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Low bone mass density at multiple skeletal sites, including the appendicular skeleton in amenorrheic runners.

The aim of this study was to investigate any difference in bone mass at different sites between female long-distance runners with amenorrhea and those with eumenorrhea. We compared 10 amenorrheic and 10 eumenorrheic athletes to determine whether athletes with amenorrhea have lower BMD in multiple skeletal regions, including weight-bearing lower limbs. The amenorrheic group had experienced menstrual dysfunction ranging from 3 to 43 months. As a further control group, 16 eumenorrheic soccer players were compared with the former two running groups regarding their BMD measurements. The two groups were matched for age, height, and amount of training. Areal bone mineral density (BMD) was measured and was found to be significantly lower in the total body, humerus, spine, lumbar spine, pelvis, femoral neck, trochanter, total femur, femur diaphysis, tibia diaphysis and in the nonweight-bearing head of the femur in the amenorrheic group. Body weight, BMI, fat mass, and body fat percent were significantly lower in the amenorrheic group. The differences in the BMD of the head, humerus, femoral neck, total femur, femur diaphysis, and tibia diaphysis disappeared when adjusted for body weight. Compared with the soccer group, the amenorrheic subjects had significantly lower BMD values at all sites except for the head, Ward's triangle, and femur diaphysis. Blood samples were obtained in the two running groups for analysis of osteocalcin, carboxy terminal telopeptide (ICTP), procollagen I (PICP), and estradiol. There were no significant differences between the groups but there was a strong tendency towards a lower estradiol level and a higher osteocalcin level in the amenorrheic group. A free estradiol index (FE2) was derived as the ratio of estradiol to sex hormone binding globulin (SHBG) and was significantly lower in the amenorrheic group. No difference in their daily intake of total energy, protein, carbohydrates, fiber, calcium, and vitamin D was observed. However, both groups showed a surprisingly low energy intake in relation to their training regimens. Stepwise regression analyses revealed that weight was the best predictor of spine BMD in both groups. Estradiol and FE2 were significant predictors of the BMD of the proximal femur in the eumenorrheic group, but did not predict any BMD site in the amenorrheic group. In conclusion, amenorrhea in athletic women affects trabecular and cortical bone in both axial and appendicular skeleton. However, some of the discrepancy can be explained by a lower body weight. Physical weight-bearing activity does not seem to completely compensate for the side effects of reduced estrogen levels even in weight-bearing bones in the lower extremity and spine.

Adolescent↗

Heterozygous manifestations in the heritable disorders of the skeleton.

Many heritable disorders of the skeleton are transmitted as autosomal recessive (AR) traits. During the past two decades, family studies have been undertaken in conditions of this type in order to detect any structural manifestations in obligate and potential heterozygotes. The positive findings that emerge from this long-term investigation are reported. In numerous other AR skeletal disorders family investigations failed to reveal any significant abnormalities in relatives of affected persons. A review of the literature elicited additional examples of heterozygote manifestation. The skeletal abnormalities in the heterozygotes are usually inconsistent and often innocuous, but they have a number of important implications: (a) identification of heterozygotes for family screening or for genetic counseling; (b) identification of heterozygotes for conventional and molecular linkage studies; (c) problems with pedigree analysis; variable expression of an autosomal dominant trait versus heterozygous manifestations in an AR disorder; (d) problems with diagnosis, e. g., does a congenital Madelung anomaly always represent the heterozygous form of Langer mesomelic dysplasia? What proportion of persons with isolated brachydactyly are heterozygotes for Grebe chondrodysplasia? It is likely that close scrutiny of first-degree relatives of persons with other AR skeletal disorders will reveal examples of heterozygous manifestations.

Bone Diseases, Developmental↗

Progressive melorheostosis in the peripheral and axial skeleton with associated vascular malformations: imaging findings over three decades.

A 28-year old woman presented with Léri's disease (melorheostosis) and the rare combination of complex vascular malformations and lymphatic anomalies. Multifocal melorheostosis was segmental and unilateral, located in the left axial and peripheral skeleton, fifth thoracic vertebral body, fifth rib. left upper limb and lumbosacral spine (third lumbar body to first sacral segment). Sacral involvement was associated with spinal canal stenosis. Additionally the patient had multiple nevi and had suffered from left hemiplegia since birth. Lymphangiectasia of the mesentery and thorax led to chylothorax resistant to therapy for which the patient underwent a pleuropericardiectomy. Death ensued due to respiratory failure.

Adult↗

Severe rhizomelic skeletal dysplasia in a museum skeleton.

We report on a skeleton dating from the last century with a severe, strictly rhizomelic shortening of all four extremities and a deformed skull. To the best of our knowledge no similar skeletal findings have been described. We suggest that this individual suffered from a hitherto unreported form of skeletal dysplasia.

Adult↗

Rbt (Rabo torcido), a new mouse skeletal mutation involved in anteroposterior patterning of the axial skeleton, maps close to the Ts (tail-short) locus and distal to the Sox9 locus on chromosome 11.

Rbt (Rabo torcido) is a new semidominant mouse mutant with a variety of skeletal abnormalities. Heterozygous Rbt mutants display homeotic anteroposterior patterning problems along the axial skeleton that resemble Polycomb group and trithorax gene mutations. In addition, the Rbt mutant displays strong similarities to the phenotype observed in Ts (Tail-short), indicating also a homeotically transformed phenotype in these mice. We have mapped the Rbt locus to an interval of approximately 6 cM on mouse Chromosome (Chr) 11 between microsatellite markers D11Mit128 and D11Mit103. The Ts locus was mapped within a shorter interval of approximately 3 cM between D11Mit128 and D11Mit203. This indicates that Rbt and Ts may be allelic mutations. Sox9, the human homolog of which is responsible for the skeletal malformation syndrome campomelic dysplasia, was mapped proximal to D11Mit128. It is, therefore, unlikely that Ts and Rbt are mouse models for this human skeletal disorder.

Animals↗

Membrane skeleton in cultured chick cardiac myocytes revealed by high resolution immunocytochemistry.

Distribution of cytoskeletal proteins with emphasis on the membrane-cytoskeleton interface was examined in cultured cardiac myocytes. Using specific antibodies recognizing alpha-sarcomeric actin, desmin, beta-tubulin, spectrin/alpha-fodrin and ankyrin, respectively, the cellular localization of these cytoskeletal proteins was detected by laser scanning confocal microscopy. In addition, the fine filamentous structure of these proteins was identified by combining silver-enhanced immunogold labelling with electron microscopy. The latter technique employed the sequence of quick-freezing, deep-etching and rotary shadowing of the specimens. Conventional transmission electron microscopy of the spherical cardiac myocytes revealed a filamentous submembranous layer, approximately 100 nm thick. Specific immunolabelling of alpha-sarcomeric actin and spectrin/alpha-fodrin as well as ankyrin was seen beneath the plasmalemma. A three-dimensional meshwork of spectrin/alpha-fodrin was shown. Numerous desmin filaments that exhibited a tortuous course throughout the cells were also observed running in parallel with the surface in the submembranous area, whereas beta-tubulin was infrequently detected in these areas. In conclusion, the present study shows that spherical cardiac myocytes contain a distinct and complex three-dimensional membrane skeleton. Major constituents of this distinct submembranous layer were spectrin/alpha-fodrin fibres as well as actin and desmin filaments.

Animals↗

Towards a new understanding and classification of chondrogenic neoplasias of the skeleton--biochemistry and cell biology of chondrosarcoma and its variants.

Despite substantial knowledge on the clinicopathology of chondrogenic skeletal neoplasms, only limited insights into the biology of the different tumor variants are available. There are virtually no established molecular markers for identification and classification of these neoplasms. In this paper, we present a systematic review of the biochemistry and cell biology of chondrogenic neoplasms of the bone focussing on our own recent investigations. The hallmark of all differentiated chondrogenic tumors is the presence of neoplastic chondrocytic cells responsible for the formation of the characteristic cartilaginous tumor matrix. These cells can show the full differentiation potential of physiologic chondrocytes depending on the tumor entity investigated. The high phenotypic diversity of physiologic chondrocytes explains the previously poorly understood, striking heterogeneity of the neoplastic cells and their surrounding extracellular matrix not only between different but also within chondrogenic tumors. In our studies, tumor classifications, so far based only on histomorphological criteria, were either confirmed or corrected: mesenchymal chondrosarcomas represent the prototypic neoplasm of pre-chondrogenic undifferentiated cells undergoing multifocal chondrocytic differentiation. Enchondromas, osteochondromas, and conventional chondrosarcomas are neoplasms of multi-phenotypically differentiated chondrocytes. Clear cell chondrosarcomas appear to be neoplasms of hypertrophic chondrocytic cells. A peculiar biology is displayed by dedifferentiated chondrosarcomas, which at least in most cases show neither "anaplasia" nor "dedifferentiation", but most likely "transdifferentiation" of part of the neoplastic cells to a cellular phenotype of a different mesenchymal differentiation lineage. Chondroblastomas do not show any chondroblastic differentiation at all. Our studies delineate molecular markers of chondrogenic neoplasms of the skeleton, which have the potential to be the basis of a new biology-orientated classification of skeletal neoplasms. The expression analysis of extracellular matrix genes, in particular of the collagen types, might be able to play herein a leading role in classification and diagnosis, similar to the cytokeratin subtypes or the CDs (cluster of differentiation) for the classification and diagnosis of neoplasms of the epithelia and the lymphatics.

Animals↗

Semi-skeletonized internal mammary grafts and phrenic nerve injury: cause-and-effect analysis.

Phrenic nerve injury after cardiac surgery increases postoperative pulmonary complications. The purpose of this study was to analyze the causes and effects of phrenic nerve injury after cardiac surgery. Prospectively collected data on 2084 consecutive patients who underwent cardiac surgery from Jan. 1995 to Feb. 2002 were analyzed. Twenty-eight preoperative and operation related variables were subjected to logistic analysis with the end point being phrenic nerve injury. Then phrenic nerve injury and 6 perioperative morbidities were included in the analysis as variables to determine their independent predictive value for perioperative pulmonary morbidity. An identical approach was used to identify the independent risk factors for perioperative mortality. There were 53 phrenic nerve injuries (2.5%). There was no phrenic nerve injury in non-coronary surgery or coronary surgery using conduits other than the internal mammary artery. The independent risk factors for phrenic nerve injury were the use of internal mammary artery (Odds ratio (OR) = 14.5) and thepresence of chronic obstructive pulmonary disease (OR = 2.9). Phrenic nerve injury was an independent risk factor (OR = 8.1) for perioperative pulmonary morbidities but not for perioperative mortality. Use of semi-skeletonized internal mammary artery harvesting technique and drawing attention to possible vascular or mechanical causes of phrenic nerve injury may reduce its occurrence. Unilateral phrenic nerve injury, although rarely life-threatening, is an independent risk factor for postoperative respiratory complications. When harvesting internal mammary arteries, it should be kept in mind avoiding stretching, compromising, or inadvertently dissecting phrenic nerve is as important as avoiding damage of internal mammary artery itself.

Adult↗

The effect of sex steroids on the skeleton in premenopausal women.

Whereas peak bone mass is genetically determined, the skeletal growth, maturation, and maintenance required to reach this peak may be influenced by physical activity, ovarian function, and nutrition. Estrogen deficiency at menopause leads to increased skeletal remodeling and loss of bone mass, which can result in osteoporotic fractures. Entering menopause with low bone mass is a risk factor itself, because bone mass predicts future risk of fracture. The administration of exogenous steroids can reverse the setting of the "mechanostat" to lower levels after ovarian dysfunction, although it is unclear whether oral contraceptives can modify bone mass in the ovulatory premenopausal woman. Our recent data suggest that the use of steroidal hormones to treat menstrual irregularity (presumably relative to ovarian dysfunction), as opposed to fertility control, is more likely to positively affect bone mass. It is even less clear whether hyperestrogenic states (e.g., pregnancy) affect the skeleton. Recent evidence from bone mass changes that occur in women with ovulatory cycles and inadequate luteal phase function suggests that progestins may also influence skeletal metabolism.

Bone Density↗

Variability of the craniofacial skeleton. III. Radiographic cephalometry of juvenile Macaca mulatta.

The variability of the craniofacial skeleton of the juvenile Macaca mulatta was studied from lateral radiographic cephalograms of twenty-three animals, using a previously described method based on fourteen lines depicting certain anatomic features. The findings, when compared to corresponding human data, revealed that a number of angular relationships are similar in this monkey and in human childrena and adults. The same is true regarding the variability of individual lines. These similarities suggest that biologic similarities exist in the cranio-facial skeletal architecture in these species. Specifically, the findings in the Macaca mulatta were in agreement with previous findings in human children and adults as regards the parallelism between the anterior parts of the neurovascular canals of the upper and lower jaws and the apparently adaptive role of the ramus and the condyle.

Age Factors↗

A cephalometric study of the craniofacial skeleton in trichorhinophalangeal syndrome.

A prominent feature of the trichorhinophalangeal syndrome is a very characteristic facies. This study quantitates differences in craniofacial skeleton between affected and unaffected members of the same kindred. Standard scores for various measurements taken from lateral cephalometric radiographs were compared for statistical significance, and these were further correlated with similar data calculated from length measurements of the middle phalanx of the second digit. The affected group had a shortened posterior face height (p less than 0.01) associated with a short mandibular ramus (p less than 0.01) as well as a reduced and superiorly deflected posterior cranial base (p less than 0.01). These craniofacial changes result in a steep inclination of the lower border of the mandible (p less than 0.01) and suggest disturbances in the epiphyseal growth sites of the skull as demonstrated by a high degree of correlation between the dysplasia of the cranial base, shortening of the posterior portion of the face, and shortening of the middle phalanx of the second digit.

Adolescent↗

Projecting the soft-tissue outcome of surgical and orthodontic manipulation of the maxillofacial skeleton.

A simple method is presented for developing one-to-one composite soft-tissue and radiographic patient images. Their use in diagnosis, treatment planning, and prediction of the outcome of surgical and orthodontic manipulations of the facial hard tissues to effect soft tissue change is discussed. Complementing cephalometric analysis and model surgery, this technique uses a 35 mm, slide, acetate tracing paper, a pencil, and a series of integumentary changes which follow rearrangements of the underlying skeleton, including the dentition, maxillae, zygomas, and nose. The pretreatment images is traced from a projected 35 mm, slide, which is sized to the cephalometric tracing to obtain a "life-sized" representation of the face. The image is then redrawn, adjusting the dysmorphic parts to the unchanged part of the face to effect balance of the profile and restore normal contours. This recreated image is used then as an objective to which the treatment planning is directed and through which it is commonly seen that the restoration of functional and esthetic balance is a mutually supportive goal. The projected image is of value to the clinician in formulating his treatment goal, but it is more valuable in the visible expression that it gives to his mental image of the ideal outcome. Moreover, it can be readily shared with the patient, who often better appreciates the changes in contours, which he sees daily, than the commonly employed profiles of cephalometric prediction, which are basically foreign to him. The technique is discussed, as are the ratios of hard-to-soft-tissue change, with case reports for demonstration.

Adult↗

Fibroosseous tumors of the facial skeleton in association with primary hyperparathyroidism: an endocrine syndrome or coincidence?

In a retrospective study of 350 cases of primary hyperparathyroidism at the University of Toronto, 5 patients had associated benign fibroosseous lesions of the facial skeleton which did not regress after successful parathyroidectomy and restoration of normocalcemia. Two of these patients were siblings and an offspring of one of these patients was recently shown to have hyperparathyroidism, suggesting that this group of patients does represent a syndrome with familial and genetic implications. At present bone disease in patients with hyperparathyroidism should be viewed with some consideration of unrelated process, and appropriate biopsy and treatment should be undertaken after its recognition.

Adenoma↗

Fibrous skeleton and ventricular outflow tracts in double-outlet right ventricle.

Twenty-four hearts in which both great arteries arose from the right ventricle were studied to establish variations present within the fibrous skeleton and infundibular morphologies. Variations were also noted in the location of the ventricular septal defect and measurements were obtained of the outlet septum and the circumferences of the arterial valves. Completely muscular subarterial infundibulums were present in only 9 (37.5%) of the hearts, with varying degrees of fibrous continuity between the leaflets of the arterial and atrioventricular valves in the remainder. The aorta was rightward and posterior in 12 (50%) of the hearts, and subaortic and subpulmonary ventricular septal defects were present in equal numbers in this group. No subaortic defects were present when the aorta was side-by-side and right-sided. No subpulmonary defects were present in hearts with a posterior aorta. The mean ratio of 0.91 +/- 0.36 for the subpulmonary to subaortic length of the outlet septum was significantly less than the value of 1.54 +/- 0.41 noted previously in hearts with tetralogy of Fallot (p less than 0.001).

Aortic Valve↗

Fibrous skeleton endocarditis: repair using Konno procedure.

Information about the surgical management of fibrous skeleton endocarditis is incomplete, as the vast majority of current literature describes the isolated repair of either the aortic or the mitral annulus, the combination rarely being addressed. Annular destruction, in the presence of endocarditis, demands extreme ingenuity for surgical treatment and cure. We describe and illustrate the Konno procedure for replacement of both infected mitral and aortic valves and repair of mycotic ventricular septal defects.

Adult↗

The effect of vibration on the skeleton, joints and muscles. A review of the literature.

Owing to the elasticity and plasticity of the skeleton, joints and muscles, the musculoskeletal system is capable of absorbing and damping mechanical vibration without damage as long as the vibration level is within tolerable limits. However, technical developments have led to the exposure of many people to intolerable variation levels with destructive changes as a result. These injuries to the musculoskeletal system continue to be the subject of research interest. Initially, the joints and joint complaints attracted the greatest attention. Vibration damping takes place mainly in the joints. The incidence of destructive joint changes has been examined in comprehensive clinical, epidemiological and radiographic studies, mainly concentrating on the joints of the hand and arm. The response of muscles to vibration is often expressed in the form of a tonic vibration reflex (TVR) which arises as a result of stimulation of the muscle spindles and therefore resembles the classic tonic stretch reflex. There is increased muscular activation for stabilisation of the joint positions, especially during whole-body vibration. Studies have also disclosed how vibration affects body equilibrium and equilibrium control and how vibration can elicit muscle pain, cramps and reduced muscular strength.

Journal Article↗

Dimensions of the temporal glenoid fossa and tooth wear in prehistoric human skeletons.

Both the mandibular condyle and the glenoid fossa remodel in response to changes in the dentition during life, although the precise relationship between teeth and joint is not clear. This study was undertaken to ascertain changes, if any, occurring in the glenoid fossae in skeletons with much tooth wear. In a collection of skulls from an excavation site on the South African coast, occlusal wear was measured using the scale devised by Molnar. The dimensions of the glenoid fossae were measured using a reflex microscope. Profiles of the glenoid fossa at right angles to a line through its medial and lateral poles provided estimates of the slope of the articular eminence in three places: centrally, and midway between this slope and each of the poles. The mediolateral profile gave an estimate of the height and gabling of the fossa. Central and lateral slope angles showed weak correlation with molar wear, and the medial but not the lateral angel was significantly different from the central. The fossa appears to remodel in response to patterns of forces generated during function, but compared to the condyle, is not as strongly influenced. This may be accounted for if the relative load-bearing areas of the condyle and fossa are considered.

Adult↗

The CDC4 gene product is associated with the yeast nuclear skeleton.

The CDC4 gene product of Saccharomyces cerevisiae is required at the late G1/S phase boundary of the cell cycle. In an attempt to better understand the function of CDC4, we performed experiments to localize this protein in the yeast cell. Using antisera, directed against a TrpE-CDC4 fusion protein, to analyze immuno-blots of different subcellular fractions from yeast, we demonstrated that the CDC4 gene product localizes in the nucleus by two different biochemical preparations of the yeast nucleoskeletal proteins. Immunofluorescence microscopy further confirmed its nuclear localization. These data support a model that includes the CDC4 gene product as a component of the yeast nuclear skeleton. The significance of this association in relationship to the biological role of CDC4 is discussed.

Cell Cycle↗