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C Magee

Publications and source records attributed to C Magee.

At least 19 recordsLinked to original sources
PubMed2000

Focal hepatic ablation using interstitial photon radiation energy.

BACKGROUND: Intratumoral ablative therapy is being used increasingly for the treatment of primary and secondary hepatic malignancies. The interstitial point-source photon radiosurgery system (PRS) is a novel ablative technique that uses radiation therapy similar in dosimetry to interstitial brachytherapy. STUDY DESIGN: To determine the feasibility, toxicity, and local tissue destructive capabilities of the PRS in the liver, preliminary studies in a nontumor-bearing canine model were examined. A 6-month survival study was conducted. Each animal received three radiation treatments, in the right, central, and left hepatic regions. Three low-dose treatments were delivered to each of six animals (group A), generating a 2.0-cm-diameter radiated sphere with a dose of 20 Gy at the lesion edge. Three high-dose treatments were delivered to each of six animals (group B), generating a 3.0-cm-diameter radiated sphere with 20 Gy at the lesion edge. RESULTS: The treatment reproducibly generated sharply demarcated hepatic ablative lesions proportional to the administered dose. Mean lesion diameter at 1 month was 1.6+/-0.2 cm in group A and 3.4+/-1.0 cm in group B. Lesion size was independent of intrahepatic location, including near vascular structures. PRS therapy, when applied to portal structures, resulted in hilar damage. Hilar damage appeared to be associated with arteriolar thrombosis and bile duct injury. Treatment of regions adjacent to large hepatic veins and the IVC was not associated with vessel thrombosis or stricture. CONCLUSIONS: PRS ablation is a generally well-tolerated method that results in consistent, well-demarcated, symmetric lesions of complete necrosis with minimal adjacent parenchymal injury. Application of such an approach for the treatment of liver tumors is promising.

Animals↗
PubMed2000

Feasibility of ablating normal renal parenchyma by interstitial photon radiation energy: study in a canine model.

BACKGROUND AND PURPOSE: A miniature photon radiosurgery system (PRS) has been described as an alternative to surgical resection and external-beam radiation for tumors and may now offer an alternative for ablation of renal lesions. We evaluated the feasibility of ablation by PRS in a normal parenchyma canine model. MATERIALS AND METHODS: Twelve mongrel dogs were used in this survival study. In the left and right kidneys of each animal, a peripheral lesion and central-hilar lesion, respectively, were induced with PRS. The probes were placed in the renal parenchyma, and local radiation of 15 Gy at a radius of 1.3 cm was delivered over 10 minutes. Serum electrolytes were measured serially. Computed tomography scans were obtained, and the animals were sacrificed for pathologic correlation. In a separate study, the liver received three additional treatments of 10 to 20 minutes of radiation. RESULTS: Eleven dogs survived this 6-month study and were sacrificed as scheduled. One animal expired after 2 weeks from radiation-induced fulminant hepatic failure with normal renal function. No other complications were observed. The average lesion size was 2.5 cm in diameter. Histologic analysis confirmed coagulative necrosis with sharp demarcation from the surrounding parenchyma. CONCLUSION: Preliminary studies demonstrate the feasibility of PRS ablation of the renal parenchyma. Further tumor model testing will be important to determine the ultimate efficacy of local photon radiation energy.

Animals↗
PubMed1999

Cellular and humoral mechanisms of vascularized allograft rejection induced by indirect recognition of donor MHC allopeptides.

INTRODUCTION: To investigate the role and mechanisms of indirect allorecognition in allograft rejection, we studied whether priming T cells with donor-derived MHC allopeptides could accelerate rejection in a vascularized allograft model. METHODS: Lewis recipients of fully mismatched Wistar Furth cardiac allografts were immunized before transplantation with donor MHC allopeptides. RESULTS: Animals immunized with immunogenic class II MHC allopeptides rejected their grafts in a significantly accelerated fashion compared with controls. Additional studies demonstrated that a single immunodominant RT1.D (HLA-DR like) allopeptide was responsible for accelerating the rejection process. Histological analysis of rejected allografts revealed marked vascular rejection in the accelerated, although not the control, group as well as severe cellular rejection. Peak production of IgM and IgG donor-specific alloantibodies was detected by flow cytometry 1 week earlier in the sera of the accelerated group compared with the control group. Immunohistological analysis of grafts from the accelerated compared with the control group showed increased endothelial deposition of IgG2b, C3, and fibrin, and up-regulation of class II MHC molecule expression. Increased intragraft expression of interferon-y and the interferon-gamma-induced chemokines, inducible protein-10 and Mig, and infiltration by activated mononuclear cells expressing CXCR3, the receptor for inducible protein-10 and Mig, was also seen. CONCLUSION: These novel data provide evidence of a definitive link between indirect allorecognition of donor-derived MHC class II peptides and the cellular and humoral mechanisms of vascularized allograft rejection.

Animals↗
PubMed1999

Immunomodulatory functions of hyaluronate in the LEW-to-F344 model of chronic cardiac allograft rejection.

BACKGROUND: CD44 is an important leukocyte cell surface glycoprotein with diverse functions including cell adhesion, homing, migration, and activation. METHODS: Because administration of the principal ligand of CD44, hyaluronate (HA), in soluble form, can inhibit CD44-HA interaction, we tested the effects of HA in vivo in an established model of chronic allograft rejection. Control F344 recipients of LEW hearts received either no treatment or low-dose cyclosporine (CsA) for 30 days from the day of transplantation. Experimental animals received 30 days of CsA in combination with 30 or 90 days of low molecular weight HA (LMW-HA). RESULTS: CsA therapy alone resulted in approximately 40% long-term (>100 days) graft survival, whereas CsA + LMW-HA (30-day and 90-day protocols) significantly increased long-term graft survival to 60% and 92%, respectively. Light microscopy and immunohistology of CsA-treated and CsA + LMW-HA-treated grafts harvested at day 30 after transplantation demonstrated that LMW-HA + CsA therapy decreased mononuclear cell infiltration and afforded better preservation of myocardial architecture. In addition, LMW-HA + CsA-treated grafts exhibited decreased expression of interferon-gamma and the growth factors transforming growth factor-beta, platelet-derived growth factor, and fibrogenic growth factor-beta. Long-term surviving grafts were assessed for arteriosclerosis, the sine qua non of chronic rejection in this model. Using a standardized scoring system, significantly less arteriosclerosis was seen in grafts from LMW-HA + CsA-treated animals at 120 days after transplantation compared with CsA alone-treated grafts. This difference was not significant, however, in grafts harvested at >150 days. CONCLUSION: This is the first report indicating that CD44-HA interactions play an important role in chronic allograft rejection.

Animals↗
PubMed1999

Immunomodulatory functions of low-molecular weight hyaluronate in an acute rat renal allograft rejection model.

Low molecular weight hyaluronate (LMW-HA) blocks interactions between T lymphocyte CD44 and hyaluronate (HA), a heteropolysaccharide that is expressed on the surface of endothelial cells and ubiquitously in the extracellular matrix. This study was undertaken to assess the ability of LMW-HA to modify the course of experimental acute renal allograft rejection. Lewis (LEW) rats were bilaterally nephrectomized and received an orthotopic, fully MHC-mismatched, Wistar-Furth (WF) kidney transplant. Animals received either no treatment, low doses of cyclosporin A (CsA) on days 0 to 5, LMW-HA on days 0 to 5, or CsA plus LMW-HA on days 0 to 5 after transplantation. With no treatment, CsA monotherapy, or HA monotherapy, animals rejected their allografts at a median of 15, 13, and 7.5 d, respectively (P = NS). In contrast, combined CsA plus LMW-HA therapy prevented acute rejection and significantly prolonged graft survival (P = 0.008) to a median of 49.0 d. CsA/LMW-HA-treated grafts also demonstrated better preservation of renal function at day 30 (serum creatinine level, 1.38+/-0.8 mg/dl), compared with surviving animals treated with CsA alone (2.9+/-0.55 mg/dl, P<0.05). Histologic graft analysis of CsA/LMW-HA-treated animals at day 7 after transplantation showed minimal rejection and leukocyte infiltration, compared with all other groups. Intragraft gene expression analysis, using semiquantitative reverse transcription-PCR, at the same time point showed reductions of CD4, CD8, and interferon-gamma transcript levels in the combined-treatment group. This is the first study demonstrating the immunomodulatory functions of LMW-HA in vivo in the setting of organ transplantation. Defining the exact mechanisms that underlie this immunomodulation may provide the rationale to develop novel strategies for use in clinical transplantation.

Adjuvants, Immunologic↗
PubMed1998

Plasma transglutaminase in hypertrophic chondrocytes: expression and cell-specific intracellular activation produce cell death and externalization.

We previously used subtractive hybridization to isolate cDNAs for genes upregulated in chick hypertrophic chondrocytes (Nurminskaya, M. , and T.F. Linsenmayer. 1996. Dev. Dyn. 206:260-271). Certain of these showed homology with the "A" subunit of human plasma transglutaminase (factor XIIIA), a member of a family of enzymes that cross-link a variety of intracellular and matrix molecules. We now have isolated a full-length cDNA for this molecule, and confirmed that it is avian factor XIIIA. Northern and enzymatic analyses confirm that the molecule is upregulated in hypertrophic chondrocytes (as much as eightfold). The enzymatic analyses also show that appreciable transglutaminase activity in the hypertrophic zone becomes externalized into the extracellular matrix. This externalization most likely is effected by cell death and subsequent lysis-effected by the transglutaminase itself. When hypertrophic chondrocytes are transfected with a cDNA construct encoding the zymogen of factor XIIIA, the cells convert the translated protein to a lower molecular weight form, and they initiate cell death, become permeable to macromolecules and eventually undergo lysis. Non-hypertrophic cells transfected with the same construct do not show these degenerative changes. These results suggest that hypertrophic chondrocytes have a novel, tissue-specific cascade of mechanisms that upregulate the synthesis of plasma transglutaminase and activate its zymogen. This produces autocatalytic cell death, externalization of the enzyme, and presumably cross-linking of components within the hypertrophic matrix. These changes may in turn regulate the removal and/or calcification of this hypertrophic matrix, which are its ultimate fates.

Amino Acid Sequence↗
PubMed1998

Clostridium difficile colitis associated with chronic renal failure.

BACKGROUND: Clostridium difficile-associated diarrhoea (CDAD) is a potentially life-threatening illness which has been shown to be more common and more severe in patients with chronic renal failure (CRF) than in other groups. A review of CDAD in our nephrology unit was carried out. METHODS: A review of microbiology and histology records identified 32 cases of CDAD in the nephrology unit over a 24-month period. Patient notes were reviewed to identify risk factors, clinical features and outcome. Available isolates of C. difficile underwent 16S ribosomal RNA typing. RESULTS: The incidence of CDAD in the nephrology unit was 10.7 per 1000 admissions, compared to 2.7 per 1000 in other areas of the hospital (P<0.0001). CDAD was considered the sole or principal cause of death in six (19%) and was considered a contributing factor in a further seven (22%). Mortality was significantly higher among patients with established CRF (P=0.04). Seven cases occurred as a cluster, over a 1-month period. Isolates from this cluster, along with comparative strains from other areas of the hospital, were found to be PCR type 1. Diarrhoea occurred in 28 (89%) of cases, pyrexia in 17 (53%) and ileus or abdominal pain in 14 (44%). Six patients responded to discontinuation of antibiotics alone and 22 required metronidazole and/or vancomycin. Three patients had colectomy and one caecostomy because of toxic megacolon. Four patients died before specific therapy could be given and in two of these cases the diagnosis was made at autopsy. Twenty-six patients had a record of recent antibiotic therapy. Of these, 15 had at least one agent considered to be inappropriate (excessively broad spectrum agent in 11, excessive duration of therapy in four). Nine patients had only received antibiotics prior to admission. CONCLUSIONS: CDAD carries a high mortality in nephrology patients, especially those with established CRF. The diagnosis may be missed if a careful antibiotic history is not taken, including agents received prior to admission. Rational antibiotic prescribing and adherence to infection control measures are vital to reduce the incidence of this serious condition.

Adult↗
PubMed1998

Multiple myeloma and renal failure: one center's experience.

Renal involvement remains a major complication of multiple myeloma, particularly in advanced disease. A retrospective analysis was performed of the modes of presentation, treatment and outcome of all patients with multiple myeloma treated in our renal unit between 1987 and 1996. Thirty-four patients were identified: in 26 (76%) the diagnosis of myeloma was made only after referral. Light chains were the most common paraprotein in both serum and urine. Twenty-one (62%) patients underwent renal biopsy: myeloma cast nephropathy was the predominant histological finding in 16 cases. Thirty-one (91%) patients had severe renal failure (GFR < 20 mL/min), with 28 (82%) requiring dialysis within 2 weeks of admission. Despite treatment of presumed precipitaing causes of acute deterioration in renal function, only 1 of these 28 patients subsequently became independent of dialysis. Most had advanced stage myeloma: 29 (85%) were Durie-Salmon stage II or III. Hypercalcemia, sepsis and pathological fractures were the principal complications. Median survival overall was 5 months. The main causes of death were withdrawal of renal replacement therapy (overwhelming myeloma, severe debilitation) and sepsis. Nineteen (56%) patients received long-term (> 1 month) renal replacement therapy with a median survival of 8 months. However, five of these (26%) have survived for more than 12 months on dialysis and report a good quality of life.

Aged↗
PubMed1997

Donor antigen is necessary for the prevention of chronic rejection in CTLA4Ig-treated murine cardiac allograft recipients.

BACKGROUND: Optimal activation of T cells requires two signals: antigen engagement through the T cell receptor and a costimulatory signal. Previous studies have shown that blockade of the CD28:B7 costimulatory pathway using the soluble fusion protein CTLA4Ig can prevent acute rejection of organ and tissue allografts; however, long-term engraftment has not been seen universally. This study was undertaken to define the role of donor antigen in inducing long-term allograft survival in CTLA4Ig-treated recipients. METHODS: A murine cardiac allograft model was employed using BALB/c donors and C57BL/6 recipients. Additional donor antigen in the form of donor splenocytes was given at the time of transplantation. Recipients were treated with a single dose of CTLA4Ig 2 days after transplantation. RESULTS: We find that a single dose of CTLA4Ig prolongs cardiac allograft survival, but permanent engraftment is not observed unless the recipients receive an injection of donor-type splenocytes. Treatment of the donor cells with CTLA4Ig does not by itself prolong allograft survival, which indicates the need for systemic treatment of the recipient. Allografts from animals not receiving donor cells show classic histologic changes of chronic rejection, and most cease function from 1 to 4 months after transplantation. Lethal irradiation of the donor cells does not appreciably affect their ability to prevent late allograft loss. CONCLUSIONS: Donor cells are required to synergize with CTLA4Ig and prevent late cardiac allograft loss in the murine system. The fact that pretreatment of the donor cells alone is not effective suggests a role for antigen presentation by recipient antigen-presenting cells in the initiation of rejection. As lethal irradiation of the donor cells does not affect their ability to promote long-term engraftment, our data suggest that long-term microchimerism is not required to prevent chronic rejection in this model.

Abatacept↗
PubMed1995

Serotonin-induced paw edema in the rat: pharmacological profile.

1. Serotonin (5-HT) induced a linear increase in paw weight in rats within 1 hr of an intraplantar injection (50 microliters vol) over a concentration range of 0.005-0.2 mg/ml. At the 0.2 mg/ml concentration, a 16-fold increase in paw weight was observed as compared to saline-injected controls. 2. Serotonin antagonists, such as LY53857, were the most effective antagonists of 5-HT induced paw swelling, producing near complete antagonism and an approximate ED50 of 0.1 mg/kg. A mixed 5-HT/histamine antagonist, cyproheptadine, also produced a nearly complete inhibition of the 5-HT response with an approximate ED50 of 1.3 mg/kg. 3. Dopamine agonists (pergolide, quinpirole), yohimbine, dexamethasone and nifedipine also produced a significant degree of antagonism of the 5-HT response. 4. Clonidine, prazocin, chlorpheniramine, cimetidine, various dopamine antagonists, imipramine, cyclosporine A, piroxicam and superoxide dismutase were all ineffective at altering the paw swelling response to 5-HT.

Adrenergic Agonists↗
PubMed1994

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Acquired Immunodeficiency Syndrome↗
PubMed1993

Paternal exposures and cardiovascular malformations. The Baltimore-Washington Infant Study Group.

Possible associations between paternal exposures and cardiovascular malformations were evaluated in the Baltimore-Washington Infant Study, a population based case-control investigation of congenital heart disease and environmental factors. Home interviews of case and control parents elicited information on parental home and occupational exposures. Analysis focused on twelve cardiac diagnostic groups and paternal exposures incurred during the six months preceding the pregnancy. Associations were identified between jewelry making and atrial septal defect (Odds ratio: 12.6; 95% confidence interval: 2.3-68.6) and membranous ventricular septal defect (8.1; 2.0-33.3), welding and endocardial cushion defect with Down syndrome (1.8; 1.1-3.0), lead soldering and pulmonary atresia (2.3; 1.1-4.9) and ionizing radiation and endocardial cushion defect without Down syndrome (4.7; 1.7-12.6). Ionizing radiation was found to be associated with endocardial cushion defect with Down syndrome only when father was present at interview (5.6; 1.7-17.9); a similar effect of father at interview was noted for paint stripping in relation to coarctation of the aorta (3.5; 1.5-8.0) and muscular ventricular septal defect (3.5; 1.5-8.5). Also, paint stripping was associated with hypoplastic left heart only in the presence of family history of cardiac defects (11.9; 2.4-60.0). This large study on cardiac diagnostic groups and specific preconceptional exposures provides new leads for further assessment of the role of paternal exposures on adverse pregnancy outcome.

Adult↗
PubMed1992

In vivo evaluation of iophendylate-cyanoacrylate mixtures.

Cyanoacrylate glue is a rapidly polymerizing agent used for vascular embolization. Polymerization occurs when the glue comes into contact with ions in the blood or on the vascular endothelium. Mixing iophendylate with cyanoacrylate causes slowing of polymerization, allowing flow-directed embolization into the nidus of an arteriovenous malformation (AVM) or the central neovascularity of a tumor or hemangioma. The authors attempted to define the relationship between the iophendylate-glue ratio and polymerization time with an in vivo swine model. In this model, glue setup occurred much more rapidly than predicted on the basis of in vitro studies. This appeared to be due to glue polymerizing on the endothelium at vessel bifurcations and at areas of acute angulation or marked vessel narrowing. On the basis of these data, the authors substantially increased the iophendylate-glue ratio in their most recent AVM embolization procedures and achieved nidus occlusion in each case. With use of the authors' guidelines, it is possible to achieve optimal distal flow-directed embolization with cyanoacrylate.

Angiography↗
PubMed1984

Bacterial transport within and among various teatcup and cluster assemblies during milking.

For evaluation of bacterial transport, two experiments were conducted. In Experiment 1, two nonconventional cluster designs were compared with a conventional assembly. These two units were: 1) conventional unit without a claw and 2) linerless unit without a claw. In Experiment 2, two nonconventional teatcup designs were compared with a conventional teatcup, all attached to a conventional claw. These two were: 1) partial linear teatcup assembly and 2) conventional teatcup with restricted linear wall movement. The three teatcups in Experiment 2 differed only in the lower part of the liner barrel; mouthpiece and short milk tube were identical. A culture of Serratia marcescens bacteria was infused throughout milking into the short milk tube at the right front teatcup assembly. Swabs of liners and teats were used to culture for Serratia marcescens. For Experiment 1, the number of contaminated teats (and liners) was 32 of 144 and 88 of 144 for the conventional cluster, 20 of 144 and 37 of 144 for the clawless cluster, and 10 of 144 and 16 of 144 for the linerless cluster. For Experiment 2, the total number of bacterial transfers was 14 of 25 for the conventional teatcup, 7 of 25 for the restricted liner, and 3 of 25 for the partial liner. These occurrences of transfer correlate well with previously measured reverse pressure gradients across the short milk tube.

Animals↗
PubMed1977

A rapid technic for quantitating wound bacterial count.

An improved technic has been developed to predict rapidly the critical number of bacteria in tissues. This technic gave reliable and accurate measurements for wounds containing more than 2 X 10(5) organisms per gram of tissue. It is fortuitous that 10(6) bacteria is the critical number of bacteria that will induced clinical infection in experimental animals and humans. The rapid slide technic is now being utilized routinely in our medical center to determine graft bed receptiveness, predict the safety of wound closure, and monitor the course of burns.

Animals↗
PubMedDate not supplied

Evaluation of venous injury caused by a percutaneous mechanical thrombolytic device.

PURPOSE: To study venous injury caused by a prototype percutaneous mechanical thrombolytic device. METHODS: Simulated thrombolysis was performed using the device, or the Fogarty balloon catheter (FBC) as control, in the infrarenal inferior vena cava (IVC) of 40 New Zealand white rabbits. Venous injury was evaluated by cavography, Evans blue dye staining, and histology at 0, 1, and 6 weeks postprocedure. RESULTS: Both devices resulted in near complete endothelial denudation acutely. No differences in reendothelialization were noted at any time in the proximal and mid-IVC, but there was significantly greater reendothelialization in the distal IVC in the rabbits treated 6 weeks earlier with the device (p < or = 0.04). Additionally, the inner luminal diameter at necropsy for the 1-week rabbits treated with the FBC was significantly narrower in the distal and middle sections of the IVC when compared with the device (p < or = 0.02 for both segments). There was no luminal diameter difference at 0 or 6 weeks. CONCLUSION: Based on a rabbit model, venous injury from the device was found to be similar to, and in the distal IVC less than, the routinely used FBC.

Animals↗