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Magnetic resonance imaging (MRI) is a powerful new tool for the study of human anatomy and pathology. By various MRI techniques, the structure of the middle and inner ears of aborted 20-week fetuses is defined and compared to gross anatomic sections. MRI's potential for evaluating temporal bone development and diseases of the ear is discussed.
A great deal of progress has been made in recent years with respect to understanding the normal and pathological anatomy of the wrist. A careful history and physical examination continued with a critical review of the standard radiographs, supplemented by additional studies as indicated, allow the astute clinician to identify specific patterns of instability and to formulate an effective treatment program for the patients. The most frequent type of ligamentous instability of the wrist was classical defined by Linscheid (1972) as "carpal injury in which a loss of normal alignment of the carpal bones develops early or late".
We investigated the effect of major histocompatibility complex class II (MHC II) knockout on the development of the mouse peripheral skeleton. These C2D mice had less skeletal development at 8, 12 and 16 weeks of age compared to wild-type C57BL/6J (B6) male mice. The C2D mice had decreased femur mechanical, geometric and compositional measurements compared to wild type mice at each of these ages. C2D femur stiffness (S), peak force in 3-pt bending (Pm), and mineral mass (Min-M) were 74%, 64% and 66%, respectively, of corresponding B6 values at 8 weeks of age. Similar differences were measured at 12 weeks (for which C2D femoral S, Pm and Min-M were 71%, 72% and 73%, respectively, of corresponding B6 values) and at 16 weeks (for which C2D femoral S, Pm and Min-M were 80%, 66% and 61%, respectively, of corresponding B6 values). MHC II knockout delays the development of adult bone properties and is accompanied by lower body mass compared to wild-type controls.
The purpose of the present study was to investigate the axial skeleton related to the notochord in human anencephalic fetuses in order to elucidate the pathogenesis. Fifteen second trimester fetuses were examined. The spine and the cranial base were dissected and radiographed. Comparison with normal fetuses was performed. Two patterns of abnormal ossification were seen. Anencephalic cases without cervical rachischisis (Groups I and II) differed markedly from cases with cervical rachischisis (Group III). Morphological characteristics, such as bilateral narrowing of the basilar part of the occipital bone combined with normal cranio-caudal dimension, were found in cases without cervical rachischisis. In these cases frontal clefting of vertebral corpora occurred. Caudocranial shortening of the basilar part of the occipital bone was found in cases with cervical rachischisis, where complete median clefting of vertebral corpora also occurred. Because the vertebral corpora and the basilar part of the occipital bone develop around the notochord, which interacts also in the process of neurulation, the defects might indicate a notochordal insufficiency. The study showed that when the initial closure of the neural groove failed, the skeletal deviations were more extensive. The study supports the hypothesis that the notochord is an important clue to an understanding of the pathogenesis in anencephaly.
PURPOSE OF THE STUDY: Many studies have indicated favorable results of decompressive surgery for symptomatic lumbar spinal stenosis. However, little is known about the osseous changes that occur at the operative sites. Postacchini in 1992 and Chen in 1994 have studied, only from plain radiographs, osseous changes at the operative sites, and have suggested that bone regrowth possibly affects the neurologic result. The aims of this study were: to assess bone regrowth at the operative site, to compare the bone regrowth rate calculated from plain radiographs and CT-Scan examinations, to determine the effects of bone regrowth on clinical outcome, to investigate the factors promoting the bone regrowth. MATERIAL AND METHOD: 28 patients who underwent decompressive surgery for lumbar spinal stenosis were retrospectively studied with an average follow-up of 8.4 years. In order to evaluate the degree of bone regrowth at the posterior arch, early postoperative radiographs and CT images of the operative sites were compared with those obtained at final follow-up. Bone regrowth at the sites operated upon was evaluated as a percentage of regrowth of the original laminectomy site based upon plain radiographs and CT images. RESULTS: Decompressive lumbar spinal stenosis is responsible for bone regrowth at the operative site in most patients. However, this regrowth was mild, the mean bone regrowth rate evaluated from plain radiographs was 12 per cent in average and the obtained from CT images was 8.2 per cent in average. Changes were found to be predominant at the facet joint level compared to the pedicle level. The evaluation of regrowth obtained from plain films and CT image examinations were compared. Radiographs seem to overestimate bone regrowth. Postoperative spinal instability was statistically significantly associated with new bone development. This variable was the only factor that affected the degree of bone regrowth. No relationship between bone regrowth and clinical outcome was found. DISCUSSION AND CONCLUSION: Natural course of laminectomy defect includes probably new bone formation in most patients. New bone results from gradual regrowth of the laminae and articular processes partially resected at surgery and from coalescence of islets of bone tissue within the tissue filling the laminectomy defect. In the present study bone regrowth rate was moderate but in other ones it was marked. If some factors (like postoperative destabilization) promoting bone regrowth were identified many remain unknown. Factors influencing rapidity of regrowth progression remain also unknown. Patient's intrinsic features such as spinal stenosis characteristics are probably closely related to quantitative and kinetic characteristics of regrowth. Consequences of bone regrowth are also variable: in some cases regrowth may reproduce pathological conditions identical previous ones, in other ones new bone spreads around the dura a mater without any nerves roots compression. Study of bone regrowth requires further research including prospective studies and using a more precise method for the regrowth evaluation.
The bone marrow of 11 patients with small-cell lung cancer, who survived more than two years following combined-modality therapy, was subjected to morphologic, cytogenetic, and bone marrow culture studies. One patient, after a prodrome of anemia and thrombocytopenia, developed acute leukemia 60 months after the start of chemotherapy. Four months before frank leukemia developed, bone marrow culture studies showed a marked inability to form colonies. Cytogenetic studies demonstrated an abnormal clone of cells that included the deletion of the long arm of chromosome 5. No morphologic abnormalities were noted in the bone marrow of any other long-term survivor; however, the mean corpuscular volume of peripheral red blood cells was greater than normal in three of four patients who remain alive and disease free. In one of these patients marrow culture studies also failed to grow colonies. The other patients showed a decreased ability to form multilineage colonies and colonies of the granulocyte-macrophage lineage in vitro compared with a control population. All patients showed some degree of aneuploidy on cytogenetic analysis; in two cases approximately 50% of cells were aneuploid. However, no clonal abnormality was detected in any patient. Follow-up for the development of secondary acute leukemia and other long-term complications continues in these patients.
Several extracellular matrices are formed by healing fractures, and the collagens within these matrices have been identified in rabbit and rat fracture models. Type III collagen is the major collagen of the fibrous matrix that forms along the periosteal surface. Type I collagen is secreted in large amounts as trabeculae of bone develop within the fibrous tissue. Type V collagen is found in both the fibrous tissue and bone; it is particularly associated with blood vessels. Type II collagen is the last of the major collagens to be synthesized; its synthesis is dependent on the mechanical conditions under which the fractures are healing. A large area of cartilage, and hence of Type II collagen, is formed only if the fracture is mechanically unstable. Of the minor collagens, only Types IX and X have been identified to date. Type IX collagen is present throughout the large areas of cartilage, and Type X is present only in calcified regions. The matrices are compared with those produced during embryonic limb development. Although cartilage in the embryo provides a rapidly growing model of the future bone, in healing fractures cartilage is produced only where the cellular environment precludes the differentiation of osteoblasts. The effects of mechanical stability on the matrices support and illustrate this conclusion.
The localisation of acute haematogenous pyogenic osteomyelitis following a local injury is well known. Whilst there is often a history of trauma in patients developing bone and joint tuberculosis, its role is obscure. Two patients are reported who developed histologically proven tuberculosis in the vicinity of closed fractures during the healing process. These two patients make a total of four so far reported.
A patient with acute monocytic leukemia who developed bone marrow necrosis following induction chemotherapy is presented. Although the bone marrow necrosis was extensive, recovery occurred, along with complete remission of leukemia. Severe bone marrow necrosis in this setting may be reversible, and continued vigorous supportive care for these patients should be strongly considered.
Some children with idiopathic hypercalciuria (IH) develop bone alterations at some stage of the disease. The aims of this study were to evaluate bone mass in 88 children with IH (G1) at the time of diagnosis and to compare the findings with data for a control group of 29 normal children (G2). Kidney and bone metabolism markers were measured in both groups, and bone densitometry was performed. Serum alkaline phosphatase, intact parathyroid hormone, urinary calcium and uric acid were significantly higher in G1, whereas urinary volume and urinary citrate excretion were lower. The following densitometric parameters were significantly lower in G1: (1) lumbar spine (L(2)-L(4)) bone mineral density (BMD), bone mineral content (BMC), BMC corrected for height and for width of the vertebra, volumetric BMD (BMDvol), and Z score; (2) whole-body BMD; (3) femoral neck BMD. Lumbar spine BMDvol was reduced (osteopenia) in 35% of the patients compared with G2. N telopeptide, a urinary marker of bone resorption, was significantly higher in G1 than in G2, and was negatively correlated with lumbar spine BMD and BMDvol. Children with urinary lithiasis or idiopathic hyperuricosuria associated with IH showed no significant differences in bone metabolism compared with children without these associations. We conclude that (1) there is an altered bone metabolism in IH, with osteopenia already present at diagnosis in 35% of the patients; (2) N telopeptide is one of the most useful markers of bone alterations in IH, especially at an early stage of the disease; (3) investigation of bone metabolism is necessary in IH to prevent future serious consequences such as osteoporosis and bone fractures.
Two seriously ill patients with renal failure developed bone marrow hypoplasia and peripheral blood cytopenias during admission to an Intensive Care Unit (ICU). Both patients were being treated with ranitidine and, in both, there was evidence of drug accumulation. Serum from the patient with the highest concentration of ranitidine inhibited granulocyte-macrophage colony growth from normal bone marrow. The addition of ranitidine to cultures of normal bone marrow also produced a concentration-dependent inhibition of colony growth. Ranitidine should be used with caution in patients with renal failure where drug accumulation may seriously impair bone marrow function.
Osteogenin, a novel bone differentiation factor isolated from bone, has been recently purified and the amino acid sequence determined. Osteogenin in conjunction with a collagenous bone matrix substratum induces cartilage and bone formation in vivo. In order to understand the developmental role of osteogenin during cartilage and bone morphogenesis we examined the binding and distribution of iodinated osteogenin in developing rat embryos. Whole embryo tissue sections were made from 11, 12, 13, 15, 18, and 20 day fetuses. The specific binding of osteogenin at different stages of rat embryonic development was determined by autoradiography. Maximal binding was observed in mesodermal tissues such as cartilage, bone, perichondrium, and periosteum. During Days 11-15, peak binding was localized to perichondrium during limb and vertebral morphogenesis. By Day 18 periosteum exhibited the highest concentration of autoradiographic grains. Osteogenin was also localized in developing membranous bones of the calvarium and other craniofacial bones. Considerably less binding was observed, in decreasing order, in muscle, liver, spleen, skin, brain, heart, kidney, and intestine. The observed maximal binding during skeletal morphogenesis implies a developmental role for osteogenin.
Avascular necrosis (AN) of bone developed in 11 of 100 children who received renal transplants from 1964 to 1977. Bones involved were femoral heads, 14; femoral condyles, 12; tall, two; and carpal naviculars, two. Seven children with symptomatic AN of the femoral heads were treated with limited weight bearing; three subsequently required arthroplasty, and degenerative joint disease developed in one. The AN at other joints healed clinically but not roentgenographically. Although the prevalence of AN decreased after 1967 coincident with a decrease in prednisone dose, children with AN received the same cumulative prednisone dose as children in a control group. Serum phosphorus levels were different in the AN and control groups, but other indexes of hyperparathyroidism were similar. The relative contributions of prednisone therapy and hyperparathyroidism to the development of AN could not be delineated.
Intermittent calcitriol therapy is commonly used to treat secondary hyperparathyroidism in patients undergoing regular dialysis, but there is little available information about the histologic response of bone to this form of therapy. Accordingly, 14 children and adolescents with biopsy-proven secondary hyperparathyroidism were treated with intermittent oral or intraperitoneal doses of calcitriol for 12 months. Biochemical indices of mineral metabolism including serum intact PTH levels were measured monthly throughout the study, and bone biopsies were repeated at the end of treatment. Before treatment, 11 patients had osteitis fibrosa and three had mild lesions of secondary hyperparathyroidism. Histologic improvement was seen in 12 of 14 patients, and osteitis fibrosa resolved in 10 of 11 cases. Bone formation decreased in all patients during intermittent calcitriol therapy, falling from 861 +/- 380 to 150 +/- 170 microns2/mm2/day, P < 0.001. Bone formation decreased to normal in six patients, but six patients developed adynamic lesions of bone with subnormal bone formation rates. Serum PTH and alkaline phosphatase levels declined in those who developed adynamic bone, but values remained elevated in patients with normal rates of bone formation at follow-up evaluation. Neither the mean dose of calcitriol nor the average dose per kilogram body weight differed in patients with adynamic lesions. Thus, adynamic renal osteodystrophy develops in a substantial number of patients during intermittent calcitriol therapy. Although declining serum PTH and alkaline phosphatase levels suggest the development of the adynamic lesion, bone formation decreases in some patients despite persistently high serum PTH levels. Calcitriol may directly suppress osteoblastic activity in patients with secondary hyperparathyroidism when given in large doses to patients undergoing peritoneal dialysis.
Cleidocranial dysplasia (CCD) is a congenital disorder of bone development characterized by persistently open or delayed closure of cranial sutures and wormian bones, hypoplastic and/or aplastic clavicles, wide pubic symphysis, dental anomalies and short stature. The condition is inherited as an autosomal-dominant trait and the human CBFA1 gene has been identified as the CCD gene. We describe a prenatal form of the skeletal disorder that included clavicular hypoplasia, absence of ossification of the cranial parietal bones and very poor ossification of the frontal and pubic bones. Growth restriction affecting only the long bones was also noted. The fetal karyotype revealed an apparently de novo balanced t(2q;6q)(q36;q16) translocation. This particular form of skeletal disorder associated with the absence of family history and an apparently de novo balanced translocation led the parents to opt for termination of the pregnancy.
BACKGROUND: The bone morphogenetic proteins (BMP) are phytogenetically conserved proteins, which are essential for embryonic development. Bone morphogenetic protein-2 (BMP-2) was recently shown to be expressed in a small sample of lung carcinomas. Studies have suggested that BMP-2 may enhance tumor growth. The present study examined which BMP family members are expressed in non-small cell lung carcinomas (NSCLC). Furthermore, the frequency of BMP-2 overexpression and the types of lung carcinomas expressing BMP-2 were determined. METHODS: Tissue samples were obtained from the operating room and frozen in liquid nitrogen. Samples included metastatic NSCLC, benign lung tumors, adenocarcinoma, squamous cell carcinoma, bronchioloalveolar, and neuroendocrine carcinomas. Paired normal lung tissues served as the controls. The BMP-2, BMP-4, BMP-6, BMP-7, and growth differentiation factor 5 (GDF-5) expressions were examined by Western blot analysis. RESULTS: The BMP-4, BMP-6, BMP-7, and GDF-5 were infrequently expressed in NSCLC. The BMP-2 was expressed in 41 of 42 NSCLC with minimal expression in normal lung tissue; BMP-2 was expressed 17 fold higher than that of normal lung tissue. The BMP-2 was over-expressed in all subtypes of NSCLC, including neuroendocrine carcinomas. The BMP-2 expression was similar between squamous cell carcinomas and adenocarcinomas; however, bronchioloalveolar carcinomas tended to have a lower level of expression. The BMP-2 was not significantly expressed in benign lung tumors. CONCLUSIONS: Bone morphogenetic protein-2 is the predominant family member expressed in NSCLC. The BMP-2 is overexpressed in the majority of human lung carcinomas independent of cell type.
Prostaglandins are potent local regulators of bone cell function and may play a critical role in both physiologic and pathologic changes in the human skeleton. The availability of cyclooxygenase-2 (COX-2)-specific inhibitors, which are likely to be used frequently and for long periods because of their improved safety profile, mandates an investigation of their possible effects on bone. This is particularly important in older individuals, who are at risk of developing bone loss as a result of estrogen deficiency and aging. This review describes the major effects of prostaglandins on bone resorption and formation and outlines an approach to further studies on the potential effect of COX-2-specific inhibitors on bone remodeling, thereby possibly answering some of the key questions about their benefits and potential risks.
Osteoprotegerin ligand (OPGL, also known as RANKL), a member of the tumor necrosis factor superfamily, is essential for mammary gland development during pregnancy in addition to key roles in the immune system and bone development. Here we show that OPGL induces beta-casein transcription through the CCAAT/enhancer-binding protein beta (C/EBPbeta). In both HC11 cell lines and primary mammary epithelial cells, OPGL stimulation triggers rapid nuclear translocation of C/EBPbeta, which is critical for the expression of the beta-casein gene. Mutation of C/EBbeta binding sites in the beta-casein gene promoter completely abrogated OPGL-induced beta-casein promoter activity. By contrast, OPGL stimulation did not result in STAT5 phosphorylation. In vivo immunohistochemistry studies further demonstrated defective nuclear translocation of C/EBPbeta, but normal STAT5 activation, in OPGL-deficient mice. These data show that OPGL is a critical activator of beta-casein gene expression via the transcription factor C/EBPbeta. Our data provide new insights into the understanding of the molecular events involved in milk protein gene expression.