Search PubMed⌕ Search

Biomedical subjects

K W Marshall

Publications and source records attributed to K W Marshall.

At least 19 recordsLinked to original sources
PubMed2000

Macromolecule and water magnetization exchange modeling in articular cartilage.

Magnetization exchange effects between the matrix macromolecules (e. g., collagen and proteoglycan) and water were examined in normal, deuterated, and proteoglycan-depleted articular cartilage. Relaxation results (T(2), T(1rho), and T(1)) suggested that a four-site exchange scheme provided an accurate model for articular cartilage relaxation and interspin group coupling details. Magnetization exchange within the collagen-bulk-water, proteoglycan-collagen, and collagen fibrillar water-collagen cartilage subsystems were quantified. Although collagen-bulk-water was the largest of the cartilage coupling subsystems ( approximately 90% signal) and is exploited in MRI, the rates of magnetization transfer (MT) within the latter subsystems were appreciably larger. Magnetization exchange rates for proteoglycan-collagen and collagen fibrillar water-collagen were 120 s(-1) and 4.4 s(-1), respectively. The observation of these latter two exchange subsystems suggested potential clinical MRI-MT applications in detecting molecular abnormalities associated with osteoarthritis.

Animals↗
PubMed2000

Amelioration of disease severity by intraarticular hylan therapy in bilateral canine osteoarthritis.

Because of its high molecular weight, the glycosaminoglycan molecule hyaluronan is responsible for the viscoelastic properties of normal synovial fluid. In osteoarthritis, the concentration and molecular weight of hyaluronan in synovial fluid is diminished: this impairs the ability of synovial fluid to effectively lubricate joints, absorb loads, and exert anti-inflammatory effects. Using a bilateral anterior cruciate-ligament transection and partial neurectomy canine model of osteoarthritis, this study examined the effect of viscosupplementation with hylan G-F 20 as a treatment for osteoarthritis. Twelve dogs underwent bilateral arthroscopic anterior cruciate-ligament transections and partial neurectomy of the knee joints. Beginning 1 week after the operation, six dogs received three weekly 500-microl injections of hylan G-F 20 in one knee and a sham injection of saline solution in the contralateral knee (early-treatment group). The remaining six animals underwent the same treatment 2 months following the procedure (late-treatment group). All dogs were killed at 8 months, and both knees were evaluated for gross pathology, histology, and proteoglycan content. In addition, with use of 500-MHz [1H] magnetic resonance spectroscopy, the synovial fluid from both knees was assessed for changes in metabolic profile. Differences in outcome were analyzed with paired t tests. Gross pathological and histological examination revealed significantly less severe changes of osteoarthritis in knees treated with hylan G-F 20 2 months after surgery than in the contralateral untreated knees. Magnetic resonance spectroscopy of the specimens in this late-treatment group showed significantly decreased glucose concentrations and significantly elevated isoleucine levels in the synovial fluid from knees treated with hylan G-F 20 compared with the controls. Previous magnetic resonance spectroscopy had shown that glucose concentrations increase with the onset of osteoarthritis and eventually diminish in end-stage osteoarthritis. The three injections of hylan were given after osteoarthritis was established, and the severity of the disease was ameliorated in the treated knees 6 months after treatment. This occurred although hylan G-F 20 is almost certainly cleared from joints by lymphatics within 4 weeks of injection, suggesting that hylan therapy can retard the progression of osteoarthritis for periods of time extending beyond the intraarticular residence time of the injected molecules and that hylan injections given at relatively early stages of osteoarthritis may have a chondroprotective effect. No changes in outcome were noted in the animals that received hylan G-F 20 immediately following surgery.

Animals↗
PubMed2000

How well does applicant rank order predict subsequent performance during radiology residency?

RATIONALE AND OBJECTIVES: Residency selection committees expend substantial time and resources on assessing the quality of residency applicants to derive an appropriate rank order for the National Residency Matching Program. The authors determined whether there is a relationship between the rank number or rank percentile of applicants selected for a residency training program and subsequent radiology residency performance. MATERIALS AND METHODS: Records of radiology residents completing their residency between 1991 and 1998 were reviewed. Available rank numbers and rank percentiles for each resident were compared with subsequent performance, as assessed subjectively by 4th-year radiology rotation evaluation forms and retrospective recall of four senior faculty members and objectively by numerical and percentile scores on the written portion of the American Board of Radiology (ABR) examinations. Correlation coefficients were obtained for each comparison. RESULTS: Rank number and rank percentile were not significantly correlated with 4th-year resident rotation evaluations or ABR written examination scores or percentiles. A small correlation existed between rank order and retrospective evaluation of resident performance by the four senior faculty. CONCLUSION: Applicant rank number and rank percentile do not correlate with subsequent radiology residency performance as assessed on rotation evaluation forms or the ABR written examinations.

Forecasting↗
PubMed2000

Intra-articular hyaluronan therapy.

The hyaluronan in normal synovial fluid plays an important role in joint homeostasis. It contributes to joint lubrication, buffers load transmission across articular surfaces, provides a renewed source of hyaluronan to joint tissues, and imparts antinociceptive and anti-inflammatory properties to synovial fluid. In osteoarthritis, the molecular weight and concentration of hyaluronan in synovial fluid are diminished. This has led to the proposition that removal of pathologic osteoarthritic synovial fluid and replacement with hyaluronan-based products that restore the molecular weight and concentration of hyaluronan toward normal levels can have beneficial therapeutic effects. This form of treatment for osteoarthritis has been termed viscosupplementation. Within the musculoskeletal community there are diverse opinions, ranging from skepticism to acceptance, about viscosupplementation as a mainstream symptom-modifying osteoarthritis therapy. This review focuses on recent basic and clinical studies dealing with mechanism of action, symptomatic efficacy, safety, and disease modification, and places these studies in context with earlier studies.

Animals↗
PubMed2000

Congenital cystic adenomatoid malformation: impact of prenatal diagnosis and changing strategies in the treatment of the asymptomatic patient.

OBJECTIVE: This study was designed to assess the effect of prenatal sonographic diagnosis on the treatment of congenital cystic adenomatoid malformation of the lung. MATERIALS AND METHODS: The medical records of 27 patients with pathologically proven congenital cystic adenomatoid malformations were retrospectively reviewed. Patients were divided into four groups based on mode of presentation: with or without abnormal findings on prenatal sonography and with or without symptoms at birth. Age at diagnosis, age at surgical intervention, complications, and length of hospital stay were recorded for each group. RESULTS: Twenty-seven patients with 31 proven congenital cystic adenomatoid malformations were included. Eleven patients underwent prenatal sonography establishing the diagnosis (6 asymptomatic at birth, 5 symptomatic), and 16 did not have a prenatal diagnosis (10 asymptomatic at birth, 6 symptomatic). In the symptomatic populations, prenatal diagnosis had no impact on age at surgery, length of stay, or surgical complication rate (p = 0.78-0.83). In the asymptomatic population, prenatal diagnosis allowed early diagnosis (p < 0.001) and resection in the asymptomatic period. It was also associated with a shorter length of stay at the time of surgical resection (mean time, 4.2 days for patients with prenatal diagnosis versus 12.9 days for those without it;p < 0.001) and with a trend toward lower serious complication rate (3 patients without prenatal diagnosis versus 1 patient with it). CONCLUSION: Prenatal sonography provides the radiologist a means to identify congenital cystic adenomatoid malformations in a population of infants who are asymptomatic at birth. Surgical intervention in the asymptomatic infant is associated with a shorter length of stay, a trend toward fewer complications, and decreased medical cost compared with intervening after symptoms develop.

Case-Control Studies↗
PubMed2000

The effects of freeze/thawing on human synovial fluid observed by 500 MHz 1H magnetic resonance spectroscopy.

OBJECTIVE: To investigate the effect of freeze/thaw and low temperature storage on the biomolecular profile of human synovial fluid (SF) using high resolution (500 MHz 1H) magnetic resonance spectroscopy (MRS). METHODS: SF was collected from 12 patients undergoing arthroscopic debridement for treatment of moderate osteoarthritis (OA). Six of the larger samples were divided into 5 parts and treated as follows: the first was analyzed with spin-echo MRS soon after arthroscopy (< 24 h); the 2nd, 3rd, and 4th parts were frozen (-75 degrees C) and thawed for a total of one, 5, and 10 freeze/thaw cycles, respectively, followed by MRS analysis; the 5th part was kept in -75 degrees C storage for > or = 1 year before MRS processing. The 6 smaller samples were divided into 2 parts, the first analyzed shortly after extraction (< or = 24 h), while the 2nd was processed after storage at -75 degrees C for > or = 1 year. Changes in measured metabolite levels were tested for significance using paired t tests. RESULTS: Freeze-thaw cycling had no statistically significant effect on the relative concentrations of endogenous metabolites measured by MRS, though it did alter individual sample results. Prolonged low temperature storage resulted in a significant drop (p < 0.05) in the signal intensities of glucose (45%), N-acetyl glycoproteins (39%), CH2-chain and CH3-terminal and resonances of lipoproteins (46 and 37%, respectively), valine (43%), leucine (35%), and isoleucine (43%). CONCLUSION: This study raises questions about routine procedures that may inadvertently affect the outcomes of quantitative SF analyses. Extended low temperature storage should be avoided as it permanently alters the biochemical profile of SF, possibly leading to erroneous conclusions about the nature of OA related changes in metabolite levels with disease progression.

Cryopreservation↗
PubMed2000

Adhesion of transplanted chondrocytes onto cartilage in vitro and in vivo.

OBJECTIVE: The specific objectives of this study using organ culture were (1) to transplant chondrocytes onto an intact cartilage surface; (2) to genetically modify endogenous and transplanted chondrocytes; and (3) to assess the ability of these cells to continually express a gene product. The specific objective with in vivo experiments was to transplant chondrocytes with intraarticular injections to cartilage. METHODS: Fluorescent membrane and intracellular dyes were used in conjunction with confocal microscopy to observe the integration of transplanted chondrocytes into cartilage both in vitro and in vivo. The distribution and duration of binding of rat, canine, and bovine chondrocytes to cartilage explants and the duration of expression of genes transduced into the transplanted chondrocytes were also determined. We used the vector AdlacZ, an E1 and E3 deleted replication defective adenoviral vector that contains the beta-galactosidase gene driven by the beta-actin promoter and the cytomegalovirus enhancer. RESULTS: The transplanted chondrocytes had a patchy distribution after in vitro or in vivo transplantation and buried themselves within the cartilage over time. Chondrocytes infected with the adenoviral vector AdlacZ soon or well after transplant to cartilage explants were maintained on the cartilage and continued throughout the duration of each trial to produce beta-galactosidase coded by the adenoviral vector. The cartilage plugs were infected with AdlacZ at 2 days or one, 2, 5, or 8 weeks after the chondrocytes were transplanted. The cartilage slices were then cultured from 15 days for chondrocytes infected at 8 weeks to 60 days for chondrocytes infected at 2 days post-transplant before determining the expression of beta-galactosidase. CONCLUSION: These results support the possibility of repairing cartilage by intraarticular injections of chondrocytes. Transduction of chondrocytes with genes producing a variety of matrix promoting proteins should further enhance the reconstruction of osteoarthritic cartilage.

Animals↗
PubMed1999

Comparative study of normal and osteoarthritic canine synovial fluid using 500 MHz 1H magnetic resonance spectroscopy.

High resolution 1H nuclear magnetic resonance spectroscopy has been used to investigate and compare the metabolic profiles of normal and osteoarthritic synovial fluids in a canine model of osteoarthritis. The spectra of osteoarthritic synovial fluid showed (a) increased concentrations of lactate, pyruvate, lipoprotein-associated fatty acids, and glycerol as well as the ketones hydroxybutyrate and hydroxyisobutyrate, (b) reduced levels of glucose, and (c) elevated levels of N-acetylglycoproteins, acetate, and acetamide compared with healthy normal canine synovial fluid. An increase was also observed in the concentrations of the amino acids alanine and isoleucine. These results suggest that (a) the intraarticular environment in canine osteoarthritis is more hypoxic and acidotic than in a normal joint, (b) lipolysis may play an increasingly important role as a source of energy in osteoarthritis, and (c) the N-acetylglycoprotein polymer component of synovial fluid (mostly hyaluronan) seems to be increasingly fragmented and degraded into acetate by way of an acetamide intermediate with progressive osteoarthritis. The observed changes in the biochemical profile of canine osteoarthritic synovial fluid may be useful in understanding alterations in joint metabolism consequent to arthritic diseases and helpful in identifying potential markers of osteoarthritis.

Animals↗
PubMed1999

Prenatal diagnosis of congenital cystic adenomatoid malformation and its postnatal presentation, surgical indications, and natural history.

BACKGROUND/PURPOSE: Regression of a cystic adenomatoid malformation (CAM) in a fetus is well described. Little, however, is known about the postnatal course of these infants. This study attempts to correlate the prenatal course of CAMs with postnatal symptoms, radiological manifestations, and need for surgery. METHODS: The clinical course of patients with a CAM diagnosed prenatally were retrospectively reviewed. Inclusion in the study required a prenatal ultrasound scan documenting a CAM. RESULTS: Over 10 years, 14 patients with a CAM were diagnosed prenatally. Six (43%) showed a partial in utero regression. Four patients were symptomatic at birth and underwent a resection as newborns. Ten patients were asymptomatic at birth, and eight of these had normal chest x-rays. Elective resection has been performed in 3 of these 10, and two additional children are scheduled to undergo an excision near 1 year of age. The remaining five patients have undergone follow-up nonoperatively for a mean of 36 +/- 15 months. Of the seven asymptomatic patients not undergoing immediate surgery, only one has shown a slight postnatal regression, despite five of these showing regression in utero. None have become symptomatic. CONCLUSIONS: The results suggest that regression of a CAM on prenatal ultrasound scan is common, but this process does not continue after birth. A normal chest x-ray does not indicate complete regression of a CAM; a computed tomography (CT) scan is required to evaluate such patients, and will generally demonstrate a CAM. Asymptomatic patients with a CAM may be followed up nonoperatively with no apparent adverse effects. The decision and timing of an excision in an asymptomatic patient remains controversial among pediatric surgeons.

Cystic Adenomatoid Malformation of Lung, Congenita↗
PubMed1999

1H NMR investigation of changes in the metabolic profile of synovial fluid in bilateral canine osteoarthritis with unilateral joint denervation.

OBJECTIVE: High resolution 1H-nuclear magnetic resonance (NMR) techniques have been used to compare the effects of unilateral knee-joint denervation on the biochemical profiles of synovial fluid in a bilateral canine model of osteoarthritis. METHOD: Paired synovial fluid samples were obtained from seven dogs all of which had previously undergone bilateral anterior cruciate ligament transection, unilateral knee denervation and contralateral sham nerve exposure. All synovial fluid samples were then analyzed using 500 MHz 1H-CPMG spin-echo NMR Spectroscopy to assess differences in endogenous metabolite levels between the paired fluids. RESULTS: The results indicate statistically significant increases in glycerol, hydroxybutyrate, glutamine/glutamate, creatinine/creatine, acetate and N-acetyl-glycoprotein concentrations in synovial fluids from denervated with respect to control knees. Furthermore, significant trends towards elevated lactate, alanine and pyruvate levels in the denervated knee fluids are consistent with our previous findings comparing NMR spectroscopy metabolic profiles of normal and osteoarthritic canine synovial fluids. CONCLUSION: This study lends support to the principle of neurogenic acceleration of OA in that the observed differences in metabolite concentrations found in the denervated knee fluids seem to correlate with metabolic changes resulting from aggravation of the OA process caused by joint denervation.

Animals↗
PubMed1999

Factors affecting the efficacy of bovine chondrocyte transplantation in vitro.

Current therapies for osteoarthritis have been primarily directed at symptom relief rather than disease modification or cure. Improved understanding of cartilage biology and metabolism has permitted exploration of disease-modifying treatments for OA. Chondrocyte transplantation is one approach to disease modification that has received increasing attention. To date, most chondrocyte transplantation has focused on surgical implantation into isolated chondral defects.Our hypothesis is that cultured chondrocytes will preferentially transplant to hyaline cartilage after intraarticular injection. The purpose of this study was to quantify chondrocyte adherence to cartilage in an in-vitro bovine explant model under differing culture conditions. The effect on chondrocyte transplantation of time, of alginate vs. monolayer culture techniques, and of differing origin of tissue explants within the knee joint were assessed. The effect on transplantation of physically modifying the explant surface was also assessed. In addition to quantification of transplantation adherence, the morphology of transplanted chondrocytes was assessed with confocal and electron microscopy. Maximal adherence occurred by 24 h post-transplantation. Baseline transplant densities exceeding 1 x 10(6) cells/cm(2)were observed on unmodified cartilage surfaces. No significant differences in binding density were noted between cartilage explants obtained from the patella, femoral condyles, tibial plateaus or the trochlear groove. In addition, no differences in chondrocyte adherence were noted in cells cultured in monolayer or alginate beads. Transplanted chondrocytes were noted to be spherical irrespective of the culture methods employed. Notably, chondrocytes demonstrated significantly improved adherence to cartilage surfaces after the superficial layer was removed as compared to normal intact cartilage surfaces (increase of 26%, P< 0. 01). This suggests that chondrocytes may preferentially adhere to cartilage surfaces where the superficial layer has been damaged, as is the case in isolated chondral lesions, or with diffuse cartilage degeneration.

Animals↗
PubMed1999

Granulocyte-colony stimulating factor (G-CSF)-primed, delayed marrow harvests as a source of hematopoietic stem and progenitor cells for allogeneic transplantation.

We evaluated the ability of G-CSF to increase the number of hematopoietic stem cells obtained by "delayed" BM harvest for allogeneic transplantation. Five normal donors received G-CSF @ 10 mcg/kg/day x 5 followed by repeat PB and BM assays at day 6 and 16, and BM harvest at day 16. Stem cells were not increased in the BM at day 16. Five patients underwent BMT and engrafted at +10 to +19 days. While the tested strategy offers no intrinsic advantages, its potential cannot be evaluated fully without alternative timing and/or additional, "early acting" growth factors.

Blood Donors↗
PubMed1999

Practical implications of cyclooxygenase-2--specific inhibitors in orthopedics.

Nonsteroidal anti-inflammatory drugs (NSAIDs) lead to severe and unpredictable side effects that are costly for individuals and the economy overall. As baby boomers enter their osteoarthritis years, there will be an increasing demand for safe and effective arthritis therapies. Animal and human data suggest that celecoxib, a cyclooxygenase-2-specific inhibitor, will provide an efficacious treatment without the side effects of conventional NSAIDs. Clinicians will need to determine individually and collegially how best to incorporate this new class of drugs into comprehensive treatment algorithms.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Resurfacing of articular cartilage explants with genetically-modified human chondrocytes in vitro.

OBJECTIVE: We are attempting to genetically-modify chondrocytes transplanted to cartilage in vitro as a prelude to gene therapy trials in patients with osteoarthritis. DESIGN: With human cartilage and chondrocytes, we have explored the duration of binding of chondrocytes to cartilage in vitro and the expression of the beta-galactosidase gene introduced into the chondrocytes through infection with an adenoviral vector both before and after transplant of the chondrocytes to cartilage. RESULTS: Transplanted chondrocytes continued to bind to cartilage explants at 45 days in our longest trial. We could successfully infect chondrocytes with adenovirus at least 35 days after we transplanted the chondrocytes to cartilage. Expression of the beta-galactosidase gene continued throughout the duration of each trial. CONCLUSIONS: These results raise the possibility of repairing and rebuilding cartilage by resurfacing the cartilage with genetically modified chondrocytes. The ability to infect chondrocytes well after transplant raises the possibility of repeated infections of surface chondrocytes as an alternative to repeated injections of chondrocytes into the joint space.

Adenoviridae↗
PubMed1998

Lymphoproliferative disorders: CT findings in immunocompromised children.

OBJECTIVE: The objective was to evaluate the CT imaging appearance, distribution of disease, type of immunocompromised state, and outcome of children with Epstein-Barr virus-induced lymphoproliferative disorders. MATERIALS AND METHODS: Medical records and imaging studies (from four tertiary children's medical centers) were reviewed for pathologically proven cases of lymphoproliferative disorders in patients less than 20 years old. Trends between the CT imaging appearance, distribution, and type of immunocompromised state and prognosis were noted and analyzed with Fisher's exact test. RESULTS: Twenty-seven cases were identified (mean age, 7 years 8 months). Eighteen children had undergone solid organ transplantation (heart, n = 9; liver, n = 7; kidney, n = 2), and four had undergone bone marrow transplantation. Five patients had primary immunodeficiencies. The CT appearance of lymphoproliferative disorders varied and included lymphadenopathy, focal mass or masses, and diffuse infiltration and enlargement of organs without focal mass. The distribution of disease included abdomen (n = 17), chest (n = 10), neck (n = 8), and brain (n = 1). In eight of nine heart transplant recipients, the disease predominantly involved the chest and neck, whereas in all seven liver transplant recipients, the disease was isolated to the abdomen (p = .001). The overall mortality rate of 44% was less related to anatomic extent (multiorgan, 46%; localized, 43%) than to type of immune dysfunction (p = .001): bone marrow transplantation (100%), primary immunodeficiency (80%), heart transplantation (55%), liver transplantation (0%), and kidney transplantation (0%). CONCLUSION: Lymphoproliferative disorders in children had a variable distribution, imaging appearance, and outcome. However, in recipients of solid organ transplants, the disease tended to occur in the anatomic region of the transplant. Mortality rates were more closely related to the type of underlying immune dysfunction than to distribution of disease.

Bone Marrow Transplantation↗
PubMed1998

Air bag-related deaths and serious injuries in children: injury patterns and imaging findings.

BACKGROUND AND PURPOSE: As of November 1, 1997, automotive air-bag deployments occurring in low-speed collisions had resulted in the deaths of 49 children and in the serious injuries of 19 children in the United States. The purpose of this study was to investigate the patterns of injury occurring in this new mechanism of pediatric trauma. METHODS: In search of common patterns of injury, three pediatric radiologists retrospectively evaluated the available autopsy and imaging studies in 11 such cases not previously reported in the medical literature, in addition to three published case studies. RESULTS: The cause of death or serious injury in every case was the direct result of neurologic injury. Injury patterns differed according to the child's age and type of restraint used at the time of collision. Crush injury to the skull predominated in infant victims traveling in rear-facing child safety seats, and both cranial and cervical spine trauma occurred in older children traveling restrained, improperly restrained, or unrestrained in the vehicle's front passenger seat. CONCLUSION: Air-bag systems pose a potentially fatal threat to the front-seat child passenger. This is directly related to the biomechanics at impact placing the child closer to the deploying air bag. An understanding of the biomechanics provides the radiologist insight into the two types of injury patterns observed.

Air Bags↗