Permanent coverage of large burn wounds with autologous cultured human epithelium.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to C C Compton.
Explore the source record for details and available documents.
A unique case of granulomatous gastritis of unknown etiology is reported. The patient, a 43-year-old Haitian woman, suffered a gastric perforation from a disease process limited to the stomach. The stomach was markedly enlarged and edematous with transmural, serpiginous granulomatous tracks throughout the gastric wall, but most numerous in the fundic region. Accompanying acute and chronic inflammatory infiltrates were scant. No microorganisms, parasites, foreign body particles, or other known granulogenic materials could be identified. Clinical and pathologic features also differed markedly from granulomatous gastritis seen in sarcoidosis, Crohn's disease, or isolated granulomatous gastritis as defined by Fahmi et al. Infection by a parasite for which man is not the definitive host seems the most likely etiology.
Explore the source record for details and available documents.
The diagnosis of fatty liver with magnetic resonance (MR) imaging was evaluated in experimental rat models of simple fatty infiltration and fatty liver with hepatocellular injury. T1 and T2 were measured ex vivo and correlated with the histologic degree of fatty infiltration. Enhancement of fatty liver with four different cells-specific contrast agents was studied with ex vivo relaxometry and in vivo MR imaging. Quantitative analysis of conventional and chemical shift MR images was correlated with biochemically determined fat content of the liver. Diet-induced simple fatty infiltration of the liver caused a decrease in T1 of 15%, whereas the T1 of L-ethionine-induced fatty liver with hepatocellular injury increased by 12%. T2 showed a positive correlation with the degree of fatty infiltration in both models. Cell-specific hepatobiliary contrast agents showed the same liver uptake and relaxation enhancement in fatty livers as in normal livers. Conventional T1-weighted images and chemical shift images showed good correlation (r = .83 and .80, respectively) between signal intensity and the degree of fatty infiltration. However, only chemical shift imaging was reliable in the diagnosis of fatty liver.
The efficacy for tumor detection of the hepatocyte-specific contrast agent gadobenate dimeglumine (gadolinium-BOPTA/Dimeg) was evaluated in four different experimental tumor models in rats. Histologic findings were correlated with quantitative data derived from ex vivo relaxometry and in vivo magnetic resonance (MR) imaging. Noninfiltrating tumors showed maximal enhancement of liver parenchyma 5-10 minutes after contrast agent administration, with a plateau over the next 30 minutes. In contrast, infiltrating tumors, which caused hepatocellular injury and inflammatory changes, delayed maximal enhancement of tumor-free parenchyma by 15-20 minutes. Nonspecific tumor enhancement depended on tumor vascularity and occurred in the early phase after contrast agent administration. Despite differences in specific enhancement of tumor-free parenchyma and nonspecific tumor enhancement, tumor-liver contrast-to-noise ratios increased 96%-248% in all tumor models 30 minutes after intravenous administration of 75 mmol/kg Gd-BOPTA/Dimeg. Gd-BOPTA/Dimeg enhanced tumor conspicuity independently of the histologic characteristics of the tumor.
The hepatocyte-specific paramagnetic magnetic resonance (MR) contrast agents manganese-DPDP [N,N'-dipyridoxylethylenediamine-N,N'-diacetate 5,5'bis-(phosphate)] and gadobenate dimeglumine were used for diagnosing chemically induced hepatitis in rats. Ex vivo liver tissue relaxation times and in vivo MR image signal-to-noise ratios were compared before and after contrast agent administration. Ex vivo relaxometry and in vivo MR imaging showed that Mn-DPDP enhanced normal and diseased livers to the same degree at all time points from 5 to 120 minutes. Gadobenate dimeglumine showed reduced T1 and T2 enhancements in hepatitis relative to those of normal liver, in the early phase (5-30 minutes). However, these effects are offsetting, and as a result, MR imaging failed to allow distinction of diseased from normal livers. This surprising result observed in vivo was in fact predicted by applying the Bloch equation to our ex vivo data. Our results show that detection and quantitation of hepatitis with MR imaging enhanced with paramagnetic cell-specific contrast agents will be more difficult than anticipated.
Morphologic features which allow the diagnosis of acute cholecystitis by ultrasound and CT have now been observed by MR. When present, thickening of the gallbladder wall, intramural abscess, pericholecystic fluid, and the presence of gallstones may be more specific than MR characterization of gallbladder bile.
PURPOSE: To determine, by decreasing hepatic perfusion during radiofrequency (RF) ablation, whether perfusion-mediated tissue cooling can explain the reduced coagulation observed in in vivo studies compared to that seen with RF application in ex vivo tissue. MATERIALS AND METHODS: RF was applied in vivo with use of cooled-tip electrodes to normal porcine liver without (n = 8) and with balloon occlusion of the portal vein (n = 8), celiac artery (n = 3), or hepatic artery (n = 2), and to ex vivo calf liver (n = 10). In vivo trials of vasopressin (0.3-0.6 U/min) infusion during RF application with (n = 10) and without (n = 2) arterial balloon occlusion were also performed. Intraoperative RF was subsequently performed in seven patients with hepatic colorectal metastases with and without portal inflow occlusion. Remote thermometry was performed in four patients. RESULTS: RF application (12 minutes) during portal venous occlusion produced larger areas of coagulation necrosis than RF with unaltered blood flow (2.9 cm +/- 0.1 vs 2.4 cm +/- 0.2 diameter; P < .01). With celiac and hepatic artery occlusion, coagulation diameter measured 2.7 cm +/- 0.2 and 2.5 cm +/- 0.1, respectively. Infusion of vasopressin without vascular occlusion reduced coagulation diameter to 1.1 cm. However, different methods of hepatic or celiac arterial balloon occlusion with simultaneous vasopressin infusion produced a mean 3.4 cm +/- 0.2 of necrosis. Coagulation in ex vivo liver was 2.9 cm +/- 0.1 in diameter. Clinical studies demonstrated greater coagulation diameter for metastases treated during portal inflow occlusion (4.0 cm +/- 1.3) than for tumors treated with normal blood flow (2.5 cm +/- 0.8; P < .05). Thermometry documented a 10 degrees C increase compared to baseline at 10 mm and 20 mm from the electrode after 5 minutes of portal inflow occlusion during constant RF application. CONCLUSIONS: Perfusion-mediated tissue cooling reduces coagulation necrosis achievable with RF ablation. Reduction of blood flow during RF application increases coagulation in both an animal model and human liver metastases.
In the dynamic and complex process of wound healing, locally produced growth factors are important mediators, although their actual roles have not been fully established. In the present study, the presence of transforming growth factor-beta1 and -alpha during the re-epithelialization of full-thickness wounds was investigated in an in vitro model of wound healing in human skin. The amounts of transforming growth factor-beta1 and -alpha secreted from the wound area were measured with enzyme immunoassays, and immunohistochemistry was used to study the localization of these two growth factors in the healing wound. The wounds were followed until they were completely re-epithelialized. The results showed a continuous increase in secreted transforming growth factor-beta1 throughout the re-epithelialization phase of healing followed by a decrease after its completion. The keratinocytes migrating out from the wound edges showed intense staining for transforming growth factor-beta1 which declined to the level of the surrounding epidermis after the wound was covered by a new epidermis. After the skin was wounded, a decrease both in secreted transforming growth factor-alpha and in immunostaining for this growth factor was apparent. Even though a minor increase in the immunoreactivity for transforming growth factor-alpha occurred after the completion of re-epithelialization, no increase in secreted transforming growth factor-alpha could be detected by enzyme immunoassay. These data suggest that keratinocytes modulate their expression of transforming growth factor-beta1 and -alpha during the wound healing process in human skin and that these changes may be controlled in part by autocrine pathways.
The changes of the biliary tree following distal bile duct obstruction and its release were confirmed by biliary scintigraphy and monitored by serial ultrasonography, computed tomography, and values of serum bilirubin and alkaline phosphatase in 14 mongrel dogs. The degree and rate of biliary dilatation were independent of cholecystectomy. The most rapid rate of extrahepatic dilatation occurred within the first 48 hours, while dilated intrahepatic ducts were first recognized three to six days after obstruction. Following release of the obstruction, the degree and rate of resolution of the biliary dilatation were independent of the duration of ligation (one vs. two weeks) and cholecystectomy. The dilatation resolved slowly. Dilated intrahepatic ducts were recognized for as long as eight to 13 days, while extrahepatic biliary dilatation was still present for 13 weeks, at which time the experiment was terminated. It is postulated that the extrahepatic biliary dilatation will approach a plateau approximately one month after total biliary obstruction. It appears that if the obstruction lasts more than one week, it results in irreversible damage to the elasticity of the extrahepatic ducts. Thus, after release of the obstruction, serial biliary imaging is indicated until a new baseline of the biliary tree diameter has been established.
Cultured epithelial autografts transplanted to homograft dermis were analyzed histopathologically from 9 days to 2.25 years after grafting and compared with cultured epithelial autografts transplanted to wound beds devoid of homograft dermis in the same patient. The results suggested that grafting to a dermal substrate accelerates biologic events in skin regeneration from cultured epithelial autografts. Both rete ridge development and normalization of the epidermal keratin program from a "hyperproliferative" to a normal pattern occurred months sooner in the cultured epithelial autografts placed on a dermal matrix. Regeneration of anchoring fibrils was also accelerated. Neither repopulation by Langerhans cells nor repigmentation appeared to be altered significantly by grafting to dermal tissue. By special stain, the elastin network of the allograft dermis could still be visualized at 2.25 years, indicating long-term persistence of the homograft matrix. By clinical assessment the rate of successful engraftment ("take rate") of cultured epithelial autografts grafted to allodermis was estimated to be about 95%, and long-term durability was excellent.
Bromocryptine-induced hypoprolactinemia produces immunosuppression capable of extending allograft survival in solid organ transplantation models, but its potential for delaying either xenogeneic or allogeneic skin graft rejection is as yet undefined. In this study the ability of bromocryptine to prolong the survival of either cutaneous human xenografts or murine allografts was compared with cyclosporin A in a mouse model. In xenograft experiments cryopreserved human cadaver skin was grafted to B6D2F1 mice. In allograft experiments skin graft donors (A/J mice) differed genetically from recipients (Balb-C mice) at the major histocompatibility locus. In the untreated control group xenograft survival averaged 7 days and allograft survival 8 days. Xenograft rejection was delayed significantly and nearly equally by both bromocryptine and cyclosporin A (mean 15 and 16 days, respectively). However, allograft rejection was delayed longer by cyclosporin A (mean 24 days; p = 0.0002) than by bromocryptine (mean 15 days; p = 0.066). Administration of porcine prolactin (1 mg) partially reversed the bromocryptine effect (mean xenograft survival, 11 days; mean allograft survival, 10 days). The results of this study suggest that the immunosuppression of prolactin release by bromocryptine may be an effective, benign means of prolonging the survival of biologic dressings (e.g., banked cadaver allograft or porcine xenograft) used for temporary wound coverage in massively burned patients.
Patchy hypopigmentation often occurs unpredictably in the skin regenerated from cultured epidermal autografts, especially when that skin is grown from frozen cells, serially passaged, or both. The impact of serial subcultivation and cryopreservation on melanocyte viability in the cultured epidermal autograft culture system was investigated. Serial subcultivation of human keratinocytes through as many as eight passages was performed, and melanocyte densities in confluent cultures at each passage were determined after specific labeling of melanocytes. The experimental cells were frozen before cultivation and between passages to determine the effect of standard cryopreservation on melanocyte survival. Freshly passaged cells that had not been frozen served as controls. Melanocytes were gradually depleted during fresh passage of epidermal cells but persisted through as many as seven passages. Freezing before or after the first passage or between subsequent passages resulted in a complete loss of melanocytes by the third or fourth passage. The findings suggest that cryopreservation should be avoided during cultured epidermal autograft production to optimize melanocyte survival and minimize pigmentation abnormalities that may occur after grafting.
We have treated 11 patients with cultured epidermal autograft (CEA) at the Indiana University Medical Center between April 1989 and January 1991. Seven of these patients had acute burns. We have followed up on five of them for at least 5 months; the remaining two are still hospitalized. Two patients had CEA applied to cover giant hairy nevi, and two were treated for hypertrophic burn scars, one of which was treated too recently to report follow-up. Consequently, we report on our experience with eight patients. At our institution we have broadened the indications for grafting with CEA to include injuries greater than 45% to 50% full-thickness and have found it a useful technique. One patient with a hairy nevus had a "take" of CEA of almost 100%, but a synechia formed along his gluteal crease. In another patient, partial loss of the graft was attributed to scratching. Long-term rubbing of a pressure stocking and splint was believed to be responsible for breakdown in the graft of the patient who had a hypertrophic scar.
Explore the source record for details and available documents.
Explore the source record for details and available documents.