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Biomedical subjects

C C Compton

Publications and source records attributed to C C Compton.

At least 109 records · Page 6Linked to original sources
PubMed1990

Cultured keratinocyte sheets enhance spontaneous re-epithelialization in a dermal explant model of partial-thickness wound healing.

An in vitro model for partial-thickness cutaneous wound healing is described in which the influence of variables present in vivo, such as blood-borne factors and inflammatory cells, is eliminated. Dermal sheets of porcine skin are maintained in culture at the air-liquid interface in serum-free medium, and re-epithelialization from the keratinocytes of the hair infundibula can be studied. Dermal sheets of different thicknesses harvested from various depths were first evaluated for viability and regenerative potential in serum-supplemented medium. Mid-dermal explants, 20/1000 inch thick, showed the greatest epithelial outgrowth from the appendigeal keratinocytes and the longest viability in vitro. Explants of this type were used in all subsequent experiments. The effects of growth factors on re-epithelialization of the explants were studied in a serum-free environment. Epidermal growth factor, cholera toxin, bombesin, and insulin-like growth factor alone and in various combinations were applied to the explant surface in aqueous solutions by micropipette. Outgrowth was assessed by computerized morphometric analysis (RS/1 program by BBN) at days four and eight. Among all factors tested, cholera toxin alone and in combination with insulin-like growth factor produced the greatest epithelial outgrowth. Nevertheless, topical applications of growth factors failed to induce complete re-epithelialization within the experimental time frame. In contrast, explants to which cultured human keratinocyte sheets were topically applied regenerated a confluent and regularly stratified epidermis within 6 d.

Administration, Topical↗
PubMed1990

Human Merkel cell regeneration in skin derived from cultured keratinocyte grafts.

Human Merkel cell regeneration in epidermis derived from cultured keratinocyte autografts was studied from 6 days to 6 years after transplantation. Cultured keratinocyte sheets derived from skin of the sole, axilla, groin, or scalp were transplanted to full-thickness wounds in 20 pediatric patients treated for massive burns or giant congenital nevi. Normal age- and site-matched skin as well as meshed split-thickness autografts from the same patients served as controls. Merkel cells were identified by immunohistochemistry using antibodies to cytokeratins #8 and #18. Cultured keratinocytes in vitro expressed no neuroendocrine markers, but nonspecific, simple-epithelial cytokeratin expression was observed in about 20% of cells. After transplantation, Merkel cells were identified only in cultured grafts derived from sole skin and appeared in the epidermis as early as 21 days postgrafting. Dermal Merkel cells were rarely observed, but their appearance invariably succeeded that of intraepidermal Merkel cells. Regenerated Merkel cells were never innervated, and their emergence was unrelated either spatially or temporally to epidermal reinnervation. In skin bridges of meshed split-thickness grafts, Merkel cells survived after degeneration of associated neurites, but no Merkel cells appeared within re-epithelialized interstices. Among the neuroendocrine markers tested, Merkel cells in cultured grafts, meshed skin grafts or normal pediatric skin expressed only neuron-specific enolase. They failed to stain for calcitonin, chromogranin A, Leu-7, synaptophysin, bombesin, or vasoactive intestinal polypeptide by immunohistochemistry. These findings suggest that: (a) Merkel cells derive from keratinocyte precursors which undergo neuroendocrine differentiation in the epidermis; (b) that keratinocyte stem cells are capable of undergoing Merkel cell differentiation postnatally; (c) that postnatal Merkel cell differentiation may be body-site dependent; and (d) that Merkel cell development and maintenance is independent of neural induction.

Antibodies, Monoclonal↗
PubMed1989

Bacterial infection is not necessary for lethal necrotizing pancreatitis in mice.

Sepsis is the most common cause of late death in pancreatitis. The presence of early bacterial infection has been correlated with the severity of the disease. A choline-deficient ethionine-supplemented (CDE) diet given to young female mice produces severe necrotizing pancreatitis that has morphologic and biochemical similarities to the human disease. We therefore searched for bacterial pancreatic infection in female CD-1 mice given the CDE diet. The mortality rate was 47.5% in mice fed the CDE diet. All of these mice had severe pancreatitis with inflammation, edema, and necrosis on histologic examination. Bacterial infection was present in 1/12 pancreatica among nonsurvivors and in 1/32 pancreatica in surviving animals (p not significant). Histologic examination showed edema to be more pronounced in surviving mice, although the overall severity of morphologic changes was not significantly different between survivors and nonsurvivors. We conclude that bacterial infection is not a determinant of the severity or lethality of experimental pancreatitis induced by the CDE diet.

Acute Disease↗
PubMed1989

Cultured epithelial autografts for giant congenital nevi.

Eight pediatric patients with giant congenital nevi confluent over 21 to 51 percent body surface area were treated by excision and grafting. The nevus was excised to the muscle fascia, and the open wound was grafted with cultured epithelial autografts and split-thickness skin grafts. The patients have been followed from 17 to 56 months. Seventeen operations were performed in the eight patients, excising a mean of 6.9 percent body surface area at each procedure. The mean duration of anesthesia was 3.7 hours, and the mean operative blood loss was 12.3 percent estimated blood volume. The mean "take" for the cultured epithelial autografts was 68 percent, and for the split-thickness skin grafts, 84 percent. Epithelialization of open wound areas adjacent to the grafts was somewhat slower for the cultured epithelial autografts than for the split-thickness skin grafts, but it led to a healed wound in all patients except one. Ten of the 17 areas grafted with cultured epithelial autografts resulted in small open wounds that required regrafting. Wound contraction under the cultured epithelial autografts and under split-thickness skin grafts was similar and depended more on the anatomic site grafted than on the type of graft employed. in 16 of 17 operations, the cultured epithelium remained as a permanent, durable skin coverage. The use of cultured epithelial autografts allowed a larger area of excision than would have been possible with split-thickness skin grafts alone and, therefore, a more rapid removal of nevus. Cultured epithelial autograft are an important new technique in the care of patients with giant congenital nevi.

Adolescent↗
PubMed1989

Experimental lymph node metastases: enhanced detection with MR lymphography.

Magnetic resonance (MR) lymphography with superparamagnetic iron oxide (AMI-25) as a contrast agent was developed in an animal model with tumor-bearing lymph nodes. After interstitial administration of 20 mumol of iron per kilogram of body weight into the footpads of rats, the T2 of popliteal and paraaortic lymph nodes decreased from 67 msec +/- 8.2 to 9.5 msec +/- 0.9 and 9.3 msec +/- 0.9, respectively. T2 relaxation times of lymph nodes containing metastases showed a significantly higher value (61 msec +/- 6.2, P less than .005) after interstitial administration of the contrast agent. Intravenous administration of AMI-25 did not produce enhancement of normal or metastatic lymph node relaxation times. The signal intensity of normal lymph nodes decreased profoundly on spin-echo MR images (repetition time of 500 msec, echo time of 30 msec) after interstitial administration, whereas lymph nodes with metastases showed no significant change in signal intensity. Experimental results indicate that MR lymphography may potentially increase the sensitivity of MR imaging the detection of lymphatic malignancy.

Animals↗
PubMed1989

Patterns of failure following local excision and local excision and postoperative radiation therapy for invasive rectal adenocarcinoma.

The clinical course of 40 patients undergoing conservative surgical excision and 26 patients undergoing local excision and postoperative radiation therapy of rectal carcinoma was reviewed. Surgical procedures were transanal excision (55 patients), Kraske procedure (ten patients), and fulguration (one patient). The five-year actuarial survival, disease-free survival, and local control of all 66 patients were 70%, 77%, and 63%, respectively. For patients undergoing local excision alone, the prognostic features of lesion size greater than 3 cm, poorly differentiated histology, invasion into muscularis propria or deeper, moderate to marked stromal fibrosis, vascular or lymph vessel invasion, fragmented resection, and positive resection margins were associated with a local failure rate of 20% or greater. Of the 26 patients receiving postoperative radiation therapy, four patients have developed local failure. For subgroups of patients with small rectal carcinomas confined to the mucosa, local excision may be a reasonable alternative to abdominoperineal resection. For tumors with deeper invasion but limited to the bowel wall, local excision plus pelvic irradiation can be offered to preserve anorectal function.

Adenocarcinoma↗
PubMed1989

Superparamagnetic iron oxide: pharmacokinetics and toxicity.

The pharmacokinetics (distribution, metabolism, bioavailability, excretion) and toxicity (acute and subacute toxicity, mutagenicity) of a superparamagnetic iron oxide preparation (AMI-25), currently used in clinical trials, were evaluated by 59Fe radiotracer studies, measurements of relaxation times, the ability to reverse iron deficiency anemia, histologic examination, and laboratory parameters. One hour after administration of AMI-25 to rats (18 mumol Fe/kg; 1 mg Fe/kg), 82.6 +/- 0.3% of the administered dose was sequestered in the liver and 6.2 +/- 7.6% in the spleen. Peak concentrations of 59Fe were found in liver after 2 hr and in the spleen after 4 hr. 59Fe slowly cleared from liver (half-life, 3 days) and spleen (half-life, 4 days) and was incorporated into hemoglobin of erythrocytes in a time-dependent fashion. The half-time of the T2 effect on liver and spleen (24-48 hr) was shorter than the 59Fe clearance, indicating metabolism of AMI-25 into other forms of iron. IV administration of AMI-25 (30 mg Fe/kg) corrected iron-deficiency anemia and showed bioavailability similar to that of commercially available IV iron preparations within 7 days. No acute or subacute toxic effects were detected by histologic or serologic studies in rats or beagle dogs who received a total of 3000 mumol Fe/kg, 150 times the dose proposed for MR imaging of the liver. Our results indicate that AMI-25 is a fully biocompatible potential contrast agent for MR.

Animals↗
PubMed1989

Primary liver tumors: diagnosis by MR imaging.

MR features of 153 proved primary liver tumors (95 malignant, 58 benign) in 55 patients with hepatocellular carcinoma (21), cholangiocarcinoma (seven), carcinosarcoma (one), hepatoblastoma (one), hemangioma (16), hepatic adenoma (four), focal nodular hyperplasia (three), leiomyoma (one), and hemangioendothelioma (one) were studied retrospectively to determine which techniques are most reliable for lesion detection and which criteria are most useful for differential diagnosis. MR data were correlated with histologic features such as fatty degeneration, fibrosis, and peritumoral edema. Unlike metastatic cancer, hepatocellular carcinoma was best detected (p less than .01) with T2-weighted pulse sequences. The mean tumor-liver T2 difference was 34.4%, while the mean T1 difference was only 21.8%. A tissue-specific diagnosis of hepatocellular carcinoma was possible in 14 of 21 patients by identification of fatty degeneration of the tumor (eight of 17), tumor capsule (five of 21), and/or vascular invasion (six of 21). MR features of peritumoral edema, present in six of 21 patients with hepatocellular carcinoma and in seven of 25 patients with metastases, were exclusively associated with malignant tumors. The large variation in tissue characteristics (relaxation times and proton density) seen in primary liver tumors necessitates the use of multiple pulse sequences to maximize lesion detection. However, the combined use of T1- and T2-weighted spin-echo and T2-weighted phase-contrast images had the advantage of distinguishing benign from malignant primary liver tumors in 48 of 55 patients in this series.

Adenoma↗
PubMed1989

Detection of hepatic metastases with MR imaging: spin-echo vs phase-contrast pulse sequences at 0.6 T.

The purpose of this study was to compare the sensitivity of T1-weighted and T2-weighted spin-echo (SE) pulse sequences with T2-weighted phase-contrast (PC) imaging techniques for the detection of hepatic metastases. Pulse-sequences performance was evaluated in 52 consecutive patients with 88 hepatic metastases who underwent MR imaging at 0.6 T. Lesion-liver contrast-to-noise ratios (CNR) on SE 260/14 (-12.4 +/- 6.7) and PC 2350/60 (+10.8 +/- 4.2) images were significantly (p less than .05) greater than on SE 2350/60 (+ 7.8 +/- 3.9), SE 2350/120 (+8.1 +/- 4.8), SE 2350/180 (+7.9 +/- 4.5), and PC 2350/30 (+4.6 +/- 2.9) images. Sensitivity for detection of 88 individual metastases was comparable on SE 260/14 (78 of 88 patients) and PC 2350/60 (81 of 88 patients) images and was significantly (p less than .05) greater than on in-phase T2-weighted SE images (TE = 60, 70 of 88 patients; TE = 120, 69 of 88 patients; TE = 180, 65 of 88 patients). Histologic analysis of tumor-free liver showed fatty change in 11 of 13 specimens available for pathologic evaluation. In all 11 of those patients, PC images increased tumor-liver contrast in comparison with the in-phase SE images. This analysis suggests that for detection of hepatic metastases at midfield strengths, the T1-weighted, short TR/short TE (SE 260/14) and the T2-weighted, phase-contrast (PC 2350/60) pulse sequences offer comparable performance.

Adult↗
PubMed1989

Skin regenerated from cultured epithelial autografts on full-thickness burn wounds from 6 days to 5 years after grafting. A light, electron microscopic and immunohistochemical study.

Regeneration of skin from cultured keratinocyte autografts used in the treatment of full-thickness burn wounds was studied in 21 pediatric patients from 6 days to 5 years after grafting. Findings were compared both to controls of age- and site-matched normal skin and to controls for epithelial wound-healing, re-epithelialized interstices of meshed split-thickness skin grafts of comparable postgrafting age. Six days after transplantation, a mildly hypertrophic, flat epidermis with all normal strata had regenerated, and the process of de novo dermal-epidermal junction formation had begun. Hemidesmosomes, basal lamina, and anchoring fibrils reformed conjointly in punctate fashion along the attachment face of the grafts. Within 3 to 4 weeks, the dermal-epidermal junction was complete, but full maturation of anchoring fibrils required more than a year. The process was comparable to that observed in meshed graft interstices. Rete ridges regenerated from 6 weeks to 1 year after grafting. The subjacent connective tissue initially healed to form normal scar, but it remodeled dramatically, regenerated elastin, and resembled a true dermis within 4 to 5 years. Meshed-graft interstice controls showed no rete ridge regeneration, subepithelial connective tissue remodeling, or elastin production up to 5 years after grafting. Langerhans cells repopulated grafts within 1 week, and normal population densities were reached within 2 to 6 months. After 1 year, Langerhans cell densities were increased compared with normal skin but were lower than those in age-matched meshed graft controls. Melanocytes were present in cultures at the time of transplantation, but functional epidermal melanin units were not seen in groin- or axilla-derived grafts for 6 to 8 weeks or in sole-derived epidermis until a year or more after transplantation. Normal histologic features were maintained for years after grafting. Transitory pathologic changes including parakeratosis, dyskeratosis, and intraepithelial friction blister formation were infrequently observed. No dysplastic or premalignant changes were seen.

Adolescent↗
PubMed1988

Ménétrier's disease. A trivalent gastropathy.

Current conceptions of Ménétrier's disease only obliquely resemble those originally described. Bona-fide cases are so uncommon that, of 125 cases diagnosed as Ménétier's disease, hypertrophic gastritis, or protein-losing gastropathy treated at the Massachusetts General Hospital during the 26-year period of 1962-1987, only six cases merited an unequivocal anatomic diagnosis. Two other cases previously described proved on review to be nondiagnostic in one instance and Campylobacter pylori gastritis in the other. Because abnormalities in the secretion of gastric acid and in the loss of protein from the stomach may coexist, a representation of each case in semiquantitative terms can be described on triaxial coordinates. Three patients had a hypercoagulable state, one in association with gastric carcinoma. One other case of gastric carcinoma and one of esophageal carcinoma coexistant with Ménétrier's disease were identified. Administration of subcutaneous heparin during the perioperative period to patients with Ménétrier's disease is appropriate regardless of whether or not hypercoagulation or carcinoma is manifest. If treatment with anticholinergic drugs and inhibitors of gastric acid secretion fails, total gastrectomy is the best solution, because it stops protein loss, eliminates hyperchlorhydria, prevents development of gastric carcinoma, and permits anastomotic reconstruction between normal esophagus and normal small bowel.

Adult↗
PubMed1988

Splenic lymphoma: ferrite-enhanced MR imaging in rats.

Ferrite, a new magnetic resonance (MR) contrast agent, was evaluated in the detection and diagnosis of splenic lymphoma. Before administration of ferrite, normal rat spleens and spleens with diffuse lymphoma showed similar in vitro relaxation times and in vivo MR imaging signal-to-noise ratios (S/N). After the administration of ferrite (50 mumol Fe/kg), the T2 time of lymphomatous spleen was 27.0 msec +/- 2.9 (mean +/- standard deviation), which was significantly greater than that of normal spleen (10.7 msec +/- 1.5, P less than .005). The S/N of ferrite-enhanced in vivo MR images of lymphomatous spleen was 12.4 +/- 0.9, which was significantly greater than normal (5.7 +/- 0.2, P less than .005). Similar experiments with animal models of micronodular lymphoma also demonstrated that ferrite-enhanced MR imaging can distinguish micronodular lymphoma from normal spleen. Benign splenomegaly, studied with an animal model of erythroid hyperplasia, showed ferrite-enhanced MR tissue characteristics that were indistinguishable from those of normal spleen.

Animals↗
PubMed1987

Ferrite-enhanced MR imaging of hepatic lymphoma: an experimental study in rats.

The purpose of this investigation was to define the potential of unenhanced and ferrite-enhanced MR to detect hepatic lymphoma. Rats were implanted with diffuse and focal hepatic lymphoma. Both in vitro measurements of relaxation times and in vivo MR imaging of normal liver and of diffuse and focal hepatic lymphoma were compared. Diffuse infiltrative hepatic lymphoma showed increased T1 (45%) and T2 (41%) relaxation times in vitro, but could not be distinguished from normal control livers on in vivo spin echo (SE) images with a repetition time of 500 msec and an echo time of 30 msec (SE 500/30) or SE 1500/60 images. Focal hepatic lymphoma showed increased T1 (185%) and T2 (115%) relaxation times relative to normal liver tissue. Focal hepatic lymphoma was undetectable on unenhanced SE 500/30 MR images (contrast-to-noise ratio, C/N = 0.4) and was slightly hyperintense on SE 1500/60 images (C/N = 1.1). Ferrite (50 mumol Fe/kg) was administered to improve tissue contrast. In normal control animals, T2 of liver in vitro decreased from 29.3 +/- 3.3 msec to 11.1 +/- 1.2 msec, and image signal-to-noise ratio (S/N) of liver in vivo decreased from 16.1 +/- 2.4 to 2.8 +/- 0.3 (p less than .005). Ferrite-enhanced diffuse hepatic lymphoma showed in vitro T2 values and in vivo MR image S/N values indistinguishable from those of normal control animals. The T2 of focal hepatic lymphoma was essentially unaltered by ferrite. On SE 500/30 images, focal hepatic lymphoma became readily detectable, quantitated by a 35-fold increase in tumor-liver C/N. We conclude that clinical studies are warranted to determine the value of ferrite enhanced MR as a technique for the enhanced detection of focal hepatic lymphoma.

Animals↗
PubMed1987

Ferrite particles: a new magnetic resonance imaging contrast agent. Lack of acute or chronic hepatotoxicity after intravenous administration.

Intravenous administration of ferrite particles may be useful as contrast agents for magnetic resonance (MR) imaging of the liver. We studied several sensitive biochemical parameters of hepatocellular function and toxicity in rats after intravenous ferrite injections to determine whether there was any evidence of iron-induced hepatotoxicity. Light microscopy and iron determinations were performed on the liver, spleen, lung, and kidney. Forty-eight hours after a massive (250 mg iron per kilogram) ferrite injection, liver, spleen, and lung nonheme iron concentrations were markedly increased. Microscopy showed this iron to be entirely in reticuloendothelial cells. Despite the large increase in hepatic iron concentration, we found no evidence of hepatic mitochondrial or microsomal lipid peroxidation or organelle dysfunction, sensitive biochemical indicators of iron-induced hepatocellular injury. At 10 to 11 weeks after administration of ferrite in smaller doses (30 mg iron per kilogram), results of all biochemical and morphologic studies were normal. Furthermore, quantitative iron determinations and microscopic studies suggest that ferrite particles may be partially degraded and that iron is cleared from the liver during a 3-month period. Because ferrite particles are taken up by reticuloendothelial cells, hepatocellular function is not impaired and iron-induced hepatocellular injury does not occur.

Animals↗
PubMed1986

Chronic acalculous gallbladder disease: multiimaging evaluation with clinical-pathologic correlation.

Despite the recent advances in hepatobiliary imaging, the diagnosis of chronic acalculous gallbladder disease remains difficult. A retrospective study was undertaken to assess the value of a multiimaging approach in detecting chronic acalculous gallbladder disease and in predicting which patients would obtain symptomatic relief after cholecystectomy. Of 199 patients with chronic cholecystitis, 26 (13%) had no gallstones. Of these 26, only 17 (65%) had symptoms related to chronic cholecystitis; in the remainder, the histologic diagnosis was made incidentally. After cholecystectomy, 13 (76%) of the 17 symptomatic patients obtained long-term symptomatic relief, while in four, the symptoms recurred. Among patients with histologic changes of chronic cholecystitis, biliary scintigraphy was the most sensitive technique (sensitivity, 89%). The sensitivity of sonography and oral cholecystography was 61.5% and 66%, respectively. However, for identifying symptomatic patients who may obtain long-term symptomatic relief after cholecystectomy, the accuracy of sonography, oral cholecystography, and biliary scintigraphy was 82%, 86%, and 38%, respectively. When two tests were in agreement the accuracy was 88%. For chronic acalculous cholecystitis, more than one study must be performed in order to make the correct diagnosis and to predict good results from cholecystectomy.

Adult↗
PubMed1985

Structure of the sinus-lining cells in the popliteal lymph node of the rabbit.

The structure of the sinus walls in the popliteal lymph node of the rabbit was studied with the electron microscope. In the marginal sinus, the endothelial cells are connected by gap junctions, puncta adherentia, and surface specializations characterized by focal approximation of the adjoining membranes without fusion. They possess large numbers of simple and compound uncoated invaginations of the plasma membrane that are closed by a diaphragm with a central thickening. The tissue strands that straddle the lumen of the sinus consist of a fibrous core containing both collagen and elastic fibers, surrounded by endothelial cells identical to those composing the outer sinus wall. Cortical sinuses that run independently of the trabeculae were identified by exploiting the fact that their endothelial cells accumulate lymph-borne ferritin, and their lumen is outlined by horseradish peroxidase administered intravenously. They are lined by a flattened, continuous endothelium and lack luminal strands. The walls of the medullary sinuses consist of endothelial cells and macrophages. The endothelial cells are interconnected by specialized junctions and contain fewer plasmalemmal vesicles than in the cortex; furthermore, dense granules are present in their cytoplasm. Macrophages adhere to the surface of the endothelial cells; typically, none of the junctional specializations that characterize the interface between endothelial cells connect endothelial cells to macrophages. However, at points along the contact region with the endothelium, the plasmalemma of the macrophage is decorated by an attachment plaque of fluffy cytoplasmic material. Sinus endothelial cells slowly accumulate lymph-borne ferritin like vascular endothelial cells elsewhere in the body, whereas macrophages contain both ferritin and engulfed erythrocytes.

Animals↗