The diagnosis and orthopaedic treatment of childhood spinal muscular atrophy, peripheral neuropathy, Friedreich ataxia, and arthrogryposis.
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Adolescent↗
Biomedical subjects
F Shapiro
Publications and source records attributed to F Shapiro.
Osteopetrosis. Current clinical considerations.
Osteopetrosis is an inherited skeletal condition characterized by increased bone radiodensity. There are three clinical groups: infantile-malignant autosomal recessive, fatal within the first few years of life (in the absence of effective therapy); intermediate autosomal recessive, appears during the first decade of life but does not follow a malignant course; and autosomal dominant, with full-life expectancy but many orthopaedic problems. The infantile variant shows a myelophthisic anemia, granulocytopenia, and thrombocytopenia, and patients eventually die from infection or bleeding or both. Neurologic sequelae include cranial nerve compression (optic nerve, blindness; auditory nerve, deafness; facial nerve, paresis), hydrocephalus, convulsions, and mental retardation. Radiographs show uniform bone density without corticomedulary demarcation, broadened metaphyses, "bone within a bone" or endobone phenomena (tarsals, carpals, phalanges, vertebra, ilium), and thickened growth plates if there is superimposed rickets. Transverse pathologic fractures occur, often followed by massive periosteal bone formation. Computed tomographic scans, magnetic resonance imaging, and bone scans provide specific information. Iliac crest bone biopsy is valuable to quantitate osteoclast and marrow changes by light and electron microscopy. Medical treatments involve high-dose calcitriol to stimulate osteoclast differentiation and bone marrow transplantation to provide monocytic osteoclast precursors. Orthopaedic problems in the intermediate and autosomal dominant forms include increased fractures, coxa vara, long-bone bowing, hip and knee degenerative arthritis, and mandibular and long-bone osteomyelitis. Cranial nerve compression also occurs. Osteotomy, plating, intramedullary rodding, and joint arthroplasty can be done, but are difficult because of bone hardness.
Anemia, Myelophthisic↗
Vertebral development of the chick embryo during days 3-19 of incubation.
Chick embryo vertebral development has been studied during the period from 3 to 19 days of incubation. Whole mount preparations stained with alcian blue for cartilage and alizarin red for bone show the vertebral bodies as cartilaginous at 5 days, with dorsal spinous processes at 6 1/2 days, the onset of bone formation at the ventral and dorsal surfaces of the bodies at 13 days, ossification extending dorsally within the neural arches at 13 1/2 days, and bone development occurring throughout the vertebrae at 16 days. Descriptions at each time period center on the thoracic vertebrae with occasional inclusion of adjacent lower cervical and upper lumbar vertebrae. Histologic development is correlated with the Hamburger-Hamilton stages, which are based on external characteristics. The notochord and neural tube are well developed by 3 days and surrounded by sclerotome, myotome, and dermatome cells. Cartilage formation in the perinotochordal region of the vertebral body is seen at 5 days and precedes development of the neural arches and spinous processes. Separate centers of chondrocyte hypertrophy occur in the body (9 days), the lateral neural arches and the dorsal spinous process. Bone formation is under way at 13 days, beginning in the vertebral bodies. Intramembranous periosteal bone formation is seen adjacent to internal regions of chondrocyte hypertrophy. Vascular invasion of hypertrophic chondrocyte regions occurs, but the mechanism of endochondral ossification differs from that of mammals. The cartilage is resorbed by multinucleated chondroclasts and marrow round cells. Clumps of growth plate cartilage cells and matrix are surrounded occasionally by newly synthesized bone, but invasion of individual hypertrophic chondrocyte lacunae by vessels with bone deposition by accompanying osteoblasts on single trabeculae of cartilage does not occur. 3H-thymidine autoradiography shows high uptake at 3 and 5 days in the germinal neuroepithelial cells of the neural tube (spinal cord) and notochord. By 7 days, notochordal uptake is markedly diminished, and no uptake of isotope occurs from 8 days onward. Spinal cord uptake is highest in the first 8 days but persists in lessened amounts to 19 days. From 5 days onward, both undifferentiated mesenchymal cells and differentiated chondrocytes show positive 3H-thymidine uptake, but labeling is never seen in hypertrophic chondrocytes.
Animals↗
Spinal fusion in Duchenne muscular dystrophy: a multidisciplinary approach.
We studied 27 Duchenne muscular dystrophy patients having spinal fusion for scoliosis. One patient died intraoperatively of cardiac arrest; all others have done well with no instances of malignant hyperthermia, postoperative ventilatory system dependence, pneumothorax, persisting infection, neurologic damage, nonunion, or pain. The anesthetic management included primarily intravenous general anesthetics with minimal myocardial depressant effects, avoiding succinylcholine and inhalation agents. Preoperative cardiac studies aided anesthetic management intra-operatively. There was an almost universal sinus tachycardia. Holter monitoring defined 4 of 16 with ventricular premature beats, 4 of 16 with atrial premature beats, and no ventricular tachycardia or atrial flutter or fibrillation. Echocardiogram demonstrated mitral prolapse in 2 of 22, frequent abnormal systolic performance with abnormal shortening fraction less than 28% in 7 of 16, and reduced rate-corrected velocity of fiber shortening in 9 of 15. Afterload was elevated in 7 of 15. The mean forced vital capacity (FVC) preoperatively was 45.3 +/- 15.9% with continuing diminution to 28.7 +/- 14.9% at 3.3 +/- 2.2 years after surgery. The main benefit of surgical stabilization is the relative ease and comfort of wheelchair seating compared with those nonoperated patients who develop progressive deformity. We have not seen lasting improvement or stabilization in FVC following surgery as decreasing function is related primarily to muscle weakness.
Adolescent↗
Light and electron microscopic abnormalities in diastrophic dysplasia growth cartilage.
Light and electron microscopic studies of diastrophic dysplasia iliac crest growth cartilage performed on five occasions in two patients from 1 to 10 years of age reveal extensive cell and matrix abnormalities at each time period. Light microscopy shows atypical chondrocytes with extreme variation in size and shape, and premature cytoplasmic degeneration, and formation of target ghost cells. Prominent, densely staining fibrotic foci are present throughout the cartilage. Ultrastructure reveals some structurally intact chondrocytes with a single large fat inclusion, slightly dilated rough endoplasmic reticulum, and abundant glycogen. As early as 1 year of age cystic degeneration of chondrocyte cytoplasm is evident with indistinct organelles seen. The cartilage matrix demonstrates a general increase in fibrous tissue as well as the fibrotic foci. The collagen in these foci is remarkably abnormal. It is composed of short, extremely broad fibrils ranging from 150 to 950 nm in width which are separated at their terminal ends but fused to each other centrally in random fashion. On cross-section there are very few round fibrils but rather a marked irregularity in shape giving the appearance of having fibrils randomly added to others to form enlarged nonuniform fibril aggregates. On longitudinal sectioning, regular cross-banding across the entire fibril width is seen but fibril splitting and aggregation are highly irregular.(ABSTRACT TRUNCATED AT 250 WORDS)
Bone Diseases, Developmental↗
Locomotor problems in infantile facioscapulohumeral muscular dystrophy. Retrospective study of 9 patients.
A retrospective study of 9 patients with infantile facioscapulohumeral muscular dystrophy defines orthopedic deformities and progression. Patients presented in the early months of life with facial diplegia. Sensorineural hearing loss occurred in 8 out of 9 with a mean onset at 5 (2-9) years. Walking began at the normal time, but worsened progressively, which was due mainly to gluteus maximus muscle weakness. Scapular winging, extreme lumbar lordosis, and foot drop were characteristic. The majority of patients (in this and other series) lose walking ability in the second decade. Efforts to control lumbar lordosis by bracing while the patients were still walking were ineffective. Control of lumbar lordosis after the patients are wheelchair-dependent is important.
Adolescent↗
Exploring the molecular basis for variability among patients with Becker muscular dystrophy: dystrophin gene and protein studies.
Becker muscular dystrophy (BMD) often results from in-frame mutations of the dystrophin gene that allow production of an altered but partially functional protein. To address potential structure-function relationships for the various domains of dystrophin, we examined both the dystrophin gene and protein in 68 patients with abnormal dystrophin. Eighty-six percent of BMD patients with dystrophin of altered size have deletions or duplications, and the observed sizes of dystrophin fit well with predictions based on DNA data. Deletions within the amino-terminal domain I tended to result in low levels of dystrophin and a more severe phenotype. The phenotypes of patients with deletions or duplications in the central rod domain were more variable. This region can be divided into three portions based on differences in clinical presentations of patients. Deletions around exons 4553 were most common and generally caused typical BMD; however, phenotypic variability among patients with similar mutations suggests that epigenetic and/or environmental factors play an important role in determining the clinical progression. In contrast, deletions or duplications in the proximal portion of this domain tended to cause severe cramps and myalgia. Finally, loss of the middle of this region probably causes a very mild phenotype, as only one such patient was found and his only symptom was elevated serum creatine phosphokinase levels.
Adolescent↗
Posttraumatic growth-plate abnormalities: MR imaging of bony-bridge formation in rabbits.
The formation of a bony bridge across the growth plate was studied with magnetic resonance (MR) imaging, tomography, and histologic examination in 12 rabbits. Histologic studies performed 0-8 weeks after the creation of a defect in the physis demonstrated transphyseal bone formation with no evidence of cartilage repair. Gadolinium enhancement indicated the development of vascularity through the plate, which preceded the formation of a bony bridge. Enhancement was faint at 4 days after surgery, was inhomogeneous at 1 week, was maximal at 2 weeks, and decreased at 3 weeks and beyond as the lesion was replaced by bone. A dark rim representing bone deposition at the periphery of the lesion was seen at 2 weeks. At 4 weeks and beyond, the bridge was seen as a dark band of dense bone or as a wider area that was isointense with adjacent fatty marrow. Abnormality in the cartilage and development of transphyseal vascularity, which precede the formation of a bony bridge after trauma, can be detected with MR imaging.
Animals↗
Defective dystrophin in Duchenne and Becker dystrophy myotubes in cell culture.
We examined normal and dystrophic human myotubes in cell culture for expression of dystrophin, the protein product of the Duchenne muscular dystrophy locus. Dystrophin levels in developing myotubes detected by Western blotting increased after 24 hours and reached maximum levels after 10 days in fusion medium. We did not detect dystrophin in myotubes cultured from Duchenne myoblasts (7 cases). Myotubes from a Becker muscular dystrophy patient's biopsy produced a lower molecular weight (approximately 408 kd) dystrophin, which was the same size in a whole muscle preparation from the same biopsy. This 408-kd dystrophin was the expected size for this Becker patient whose DNA was deleted for exons 45-48 of the Duchenne gene. This cell culture system will allow a detailed analysis of the effects of potential pharmacologic agents on steady-state dystrophin levels.
Adult↗
MR imaging of fractures of the growth plate.
In order to assess whether MR imaging could be used to evaluate posttraumatic abnormalities of the growth plate cartilage, 28 MR imaging examinations of 26 physeal fractures were performed from 4 days to 2 years after injury. Twelve patients were studied within 6 months of the fracture. MR imaging changed the Salter-Harris classification in six. Interruption of the growth plate detected on T2-weighted images was associated with subsequent growth anomaly in six of eight patients. Horizontal fracture of the physis without interruption was associated with growth disturbance in only one of four patients. Sixteen growth plates were studied beyond 6 months after injury. Twelve had physeal bars and abnormal growth. Of four patients without physeal abnormality on MR imaging, two had normal growth and two had mild deformity. Our results show that MR imaging defects abnormalities in the cartilage that are associated with subsequent growth disturbances and provides accurate mapping of physeal bridging and associated growth abnormalities that have already occurred.
Adolescent↗
Comparison of patient and technique survival in continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis: a multicenter study.
Patient and technique survival were compared in adult patients new to continuous ambulatory peritoneal dialysis (CAPD) or (primarily) center hemodialysis (HD) in the time period 1981 to 1983, and followed-up in March 1985. Risk factors were identified at entrance into the study, and results were analyzed using Cox's proportional hazards model. For nondiabetic patients, the difference in survival which favored CAPD (relative risk = 0.62) was not significant at the 5% level (p = 0.08). Age was a significant risk factor in both groups. The average number of hospital visits was the same; however, CAPD showed a small but significant increase in average annual hospital days per year (10.14 vs. 9.18). For diabetic patients, there was no significant difference in survival between CAPD and HD. The CAPD group showed a significant increase in hospital visits (relative risk 1.81 vs. 1.40) and average hospital days per year (19.43 vs. 13.41). Both CAPD groups showed significantly higher treatment changeover rates.
Adult↗
Eye movement desensitization: a new treatment for post-traumatic stress disorder.
The use of saccadic eye movements for treating post-traumatic stress disorder is described. The procedure involves eliciting from clients sequences of large-magnitude, rhythmic saccadic eye movements while holding in mind the most salient aspect of a traumatic memory. This results in (1) a lasting reduction of anxiety, (2) changes in the cognitive assessment of the memory, and (3) cessation of flashbacks, intrusive thoughts, and sleep disturbances. The procedure can be extremely effective in only one session, as indicated by a previous controlled study and a case history presented here. It does not require a hierarchical approach, as in desensitization, or the elicitation of disturbingly high levels of anxiety over a prolonged period of time, as in flooding. Some speculations are offered concerning the basis for the effectiveness of the procedure.
Arousal↗
Non-apatitic environments in bone mineral: FT-IR detection, biological properties and changes in several disease states.
Resolution enhanced FT-IR spectroscopy shows that non-apatitic environments of phosphate and carbonate ions occur in bone mineral. The spectroscopic characteristics of these environments and their chemical and biological properties are reviewed. The potential effectiveness of FT-IR for the detailed study of bone mineral changes in bone disease is shown by analysis of several samples.
Animals↗
Variable osteoclast appearance in human infantile osteopetrosis.
A light and transmission electron microscopic (TEM) study of iliac crest metaphyseal bone from nine patients with infantile osteopetrosis demonstrates a variable spectrum of osteoclast abnormalities. All bone was obtained at biopsy before treatment. The average age at biopsy was 6 months with a range from 1 to 12 months. Osteoclast number was always increased and the cells were always appropriately positioned in relation to bone and cartilage. Osteoclast number, size, and nucleation varied from midly to markedly increased. In those with only a mild-to-moderate osteoclast increase, the marrow had an otherwise near-normal appearance with a good complement of hematopoietic cells. In those with markedly increased osteoclasts (hyperosteoclastic state) there were only scanty collections of hematopoietic cells. Light microscopic histomorphometry documented the percentage of bone and cartilage surfaces covered by osteoclasts. Controls from areas of greatest osteoclast presence documented a 5% coverage. One osteopetrotic patient registered a 4.8% value with all others elevated from 7.6 to 27.9%. Quantitative electron microscopy showed the ruffled border-clear zone complex to be absent or markedly diminished in seven of the nine patients. In two, however, osteoclast profiles had abundant ruffled border-clear zone complexes. Patients with the hyperosteoclastic bone marrow were more severely affected clinically. Light and TEM studies of marrow biopsies in initial assessment of osteopetrosis establish a baseline profile, may provide prognostic information, and allow for more meaningful treatment follow-up.
Child, Preschool↗
The Swedish medical care programs: an interim assessment.
The medical care program (MCP) concept emerged from a conviction that it would be possible to combine biomedical knowledge about a certain disease, principles of care and an efficient organization into a holistic approach to care. The purpose of the present review of nine MCPs was to: (1)provide and overview of MCP development and and evaluation in the Stockholm County; (2) present different perspectives regarding the current status of the MCP policy and future developments; and (3) contribute to a discussion of factors which enhance or block the effectiveness of MCPs. Information was gathered during interviews with 32 representatives of professionals and interest groups. The majority of MCPs were initiated by medical professionals while two, the program for alcohol disorders and that for rheumatoid diseases, were initiated by politicians or the rheumatoid patients. Three central problems were identified: (1) the original desire for standardization and the emergent demand for local variation; (2) ambiguities about specific roles of the newly developing general practitioners; and (3) lack of resources to develop, implement and evaluate MCPs to the standards of the original concept. The experience of the MCPs certainly has increased understanding of the policy-program-implementation-outcome process and inevitable gaps that materialize as policy struggles towards implementation.
Evaluation Studies as Topic↗
Cortical bone repair. The relationship of the lacunar-canalicular system and intercellular gap junctions to the repair process.
Repair of cortical bone was studied in 2.4-millimeter-diameter mid-diaphyseal femoral and tibial defects in young New Zealand White rabbits using light microscopy, transmission electron microscopy, and histomorphometry. The initial source of repair tissue is the marrow. Vessels grow into the defect, accompanied by undifferentiated mesenchymal cells. Woven bone is synthesized initially at the periphery of the defect on pre-existing cortex. Differentiating mesenchymal osteoblasts surround themselves with osteoid in a woven conformation. Once a scaffold has formed, surface osteoblasts align themselves in a regular array on the woven matrix surface and synthesize osteoid in a lamellar conformation. The long axes of the repair vessels, lamellae, and osteocyte lacunae are perpendicular to the long axis of the bone. Polarized-light microscopy showed maintenance of this pattern at six, eight, and twelve weeks, even when the defect was filled with lamellar bone. Remodeling is performed slowly by osteoclast cutting cones over a period of several months. The lacunar-canalicular system is clearly demonstrated in plastic-embedded, toluidine blue-stained sections. A canaliculus passes into or away from a lacuna every 1.9 micrometers over the entire osteocyte perimeter. Undifferentiated mesenchymal cells have no processes, as seen by transmission electron microscopy, but soon sprout a florid array of processes as differentiation to early mesenchymal osteoblasts proceeds. Osteoblast and osteocyte cell processes are packed with intermediate filaments that are continuous with those in the cell bodies. Intercellular gap junctions are seen between surface osteoblasts, between osteoblasts and underlying osteocytes, and between osteocyte cell processes in the canaliculi.
Animals↗
Longitudinal growth of the femur and tibia after diaphyseal lengthening.
Growth of the femur and tibia after lengthening of their diaphyses, which had been performed several years before skeletal maturity, was assessed in eighteen patients by serial orthoroentgenograms. The rate of growth of the lengthened femora, which had been congenitally short, increased after each of seven lengthening procedures, from an average preoperative rate of 82 per cent of the normal side to 90 per cent of the normal side. The amount of surgical lengthening was similar for the femora and the tibiae, averaging 18 per cent of the preoperative length of the bone in the femora and 20 per cent of the preoperative length of the bone in the tibiae. However, the rate of growth of the lengthened tibiae decreased after each of eleven lengthening procedures (six performed for a congenital short tibia; three, for patients who had Ollier's disease; one, for a patient who had poliomyelitis; and one, for a patient who had hemangiomas), from an average preoperative rate of 88 per cent of normal to an average of 64 per cent of normal.
Bone Lengthening↗