Biomedical subjects
Publications and source records attributed to J N Weinstein.
The goals of treatment of spine tumors should focus on: obtaining a definitive diagnoses through an appropriate biopsy or primary excision, institution of appropriate surgical or nonsurgical treatment as indicated by tumor type at the time of the initial procedure, preservation or restoration of normal neurologic function, and maintenance of spinal stability.
In order to document the differences in survival between patients with solitary plasmacytoma and those with multiple myeloma involving the spine, we have reviewed the cases of 12 patients with solitary plasmacytoma of the vertebral column treated at the University of Iowa and an additional 72 cases reported in the literature. All patients were followed for 2 years or more without evidence of disseminated disease. The mean disease-free interval for 84 patients was 76 months; 44% of the patients developed disseminated disease, 2-13 years after diagnosis. The 5-year, disease-free survival was 60%. In our study group, survival following dissemination was limited, with a mean of 17 months. This review of 84 cases of solitary plasmacytoma of the spine confirms the significantly greater survival of patients with solitary plasmacytoma, and supports the use of radiotherapy as the treatment modality of choice.
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The requirements for the induction of IL-2 receptor expression following lymphocyte stimulation in vitro are well understood but little is known about the role of IL-2 and the IL-2 receptor in lymphocyte activation in vivo. Following the subcutaneous injection of concanavalin A, cells from popliteal and lumbar lymph nodes draining the footpad became enlarged and expressed the IL-2 receptor. At the peak of the response, 9-15 hr after injection, more than 70% of all cells were IL-2 receptor positive; the majority were T cells of both Lyt-2+ and L3T4+ subsets. IL-2 receptor expression was closely associated with both spontaneous and IL-2-driven proliferation. Analysis of the biodistribution of 125I-labeled concanavalin A revealed that much of the injectate remains in the footpad injection site but the mitogen also accumulates in the draining lymph nodes and eventually in the major organs. This model of lymphocyte activation was used to demonstrate that in vivo cyclosporin A inhibits both IL-2 receptor expression and the induction of spontaneous proliferation.
This report addresses the long-term results of nonoperative treatment for fractures of the thoracolumbar spine. Forty-two patients meeting specified inclusion criteria were contacted and completed questionnaires. In all cases, nonoperative treatment was the only treatment received. The average time from injury to follow-up was 20.2 years (range, 11 to 55 years). The average age at follow-up was 43 years (range, 28 to 70 years). There were 31 men and 11 women in this series. Seventy-one percent of the injuries were the result of motor vehicle accidents. The most common sites of injury were T12-L2, which accounted for 64% of the injuries. Seventy-eight percent of the patients had no neurologic deficits at the time of injury. At follow-up, the average back pain score was 3.5, with 0 being no pain at all and 10 being very severe pain. No patient demonstrated a decrease in their neurologic status at follow-up, and no patient required narcotic medication for pain control. Eighty-eight percent of patients were able to work at their usual level of activity. Follow-up radiographs revealed an average kyphosis angle of 26.4 degrees in flexion and 16.8 degrees in extension. The degree of kyphosis did not correlate with pain or function at follow-up. Based on this review, nonoperative treatment of thoracolumbar burst fractures remains as a viable alternative in patients without neurologic deficit and can lead to acceptable long-term results.
The effect of a "pure" cyclic flexion bending moment on the three-dimensional load-displacement behavior of fresh ligamentous lumbar spine was investigated. The load-displacement behavior, for 11 L1-sacrum specimens, pre- and post-cyclic fatigue bending tests were quantified using a Selspot II system. A special fixture was designed to mount the specimen within the MTS system to administer "pure" cyclic flexion bending, under displacement control, for 5 hours. The testing was accomplished in a 100% humidity chamber at 0.5 Hz. The maximum cyclic bending moment, based on the literature dealing with loads experienced by the spine during activities involving lifting, was set at 3.0 Nm. An increase in motion of the order of 10% in the extension loading mode was observed. The increase in motion in other loading modes was not significant. In the extension loading mode, the increase in the anteroposterior displacement (retrodisplacement) in general was higher than the corresponding rotation component. The results suggest that the bending moment of low magnitude, usually experienced by the spine during activities of daily living, alone may not trigger the mechanical failure processes in the disc. The presence of high axial compressive loads on the disc seems to be the main contributing factor in this process. The presence of bending moments and axial twist along with axial compressive load may accelerate the unstable processes leading to low back pain.
Three-dimensional nonlinear finite element models of the intact L4-5 one motion segment/two-vertebrae and L3-5 two motion segments/three-vertebrae were developed using computed tomography (CT) films. The finite element mesh of the L4-5 motion segment model was modified to simulate bilateral decompression surgery. The mesh was further altered to achieve stabilization, using an interbody bone graft and a set of Steffee plates and screws. The model behavior of the intact specimen in all loading modes and of the stabilized model in compression, flexion, and extension modes were studied. The stresses in the cancellous bone region were found to decrease. The interbody bone graft, due to an overall decrease in stresses in the bone below the screw, transmits about 80% of the axial load as compared with 96% transmitted by an intact disc in an intact model. Thus, the use of a fixation device induces a stress shielding effect in the vertebral body. The results indicate that although the bone graft transmits lesser loads than the intact disc, it is active in transmitting loads. The presence of low stresses in the cancellous bone region and high localized stresses in the cortical pedicle region surrounding the screw, compared with the intact case, suggests that the screws are likely to become loose over time. The use of an interbody bone graft alone or in combination with any existing fixation device also induces higher stresses at the adjacent levels. This may be responsible for the adverse iatrogenic effects seen clinically.
The increased popularity of pedicle fixation prompted research to address two issues: the reliability and validity of roentgenograms as a technique for evaluating the success of pedicle fixation, and the effects of surgical factors on successful fixation. Thus, does approach--the point and angle of screw insertion, surgeon experience, practice, level of the spine involved, and screw size--effect success of pedicle fixation? Eight fresh thoracolumbar spines were harvested and cleaned of all soft tissues. Two surgeons, one more experienced in pedicle fixation than the other, used two pedicle fixation approaches (Weinstein and Roy-Camille) on both the left and right sides at levels T11-S1 of each specimen. All screws were placed under anteroposterior (AP) and lateral c-arm control. For specimens 1 to 3, 5.5 mm screws were used at T11-L1, and 7.0 mm screws at L2-S1. Unacceptable failure rates at L2 and L3 for the first three specimens resulted in a change of instrumentation for the remaining specimens, with 5.5 mm screws used at T11-L3 and 7.0 mm screws at L4-S1. When surgeons completed the fixations for a specimen, AP and lateral roentgenograms were taken and both surgeons independently evaluated the films to assess the success of each fixation. Failure was defined as evidence of any cortical perforation on any side of the pedicle in or outside of the spinal canal. After completing the roentgenogram evaluation, the specimen was transected in the midline, and the success of each pedicle fixation was evaluated by visual/tactile inspection. There were no disagreements between surgeons on the visual/tactile evaluations of the specimens.(ABSTRACT TRUNCATED AT 250 WORDS)
Epidural injection of steroid and local anesthesia can be used to treat low back pain. The injection is best performed with fluoroscopic control, with needle placement documented by means of a limited epidurogram. The technique was used in 116 patients; there were only three failures (2.5%) and one complication.
The extracorporeal shock wave lithotriptor (ECSWL) is a machine that generates shock waves that transfer energy through biologic materials. This study focused the wave at a composite bone-cement (polymethylmethacrylate) interface and evaluated the effects both quantitatively and qualitatively. Six matched sets of dog femora were selected. The intramedullary canals were packed uniformly with cement. One of the set was randomly selected for treatment with impulses while the other served as the control. The bone was then sectioned transversely into discs, and scanning electron microscopy and mechanical push-out studies were performed. The results indicated that the ECSWL does have a loosening effect on the bone-cement interface. Using a paired Student's t-test, the shear strength was significantly less in the treated group than in the control (p less than 0.003). Microscopically, the treated specimens revealed relative sparing of the surrounding bone. At the bone-cement interface, however, microfractures, loose bodies, and widening were seen. Revision total arthroplasty has a significant morbidity, which can be partially attributed to cement extraction. The results of this study indicate that the ECSWL may be a useful adjunct in revision surgery by facilitating the extraction of polymethylmethacrylate and thereby reducing the morbidity.
Serial gamma camera imaging was performed in 11 patients with cutaneous T-cell lymphoma after s.c. injection between the toes of 111In-labeled T101, a pan T-cell monoclonal antibody. Two of the patients also received 111In-labeled 9.2.27, an isotype-matched control monoclonal antibody. Three doses of T101 (0.1, 0.5, and 1.0 mg), coupled with 0.5 mCi 111In, were used to measure lymph node uptake and dose response. A single 0.5-mg (0.5 mCi) dose of 111In-9.2.27 was used as control antibody to assess nonspecific uptake. Low-dose (0.1 mg) T101 administration produced rapid, intense uptake in inguinal-femoral and iliac nodes with minimal uptake in the paraaortic nodes and liver. The 0.5-mg dose and higher produced consistent uptake in all subdiaphragmatic nodes with greatest accumulation of liver activity at the 1.0-mg dose. In the two control studies, the ratio of specific:nonspecific antibody uptake in the inguinal-femoral, iliac, and paraaortic nodes averaged 7.7,5.9, and 1.9 at 48 h, respectively. In another patient, inguinal-femoral node biopsy contained over 2% of the injected dose of 111In-T101 per gram at 7 days. These findings suggest efficient and specific antibody binding in nodes nearest to the injection site, with progressive uptake of remaining antibody in more distant nodes as proximal sites approach saturation. Higher doses increase overflow of unbound antibody into the systemic circulation. There appears to be an optimal s.c. dose of approximately 0.5 mg (0.25 mg/foot) for T101 immunolymphoscintigraphy of subdiaphragmatic lymph nodes in patients with cutaneous T-cell lymphoma.
Quantitative pharmacokinetic measurements of uptake and metabolism for two murine immunoglobulin G1 (IgG1) monoclonal antibodies (anti-Lyb8.2, MOPC-21) and their F(ab')2 and Fab' fragments were obtained following i.v. administration into C57BL/6 mice. Anti-Lyb8.2 antibody, reactive with the allelic Lyb8.2 murine B cell antigen, was labeled with 125I, and MOPC-21, an antibody with no known target antigen, was labeled with 131I. The two IgG or their fragments were co-injected, and all major organs were analyzed. Specific uptake of anti-Lyb8.2 IgG, F(ab')2, and Fab' was observed in the spleen with maximum peak values occurring at 1 to 2 hr. For MOPC-21, blood and organ kinetics was indicative of a nontargeted IgG molecule. The kidneys showed significant and rapid uptake of anti-Lyb8.2 and MOPC-21 Fab' fragments. This uptake by kidneys attenuated the maximum peak values of anti-Lyb8.2 Fab' in spleen. Multiexponential data fitting provided mean residence times (MRT) for each organ. The MRT for anti-Lyb8.2 in all organs were greater than those for its F(ab')2 and Fab' fragments. Only the kidneys showed greater MRT for Fab' than for F(ab')2. Blood, spleen, kidneys, and carcass exhibited substantial differences across fragments. When total body MRT for each fragment was compared with that of the respective parent IgG molecule, a progressive decline was observed. For MOPC-21, the decrease in total body MRT for F(ab')2 demonstrates the influence of the Fc portion of the molecule on IgG1 metabolism. This organ-by-organ data set may be pertinent to other monoclonal antibodies and their fragments and should help in optimizing delivery of these molecules to specific sites in vivo for immunologic and clinical purposes.
Despite improved resolution with new imaging techniques, surgical confirmation of mediastinal lymph node status is often required for reliable staging of patients with non-small cell lung cancer. Recent scintigraphic studies suggest that s.c. administration of radiolabeled antibodies can be more efficient than the i.v. route for targeting regional lymph nodes in animals and humans. To determine if this approach could be applied to the lymphatics of the lung, we injected both specific and irrelevant radiolabeled monoclonal antibodies via a flexible fiberoptic bronchoscope through the mucosa of lobar bronchi in normal dogs. The injected antibodies were expected to drain by way of local lymphatic vessels toward the central lymph nodes, in effect following the same pathway as do cells metastasizing to these nodes during early regional tumor dissemination. To accomplish this, anesthetized dogs were intubated and then coinjected with the two labeled antibodies [600 microCi/100 micrograms (total)] through a fiberoptic bronchoscope. The animals were serially imaged and then autopsied 14-36 h after injection. Individual hilar and carinal nodes contained over 1% of the injected 131I-labeled specific antibody dose and the average selectivity was 2.5:1 with respect to a coinjected irrelevant IgG. Distant organs (mesenteric lymph node, liver, spleen, bone marrow, and lung parenchyma other than the injection site) contained much less radioactivity, and those sites accumulated a greater fraction of the non-specific labeled antibody. The ratio of iodine-131 to iodine-125 counts between hilar/carinal lymph nodes and abdominal lymph nodes ranged from 15:1 to 100:1. These initial studies indicate efficient delivery of antibody to a subset of the regional nodes via pulmonary lymphatics. They suggest the feasibility of this technique which may be of use in the detection and perhaps therapy of human lung cancer metastases in regional lymph nodes.
Using data from 12 patients, we have analyzed the pharmacokinetics of 111In-9.2.27, an antimelanoma monoclonal antibody, following i.v. infusion. Plasma data and scintillation camera images obtained from patients receiving either 1, 50, or 100 mg of monoclonal antibody indicated dose-dependent (i.e., saturable) kinetics. Based on these observations and known immunoglobulin kinetics, we developed a nonlinear compartmental model to describe the biodistribution of 111In-9.2.27 and the other coinjected 111In-associated compounds. The model included (a) three compartments representing intact 111In-9.2.27 ("plasma," "nonsaturable," and "saturable binding" compartments), (b) four compartments representing 111In-diethylenetriaminepentaacetic acid, and (c) one compartment representing 111In in an undetermined chemical form ("extravascular delay" compartment). Analysis of the rate of urinary excretion relative to plasma concentration indicated that the saturable binding compartment was a site for catabolism of monoclonal antibody. Further examination of the urinary data, together with previous studies of the site(s) of immunoglobulin catabolism, suggested that additional elimination took place from either the plasma or the nonsaturable compartment. The model indicated that to fill the saturable sites would require a dose of approximately 0.5 mg and suggested that greater than 3.5 mg would maintain saturation for 200 h. Computer integration of gamma camera counts over the spleen revealed a clear saturable component of uptake, whereas integration over the liver showed no such pattern. The proposed model was fitted to the liver and spleen imaging data by summing fractions of model simulations of each compartment. That analysis confirmed the suspected saturable uptake by the spleen (21% of the saturable binding compartment) and revealed a quantitatively important component of saturation in the liver (35% of the saturable binding compartment) that was not obvious from initial examination of the images. When the results were expressed on a concentration basis, the spleen accounted for 247% of the saturable compartment per kg, whereas the liver accounted for 25%/kg. The bone marrow also showed saturable uptake; hence, the saturable uptake may relate to the sinusoidal blood supply characteristic of liver, spleen, and marrow. The model predicts the dose levels required to overcome saturable background, suggests appropriate doses and schedules for cold loading strategies, and provides a format for explicit inclusion of tumor antigen.
The tissue localization of a radiolabeled monoclonal antibody directed against a mouse Class I major histocompatibility antigen has been determined in mice following i.v. and s.c. administration. When labeled antibody was given s.c., radioactivity rapidly accumulated in regional lymph nodes draining the injection site, allowing visualization of the nodes by gamma camera imaging within minutes of injection. At 2 h after s.c. injection, radioactivity in regional nodes was present largely as intact antibody, but considerable degradation of antibody present in nodes was noted by 12 h after injection. Since little of the radioactivity reached the blood stream, visualization of regional nodes was possible for long periods after dosing. In contrast, antibody given i.v. showed no significant accumulation in lymph nodes at any time after dosing.
Ia molecule (Ek,b beta:Ek alpha or Ak beta:Ak alpha)-containing planar membranes were constructed with cholesterol and a 9:1 molar ratio of the phospholipids dipalmitoyl phosphatidylcholine and dilinoleoyl phosphatidylcholine. This lipid composition was found to be optimal for the stimulation of T cell hybridomas of different specificities. Use of this system allowed the detection of weak responses not measurable when other artificial membranes were used. Activation of the cytochrome c, Ek,b beta:Ek alpha-reactive hybridoma 2B4.11 using such membranes resulted in responses comparable to those found using antigen-presenting cells (APC); that is, similar amounts of IL-2 were produced at the same concentrations of antigenic peptides. Presentation of moth and pigeon cytochrome c peptides by Ek beta:Ek alpha- or Eb beta:Ek alpha-reconstituted membranes resulted in 2B4.11 response patterns similar to those previously described using B10.A or B10.A(5R) APC. These data conclusively demonstrate that differential stimulation by moth and pigeon cytochrome c peptides depends solely on structural differences in the E beta:E alpha molecules used for antigen presentation.
Little information is available regarding the long-term results of nonoperative treatment for fractures of the thoracolumbar spine. One thousand six hundred ninety-one fractures of the spine seen at the University of Iowa from 1935 to 1975 were reviewed; 83 fractures met strict inclusion criteria of fractures involving T10-L5. In all cases, nonoperative treatment was the only treatment received. 42 patients (51 per cent) were contacted and completed questionnaires. Twenty (48%) of these 42 patients also returned to University Hospital for a complete physical examination as well as anteroposterior and lateral flexion-extension radiographs. The average time from injury to follow-up was 20.2 years, (range 11-55 years). The average age at follow-up was 43 years (range 28-70). There were 31 men and 11 women. Seventy-one percent of the injuries were the result of motor vehicle accidents. The most common sites of injury were T12-L2, which accounted for 64% of the injuries; 78% of the patients had no neurologic deficits at the time of injury. At follow-up, the average back pain score was 3.5, (0 = no pain at all, and 10 = very severe pain). No patient demonstrated a decrease in neurologic status at follow-up, and no patient required narcotic medication for pain control. Eighty-eight percent of the patients were able to work at their usual level of activity. Follow-up radiographs revealed an average kyphosis angel of 26.4 degrees in flexion and 16.8 degrees in extension. The degree of kyphosis did not correlate with pain or function parameters in the 20 examined patients.(ABSTRACT TRUNCATED AT 250 WORDS)
To determine the long-term effects of lower lumbar fusion, 94 subjects were catalogued from medical records. They had a lumbar arthrodesis at the third lumbar level or below and their operations were performed before 1964. Twenty-four were not located and 8 were deceased. Sixty-two subjects (72% of available sample) completed a telephone interview; 52 subjects completed a comprehensive low back questionnaire; and 33 subjects returned for physical examination, flexion-extension lateral lumbar spine films, and a limited computerized axial tomographic (CAT) scan. In general, the subjects who returned for complete evaluation were representative of the larger sample. Forty of 62 patients were men. Ages ranged from 41 to 83 years; the median age was 66 years, 6 months. Follow-up ranged from 21 to 52 years; the median follow-up was 33 years. Forty-four percent (27/61) were currently experiencing low-back pain, 57% (35/61) had back pain in the last year. Fifty-three percent (33/62) were using medication. Fifteen percent (9/62) had undergone repeat lumbar surgery, however, only 5% (3/62) required surgery as a late sequela (more than 10 years postoperatively). Forty-two percent (14/33) had lumbar spinal stenosis, but only 15% (5/33) had dural tube measurements less than 100 mm2. Segmental instability above the fusion was present in 45% (15/33). There was a significant correlation between segmental instability and lumbar spinal stenosis (r = .57, P less than .01). Neither radiographic condition correlated with symptoms, however.(ABSTRACT TRUNCATED AT 250 WORDS)