Biomedical subjects
Publications and source records attributed to J V Luck.
The evaluation of musculoskeletal impairment and disability is an integral part of office practice in orthopedics. Proper performance of this function requires a clear understanding of the evolution and present structure of disability systems and the strengths and weaknesses of impairment rating methodologies.
During the working years, rheumatic conditions are the foremost cause of disability in the United States. Disability evaluation for Social Security applicants and Workers' Compensation patients is commonplace in orthopedic practices. Yet, formal education in this aspect of patient care is rare both during and after residency. Because of a lack of understanding and sophistication the physician who knows the patient better than any other evaluator often play a minor role in the determination of disability. Disability Evaluation Under Social Security--A Handbook for Physicians lists the medical criteria necessary for qualification. Severely disabled arthritis patients will not always fit into these various categories and may have to be considered under the rule of medical equivalency. Workers' Compensation statutes vary somewhat from state to state but generally include disability criteria. Familiarity with these criteria and the process involved will allow the orthopedist to communicate more meaningfully with administrators and will reduce much of the frustration and some of the cost inherent in this system. When subjective complaint (illness) is in excess of apparent organic pathology (disease), team evaluation under the direction of the treating physician will help sort out the dilemma and develop a treatment plan. One hopes that this will bring the illness more in line with the disease, and thus reduce the disability.
Wide resection is an acceptable alternative to amputation for the management of primary sarcomas of the long bones or pelvis. The resected bone can be debrided of gross tumor tissue, autoclaved, and then replaced over intramedullary fixation to reconstruct the limb anatomically. The procedure can be combined with prosthetic reconstruction of adjacent joints with sufficient strength to allow early unprotected weight-bearing. Resection and replacement for 28 low-grade (G1) and 14 selected high-grade (G2) sarcomas were performed in 42 patients. The hemipelvis was resected and replaced four times, the proximal or distal femur 28 times, the proximal or distal tibia eight times, and the proximal humerus two times. Replacement of an adjacent joint, most commonly using a long-stemmed hip or knee prosthesis, was accomplished in 33 patients. All patients had been followed for a minimum of two years, nine months after treatment. The mean follow-up period is four years, ten months. Six individuals, all with high-grade sarcomas, developed tumor-related complications. Two evidenced a local recurrence of tumor, and four developed distant metastases. None of the patients with low-grade sarcomas developed a recurrence or metastases. Fifteen patients suffered complications unrelated to tumor control; 13 required reoperation, including two who required amputations for persistent pseudoarthrosis and graft infection, respectively. There was one other infection, successfully eradicated by drainage followed by local and systemic antibiotics. Due to mechanical failure or loosening, six patients were treated by successful revision of their joint arthroplasties. Two years after initial surgery, five patients had failures of union at the graft-host junction. Four healed after cancellous grafting and one was revised to a custom prosthesis. There were no late fatigue fractures of the grafts. The technique does not compromise the margins for adequate tumor resection. It preserves a graft strong enough to support a joint arthroplasty and to allow early weight-bearing with a low risk of pseudarthrosis or late fatigue fracture.
From mid-1967 to mid-1983, three hundred fifty surgical operations were performed on 163 patients with hemophilia A, without factor VIII inhibitor. One death occurred, in a patient with a serious head injury. Postoperative hemorrhages occurred after 23% of operations, but the incidence after surgery on the knee, 40%, was decidedly higher than the 15% incidence after operations at other sites. Concurrent plasma factor VIII levels were over 0.40 units/mL in 72% of instances and under 0.30 units/mL in only 15% of instances. The incidence of postoperative hemorrhage did not change over the study period despite a threefold increase in typical dosage of factor VIII (from 600 to 2,000 units/kg per operation) and doubling of typical trough factor VIII levels (from 0.37 units/mL to 0.70 units/mL). Circulating factor VIII levels apparently are not the sole determinants of postoperative bleeding in hemophilia A.
Explore the source record for details and available documents.
Osteosarcoma (OS) is a malignant neoplastic disease of the bone, of mesenchymal origin and with considerable morphologic heterogeneity, consisting of malignant stoma with evidence of malignant osteoid, bone and/or cartilage production. The mammalian homeobox (HOX) represents a highly conserved DNA motif of 183 base pairs, encoding the 61 amino acid DNA-binding homeodomain, through which the HOX gene products regulate the transcription of other genes involved in onto- and histogenesis. Re-expression of HOX proteins has been identified in a wide variety of neoplastically transformed cell types and it seems that the HOX genes represent yet another family of oncofetal antigens involved in both normal development and oncogenesis, as well as tumor tissue progression. During this study, the expression pattern of three HOX gene products (HOX-C6, -B3, and -B4) was examined immunocytochemically in human osteosarcoma (OS) tissues. In all observed (16/16) OS cases, HOX-C6 was present in over 90% of the neoplastically transformed cells (+4), demonstrating a high to medium grade (A to B) staining intensity. Similar results were obtained in OS cells for the other two observed proteins (HOX-B3 and -B4; over 90% or +4 and a high to medium grade staining intensity or A and B). The significance of the expression of class I HOX proteins in the pathobiology, diagnosis and prognostication of human OS should be established by further investigations.
Parosteal osteosarcoma carries the best prognosis of all forms of osteogenic sarcoma. In our series of cases, adequate resection of low- and moderate-grade lesions has resulted in long-term survival without any evidence of residual disease. Small lesions of less than 5 cm diameter and low grade cellular atypism are treatable by an en bloc resection with 2.5 cm margins of normal bone. Larger lesions, of Grade I-II malignancy, are more successfully treated by a two-stage resection spaced six months apart. Recurrences of low-grade tumors are also successfully treated by this method. Grade III lesions, and all those with intramedullary involvement, should be treated by measures appropriate for other types of high-grade osteogenic sarcoma. Special problems encountered in resection surgery are managed by prevention of pathologic fracture, bone grafts, avoidance or repair of major neurovascular structures, and preservation of joint function.
Noninvasive, pulsed electromagnetic field treatment, when properly employed, was effective in securing healing of ununited fractures in 64.4% of 149 patients. The effectiveness of this modality can be ascertained after three months of intensive use in more than 85% of patients, thus enabling the clinician to decide to terminate treatment, continue electrostimulation, or abandon it in favor of another treatment modality. The success of treatment is dependent upon certain variables. Anatomic location of the nonunion is important. Higher healing rates were noted in the tibia than in the femur or humerus. In some conditions, combined electrostimulation and bone grafting was more effective than either measure alone. Young patients healed more rapidly than older patients. Electrostimulation is more effective when instituted within two years of the original fracture than when started at longer intervals after the injury. Infection, either quiescent or actively draining, does not seem to affect the overall results. Of greatest importance is patient adherence to the treatment protocol as outlined, with emphasis placed on adequate immobilization of the fracture and absolute nonweight-bearing during treatment. Considering these factors and in light of the very rare frequency of short-term side effects, the use of pulsed electromagnetic fields appears to be a reasonable choice of treatment in the management of ununited fractures.
Explore the source record for details and available documents.
During a systematic screening of melanoma infiltrating mononuclear and polynuclear immunological effector cells we employed 10 well characterized monoclonal antibodies, directed against leukocyte differentiation antigens, and the alkaline phosphatase conjugated, indirect, streptavidinbiotin immunocytochemical antigen detection technique and when necessary, the recently developed antigen retrieval method to enhance the intensity of the immunoreactivity to characterize the heterogeneous infiltrate of human primary (n = 30) and metastatic (n = 10) melanomas. Our study is the first to employ formalin fixed, paraffin embedded tissue sections in seeking to determine the ex vivo presence of tumor infiltrating leukocytes, including T lymphocytes, in human melanomas. We established the presence of some type of melanoma infiltrating host's immunological effector cells in all 40 observed melanoma cases'. More specifically, we found NK cells, macrophages and granulocytes in 30 out of 30 PMs and 10 out of 10 MMs. These effector cells represented the vast majority (> 80%) of the melanoma infiltrating immunocompetent cells. T lymphocytes were observed in 20 out of 30 PMs and 6 out of 10 MMs, but their numbers represented only between 5% to 10% of the heterogeneous leukocytic infiltrate. B cells were found in 22 out of 30 PMs and 8 out 10 MMs, their numbers representing less than 5%. Presence of cells of the dendritic reticulum, involved in antigen presentation was not determined in any of the observed PMs and MMs. There were more than enough macrophages and neutrophils, cells which are deeply involved in antigen presentation and, as previously mentioned, we found these cells within the melanomas. Thus defective antigen presentation cannot be the reason for the small proportion of T lymphocytes. What is to blame is probably the increased dedifferentiation of the melanoma immunophenotype (IP) to a degree that MHC class I molecules and the antigens complexed with them are lost and therefore there is nothing to be recognized by the T lymphocytes. In view of these results it is our-opinion that following the initial non-specific immune reaction, which may not be tumor specific, the specific immune response of effector T cells takes over. After significant IP changes by the majority of melanoma cells, including the internalization or shedding of MHC class I antigens, these highly specialized cells are no longer effective and the immune system responds by causing the reappearance of NK cells, macrophages and granulocytes. Thus, the relationship between melanoma and the host's immune system is evolutionarily dynamic: changes are readily made by either side when necessitated.
The phenomenon of multidrug resistance (MDR) is characterized by resistance to several unrelated cytotoxic agents, such as anthracyclines, vinca alkaloids and epipodophylline derivatives. MDR has been described frequently in human breast carcinoma (BC), as has the alteration of the p53 gene, responsible for ensuring the integrity of the genome. The most well known type of MDR is associated with the overexpression of a 170kD glycoprotein (p170). This mechanism of MDR is the result of increased transcription of the mdr 1 gene. The p170 glycoprotein in normal cells with excretory functions is a permanent component of a membrane transport system and an increase in its expression, such as that which occurs in neoplastically transformed cells, results in increased drug efflux and decreased intracellular drug concentration. The present immunocytochemical study was carried out on routine, formalin fixed, paraffin-wax embedded, 3-4 microns thick tissue sections of 15 breast carcinomas, treated at the University of Southern California. The immunoperoxidase antigen detection protocol, developed by Hsu et al (1981) was employed using three anti-p170 monoclonal antibodies (MoABs), JSB-1, C-219 and C-494 (Signet Laboratories, Dedham, MA, USA), and the anti-p53 MoAB PAb1801 (NeaMarkers, Inc., Fremont, CA, USA). 14/15 BCs contained large proportions of cells which displayed the characteristic transmembrane localized expression of p170. All 15 BCs were comprised of distinct groups of cells which accumulated p53 in their nucleus and occasionally in their cytoplasm. A distinct, heterogeneous immunophenotype (IP) of the cells comprising the tumor microenvironment and different grades of neoplastic differentiation was also observed. In 5/15 BC cases intense immunoreactivity, correlating with p170 overexpression, was detected. The 15 BCs exhibited different staining patterns typical for each anti-p170 MoAB. MoAB JSB-1 reacted strongly with the transmembranic antigen epitope, as did MoAB C-494, the long incubation time employed with MoAB C-219, on the other hand, resulted in inhomogeneous cytoplasmic staining. Previous reports suggest a direct correlation between the presence of the p170 glycoprotein in human cancer cells and the poor response to chemotherapy. Furthermore, the genetic instability, which is the consequence of the loss of wild-type p53 function, may be the underlying property which allows highly malignant cells to amplify the mdr 1 gene and thus become resistant to a wide spectrum of cytotoxic drugs.
Several growth factors and proto-oncogenes play a leading regulatory role during human carcinogenesis. In this systematic immunocytochemical study we observed the expression (overexpression) of the c-erbB-2 and c-erbB-3 oncoproteins in 30 primary cutaneous malignant melanomas (CMMs), 10 already metastasized malignant melanomas (MMMs) and 15 lymph-node negative breast carcinomas (BCs). Both oncoproteins were expressed as a result of either oncogene amplification or post-translational stabilization c-erbB-2 alone is unable to bind neuregulins, but it is able to act as a pan c-erbB receptor subunit. Heterodimerization between cerbB-2 and c-erbB-3 is required to initiate neuregulin directed signal transduction. We employed an indirect, four step streptavidinbiotin conjugated immunocytochemical technique for antigen detection. The visualization of the primary antigen-antibody reaction was carried out with alkaline phosphatase or immunoperoxidase labeling and the use of the appropriate enzymatic substrates. The presence of c-erbB-2 oncoprotein was detected in 12/30 CMMs, 8/10 MMMs and 6/15 BCs, while c-erbB-3 was identified in 14/30 CMMs, 7/10 MMMs and 6/15 BCs. The intensity of the cell membrane localized immunoreactivity was observed to be greater when the c-erbB-2 oncoprotein was targeted (A, AB and B). The c-erbB-3 oncoprotein was also detected in the cytoplasm with medium intensity (B, BC and C). Unfortunately, little is known concerning the range of oncoprotein overexpression after formalin fixation and paraffin embedding. We demonstrated overexpression localized to several cell clones within the oncoprotein positive population of malignant cells. The immunocytochemically defined extent of expression of both oncoproteins was between 10-40% (+ to +2) of the total cell population in the malignant melanomas and 20-35% (+2) of the total cell population in the BCs. In conclusion a) the results of the present study demonstrate the presence of c-erbB-2 and c-erbB-3 oncoprotein expression (overexpression) in melanoma and breast carcinoma, and b) oncogene receptor directed immunotherapy, as part of a more individualized anti-cancer treatment, represents a potentially valuable targeted treatment for the future.
When combining clinical examination, laboratory information and noninvasive imaging studies the differential diagnosis of bone lesions is narrowed. For those who are not experts in the field the major purpose of the IOC is to insure that adequate tissue has been obtained and to triage the tissue in the process preparing imprints, whenever possible; fixing some tissue for possible electron microscopic review; placing some tissue in B5 fixative for better cytologic detail; and to save some undecalcified tumor tissue in formalin in case immunostaining procedures are required. Most community pathologists should not be attempt to make an absolute diagnosis at the time of IOC, in many cases. The surgeon should always be warned that despite seeming benignancy 50% of primary bone tumors are malignant, that benign lesions can prove to be low grade sarcomas after full review, and vice versa that occasional cellular, "pleomorphic" lesions can be benign (aneurysmal bone cyst, early reparative and pseudosarcomatous lesions). Following review of the permanent sections, and other appropriate procedures an accurate diagnose is possible in the majority of cases. If the diagnosis is particularly difficult or questionable the above materials can be sent to a bone tumor specialist.