Biomedical subjects
Publications and source records attributed to R M Kay.
Retinoblastoma, though uncommon, frequently is associated with other second malignant neoplasms, especially bone sarcomas. These second neoplasms can occur in sporadic cases of retinoblastoma, though they more commonly are associated with genetic forms of the disease. This is the first known report of 2 histologically distinct bone sarcomas in a patient with retinoblastoma.
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Pigmented villonodular synovitis is a well-described disease that almost universally involves a single site. This is a report of an unusual case of multiple site involvement of pigmented villonodular synovitis in a child. In addition to multiple site involvement, the case is unusual for several reasons: asymmetric involvement, involvement of both upper and lower extremities, involvement of the pes anserine tendons, and the patient is an otherwise healthy child.
The results of all primary cemented total hip arthroplasties that were performed at UCLA Medical Center between 1974 and 1982 and had at least 1 year of follow-up evaluation were reviewed. Five hundred ninety-seven hips were implanted in 513 patients receiving a T28 (81%), a TR28 (16%), or a Charnley (3%) prosthesis (all from Zimmer, Warsaw, IN). The overall 15-year survival of the implants was 82%, although age at surgery was a strong predictor of implant failure (P < .001). The 15-year aseptic revision estimate was 37% in those patients younger than 50 at implantation, 17% in those patients aged 50 to 60 at implant surgery, and 4% in patients older than 60 at surgery. After adjustment for patient age, primary etiology was not significantly related to implant failure. Sepsis necessitated revision in 2.6% of the patients by 10 years. Lucencies throughout all three acetabular zones were noted in 45% of patients with long-term follow-up evaluation; however, this "radiographic loosening" was not a good indicator of impending clinical failure. (Only 49% of these components required revision in the ensuing 10 years following evidence of radiographic loosening.) The results for the younger patients are markedly inferior to those for older patients. Excellent results obtained with earlier prosthetic designs and cementing techniques make cemented hip arthroplasty a strong contender for the method of choice in the older patient.
Sows and gilts on a breeding and finishing unit seroconverted to porcine reproductive and respiratory syndrome (PRRS) virus between February and March 1992. The signs of the disease progressed through the breeding herd to the piglets, weaners, growers and finally the finishing pigs. Forty-eight finishing pigs, on a nutritional experiment in which the individual pigs' food intake was recorded daily, showed signs of PRRS and later of swine influenza virus infection. Blood samples collected at slaughter from 47 of the pigs were seropositive to PRRS virus but seronegative to swine influenza virus. However, an immunocytochemical examination of a representative sample of the lungs of the pigs showed that swine influenza virus was present, despite the negative serological results. The infection of the finishing pigs with PRRS virus was associated with recurrent periods of inappetence and a decline in growth rate and performance. The total financial loss from the sequential infection with the two viruses, in a herd without high health status, was estimated at approximately 7 pounds per pig.
We have generated transgenic mice that contain human-sequence Ig miniloci and, because they are also homozygous for a targeted disruption of their endogenous heavy chain genes, must rely on the transgene sequences for B cell receptor expression. Although the human transgenes contain only a fraction of the intact human heavy chain locus, these defined sequences are able to at least partially restore the humoral immune system in the mouse. B cells expressing human heavy chains develop in the bone marrow, populate peripheral lymphoid tissue and respond specifically to antigen. Furthermore, the heavy chain transgenes contain both human mu and gamma 1 coding exons as well as the respective mu and gamma 1 switch regions. The sequences included within the transgene are sufficient to direct class switch recombination. Transgene sequences are also sufficient to direct somatic mutation of the class-switched heavy chain genes. These observations define the upper limit of the cis-acting sequences necessary to direct heavy chain class switching and somatic mutation.
Diagnosis and treatment of avascular necrosis of the hip has long been predicated on the evaluation of plain radiographs, though other modalities (such as magnetic resonance imaging) are being increasingly used to aid in this evaluation. The Ficat classification is commonly used to assess plain radiographs and to help determine what treatment is appropriate for a given patient. It also is used to help evaluate patient outcome after surgical or nonsurgical treatment. This study was designed to evaluate the adequacy of plain radiographs in the evaluation of avascular necrosis of the hip. The plain radiographs of 25 hips with avascular necrosis were analyzed on 3 occasions by 6 readers (450 total readings). A clinically significant difference in radiographic staging was defined as a Stage I or II reading of the radiographs of a given hip on 1 reading and a separate reading of the same radiographs as Stage III or IV. By this definition, interobserver variability for the first reading resulted in clinically significant differences in 10 (40%) of the 25 hips. Intraobserver variability resulted in clinically significant differences for 10 (40%) of the 25 hips as well. The most experienced readers in the study (a total joint specialist and a musculoskeletal radiologist) were consistent internally in their readings in 90% of cases, and had a clinically significant difference in only 1 case (1%); however, these same 2 readers disagreed with one another on the staging of 9 (36%) of 25 hips, with 4 (16%) of 25 hips having a clinically significant difference in readings.(ABSTRACT TRUNCATED AT 250 WORDS)
Eighty seven patients with 88 fractures were retrospectively reviewed to assess the effect of postoperative prophylaxis on the formation of heterotopic ossification (HO). Sixty eight patients with 69 acetabular fractures were followed for an average of 21 months (range, 3-98 months). The grade of HO was assessed using the Brooker classification system. Thirty four fractures had no prophylactic treatment, 30 were treated prophylactically with indomethacin, two with radiation therapy, and three with both indomethacin and radiation. Twenty (59%) of 34 untreated fractures developed HO, of which nine (26%) were Grade III or IV. Thirteen (43%) of 30 fractures treated with indomethacin developed HO, of which 5 (16%) were Grade III and none were Grade IV. Twenty one of 24 fractures were stabilized through the extended iliofemoral approach; 13 of these had no prophylaxis. Eleven of the 13 developed HO; eight were Grade III or IV (62%). Seven of eight fractures treated with indomethacin following the extended iliofemoral approach developed HO; one was Grade III (13%) and non Grade IV. There was no significant difference between 13 patients who were not treated prophylactically and 18 indomethacin treated patients stabilized through the Kocher-Langenbeck approach. Only one of 11 patients had HO (Grade I) following an ilioinguinal approach. Postoperative radiation therapy, with or without indomethacin, resulted in three patients with Grade 0 HO (all radiated 1-4 days post surgery), one with Grade II (radiated postoperative Day 8), and one with Grade III HO (significant delay in surgery with preoperative Grade III HO of the hip).(ABSTRACT TRUNCATED AT 250 WORDS)
Benign giant cell tumor of bone, despite being classified as benign, has the unusual ability to metastasize. Metastasis of such a tumor has been thought to be rare, with only approximately 50 such cases having been reported. However, as awareness of the metastatic potential of these tumors has increased, and methods of detection have improved, metastasis of benign giant cell tumor has been increasingly recognized. Six patients with pulmonary metastasis of giant cell tumor have been treated at a Los Angeles hospital since 1980. This represents 9.1% of all patients treated for benign giant cell tumor of bone over the same period at this institution, a higher rate than that encountered in previously published series. The early detection and treatment of this tumor is important, because those with complete resection of tumor have the best prognosis. The nature of these pulmonary metastases remains unpredictable, however, as evidenced by two of the cases in this series: one of spontaneous regression, and another of death caused by pulmonary failure.
A custom-designed, hydroxyapatite-coated distal femoral replacement was developed and implanted in five individuals at the authors' hospital. The indications for this type of prosthesis were a multiply failed cemented endoprosthesis in two individuals; a revision of an infected, previously cemented endoprosthesis in another; a primary low-grade sarcoma in a fourth, and a stage III giant cell tumor in the final individual. Mean follow-up time was 3.3 years (range, 2.9-3.5 years). The functional results, based on the Musculoskeletal Tumor Society (MSTS) criteria, were excellent in one patient (20%) and good in four patients (80%). Musculoskeletal Tumor Society functional scores ranged from 25 to 35 (mean, 29.8). No patient had thigh pain. All the femoral components appeared well fixed on radiographic evaluation. These preliminary results indicate that a hydroxyapatite-coated distal femoral replacement may represent a viable alternative to a cemented endoprosthesis for aggressive benign lesions and low-grade sarcomas requiring resection. In addition, it appears to be a viable solution for failed cemented endoprostheses in individuals who have survived their disease.
A successful case of total elbow allograft after removal of a twice-failed total elbow prosthesis is reported. The patient, a disabled 63 year old at the time of allograft implantation, can now perform all activities of daily living, including household chores. Both the humeral and ulnar allografts have incorporated, and there is no evidence of degenerative changes or allograft resorption two years nine months postoperatively.
Although previously unreported in the orthopaedic literature, hepatocellular carcinoma metastasizes to bone in 2 to 20% of cases. The poor prognosis associated with this tumor often results in patient demise before the need for orthopaedic intervention. A liver transplant recipient with no known history of hepatocellular carcinoma was diagnosed with this tumor when open reduction and internal fixation of an impending pathologic femoral fracture were performed. Metastatic hepatocellular carcinoma should be considered in the differential diagnosis of a lytic osseous metastasis in appropriate patient populations.
We have developed a method for the introduction of yeast artificial chromosomes (YACs) into transgenic mice. An 85 kilobase (kb) fragment of the human heavy chain immunoglobulin gene was cloned as a YAC, and embryonic stem cell lines carrying intact, integrated YACs were derived by co-lipofection of the YAC with an unlinked selectable marker. Chimaeric founder animals were produced by blastocyst injection, and offspring transgenic for the YAC were obtained. Analysis of serum from these offspring for human heavy chain antibody subunits demonstrated expression of the YAC-borne immunoglobulin gene fragment. Co-lipofection may prove to be a highly-successful means of producing transgenic mice containing large gene fragments in YACs.
We have generated transgenic mice that express a diverse repertoire of human sequence immunoglobulins. The expression of this repertoire is directed by light and heavy chain minilocus transgenes comprised of human protein coding sequences in an unrearranged, germ-line configuration. In this paper we describe the construction of these miniloci and the composition of the CDR3 repertoire generated by the transgenic mice. The largest transgene discussed is a heavy chain minilocus that includes human mu and gamma 1 coding sequences together with their respective switch regions. It consists of a single 61 kb DNA fragment propagated in a bacterial plasmid vector. Both human heavy chain classes are expressed in animals that carry the transgene. In light chain transgenic animals the unrearranged minilocus sequences recombine to form VJ joints that use all five human J kappa segments, resulting in a diversity of human-like CDR3 regions. Similarly, in heavy chain transgenics the inserted sequences undergo VDJ joining complete with N region addition to generate a human-like VH CDR3 repertoire. All six human JH segments and at least eight of the ten transgene encoded human D segments are expressed. The transgenic animals described in this paper represent a potential source of human sequence antibodies for in vivo therapeutic applications.
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Clones of complementary DNA encoding the human lymphokine known as granulocyte-macrophage colony-stimulating factor (GM-CSF) were isolated by means of a mammalian cell (monkey COS cell) expression screening system. One of these clones was used to produce recombinant GM-CSF in mammalian cells. The recombinant hematopoietin was similar to the natural product that was purified to apparent homogeneity from medium conditioned by a human T-cell line. The human T-cell GM-CSF was found to be 60 percent homologous with the GM-CSF recently cloned from murine lung messenger RNA.
Limited information is available on the mechanism by which changes in nutrient intake influence plasma lipids. We compared the effects on plasma lipoprotein levels of 3 dietary modifications involving changes in total fat intake (27-40% of calories), cholesterol intake (100-250 mg/1000 kcal), the dietary polyunsaturated to saturated fatty acid ratio (0.3-1.0) and intake of vegetable-derived fiber and protein. On these 3 diets, plasma low density lipoprotein was reduced by 26-34%. Fecal bile acid excretion was similar on all diets (363-379 mg/day). There was no alteration in fecal bile acid output associated with an increase in polyunsaturated or total fat intake. Sterol balance became significantly more negative during consumption of only 1 of the 3 cholesterol-lowering diets. The observed reduction in plasma cholesterol levels was not associated with an increase in fecal bile acid output suggesting that diet-induced changes in circulating cholesterol are not maintained by an increase in sterol turnover but may reflect alterations in hepatic cholesterol and lipoprotein synthesis.