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Biomedical subjects

L Peterson

Publications and source records attributed to L Peterson.

At least 19 recordsLinked to original sources

Immature porcine knee cartilage lesions show good healing with or without autologous chondrocyte transplantation.

OBJECTIVE: The purpose of this study was to find out how deep chondral lesions heal in growing animals spontaneously and after autologous chondrocyte transplantation. METHODS: A 6mm deep chondral lesion was created in the knee joints of 57 immature pigs and repaired with autologous chondrocyte transplantation covered with periosteum or muscle fascia, with periosteum only, or left untreated. After 3 and 12 months, the repair tissue was evaluated with International Cartilage Repair Society (ICRS) macroscopic grading, modified O'Driscoll histological scoring, and staining for collagen type II and hyaluronan, and with toluidine blue and safranin-O staining for glycosaminoglycans. The repair tissue structure was also examined with quantitative polarized light microscopy and indentation analysis of the cartilage stiffness. RESULTS: The ICRS grading indicated nearly normal repair tissue in 65% (10/17) after the autologous chondrocyte transplantation and 86% (7/8) after no repair at 3 months. At 1 year, the repair tissue was nearly normal in all cases in the spontaneous repair group and in 38% (3/8) in the chondrocyte transplantation group. In most cases, the cartilage repair tissue stained intensely for glycosaminoglycans and collagen type II indicating repair tissue with true constituents of articular cartilage. There was a statistical difference in the total histological scores at 3 months (P=0.028) with the best repair in the spontaneous repair group. A marked subchondral bone reaction, staining with toluidine blue and collagen type II, was seen in 65% of all animals. CONCLUSIONS: The spontaneous repair ability of full thickness cartilage defects of immature pigs is significant and periosteum or autologous chondrocytes do not bring any additional benefits to the repair.

Animals↗

Clonal growth of human articular cartilage and the functional role of the periosteum in chondrogenesis.

OBJECTIVE: Clinical cartilage repair with transplantation of cultured chondrocytes, the first described technique introduced in 1994, includes a periosteal membrane but today cells are also implanted without the periosteal combination. The aim of this study was to see if the periosteum had more than a biomechanical function and if the periosteum had a biological effect on the seeded cells tested in an agarose system in which the clonal growth in agarose and the external growth stimulation could be analysed. METHODS: Four different experiments were used to study the growth of human chondrocytes in agarose and the periosteal influence. Human chondrocytes were isolated and transferred to either primary or secondary agarose culture. After 4 weeks, the total number of clones >50 microm was counted. Cocultures of chondrocytes and periosteal tissue, cultures of chondrocytes with conditioned medium from chondrocytes, periosteal cells and fibroblast were used to study a potential stimulatory effect on growth and different cytokines and growth factors were analysed. RESULTS: It was found that the human chondrocytes had different growth properties in agarose with the formation of four different types of clones: a homogenous clone without matrix production, a homogenous clone with matrix production, a differentiated clone with matrix production and finally a differentiated clone without matrix production. The periosteum exerted a paracrine effect on cultured chondrocytes in agarose resulting in a higher degree of cloning. The chondrocytes produced significant amounts of interleukin (IL)-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor (TGF)-beta. The periosteum produced significant amounts of IL-6, IL-8 and TGF-beta. Cocultures of chondrocytes and periosteum demonstrated a potentiation of IL-6 and IL-8 release but not of TGF-beta and GM-CSF. CONCLUSION: Articular chondrocytes are able to form clones of different properties in agarose and the periosteum has a capacity of stimulating chondrocyte clonal growth and differentiation and secretes significant amounts of IL-6, IL-8, GM-CSF and TGF-beta. It may be that the repair of cartilage defects with seeded chondrocytes could benefit from the combination with a periosteal graft. The production of TGF-beta by implanted chondrocytes could influence the chondrogenic cells in the periosteum to start a periosteal chondrogenesis and together with the matrix from implanted chondrocyte production, a repair of cartilaginous appearance may develop; a dual chondrogenic response is possible.

Adult↗

Cyclosporine inhibits the development of green fluorescent protein (GFP)-specific immune responses after transplantation of GFP-expressing hematopoietic repopulating cells in dogs.

Green fluorescent proteins (GFPs) have been widely used to monitor gene transfer and expression after lentiviral and oncoretroviral transduction of hematopoietic cells. Studies have shown a complete disappearance of GFP-containing cells after transplantation of GFP-transduced repopulating cells in nonhuman primates that was further shown to be mediated by transgene-specific immune responses. We wished to evaluate whether cyclosporine could prevent immune responses to GFP. We first determined whether an immune response to GFP was responsible for the disappearance of gene-modified cells in dogs. We performed immune assays in two dogs transplanted with lentivirally transduced CD34+ cells. Blood samples were obtained twice per week for up to 800 days and the GFP transgene product was measured by flow cytometry in blood leukocytes. Peripheral blood leukocytes were stimulated in vitro for 5 days, using a panel of GFP peptides. Intracellular levels of tumor necrosis factor alpha (TNF-alpha), measured by flow cytometry, and T cell proliferation after GFP peptide stimulation were measured. Dogs that exhibited a decrease in GFP marking developed potent immune responses in vitro to the transgene product GFP as shown by an increase in GFP-specific TNF-alpha production (p < 0.05) when compared with nontransplanted controls. T cells from dogs with low GFP marking exhibited a significant increase in proliferation in response to GFP peptide stimulation in vitro (p < 0.05). To study whether cyclosporine could inhibit the development of GFP-specific immune responses, we treated five dogs with cyclosporine after transplantation of GFP-transduced hematopoietic cells. Dogs treated with cyclosporine after hematopoietic stem cell transplantation showed stable GFP marking in blood leukocytes over 800 days. Our data suggest that cyclosporine prevents immunoactivation against transgene products after transplantation of GFP-transduced hematopoietic stem cells as indicated by stable GFP marking.

Animals↗

Subchondral bone reaction associated with chondral defect and attempted cartilage repair in goats.

Repair of cartilage damage with autologous chondrocyte transplantation (ACT) has become popular in clinical use during the past few years. Although clinical results have mostly been successful, several unanswered questions remain regarding the biological mechanism of the repair process. The aim of this study was to develop a goat model for ACT. The repair was not successful due to the graft delamination, but we characterize the subchondral changes seen after the procedure. A chondral lesion was created in 14 goat knees, operated on 1 month later with ACT, and covered with periosteum or a bioabsorbable poly-L/D-lactide scaffold. After 3 months, only two of the five lesions repaired with ACT showed partly hyaline-like repair tissue, and all lesions (n = 4) with the scaffold failed. Even though the lesions did not extend through the calcified cartilage, the bone volume and collagen organization of bone structure were decreased when assessed by quantitative polarized light microscopy. There was a significant loss of bone matrix and distortion of the trabecular structure of subchondral bone, which extended several millimeters into the bone. The subchondral bone demonstrated strong hyaluronan staining in the bone marrow and cartilaginous areas with signs of endochondral ossification, suggesting structural remodeling of the bone. The goat model used here proved not to be an optimal model for ACT. The changes in subchondral bone may alter the biomechanical properties of the subchondral plate and thus the long-term survival of the repair tissue after ACT.

Animals↗

Sustained multilineage gene persistence and expression in dogs transplanted with CD34(+) marrow cells transduced by RD114-pseudotype oncoretrovirus vectors.

Previous studies have shown that the choice of envelope protein (pseudotype) can have a significant effect on the efficiency of retroviral gene transfer into hematopoietic stem cells. This study used a competitive repopulation assay in the dog model to evaluate oncoretroviral vectors carrying the envelope protein of the endogenous feline virus, RD114. CD34-enriched marrow cells were divided into equal aliquots and transduced with vectors produced by the RD114-pseudotype packaging cells FLYRD (LgGLSN and LNX) or by the gibbon ape leukemia virus (GALV)-pseudotype packaging cells PG13 (LNY). A total of 5 dogs were studied. One dog died because of infection before sustained engraftment could be achieved, and monitoring was discontinued after 9 months in another animal that had very low overall gene-marking levels. The 3 remaining animals are alive with follow-ups at 11, 22, and 23 months. Analyses of gene marking frequencies in peripheral blood and marrow by polymerase chain reaction revealed no significant differences between the RD114 and GALV-pseudotype vectors. The LgGLSN vector also contained the enhanced green fluorescent protein (GFP), enabling us to monitor proviral expression by flow cytometry. Up to 10% of peripheral blood cells expressed GFP shortly after transplantation and approximately 6% after the longest follow-up of 23 months. Flow cytometric analysis of hematopoietic subpopulations showed that most of the GFP-expressing cells were granulocytes, although GFP-positive lymphocytes and monocytes were also detected. In summary, these results show that RD114-pseudotype oncoretroviral vectors are able to transduce hematopoietic long-term repopulating cells and, thus, may be useful for human stem cell gene therapy.

Amino Acid Transport System ASC↗

Health economics benefits following autologous chondrocyte transplantation for patients with focal chondral lesions of the knee.

Autologous chondrocyte transplantation (ACT) for the treatment of cartilage injuries has been in clinical use for several years. Since this new technique is potentially more costly and invasive than traditional conservative therapies, we evaluated the effect of ACT on clinical outcome, absenteeism, disability status, and total direct economic burden in 57 patients with full-thickness chondral lesions of the knee treated between 1987 and 1996. Patients graded good or excellent following ACT in the treatments groups were: femoral condyles (28/33), femoral condyles with anterior cruciate ligament (ACL) repair (5/5), osteochondritis dissecans (7/8), and patellar lesions (9/11). Pre-ACT, 57/57 patients were disabled and post-ACT (mean follow-up 7.3 years) 44/57 had no sickness, 10/57 had minor disability, and 1/57 was disabled. Two of the 57 patients suffered re-injury during the follow-up time. In the 10-year period prior to ACT, the average cost of absenteeism and surgery was SEK 982,457 ($ 122,807) and SEK 47,000 ($ 5,875), respectively, compared to the post-ACT period where both absenteeism and medical costs were dramatically reduced: SEK 9,508 ($ 1,189) and SEK 7,050 ($ 881), respectively. In conclusion, 49 of the 57 patients improved clinically as a result of the ACT treatment. A dramatic cost-saving effect was demonstrated over a projected 10-year period due to reduced absenteeism and disability.

Absenteeism↗

Follicular dendritic cell tumor presenting in the lung: a case report.

An example of extranodal follicular dendritic cell sarcoma (FDCS) presenting in the lung, a heretofore unreported site, is described. Macroscopically, a 9.5-cm, tan-white, dominant mass and multiple smaller parenchymal and pleural nodules were identified. Microscopically, the tumor was composed of spindled cells with uniform cytologic features arranged in short, intersecting fascicles and intermixed small lymphocytes and plasma cells. One of 4 peribronchial and hilar lymph nodes evaluated microscopically was focally involved by the process. Immunohistochemically, the neoplastic spindled cells expressed complement receptors CD21 and CD35 and low-affinity nerve growth factor receptor but did not express keratin (AE1/AE3 and CAM5.2), CD45 (leukocyte common antigen), CD20 (L26), S-100 protein, muscle-specific actin, or gp100 protein (HMB45). Ultrastructurally, the tumor cells have complex interdigitating cell surface processes and desmosomes. Epstein-Barr virus (EBV) was not detected in the tumor cells by in situ hybridization for EBV-encoded RNA or by polymerase chain reaction for viral DNA. FDCS should be considered in the differential diagnosis of any spindled-cell tumor with interspersed chronic inflammatory cells occurring in the lung. An immunohistochemical panel, including anti-CD21 and -CD35, can assist in its diagnosis, especially with small bronchial biopsy specimens. 2001 by W.B. Saunders Company.

Adult↗

Compliance with fecal occult blood test screening among low-income medical outpatients: a randomized controlled trial using a videotaped intervention.

BACKGROUND: Morbidity and mortality from colorectal cancer (CRC) are heightened among the socioeconomically disadvantaged. METHOD: A randomized controlled trial was conducted to evaluate the efficacy of a videotaped intervention using peer educators as well as a health professional to increase compliance with fecal occult blood test (FOBT) screening. Participants were 160 older individuals attending a medical outpatient clinic. Compliance with FOBT use was the dependent measure. Demographic variables, family history of CRC, viewing the videotape, perceived risk, self-efficacy, physician recommendation, knowledge about CRC screening, and intent to use the FOBT were independent measures. RESULTS: Approximately 41% of participants complied with FOBT screening. Significant relationships were found between intent and family history of CRC, viewing the video, perceived risk, self-efficacy, and CRC knowledge. However, none of these variables was significantly related to compliance with FOBT use. CONCLUSIONS: Although modest compliance rates were shown for both experimental and control groups, their compliance did not differ significantly. Further investigation of the impact of a video as part of an enhanced intervention program should be considered.

Analysis of Variance↗

Autologous chondrocytes used for articular cartilage repair: an update.

Articular cartilage in adults has a poor ability to self-repair after a substantial injury; however, it is not known whether there is a cartilage resurfacing technique superior to the existing techniques. It is not satisfactory that at the beginning of the new millennium, there still is a lack of randomized studies comparing different cartilage repair techniques and there still is little knowledge of the natural course of a cartilaginous lesion. To date, various articular cartilage resurfacing techniques have the potential to improve the repair of cartilage defects and reduce the patient's disability. One such cartilage repair technique is autologous chondrocyte transplantation combined with a periosteal graft. Since the first patient was operated on in 1987, much interest in cartilage repair and cell engineering has emerged. The experience with autologous chondrocyte transplantation during the past 13 years with in vitro chondrocyte expansion, cartilage harvest, and postoperative biopsy technique is discussed, and the latest followup of 213 consecutive patients in different subgroups with 2 to 10 years followup is presented. The technique gives stable long-term results with a high percentage of good to excellent results (84%-90%) in patients with different types of single femoral condyle lesions, whereas patients with other types of lesions have a lower degree of success (mean, 74%).

Adult↗

Maternal use of baby walkers with young children: recent trends and possible alternatives.

OBJECTIVES: To examine recent trends in baby walker and exersaucer use, and to assess maternal motivations for choosing to use or not use these devices with children. SETTING: Small, Midwestern city in the United States. METHODS: Retrospective telephone survey with a sample of 329 mothers who provided information about their use of walkers and exersaucers with 463 children born in Columbia, Missouri between January 1994 and April 1999. RESULTS: Baby walker use in the sample declined fairly steadily from 1994 to 1999, whereas exersaucer use increased during the same period. Altogether 88% of mothers were aware of the injury risks associated with walkers, and this knowledge was the most commonly reported reason for abstaining from walker use. Remarkably, 38% of participants with knowledge of walker risks nevertheless used these devices. Participants reported many reasons for using walkers and exersaucers, including child entertainment, perceived developmental benefit, easy availability, and improved safety of exersaucers. CONCLUSIONS: Public knowledge of the hazards of walkers seems to be high, and this awareness is a likely factor in many caregivers' decisions not to use them. Future interventions should focus particular attention on those caregivers who continue to use walkers despite knowledge of the associated risks. In addition to persuasive interventions, alternatives to walkers should be encouraged. Exersaucers represent one viable alternative, and should be promoted as such by the media, pediatricians, and other child care professionals.

Chi-Square Distribution↗

Simvastatin has anti-inflammatory and antiatherosclerotic activities independent of plasma cholesterol lowering.

Inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, such as simvastatin, lower circulating cholesterol levels and prevent myocardial infarction. Several studies have shown an unexpected effect of HMG-CoA reductase inhibitors on inflammation. Here, we confirm that simvastatin is anti-inflammatory by using a classic model of inflammation: carrageenan-induced foot pad edema. Simvastatin administered orally to mice 1 hour before carrageenan injection significantly reduced the extent of edema. Simvastatin was comparable to indomethacin in this model. To determine whether the anti-inflammatory activity of simvastatin might affect atherogenesis, simvastatin was tested in mice deficient in apoE. Mice were dosed daily for 6 weeks with simvastatin (100 mg/kg body wt). Simvastatin did not alter plasma lipids. Atherosclerosis was quantified through the measurement of aortic cholesterol content. Aortas from control mice (n=20) contained 56+/-4 nmol total cholesterol/mg wet wt tissue, 38+/-2 nmol free cholesterol/mg, and 17+/-2 nmol cholesteryl ester/mg. Simvastatin (n=22) significantly (P<0.02) decreased these 3 parameters by 23%, 19%, and 34%, respectively. Histology of the atherosclerotic lesions showed that simvastatin did not dramatically alter lesion morphology. These data support the hypothesis that simvastatin has antiatherosclerotic activity beyond its plasma cholesterol-lowering activity.

Administration, Oral↗

Decreasing children's risk taking on the playground.

Playground mishaps are some of the most common sources of injury and are the leading killer of children. The present study used a multiple baseline design across three classrooms (N = 379 children). With minimal teaching and rewards, children decreased and maintained decreased risky playground behaviors on slides. Floor effects on climbers prevented the demonstration of similar effects. The decreases seen in risky slide behavior are discussed within the context of preventive safety training for playground injuries.

Child↗

Expansions of clonal and oligoclonal T cells in B-cell chronic lymphocytic leukemia are primarily restricted to the CD3(+)CD8(+) T-cell population.

B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of mature-appearing clonal B cells exhibiting coexpression of CD5 and CD23. In addition to the accumulation of neoplastic B cells, numerous T-cell abnormalities also occur in B-CLL patients. In this study, the presence, and distribution within the T-cell subsets, of clonal/oligoclonal T cells was studied. Multicolor flow cytometric techniques were employed using combinations of anti-CD3, anti-CD4, and anti-CD8 antibodies coupled with antibodies specific for V(alpha) and V(beta) T-cell receptor (TCR) epitopes. Molecular studies of TCR gene sequences were done to confirm the presence of clonal/oligoclonal T-cell populations. In the flow cytometric studies, examination of V(alpha)/V(beta)expression found evidence of clonal/oligoclonal expansion in 9 of 19 patients studied. In eight of the nine patients, the expansions were restricted to the CD3(+)CD8(+) cell population. Molecular analyses were performed in 16 patients, 12 of whom showed a clonal or oligoclonal pattern. Of the four patients who were negative in the molecular analyses, all demonstrated flow cytometric evidence of clonal/oligoclonal expansions. Thus, when the flow cytometric and molecular analyses were considered together, all 16 patients for whom parallel analyses were done showed evidence of clonal/oligoclonal expansions. These results confirm previous work demonstrating that the majority of B-CLL patients harbor clonal/oligoclonal expansions within the T-cell population. Additionally, based on the relative numbers of cells expressing specific V(alpha) or V(beta)epitopes, these results show that these expansions occur primarily within the CD3(+)CD8(+) T-cell population.

Aged↗

Linking childhood sexual abuse and abusive parenting: the mediating role of maternal anger.

OBJECTIVE: This study had two primary objectives: First, to examine the association between childhood sexual abuse (CSA) and later parenting characteristics, particularly physical abuse potential, and second, to explore maternal anger as a mediator of the relationship between CSA and adult physical abuse potential. METHOD: Utilized a community sample of low SES participants that included 138 mothers classified as having experienced CSA, and a comparison group of 152 non-sexually abused mothers. Parenting variables examined included the mothers' physical abuse potential, nurturance toward their children, unrealistic developmental expectations of children, as well as frequencies of spanking and general punishment. Data was collected via interview and other self-report measures. RESULTS: Even after controlling for mothers' childhood experience of Physical abuse, CSA significantly predicted adult risk of physically abusing one's own children. Further, maternal anger was confirmed as a mediator of the relationship between having been sexually abused as a child and the potential for physically abusing one's own children. CONCLUSIONS: CSA may be a risk factor for subsequent physically abusive parenting, while anger appears to play a significant role in mediating this relationship. Findings are discussed in the context of current knowledge concerning the impact of child sexual abuse and the processes contributing to abusive parenting.

Adult↗

Two- to 9-year outcome after autologous chondrocyte transplantation of the knee.

Autologous cultured chondrocyte transplantation was introduced in Sweden in 1987 for the treatment of large (1.5-12.0 cm2) full thickness chondral defects of the knee. The clinical, arthroscopic, and histologic results from the first 101 patients treated using this technique are reported in this study. Patients were assessed retrospectively using three types of endpoints: patient and physician derived clinical rating scales (five validated and two new); arthroscopic assessment of cartilage fill, integration, and surface hardness; and standard histochemical techniques. Ninety-four patients with 2- to 9-years followup were evaluable. Good to excellent clinical results were seen in individual groups as follows: isolated femoral condyle (92%), multiple lesions (67%), osteochondritis dissecans (89%), patella (65%), and femoral condyle with anterior cruciate ligament repair (75%). Arthroscopic findings in 53 evaluated patients showed good repair tissue fill, good adherence to underlying bone, seamless integration with adjacent cartilage, and hardness close to that of the adjacent tissue. Hypertrophic response of the periosteum or graft or both was identified in 26 arthroscopies; seven were symptomatic and resolved after arthroscopic trimming. Graft failure occurred in seven (four of the first 23 and three of the next 78) patients. Histologic analysis of 37 biopsy specimens showed a correlation between hyalinelike tissue (hyaline matrix staining positive for Type II collagen and lacking a fibrous component) and good to excellent clinical results. The good clinical outcomes of autologous chondrocyte transplantation in this study are encouraging, and clinical trials are being done to assess the outcomes versus traditional fibrocartilage repair techniques.

Activities of Daily Living↗