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Volume maintenance of inlay bone grafts in the craniofacial skeleton.

Although the clinical use of inlay bone grafts is widespread in craniofacial surgery, the dynamics of inlay bone grafting to the craniofacial skeleton have never been well characterized. Previous work demonstrated that volume maintenance of bone grafts in the onlay position is a consequence of their microarchitectural features, rather than their embryological origins. The purpose of this study was to investigate whether the properties determining the volume maintenance of bone grafts in the onlay position in the craniofacial skeleton could be extended to bone grafts in the inlay position. It was hypothesized that volume maintenance of an inlay bone graft could be better explained on the basis of the microarchitectural features of the graft (cortical versus cancellous composition), rather than its embryological origin (membranous versus endochondral), and that the primary determinant of bone graft behavior is the interaction between the microarchitectural features of the bone graft and the local mechanical environment in which the bone graft is placed. Cortical and cancellous bone grafts were harvested from the iliac crest (endochondral origin) of 25 New Zealand white rabbits, and cortical bone was harvested from the mandible (membranous origin) of each rabbit. Four 7-mm trephine holes were made in the cranium of each rabbit, posterior to the coronal suture. Each defect was filled with endochondral cortical bone, endochondral cancellous bone, or membranous cortical bone or was left as an ungrafted control specimen. Animals were killed at 3, 8, or 16 weeks. Crania were subjected to micro-computed tomographic and histological assessments. Micro-computed tomographic analysis demonstrated significant increases in actual bone volume from time 0 to the time of death for all types of grafts. Cortical bone demonstrated significant increases in space-occupying volume at all time points. By 16 weeks, no statistically significant difference in either the actual bone volume or the space-occupying volume according to graft type could be detected. There was no resorption of the inlay bone grafts; in fact, all bone types exhibited increased volume. Cancellous bone demonstrated the greatest capacity to increase actual bone volume. All bone graft types seemed to reach a steady-state bone volume, as if controlled by a local regulator. The regulator is likely the local mechanical environment in which the grafts were placed, as corroborated by the findings that the bone grafts seemed to recapitulate the characteristics of the bone in which they were placed, rather than maintaining their native characteristics.

Animals↗

Routine skeleton radiography using a flat-panel detector: image quality and clinical acceptance at 50% dose reduction.

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate image quality and clinical acceptance of a large-area, flat-panel X-ray detector for routine skeleton examinations at 50% dose reduction. METHODS: A total of 153 examinations (307 images) of 100 consecutive patients were evaluated. The cesium iodide-amorphous silicon active-matrix imager had a panel size of 43 x 43 cm, a matrix of 3000 x 3000, and a pixel pitch of 143 microm. All images were obtained with a kilovoltage setting identical to conventional radiographies of speed class 400. The amperage values were reduced by 50% compared with standard dose. Images were presented to 3 radiologists, who subjectively rated image quality on a 4-point scale according to 5 criteria (bone cortex, bone trabecula, soft tissue, overall contrast, and overall impression). Three trauma surgeons rated the clinical acceptance on a 4-point scale. Clinical acceptance was defined as directly derived consequences or therapy based on the presented image quality. For both evaluations, 1 represented excellent, 2 represented good, 3 represented moderate, and 4 represented nondiagnostic image quality/clinical acceptance. Intermediate scores at 0.5 intervals were allowed. RESULTS: The mean values for all 5 image quality criteria were rated good or excellent (< or = 2). A total of 4.2% (13 of 307) of the images were rated 2.5 to 3.5 concerning the overall impression. None of the imaging features was ranked more than 3.5 by any radiologist. The mean value of the clinical acceptance was between good and excellent (1.47). A total of 98.7% (151 of 153) of the examinations were rated < or = 2.5; 1.3% (2 of 153) of examinations were of moderate clinical acceptance (< or = 3.5). None of the examinations was of nondiagnostic image quality or clinical acceptance (>3.5); therefore, no study had to be repeated. CONCLUSION: Routine skeleton images with 50% dose reduction yield good image quality and good clinical acceptance. In cases with abundant soft tissue, less dose reduction or standard dose is required.

Adult↗

Antitumour activity of purified arabinogalactan-peptidoglycan complex of the cell wall skeleton of Rhodococcus lentifragmentus.

Antitumour activity of arabinogalactan peptidoglycan (AP) complex (peptidoglycan and arabinogalactan liberated by an acid or alkaline treatment from Rhodococcus lentifragmentus AN-115 cell wall skeleton) was examined in mice and compared with that of the cell wall skeleton. The growth of syngeneic fibrosarcoma Meth A cells after implantation in BALB/c mice was significantly suppressed by AP complex, and also regressed after intratumoral injection of AP complex on days 1, 4 and 7 after tumour implantation. Although the activity of peptidoglycan was less than that of AP complex, peptidoglycan also showed both tumour-suppressive and regressive activities. Arabinogalactan did not show antitumour activity. It is interesting that peptidoglycan has an important role in the effect against tumours.

Animals↗

IKK1-deficient mice exhibit abnormal development of skin and skeleton.

IkappaB kinases (IKKs) IKK1 and IKK2 are two putative IkappaBalpha kinases involved in NF-kappaB activation. To examine the in vivo functions of IKK1, we generated IKK1-deficient mice. The mutant mice are perinatally lethal and exhibit a wide range of developmental defects. Newborn mutant mice have shiny, taut, and sticky skin without whiskers. Histological analysis shows thicker epidermis, which is unable to differentiate. Limbs and tail are wrapped inside the skin and do not extend properly out of the body trunk. Skeleton staining reveals a cleft secondary palate, split sternebra 6, and deformed incisors. NF-kappaB activation mediated by TNFalpha and IL-1 is diminished in IKK1-deficient mouse embryonic fibroblast (MEF) cells. The IKK complex in the absence of IKK1 is capable of phosphorylating IkappaBalpha and IkappaBbeta in vitro. Our results support a role for IKK1 in NF-kappaB activation and uncover its involvement in skin and skeleton development. We conclude further that the two related kinases IKK1 and IKK2 have distinct functions and can not be substituted for each other's functions.

Animals↗

A review on MR vascular image processing: skeleton versus nonskeleton approaches: part II.

Vascular segmentation has recently been given much attention. This review paper has two parts. Part I of this review focused on the physics of magnetic resonance angiography (MRA) and prefiltering techniques applied to MRA. Part II of this review presents the state-of-the-art overview, status, and new achievements in vessel segmentation algorithms from MRA. The first part of this review paper is focused on the nonskeleton or direct-based techniques. Here, we present eight different techniques along with their mathematical foundations, algorithms and their pros and cons. We will also focus on the skeleton or indirect-based techniques. We will discuss three different techniques along with their mathematical foundations, algorithms and their pros and cons. This paper also includes a clinical discussion on skeleton versus nonskeleton-based segmentation techniques. Finally, we shall conclude this paper with the possible challenges, the future, and a brief summary on vascular segmentation techniques.

Algorithms↗

Erythrocyte membrane skeleton abnormalities in hereditary spherocytosis.

Erythrocyte ghosts from eight individuals with hereditary spherocytosis have been compared with respect to their protein compositions as judged by SDS gel electrophoresis, their ease of spectrin extractability, and their freeze-etch electron microscopic appearance after incubation in condition designed to promote aggregation of the intramembrane particles. Four of these HS cases were unrelated, while the other four represented two generations from a single family, including a pair of identical twins, one of whom had not undergone splenectomy when this investigation was initiated. Of the four unrelated cases, one showed no departures from normal under the conditions of this investigation, whereas the other three exhibited features which suggested a membrane skeleton lesion. In one of these there was a reduced proportion of spectrin tetramers relative to dimers in 4 degrees C extracts, while the two remaining cases exhibited abnormal intramembrane particle aggregation. The four related cases had almost identical variations from normal. Spectrin was not extractable from their ghost membranes during a mild extraction incubation which removed spectrin from normal control ghosts. However, the intramembrane particle aggregation subsequently induced in these ghosts was of a degree unobtainable in normal ghosts without such spectrin extraction. In addition the ghosts from one twin, the only one of these patients who had not undergone splenectomy at the start of this investigation, showed a reduced amount of band 4.2. However, when this patient's blood was re-tested after splenectomy, this protein was found to be at normal levels. Our results support the view that hereditary spherocytosis is not a single disease, but is rather a term used to describe a variety of different molecular lesions of the erythrocyte membrane skeleton with similar clinical manifestations.

Actins↗

Evaluation of bone mineral density of the peripheral skeleton in pre- and postmenopausal women with newly diagnosed endogenous Cushing's syndrome.

OBJECTIVE: Cushing's syndrome (CS) is a well recognized cause of bone loss. Although many previous studies have shown decreased bone mineral density (BMD) in the lumbar spina and proximal femur of patients with endogenous CS, so far, the data estimating BMD in their peripheral skeleton are sparse. The aim of the present study was to evaluate BMD in the forearm and heel of women with newly diagnosed CS and to investigate its possible correlation with serum osteocalcin (BGP) and 24-hour urinary free cortisol levels (UFC). PATIENTS AND METHODS: BMD in the forearm (distal and ultradistal area) of 29 (13 premenopausal and 16 postmenopausal) women with newly diagnosed CS (18 with pituitary adenoma, 10 with adrenal tumor and 1 with ectopic) was measured by dual x-ray absorptiometry (DEXA) and was compared with BMD of 29 age, body mass index (BMI)- and oestrogen status matched healthy controls. Furthermore, in 18 (9 premenopausal and 9 postmenopausal) of the above patients (14 with pituitary adenoma, 5 with adrenal tumor and 1 with ectopic) broadband ultrasound attenuation (BUA) by quantitative ultrasound (QUS) of the heel was estimated and 18 age-, BMI- and oestrogen status matched healthy women served as controls. In all the patients serum BGP and UFC were measured at the time of diagnosis of CS. RESULTS: Compared to their matched controls, BMD in the forearm and BUA values in the heel did not differ in the premenopausal women with CS, while in the postmenopausal group BMD in the forearm was decreased (P < 0.05) but not BUA. Apart from a weak negative correlation between serum BGP and BMD in the ultradistal site of the forearm in premenopausal women (P = 0.05), serum BGP and UFC did not show significant correlation with BMD or BUA. CONCLUSIONS: BMD in the forearm is reduced only in postmenopausal women with newly diagnosed endogenous CS, while BUA in the heel is unaffected in both pre- and postmenopausal patients. Moreover, serum BGP and UFC do not seem to be relevant markers for assessing bone loss in the peripheral skeleton at the time of diagnosis of hypercortisolemia.

Absorptiometry, Photon↗

Prokaryotic hopanoids: the biosynthesis of the bacteriohopane skeleton. Formation of isoprenic units from two distinct acetate pools and a novel type of carbon/carbon linkage between a triterpene and D-ribose.

Incorporation of 13C-labelled acetate into the hopanoids of the purple non-sulfur bacteria Rhodopseudomonas palustris and Rhodopseudomonas acidophila and the facultative methylotroph Methylobacterium organophilum showed that the bacteriohopane skeleton is built from an unique carbon/carbon linkage between the triterpenic hopane moiety and the C-5 carbon of a D-ribose derivative arising from the non-oxidative pentose phosphate pathway. Furthermore a probable compartmentation of the acetate metabolism could be observed in these bacteria. Whereas exogenous acetate was directly incorporated into the glucose derivatives and poly-(3-hydroxybutyrate), the isoprenic units were apparently solely synthesized from two acetate units arising from the glyoxylate cycle and a third one issued either from the glyoxylate cycle or from the Entner-Doudoroff pathway of glucose catabolism. Although an unknown biosynthetic pathway different from that usually proposed for isoprenoid biosynthesis can not be excluded, the former hypothesis explained all labelling patterns observed on the triterpenic skeleton.

Acetates↗

Bone mass of the axial and the appendicular skeleton in women with Colles' fracture: its relation to physical activity.

The aim of this investigation was to elucidate whether Colles' fractures in middle-aged women were indicative of generalized bone loss (osteopenia) and whether bone mass of the axial and the appendicular skeleton was related to the extent of daily physical activity. Thirty-six patients (aged 50-73 years) with previous Colles' fracture were studied. The median time elapse after the injury was 18 months (range 9-20.5 months). Bone mineral content of the 2nd, 3rd, and 4th lumbar vertebrae (lumbar BMC) and both distal forearms (forearm BMC) were determined to dual-photon (153Gd) absorptiometry. The physical activity level was graded according to a standard interview and a bicycle ergometer test. Mean lumbar BMC was reduced by 9% compared to age-matched normal women (p less than 0.05), mean forearm BMC was reduced by 5% (NS). Twenty patients showed spinal osteopenia by either conventional radiography or absorptiometry (95% confidence limits 38-72%). The fracture-related bone loss from the forearms was most prominent when the fracture had occurred in the dominant forearm, suggesting that the loss of 'dominant' forearm activity per se results in bone loss. No relation between working capacity and forearm BMC was found. However, the working capacity was positively related to lumbar BMC (P less than 0.01), even if the common relationship to age was eliminated (P less than 0.05). The data suggest that the bone mass of the axial skeleton reflects the extent of daily physical activity. Patients with Colles' fractures represent an easily definable population which might benefit from prophylactic measures against vertebral bone loss and compression fractures. One of these could be physical exercise.

Aged↗

POSSIBLE RELATIONSHIP BETWEEN TETRACYCLINE STABILITY AND EFFECT ON FOETAL SKELETON.

A possible relationship between stability of a tetracycline and persistence in the foetal skeleton is discussed; it seems that the greater the stability of a tetracycline, the more it may interfere with bone-forming processes. Therefore, assuming that limited instability does not impair antibiotic potency in vivo, the use of a low-stability tetracycline seems to be a safer form of treatment in order to avoid undesired effects on the foetal skeleton.

Abnormalities, Drug-Induced↗

The physiological basis of training the skeleton. The Sir Frederick Smith Memorial Lecture.

The skeleton consists of a series of elements with a variety of functions. In locations such as the skull, where shape or protection are of prime importance, the bone's architecture is achieved during growth under predominant genetic control. In locations such as the limbs, where the ability to withstand repetitive loading is important, only the general form of the bone will be achieved as a result of growth alone, the remaining characteristics resulting from an adaptive response to functional load bearing. In the horse, this functional load-bearing will be provided by the animal's natural activity pattern in box or paddock supplemented by the specific activities of the training regimen. It is the adaptive response to the total activity pattern that influences bone modelling and remodelling and so determines the bone's architecture. The objective of the training regimen is to ensure that this response achieves an appropriate match between bone architecture and the loads it is required to withstand during both training and athletic performance. We propose that for the match between architecture and load-bearing to be established, and maintained, subsequently, bone cells must be able to 'assess' directly or indirectly the functional strains produced within the bone tissue. Because these strains are used as feedback they are both the objective of functionally adaptive modelling and remodelling, and the stimulus for its control. The mechanisms whereby bone cells control skeletal modelling and remodelling to produce a functionally competent skeleton are unknown although some of the factors and sequence of events involved are presented here. The extent to which variation in training regimen affects bone architecture has not been studied systematically in any species.

Adaptation, Physiological↗

Kinetics of rapid 45Ca uptake into chick skeleton in vivo: effects of microwave fixation.

We have investigated uptake kinetics for 45Ca labels acutely administered as single intravenous injections into twelve-day-old chicks in vivo. Effects of microwave fixation on this process have also been studied. Rapid uptake of 45Ca was demonstrated into the skeleton with approximately 40% of injected label being found in the skeleton within the first 15 min. By 45 min tissue 45Ca levels had stabilized and showed little change during the following 90 min. Soft tissue isotope levels declined during the period from 3 to 135 min following injection. These data were obtained from animals in which tissue isotope levels were stabilized by fixation with microwaves at the point of killing by cervical dislocation. In animals where the microwave fixation step was omitted and tissues were dissected for counting at least 1 h after killing, 45Ca levels in both skeletal and soft tissues were 15-20% higher than in those from microwave groups during the period 3-15 min after injection. In a separate experiment, groups of chicks killed by cervical dislocation 3 min after isotope injection were fixed with microwaves at time intervals ranging from 0 to 45 min post-mortem. Isotope levels in femur increased with time and were significantly higher in groups in which fixation was carried out 12 and 45 min after death when compared with those fixed at the point of death. Data in calvarium reflected those in femur but were not statistically significant at the time intervals tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Protofilament and hexagon: a three-dimensional mechanical model for the junctional complex in the erythrocyte membrane skeleton.

It is a long-standing mystery why erythrocyte actin filaments in the junctional complex (JC) are uniformly approximately 37 nm and the membrane skeleton consists of hexagons. We have previously proposed that a "molecular ruler" formed by E-tropomodulin and tropomyosin 5 or 5b functions to generate protofilaments of 12 G actin under mechanical stress. Here, we illustrate that intrinsic properties of actin filaments, e.g., turns, chemical bonds, and dimensions of the helix, also favor fragmentation into protofilaments under mechanical stress. We further construct a mechanical model in that a pair of G actin is wrapped around by a split alpha and beta spectrin, which may spin to two potential positions, and stabilize to one when the tail end is restricted. A reinforced protofilament may function as a mechanical axis to anchor three (top, middle, and bottom) pairs of Sp. Each Sp pair may wrap around the protofilament with a wide dihedral angle (approximately 166.2 degrees) and a minimal axial distance (2.75 nm). Such three Sp pairs may spiral down (right handed) the protofilament from the pointed end with a dihedral angle of approximately 55.4 degrees in between the Sp pairs. This first three-dimensional model of JC may explain the hexagonal geometry of the erythrocyte membrane skeleton.

Actin Cytoskeleton↗

Generating diverse skeletons of small molecules combinatorially.

Lack of efficient access to collections of synthetic compounds that have skeletal diversity is a key bottleneck in the small-molecule discovery process. We report a synthesis strategy that involves transforming substrates with different appendages that pre-encode skeletal information, named sigma elements, into products that have different skeletons with the use of common reaction conditions. With this approach, split-pool synthesis can be used to pre-encode skeletal diversity combinatorially and thereby generate such small molecules very efficiently. A split-pool synthesis of more than 1000 compounds produced overlapping, combinatorial matrices of molecular skeletons and appended building blocks in both enantiomeric and diastereomeric forms.

Acetylation↗

Association between osteoarthritis of the hand and knee in a population of skeletons from London.

OBJECTIVE: To examine the relation between osteoarthritis of the hand and knee in a group of skeletons dating to the 18th and early 19th centuries from two sites in London. METHODS: This was a case-control study of 115 cases and controls matched for age and sex. Cases were skeletons with osteoarthritis of the hands; cases and controls were assessed for the presence of osteoarthritis of any compartment of the knee. RESULTS: Cases had a significant odds ratio (OR) for osteoarthritis of the knee compared with controls: OR 5.98, 95% confidence interval (CI) 1.25 to 56.37. Cases with osteoarthritis of the distal interphalangeal (DIP), proximal interphalangeal (PIP), and first carpometacarpal (CMC1) joints had increased but non-significant odds ratios for osteoarthritis of the knee in the order DIP > PIP > CMC1. Cases with multifocal osteoarthritis of the hands had a significantly increased odds ratio for osteoarthritis of the knee: OR 11.67, 95% CI 1.13 to 379.57. CONCLUSIONS: The study confirms the association between osteoarthritis of the hand and the knee seen in contemporary populations and suggests that it is not of very recent origin.

Adult↗

Arthritis in Saxon and mediaeval skeletons.

Examination of 400 Saxon, Romano-British, and mediaeval skeletons from seven archaeological excavations in the west of England showed an unexpectedly high incidence of osteoarthritis and osteophytosis. Three skeletons had evidence of an erosive peripheral arthritis-one with probable gout, one probable psoriatic arthropathy, and one with possible rheumatoid arthritis. The pattern and types of rheumatic disease, and the resultant disability, were apparently different. An exuberant form of large joint osteoarthritis was common and rheumatoid arthritis and similar diseases rare.

Adult↗

Local bone mineral response to brief exercise that stresses the skeleton.

OBJECTIVE: To compare grip strength and bone mineral content in the forearm in women and to test the effects on bone mineral content of short periods of exercise that stresses the skeleton. DESIGN: Assessment of both wrists in 69 volunteers and of the non-fractured wrist in 30 patients followed by an exercise regimen entailing squeezing a tennis ball as hard as possible for 30 seconds each day for six weeks. SETTING: Old people's homes and outpatient departments of Hammersmith and Northampton general hospitals. PATIENTS: 99 Women, of whom 69 were volunteers and 30 had a fractured forearm. MAIN OUTCOME MEASURE: Grip strength and bone mineral content after six weeks and at six months after the exercises had stopped. RESULTS: The bone mineral content of the women's forearms was measured with a densitometer and the grip strength with a semi-inflated bag connected to an anaeroid barometer. Measurements before exercise showed that the two variables correlated closely, irrespective of age, and that there were significant differences in both between the dominant and non-dominant arms of the volunteers. After six weeks of exercise there was a mean increase in grip strength of 14.5% (95% confidence interval 9.9 to 19.2%) and in bone mineral content of 3.4% (1.4 to 5.3%) in the stressed forearms of the 77 women who attended for examination. After six months without exercise the improvements in the 33 women who attended for follow up had reversed. Women who had had a fractured forearm (n = 13), however, had continued to gain grip strength and bone mineral content in the arm that had not been injured. CONCLUSIONS: Grip strength in the forearm is a good indicator of bone mineral content. Both variables may be increased by brief periods of stressful exercise. If this principle can be applied to the whole skeleton it may provide a means of reversing osteoporosis.

Bone and Bones↗

Percutaneous needle biopsy of the irradiated skeleton.

Percutaneous needle biopsy was performed in 20 patients who had radiologic abnormalities after irradiation of the skeleton. The biopsies were performed to determine the nature of the bone changes and to differentiate radiation necrosis from metastases or local tumor extension. Eleven patients had tumors, two of which were radiation-induced sarcomas; nine patients did not show evidence of tumor. One patient had osteomyelitis rather than the suspected tumor. The value of percutaneous needle biopsy in the postirradiated skeleton is discussed.

Adolescent↗