generated mice with a targeted disruption of this proteinase. Cathepsin-K-deficient mice survive and are fertile, but display an osteopetrotic phenotype with excessive trabeculation of the bone-marrow space. Cathepsin-K-deficient osteoclasts manifested a modified ultrastructural appearance: their resorptive surface was poorly defined with a broad demineralized matrix fringe containing undigested fine collagen fibrils; their ruffled borders lacked crystal-like inclusions, and they were devoid of collagen-fibril-containing cytoplasmic vacuoles. Assaying the resorptive activity of cathepsin-K-deficient osteoclasts in vitro revealed this function to be severely impaired, which supports the contention that cathepsin K is of major importance in bone remodeling.

Animals↗
PubMed1978

Renal osteodystrophy in end-stage renal failure.

Renal osteodystrophy has many skeletal pathologic features, eg, fibroosteoclasia (osteitis fibrosa), osteomalacia, osteopenia, pseudofracture, cyst formation, and osteosclerosis. Many of these are caused by the secondary hyperparathyroidism that usually accompanies renal failure. Derangements in parathyroid hormone secretion, calcium and phosphate metabolism, and renal production of 1,25-dihydroxycholecalciferol (the most active form of vitamin D) are all interrelated and pathogenetic features of renal osteodystrophy. Types of abnormalities detected radiologically vary with patient age, type of management, and duration of hemodialysis, as well as with techniques and type of film used and interest of the radiologist. An x-ray film of the hands should always be made--it will show subperiosteal resorption in a large number of patients on dialysis. Prevention and management of renal osteodystrophy hinge on control of hyperphosphatemia and hypocalcemia.

Bone and Bones↗
PubMed2004

Angiogenesis and anti-angiogenic therapy in myelofibrosis with myeloid metaplasia.

Myelofibrosis with myeloid metaplasia (MMM) is a clonal stem cell disorder that is characterized by florid bone marrow stromal reaction including collagen fibrosis, osteosclerosis, and angiogenesis. Almost all patients with MMM display increased bone marrow microvessel density (MVD) and the extent is among the highest in hematological malignancies. This particular information has encouraged the therapeutic use of anti-angiogenic drugs in MMM. In the current review, we summarize the general concepts regarding angiogenesis, assessment of angiogenesis in hematological malignancies and then the current literature on angiogenesis and anti-angiogenic therapy in MMM.

Angiogenesis Inhibitors↗
PubMedDate not supplied

Orthopaedic rehabilitation in a case of Tay-syndrome.

This paper reports on the orthopaedic rehabilitation of a patient with Tay-syndrome. Tay-syndrome is a rare monogen-inherited ektodermal dysplastic syndrome with ichtyosis, fragility of the hair and physical and mental retardation. The congenital ichtyosis is ubiquitous. Only the skin on the flexion side of the extremity joints are not involved (orthocerathosis combined with paraceratotic strings). In this case, a young boy developed bilateral subluxation of the hips and was not able to stand or walk freely. Contemporary pre- and neonatal care has prolonged the survival of newborns with severe genodermatoses, including this syndrome. In this case, it has provided the necessity for orthopaedic treatment of the problems caused by osteosclerosis and muscular spasticity.

Bacterial Infections↗
PubMed1989

[Bourneville's disease of the bones or metastasis? Apropos of a case].

Tuberous sclerosis or Bourneville's disease is a phakomatosis with common but paucisymptomatic bone localisations. Some osseous lesions, of osteosclerotic type, can be radiologically diagnosed as primary or secondary malignant disorders. We describe a case of Bourneville's disease with bone involvement, radiologically characterized by osteosclerosis areas of the spine and the pelvis. Interestingly, bone scintiscan was normal. The absence of primary malignancy, the stability of control bone X-ray films, the clinical status and the family history, together with the pathognomonic radiological feature of the hands support the diagnosis of tuberous sclerosis with bone involvement.

Aged↗
PubMed1999

Localization of the gene for sclerosteosis to the van Buchem disease-gene region on chromosome 17q12-q21.

Sclerosteosis is an uncommon, autosomal recessive, progressive, sclerosing, bone dysplasia characterized by generalized osteosclerosis and hyperostosis of the skeleton, affecting mainly the skull and mandible. In most patients this causes facial paralysis and hearing loss. Other features are gigantism and hand abnormalities. In the present study, linkage analysis in two consanguineous families with sclerosteosis resulted in the assignment of the sclerosteosis gene to chromosome 17q12-q21. This region was analyzed because of the recent assignment to this chromosomal region of the gene causing van Buchem disease, a rare autosomal recessive condition with a hyperostosis similar to sclerosteosis. Because of the clinical similarities between sclerosteosis and van Buchem disease, it has previously been suggested that both conditions might be caused by mutations in the same gene. Our study now provides genetic evidence for this hypothesis.

Adult↗
PubMed2003

Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density.

Bone is a dynamic tissue that is subject to the balanced processes of bone formation and bone resorption. Imbalance can give rise to skeletal pathologies with increased bone density. In recent years, several genes underlying such sclerosing bone disorders have been identified. The LDL receptor-related protein 5 (LRP5) gene has been shown to be involved in both osteoporosis-pseudoglioma syndrome and the high-bone-mass phenotype and turned out to be an important regulator of peak bone mass in vertebrates. We performed mutation analysis of the LRP5 gene in 10 families or isolated patients with different conditions with an increased bone density, including endosteal hyperostosis, Van Buchem disease, autosomal dominant osteosclerosis, and osteopetrosis type I. Direct sequencing of the LRP5 gene revealed 19 sequence variants. Thirteen of these were confirmed as polymorphisms, but six novel missense mutations (D111Y, G171R, A214T, A214V, A242T, and T253I) are most likely disease causing. Like the previously reported mutation (G171V) that causes the high-bone-mass phenotype, all mutations are located in the aminoterminal part of the gene, before the first epidermal growth factor-like domain. These results indicate that, despite the different diagnoses that can be made, conditions with an increased bone density affecting mainly the cortices of the long bones and the skull are often caused by mutations in the LRP5 gene. Functional analysis of the effects of the various mutations will be of interest, to evaluate whether all the mutations give rise to the same pathogenic mechanism.

Amino Acid Sequence↗
PubMed1997

Localization of a gene for autosomal dominant osteopetrosis (Albers-Schönberg disease) to chromosome 1p21.

Albers-Schönberg disease, the classical form of osteopetrosis, is an autosomal dominant condition with generalized increased skeletal density due to reduced bone resorption. Characteristic radiological findings are generalized osteosclerosis, with, most typically, end-plate sandwichlike thickening of the vertebrae (Rugger-Jersey spine) and the bone-within-bone (endobones) phenomenon. We studied an extended kindred with Albers-Schönberg disease and found linkage with several markers from chromosome 1p21. The Albers-Schönberg gene is located in a candidate region of approximately 8.5 cM flanked by markers D1S486 and D1S2792. A maximum LOD score (Z(max)) of 4.09 was obtained in multipoint analysis at loci D1S239/D1S248. Possible linkage of osteopetrosis to this chromosomal region was analyzed because the CSF-1 gene, which is mutated in the op/op mouse model for osteopetrosis, is located in 1p21. However, SSCP and mutation analysis in patients did not reveal any abnormality, which excludes the CSF-1 gene as the disease-causing gene. This was confirmed by refined physical mapping of the CSF-1 gene outside the candidate region for the Albers-Schönberg gene. The identification of the molecular defect underlying Albers-Schönberg disease will therefore be dependent on the isolation of other genes from an 8.5-cM candidate region on chromosome 1p21.

Chromosomes, Human, Pair 1↗