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Biomedical subjects

S L Weinstein

Publications and source records attributed to S L Weinstein.

At least 19 recordsLinked to original sources

Bacterial lipopolysaccharide induces tyrosine phosphorylation and activation of mitogen-activated protein kinases in macrophages.

Bacterial lipopolysaccharide (LPS) is a potent activator of antibacterial responses by macrophages. Following LPS stimulation, the tyrosine phosphorylation of several proteins is rapidly increased in macrophages, and this event appears to mediate some responses to LPS. We now report that two of these tyrosine phosphoproteins of 41 and 44 kDa are isoforms of mitogen-activated protein (MAP) kinase. Each of these proteins was reactive with anti-MAP kinase antibodies and comigrated with MAP kinase activity in fractions eluted from a MonoQ anion-exchange column. Following LPS stimulation, column fractions containing the tyrosine phosphorylated forms of p41 and p44 exhibited increased MAP kinase activity. Inhibition of LPS-induced tyrosine phosphorylation of these proteins was accompanied by inhibition of MAP kinase activity. Additionally, induction of p41/p44 tyrosine phosphorylation and MAP kinase activity by LPS appeared to be independent of activation of protein kinase C, even though phorbol esters also induced these responses. These results demonstrate that LPS induces the tyrosine phosphorylation and activation of at least two MAP kinase isozymes. Since MAP kinases appear to modulate cellular processes in response to extracellular signals, these kinases may be important targets for LPS action in macrophages.

Amino Acid Sequence

Scoliosis in pediatric Chiari malformations without myelodysplasia.

A prospective study was undertaken in 1985 to better understand how the surgical manipulation of hindbrain herniation affected abnormal spinal curvature. Eleven patients under 16 years of age with Chiari malformation (not associated with myelodysplasia) and scoliosis of at least 15 degrees were studied. The mean curve angle at the time of original treatment was 29 degrees, with the convexity to the right in seven patients. The curvature was rapidly progressing in four patients. The most common presenting signs were myelopathy and weakness. Investigative procedures included spine radiographs with the patient standing and magnetic resonance (MR) imaging of the brain, spinal cord, and craniovertebral junction. Eight children had associated hydrosyringomyelia. Surgical intervention consisted of a dorsal posterior fossa decompression in all patients and a transoral ventral decompression of the cervicomedullary junction in five. All patients were followed at 3, 6, and 12 months, and at yearly intervals thereafter with clinical evaluations, spine radiographs in the standing position, and postoperative MR imaging. The mean follow-up period was 35 months. The scoliosis improved in eight patients, stabilized in one, and progressed in two. Only one child required postoperative spinal fusion and instrumentation for progression of scoliosis. Hematomyelia or hematobulbia was associated with persistent scoliosis in two patients. The presence of hydrosyringomyelia and bone erosion did not preclude curve improvement. All patients under 10 years of age had resolution of their scoliosis, despite preoperative curves of more than 40 degrees. These findings emphasize the importance of early surgical intervention, with the restoration of normal cerebrospinal fluid dynamics at the craniovertebral junction in children with symptomatic Chiari malformations.

Adolescent

Congenital hip dislocation. Long-range problems, residual signs, and symptoms after successful treatment.

In the treatment of congenital dislocation of the hip, reduction must be obtained and maintained to provide the proper stimulus for resumption of normal hip joint growth and development. Subluxation and avascular necrosis must be avoided, as degenerative joint disease is certain to occur. Acetabular dysplasia leads to degenerative joint disease with time, although no roentgenographic parameters are predictive. "Normal" hip joint anatomy may fail to develop, depending on the age of the patient at reduction and the growth potential of the acetabular cartilage. However, as normal anatomy as can be achieved should be restored at the age of maturity. This should provide the best possible mechanical environment to avoid exceeding the pressure tolerance level of the hip joint articular cartilage, thereby avoiding degenerative joint disease.

Hip Dislocation, Congenital

The weight-bearing abduction brace for the treatment of Legg-Perthes disease.

We reviewed the cases of thirty-one patients (thirty-four hips) who had had severe Legg-Perthes disease (Catterall group III, five hips and group IV, twenty-nine hips) and had been treated with a weight-bearing abduction orthosis, to determine the effectiveness of the brace. The mean age of the patients when they were first seen was six years (range, three to twelve years). The mean duration of follow-up was seven years (range, two to thirteen years). At the most recent follow-up, all hips were rated with the method of Mose and the classification of Stulberg et al. According to the criteria of Mose, no hip had a good result, twelve (35 per cent) had a fair result, and twenty-two (65 per cent) had a poor result. On the basis of the classification of Stulberg et al., there were fourteen (41 per cent) class-II results, eighteen (53 per cent) class-III and IV results, and two (6 per cent) class-V results. Although containment is the most widely accepted principle of treatment for patients who have Legg-Perthes disease, and the Atlanta Scottish Rite-type orthosis is the most commonly used orthosis for this condition, there are few clinical data supporting the effectiveness of this device. On the basis of our results, we do not recommend the use of a weight-bearing abduction brace for the treatment of severely involved hips.

Child

Bacterial lipopolysaccharide stimulates protein tyrosine phosphorylation in macrophages.

Lipopolysaccharide (LPS), a membrane component of Gram-negative bacteria, stimulates immune responses by activating macrophages, B lymphocytes, and other cells of the immune system. The mechanisms by which LPS activates these cells are poorly characterized. Since protein tyrosine phosphorylation appears to be a major intracellular signaling event that mediates cellular responses, we examined whether LPS alters tyrosine phosphorylation in macrophages. We found that Escherichia coli K235 LPS increased tyrosine phosphorylation of several proteins in the RAW 264.7 murine macrophage cell line and in resident peritoneal macrophages from C3H/HeSNJ mice. Changes in tyrosine phosphorylation were detectable by 4-5 min, reached a maximum by 15 min, and declined after 30-60 min. Protein tyrosine phosphorylation increased following stimulation with LPS at 100 pg/ml and was maximal with 10 ng/ml. Similar changes in tyrosine phosphorylation were induced by Salmonella minnesota R595 LPS and by the biologically active domain of LPS, lipid A, but not by the inactive lipid A derivative N2-monoacylglucosamine 1-phosphate. Phorbol 12-myristate 13-acetate also stimulated protein tyrosine phosphorylation, but some of the modulated proteins were different than those phosphorylated by LPS. Treatment of RAW 264.7 cells with a tyrosine kinase inhibitor, herbimycin A, inhibited both LPS-stimulated tyrosine phosphorylation and LPS-stimulated release of arachidonic acid metabolites. Thus, increased protein tyrosine phosphorylation is a rapid LPS-activated signaling event that may mediate release of arachidonic acid metabolites in RAW 264.7 cells.

Animals

Long-term follow-up of slipped capital femoral epiphysis.

The data on 155 hips in 124 patients who had slipped capital femoral epiphysis were retrospectively reviewed at a mean follow-up of forty-one years after the onset of symptoms. The slips were classified, by the duration of symptoms, as acute, chronic, or acute on chronic. As determined by the head-shaft angle, 42 per cent of the slips were mild; 32 per cent, moderate; and 26 per cent, severe. Reduction was performed in thirty-nine hips, and realignment was done in sixty-five hips. Treatment of chronic slips included symptomatic only in 25 per cent of the hips, a spica cast in 30 per cent, pinning in 24 per cent, and osteotomy in 20 per cent. The Iowa hip-rating and the radiographic classification of degenerative joint disease were determined at follow-up; both worsened with increasing severity of the slip and when reduction or realignment had been done. Osteonecrosis (12 per cent) and chondrolysis (16 per cent) also were more common with increasing severity of the slip and when reduction or realignment had been performed; both led to a poor result. Deterioration over time was most marked with increasing severity of the slip. The natural history of the malunited slip is mild deterioration related to the severity of the slip and complications. Techniques of realignment are associated with a risk of appreciable complications and adversely affect the natural history of the disease. Regardless of the severity of the slip, pinning in situ provided the best long-term function and delay of degenerative arthritis, with a low risk of complications.

Adolescent

The effects of contact pressure elevations and aseptic necrosis on the long-term outcome of congenital hip dislocation.

The relationship between excessive articular contact pressure, aseptic necrosis, and the long-term outcome with unilateral congenital dislocation of the hip (CDH) was studied in a series of 84 patients treated by closed reduction and followed for an average of 29.2 years. Contact stress was estimated from archived radiographs taken at the time of maturity and at several follow-up visits. At a recent review, each patient was rated both clinically for pain and function and radiographically for deformity, degeneration, and aseptic necrosis. For each of 431 archived films, articular contact stress (force/area) was estimated mathematically, based upon a frontal plane equilibrium (force) analysis and a landmark-based inference of three-dimensional head surface (area). Good correlation with final deformity (Spearman rho = 0.78) was obtained when the hips were ranked in terms of a new cumulative overpressure index Pc, defined as a time-pressure product involving years of pressure exposure beyond a 2 MPa pressure damage level. An unsatisfactory outcome occurred in 90.4% of the hips experiencing Pc greater than 10 MPa-years (most of which had aseptic necrosis involvement), whereas the outcome was satisfactory in 80.9% of hips with Pc less than 10 MPa-years.

Adolescent

Validity and reliability testing of the Scoliometer.

This study was designed to evaluate the Scoliometer, an instrument that measures axial trunk rotation in individuals with scoliosis. The objectives included determining 1) the Scoliometer's screening capability and validity and 2) the intrarater and interrater reliability of Scoliometer measurements. Scoliometer measurements made by two raters on 65 persons with idiopathic scoliosis were correlated with radiographic assessment of vertebral (pedicle) rotation and lateral curvature (Cobb method). Correlation ranged from .32 to .46 with pedicle rotation and from .46 to .54 with the Cobb angle. Frequency analysis revealed relatively good specificity, sensitivity, and predictive capability of the Scoliometer. Intrarater and interrater reliability coefficients were high (r = .86-.97). These results indicate good measurement reproducibility. The less-than-optimal between-method correlation coefficients suggest that the validity of Scoliometer measurements is not sufficient to use this method alone for determining patient diagnosis and management. Based on the positive-frequency analysis, however, the use of this tool as a screening device would be appropriate.

Adolescent

Compound muscle action potentials and spinal evoked potentials in experimental spine maneuver.

In this study, the authors evaluated the effects of spine manipulations, similar to those used in scoliosis surgery, on the compound muscle action potential (CMAP) and spinal evoked potential (SEP) in 25 cats: a distraction maneuver was performed in ten, a rotation in five, and a combined (distraction and rotation) procedure in ten cats. Compound muscle action potential was only minimally changed by the rotation maneuver alone in all five cats. Distraction resulted in earlier deterioration of CMAP than SEP; when CMAP was no longer elicitable in ten cats, seven still showed measurable SEP. All ten cats became paraplegic. With the combined procedure, both CMAP and SEP were abolished earlier than with distraction alone. This was observed in all ten cats becoming paraplegic. The authors further extended the study to ten rabbits having experimentally induced scoliosis. Following corrective surgery with distraction and derotation, eight rabbits lost both CMAP and SEP. Two lost CMAP with still recordable SEP. All ten rabbits became paraplegic. These findings suggest that monitoring CMAP is a more sensitive measure than SEP, and that the spinal cord is more vulnerable to a combined distraction and derotation maneuver than to either one alone.

Action Potentials

Adolescent idiopathic scoliosis: prevalence and natural history.

The natural history presented in this chapter applies only to AIS. Other types of scoliosis have their own natural history and associated problems that may significantly affect the ability of the patient to meet the demands of daily life. Increased public awareness and screening clinics have resulted in an increased number of children referred for orthopaedic opinion, less severe curve magnitude at initial detection, and earlier institution of treatment. Treatment of each patient must be individualized, taking into consideration the probability of curve progression based on curve magnitude, skeletal maturity, sexual maturity, and age (Table 6-7). Overdiagnosis and unnecessary treatment must be avoided. As our knowledge of the natural history of AIS expands, treatment decisions can be based on objective rather than subjective data. Any proposed treatment of this condition must have a reasonable chance of altering the natural history in a positive way. The information available on natural history has been accumulated on relatively small groups of patients and the conclusions presented represent generalities. There are probably many "natural histories" for AIS, especially with reference to curve progression; therefore, treatment decisions must be individualized. Long-term results of various treatments for scoliosis must take into consideration the natural history of the disorder.

Adolescent

[Idiopathic scoliosis in adolescence. Incidence and progression of untreated scoliosis].

Decision making in adolescent idiopathic scoliosis (AIS) requires a thorough knowledge of the natural history. Treatment decisions must be individualized based on the probabilities of progression. Any treatment for AIS must influence the "natural history" in a positive way. The natural history of AIS with reference to back pain, effects on pulmonary function, psychosocial effects, mortality, effect on pregnancy and risks of progression in the immature and mature patient are presented.

Adolescent

Dissociation of muscle action potentials and spinal somatosensory evoked potentials after ischemic damage of spinal cord.

In patients undergoing spinal fusion and Cotrel-Dubousset instrumentation we recorded compound muscle action potentials (CMAP) from the lower limb and spinal somatosensory evoked potentials (SSEP) from the caudal epidural space after direct stimulation of rostral spinal cord via epidural electrodes. In three of 30 patients tested, the derotation maneuver altered CMAP but not SSEP. In ten dogs, we observed similar dissociation with decrease or disappearance of CMAP amplitude and unchanged SSEP after ligation of the thoracoabdominal aorta or intercostal arteries at each level. In contrast, both CMAP and SSEP were unchanged by clamping the artery at the lumbar level. This is likely due to the lack of collateral vascular flow at the thoracic cord level, the anterior cord in particular, which is mainly supplied by a single large radicular artery (Adamkiewicz artery). These findings support that the CMAP and SSEP are mediated through two independent pathways located in the anterior and posterior spinal cord, respectively. We postulate that the dissociate alteration of CMAP and SSEP by derotation maneuver is due to greater vulnerability of the anterior cord or motor tract to ischemia caused by the displacement of anterior spinal or radiculomedullary artery. Therefore, the patients requiring major derotation procedure would benefit from CMAP monitoring, which provides more sensitive measure of anterior cord function that the conventional SSEP monitoring.

Action Potentials

The possible role of dopamine autoreceptors in neuroleptic atypicality.

Different brain pathways have been shown to subserve the therapeutic effects of neuroleptics and their extrapyramidal side effects. Agents which can discriminate between these pathways, therefore, might be able to produce 'atypical' clinical effects. Molindone, a novel neuroleptic of the indoleamine class, has been shown in basic paradigms to discriminate between brain dopaminergic systems by virtue of its ability to preferentially inhibit dopamine autoreceptors (DARs). Clinical studies suggest that molindone may be less likely than traditional neuroleptics to induce tardive dyskinesia and that molindone may preferentially ameliorate some negative schizophrenic symptoms. We suggest that the distinct clinical effects of molindone result from its ability to block DARs.

Animals

Spike osteotomy for angular deformities of the long bones in children.

We reviewed the results of fifty consecutive spike osteotomies that were performed in thirty-five children for the treatment of angular deformity of a long bone. After forty-three of the procedures, the radiographs were adequate to assess the stability of the fragments. At the time of healing, the average loss of correction from the position that had been accepted at operation was 2 degrees in the anterior-posterior plane and 1.2 degrees in the lateral plane. In four limbs, more than 5 degrees of correction had been lost. No patient lost more than 10 degrees of correction. The rates of complications and of recurrence were similar to those of other reported series. We concluded that the spike osteotomy is safe and effective.

Adolescent