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Biomedical subjects

F Shapiro

Publications and source records attributed to F Shapiro.

At least 19 recordsLinked to original sources

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

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

Gross and histological abnormalities of the talus in congenital club foot.

Gross and histological abnormalities were demonstrated in a club-foot talus from a boy with multiple congenital anomalies who died when he was nine days old. Both tali were studied, the one from the club foot and the one from the normal foot. The gross anomalies involved the smaller size of the club-foot talus and the increased medial deviation of a stunted, misshapen head and neck region. Serial histological sections of both tali allowed for a three-dimensional geometric appreciation of both bones and an assessment of the nature and extent of histological and cytological features. The ossification center of the club-foot talus was absolutely and relatively smaller than that of the normal talus. It was eccentrically positioned, being more lateral and anterior than that of the normal talus. The marked histological abnormalities seen in the head and neck region of the club-foot talus involved extensive breaching of the endochondral sequence by vessels. The posterior aspect of the endochondral sequence and ossification center was normal. The extra-osseous and intra-osseous blood supply of the two tali was normal with the exception of the increased and irregular breaching of the endochondral sequence in the club-foot talus. This study demonstrates histological abnormalities in the head and neck region of the club-foot talus, which was most abnormal grossly. The eccentric position of the secondary ossification center as well as its related vascular abnormalities do not support a theory of developmental arrest of the talus but appear sufficiently abnormal to support the theory of a primary defect in the cartilage anlage. Clinically, one must bear in mind that early open reduction of the talocalcaneal navicular joint in a foot such as this would have served to reposition the navicular onto a talus that still was structurally abnormal.

Clubfoot

Dietary management of patients with diabetes treated by hemodialysis.

Early experience with the treatment of patients with insulin-dependent diabetes and renal failure by chronic hemodialysis indicated a high mortality and increased incidence of medical complications. Since 1972, a marked improvement in survival and reduction in incidence of complications has been attributed to more rigorous control of fluid overload, hypertension, and blood sugar levels by insulin therapy and careful dietary management. A diet has been developed which combines the diet used by dialysis patients with suitable modifications for the insulin-dependent patient with diabetes. The importance of patient education is stressed in an attempt to improve patient compliance.

Diabetes Mellitus

Unsolved technical problems of maintenance dialysis.

The present paper describes some of the technical inadequacies in the clinical practice of dialysis. Problem areas of hemodialysis, i.e., those related to blood access, dialyzer and delivery system, are treated in depth. Corollaries with peritoneal dialysis are obvious. Research priorities, in particular development of a more sophisticated delivery system, are suggested. The intent of this discussion is to outline a rational progression in improvement of care of the end-stage renal disease patient.

Kidneys, Artificial

Organization and cellular biology of the perichondrial ossification groove of ranvier: a morphological study in rabbits.

The perichondrial ossification groove of Ranvier, a circumferential groove in the periphery of the epiphyseal cartilage, was studied in rabbits whose ages ranged from one week to eight months using light and electron microscopy, autoradiography after labeling with 3H-thymidine, 3H-proline, and 3H-glucosamine, and histochemical staining for proteoglycans and alkaline phosphatase. By these methods, three groups of cells were identified within the groove: 1. A group of densely packed cells deep in the groove, which are the progenitor cells for the osteoblasts that form the bone bark, a cuff of bone surrounding the epiphyseal growth-plate region and the adjacent part of the metaphysis. 2. A group of more widely dispersed, relatively undifferentiated mesenchymal cells and fibroblasts, some of which are chondroblast precursors that probably contribute to appositional chondrogenesis and growth in width of the epiphyseal cartilage. 3. Fibroblasts and fibrocytes among sheets of highly oriented and organized collagen fibers which form a fibrous layer that is continuous with the outer fibrous layer of the periosteum and with the perichondrium. This layer also sends fibers into the epiphyseal cartilage and anchors the periosteum firmly to the epiphyses as bone growth proceeds.

Animals

Carbenicillin inactivation of aminoglycosides in patients with severe renal failure.

Carbenicillin appears to produce clinically important inactivation of aminoglycoside antibiotics in patients with severe renal failure. If combination carbenicillin/aminoglycoside therapy is used in patients with severe renal failure, the dose of carbenicillin must be adjusted to renal function and serum levels of both drugs should be monitored. Even with therapeutic serum carbenicillin levels (100-200 mug/ml), large doses of aminoglycosides may be required to achieve therapeutic serum levels and this may increase the risk of toxicity.

Aged

The Mitchell distal metatarsal osteotomy in the treatment of hallux valgus.

Many of the fair and poor results are directly traceable to errors in technique. Patient selection is also important. The operation can be done in adolescents since there is no growth plate at the distal end of the first metatarsal. We do not currently recommend this procedure for those over 60, for those with first metatarsophalangeal osteoarthritis or hallux rigidus or for those with moderate or severe rheumatoid arthritis. For these patients we usually do a Keller excisional arthroplasty. Our use of the osteotomy-bunionectomy operation for the patient with hallux valgus with an associated metatarsalgia or short first metatarsal has now become more cautious. We feel that the operation is not indicated for those with significant preoperative metatarsalgia, especially if the first metatarsal is shorter than the second, or for those whose first metatarsal is more than 4 or 5 millimeters shorter than the second, regardless of preoperative metatarsalgia. In these patients a McBride procedure or a proximal opening-wedge osteotomy is done.

Adolescent

Medical services at outdoor music festivals. Risks and recommendations.

Those planning provision of medical services should consider the type of music, the anticipated size of the crowd, the locale, the available local resources, the length of the festival, the numbers and types of patients to be treated, and especially the potential criminal and civil liability.

Emergency Medical Services