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Biomedical subjects

S L Weinstein

Publications and source records attributed to S L Weinstein.

At least 55 records · Page 3Linked to original sources
PubMed1995

Packed red cells in acute blood loss: dilutional coagulopathy as a cause of surgical bleeding.

The purpose of this study was: 1) to define coagulation abnormalities in patients who receive red cell concentrates rather than whole blood for large volume blood loss (greater than 0.5 blood volume); and 2) to determine when coagulation abnormalities lead to increased bleeding in the massively transfused surgical patient. We studied 32 ASA physical status I or II patients (mean age 15.6 +/- 2.3 yr) who lost more than 50% of their blood volume during elective posterior spinal stabilization. Crystalloid solutions and packed red cell concentrates were used to replace blood and fluid losses. Invasive hemodynamic measures, urinary output, and serial hematocrit determinations were used to help maintain a constant intravascular volume and confirm the estimates of blood loss. The quality of hemostasis was assessed during operation. In 15 of the 32 patients, surgical hemostasis remained effective throughout posterior spinal fusion. A coagulation profile (prothrombin time [PT] and activated partial thromboplastin time [aPTT], platelet count, and fibrinogen) was measured at the conclusion of operation in these patients. In 17 patients, increased surgical bleeding as a result of decreased clot formation and increased bleeding from the wound was present. In these 17 patients at the time increased bleeding was diagnosed, hemostatic tests (PT, aPTT, fibrinogen, platelet count, and coagulation factor assays V, VIII, and IX) were obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Examination of the role of MAP kinase in the response of macrophages to lipopolysaccharide.

Although the mechanism by which macrophages and other mammalian cells recognize LPS is still only partially understood, there has been considerable recent progress in unraveling the mechanisms by which putative cell surface LPS receptors transmit information of ligand binding to the interior of the cell. In macrophages, LPS induces protein tyrosine phosphorylation of a handful of proteins. We have identified two of the more prominent phosphorylated proteins as p42 and p44 MAP kinases. In addition, we have examined the role of MAP kinases in the macrophage response to LPS by utilizing a regulatable form of Raf-1 to activate MAP kinases independently of LPS. These experiments suggest that MAP kinases participate in LPS signaling, but also demonstrate that activation of MAP kinases cannot account for all of the intracellular events triggered by LPS. Therefore LPS must activate other signaling events that contribute to NF-kappa B activation and TNF-alpha mRNA accumulation and protein secretion.

Animals↗
PubMed1994

The long-term functional and radiographic outcomes of untreated and non-operatively treated metatarsus adductus.

Thirty-one patients (forty-five feet) who had metatarsus adductus were evaluated at our institution and were followed for an average of thirty-two years and six months. Of these thirty-one patients, twenty-one (thirty-one feet) were examined clinically and radiographically. Information on the remaining ten patients (fourteen feet) was obtained by letter or telephone, or both. Twelve patients (sixteen feet) who had a passively correctable deformity (mild or moderate) at the time of the initial presentation had no treatment. Twenty patients (twenty-nine feet) who had a partly flexible or rigid deformity (moderate or severe) at the time of the initial presentation were managed with serial manipulation and application of plaster holding casts. (One patient who had a bilateral deformity had no treatment on one side and conservative management on the other). The results were good in all sixteen of the untreated feet and in twenty-six (90 per cent) of the twenty-nine feet that had been conservatively treated. There were no poor results. The passively correctable deformities resolved spontaneously. Radiographs showed an obliquity of the medial cuneiform-metatarsal joint in twenty-one (68 per cent) of the thirty-one feet that were examined clinically and radiographically. Similar findings were observed in four of eleven contralateral, normal feet. Hallux valgus was not a common outcome. No patient had operative correction.

Activities of Daily Living↗
PubMed1994

Closed reduction for congenital dysplasia of the hip. Functional and radiographic results after an average of thirty years.

The functional and radiographic results of closed reduction in 152 congenitally dislocated hips of 119 patients who had been managed between 1938 and 1969 were reviewed retrospectively. The average age of the patients at the time of the reduction was twenty-one months (range, one to ninety-six months). At the time of the latest follow-up evaluation, the average age was thirty-one years (range, sixteen to fifty-six years). The average duration of follow-up was thirty years (range, fifteen to fifty-three years). At the latest follow-up evaluation, the Iowa hip rating averaged 91 points (range, 38 to 100 points) and the Harris hip score averaged 90 points (range, 33 to 100 points). Thirty-five hips were rated Severin Class I; thirty-five, Class II; twenty-eight, Class III; fifty-three, Class IV; and one, Class VI. Disturbance of growth in the proximal end of the femur occurred in ninety-one hips (60 per cent). Eight contralateral hips that had appeared normal also demonstrated disturbance of proximal femoral growth. In many hips, partial physeal arrest could not be determined for ten to twelve years after the reduction. Seventeen hips (twelve patients) had a total replacement when the patients were an average age of thirty-six years (range, nineteen to fifty-three years). Sixty-five hips (43 per cent) had radiographic evidence of degenerative joint disease. Patients who did not have a growth disturbance of the proximal end of the femur or evidence of subluxation tended to function extremely well for many years despite a radiographic result that was less than anatomical. Function tended to deteriorate with time, even in the absence of disturbance of growth in the proximal end of the femur. Despite generally good function at the latest follow-up evaluation, the prognosis for these patients remained guarded.

Adolescent↗
PubMed1993

Lipopolysaccharide-induced protein tyrosine phosphorylation in human macrophages is mediated by CD14.

Induced protein tyrosine phosphorylation is an early intracellular event in LPS-stimulated murine macrophages that appears to play a role in signal transduction. We have now demonstrated that LPS also increases protein tyrosine phosphorylation in human monocyte-derived macrophages and in the human monocytic cell line, THP-1. This response was rapidly elicited by biologically active forms of LPS or lipid A, at concentrations of these bacterial components that stimulate anti-bacterial responses by human macrophages. Inhibition of the LPS-induced tyrosine phosphorylation response with the tyrosine kinase inhibitor, herbimycin A, was accompanied by the inhibition of the secretion of TNF-alpha by human macrophages. These results extend previous work with murine macrophages and provide further support for the hypothesis that induced protein tyrosine phosphorylation is an important signaling reaction in macrophages after LPS exposure. In addition, CD14, which is thought to be a receptor for LPS, appeared to mediate the induced phosphorylation response in human macrophages and THP-1 cells at low LPS concentrations. Two antibodies against CD14, 3C10 and 60b, which have been shown to prevent LPS binding to CD14, specifically inhibited the protein tyrosine phosphorylation induced by nanogram per milliliter concentrations of LPS in these cells. The antibody-mediated inhibition did not appear to involve engagement of surface FcR because a preparation of F(ab')2/Fab fragments of the 60b antibody also prevented LPS-induced tyrosine phosphorylation. At higher concentrations of LPS (> or = 10 ng/ml), however, anti-CD14 antibodies did not prevent the induction of protein tyrosine phosphorylation, suggesting that a lower affinity CD14-independent pathway also mediates the tyrosine phosphorylation response. Because CD14-dependent and CD14-independent recognition of LPS appear to lead to the same functional responses by macrophages, induced protein tyrosine phosphorylation may be part of a shared intracellular signaling pathway.

Antigens, CD↗
PubMed1993

Duchenne muscular dystrophy: deficiency of dystrophin-associated proteins in the sarcolemma.

Dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene, is a major component of the subsarcolemmal cytoskeleton and exists in a large oligomeric complex tightly associated with several sarcolemmal glycoproteins which provide a linkage to the extracellular matrix protein, laminin. In the present study, we investigated the status of the dystrophin-associated proteins in the skeletal muscle from 17 DMD patients of various ages. The results revealed a dramatic reduction in all of the dystrophin-associated proteins in the sarcolemma of DMD muscle compared with normal muscle and muscle from a variety of other neuromuscular diseases. This abnormality was common in all 17 DMD patients, irrespective of age. Our results indicate that the absence of dystrophin leads to the loss in all of the dystrophin-associated proteins, which renders DMD muscle fibers susceptible to necrosis. The analysis of dystrophin-associated proteins is important in the assessment of experimental therapies that attempt to replace dystrophin in DMD muscle.

Adolescent↗
PubMed1993

The natural history and long-term follow-up of Scheuermann kyphosis.

Sixty-seven patients who had a diagnosis of Scheuermann kyphosis and a mean angle of kyphosis of 71 degrees were evaluated after an average follow-up of thirty-two years (range, ten to forty-eight years) after the diagnosis. All sixty-seven patients completed a questionnaire; fifty-four had a physical examination and radiographs; fifty-two, pulmonary function testing; and forty-five, strength-testing of the trunk muscles. The results were compared with those in a control group of thirty-four subjects who were matched for age and sex. The patients who had Scheuermann kyphosis had more intense back pain, jobs that tended to have lower requirements for activity, less range of motion of extension of the trunk and less-strong extension of the trunk, and different localization of the pain. No significant differences between the patients and the control subjects were demonstrated for level of education, number of days absent from work because of low-back pain, extent that the pain interfered with activities of daily living, presence of numbness in the lower extremities, self-consciousness, self-esteem, social limitations, use of medication for back pain, or level of recreational activities. Also, the patients reported little preoccupation with their physical appearance. Normal or above-normal averages for pulmonary function were found in patients in whom the kyphosis was less than 100 degrees. Patients in whom the kyphosis was more than 100 degrees and the apex of the curve was in the first to eighth thoracic segments had restrictive lung disease. Five patients had an unexplained, mildly abnormal neurological examination. Mild scoliosis was common; spondylolisthesis was not observed.

Activities of Daily Living↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗