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Biomedical subjects

C Compton

Publications and source records attributed to C Compton.

At least 19 recordsLinked to original sources

Protocol for the examination of specimens removed from patients with gastric carcinoma: a basis for checklists. Members of the Cancer Committee, College of American Pathologists, and the Task Force for Protocols on the Examination of Specimens From Patients With Gastric Cancer.

A protocol for the pathologic examination and reporting of specimens from patients with gastric carcinoma has been developed by the Cancer Committee of the College of American Pathologists and a multidisciplinary task force of specialists dealing with patients with gastric carcinoma. The protocol incorporates all basic pathology data of diagnostic and prognostic significance appropriate for the treatment of patients with gastric carcinoma. The purpose of the protocol is to serve as a basis for the development of checklists, as on outline for full narrative reporting, as a basis for research protocols, or as a guide for other types of synoptic or reporting formats. The protocol is stratified to accommodate the surgical procedures usually employed for gastric carcinomas, including acquisition of cytologic specimens, incisional endoscopic biopsy, excisional biopsy, and gastric resection (partial or complete). Explanatory notes detailing specific procedures and rationales for documentation of specific pathologic data are included in the protocol. The protocol uses the staging system for gastric carcinoma defined by the American Joint Committee on Cancer and the International Union Against Cancer.

Biopsy

Control of hypertrophic scar growth using selective photothermolysis.

BACKGROUND AND OBJECTIVE: Previous studies have shown a clinical improvement of hypertrophic scars (HS) after treatment with a pulsed dye laser. The objective of this study was to investigate the effects of variations in pulse wavelength and energy density on HS tissue using human HS implanted in athymic mice. STUDY DESIGN/MATERIALS AND METHODS: Small pieces (approximately 1 mm3) of HS tissue were implanted into athymic mice and allowed to grow for 5 days. The implant site was then exposed to a single 450 microseconds pulse, and implant growth and histology were monitored for an additional 12 days. Laser wavelength and energy density ranges tested were 585-600 nm and 2-10 J/cm2, respectively. RESULTS: Using a wavelength of 585 nm, laser treatment inhibited implant growth by 70% at 6 J/cm2 and 92% at 10 J/cm2, respectively. The inhibitory effect decreased as the laser wavelength was increased from 585 to 600 nm. A widespread destruction of the implant microvasculature with a minor effect on surrounding extracellular matrix at the highest light dose were observed. CONCLUSION: Pulsed laser treatment inhibits HS implant growth in nude mice. This effect is likely mediated by selective photo-thermolysis of the implant microvasculature.

Animals

Evening dosing is associated with higher plasma concentrations of pranlukast, a leukotriene receptor antagonist, in healthy male volunteers.

AIMS: To study the magnitude of differences in the pharmacokinetics of pranlukast, after morning and evening administration. METHODS: Pranlukast (300 mg) was administered to 12 healthy male volunteers on two separate occasions, either in the morning or evening. Both doses were given 30 min after a standard high fat content meal. Blood samples were collected up to 18 h postdose. Plasma was assayed by high performance liquid chromatography. Standard pharmacokinetic and statistical analyses were performed. RESULTS: Statistically significant (P < 0.05) increases were noted in AUC(o,t) (56%) and tmax (2.5 h) after evening administration. Cmax was 14% higher after evening dosing (95% C.I. 0.71-1.84). CONCLUSIONS: Pranlukast bioavailability is apparently increased after evening dosing as compared with morning administration. Higher night-time and early morning plasma concentrations may confer additional therapeutic benefit at a time when asthmatics are at greatest risk of developing bronchospasm.

Adult

Human dermal microvascular endothelial cells express the 140-kD isoform of neural cell adhesion molecule.

It has only recently been appreciated that the level of gene expression of cell surface markers can be different in endothelial cells derived from different anatomical sites, and that these differences can persist in vitro. In this study, we identify an immunoglobulin gene superfamily member, neural cell adhesion molecule (NCAM), that is expressed on the cell surface of human dermal microvascular endothelial celis but not on umbilical vein, pulmonary vein, aorta, or pulmonary artery derived endothelial cells. By western blot analysis, we identified the 140 kD isoform of NCAM on the surface of human dermal microvascular endothelial cells (HDMEC) derived from dermis. Isolates of HDMEC from human foreskin reproducibly expressed high levels of cell surface immunoreactive protein. In contrast, endothelial cells from large vessels never expressed NCAM constitutively and could not be induced to express NCAM by three proinflammatory cytokines. Western blot analysis of membrane preparations of HDMEC indicated that NCAM protein migrated as a single species with a molecular mass of 140 kD. RT-PCR identified NCAM mRNA in HDMEC cells. The potential for expression of NCAM on small vessels in skin can be interpreted in different ways. Members of the immunoglobulin gene family, including ICAM-1, ICAM-2, and VCAM-1, can be expressed on the cell surface of all endothelial cells and serve as adhesion molecules for leukocytes. It is also possible that, by analogy, NCAM serves as a ligand for a receptor on leukocytes, particularly those that also express NCAM (e.g., natural killer cells). Alternatively, it is possible that NCAM expression permits endothelial cell-cell adhesion, enhancing the structural integrity of microvessels or facilitates neural interactions with microvascular endothelium.

Antibodies, Monoclonal

Cultured epidermal autografts and allodermis combination for permanent burn wound coverage.

Cultured epidermal autografts (CEA) have been shown to be an effective permanent skin replacement for major burn injuries, but are more sensitive to adverse conditions than split thickness grafts (Clarke et al., 1988). Cuono et al. (1986, 1987) have described the successful use of engrafted allodermis as a wound bed for cultured grafts. We report on a method of preparing allodermis and grafting CEA in five patients with major burns (48-70 per cent TBSA, average 59.6 per cent). The average age was 38.8 years (20-60 years). All full thickness wounds were excised down to fat within 7 days of admission, and covered with meshed split thickness cryopreserved homograft. Over the ensuing 2-3 weeks, the homograft became engrafted. At surgery, the allo-epidermis was removed, leaving the dermal components as a viable bed for the CEA. Keratinocytes derived from a full thickness biopsy were grown to confluence by the method of Rheinwald and Green (1975), and 25 cm2 sheets were stapled to Vaseline gauze backings and applied to freshly excised wounds. Seven to 10 days after surgery, the gauze backings were removed. The average take ranged from 87-100 per cent (average 93.6 per cent). Follow-up for up to 4 years shows supple skin that has been durable, and resistant to trauma and infection.

Adult

TGF-beta 1 gene expression in cultured human keratinocytes does not decrease with biologic age.

The biologic activity of cultured epithelial grafts is believed to diminish with increasing cellular age. Therefore, keratinocytes from young donors are used preferentially in the production of cultured allografts for wound treatment. However, the impact of biologic age on cytokine gene expression by human keratinocytes has not been previously investigated. In this study, transforming growth factor-beta 1 (TGF-beta 1) gene expression in human keratinocytes derived from normal foreskins of males ranging in age from 7 months to 82 years was analyzed. Keratinocytes were harvested from fresh specimens and cultivated in vitro on 3T3 fibroblast feeder layers through second passage. The cells were analyzed both qualitatively and semiquantitatively for TGF-beta 1 gene expression using three separate techniques: in situ hybridization, Northern hybridization, and competitive polymerase chain reaction. By in situ hybridization, the signal representing TGF-beta 1 transcript was detected in cells in all layers of the stratified cultures, and immunohistochemical staining for TGF-beta 1 protein was equally intense in all layers. Northern blots of total RNA extracted from the cultivated cells showed no decrease in band density with increasing biologic age. Likewise, no decrease in TGF-beta 1 mRNA levels with biologic age was observed using a semiquantitative polymerase chain reaction assay. These results indicate that the potential for TGF-beta 1 gene expression in cultured foreskin keratinocytes does not decline with increasing cellular age. The findings imply that the clinical performance of cultured grafts, at least as it relates to the elaboration of this growth factor, may not be significantly altered by the biologic age of the keratinocyte donor.

Adult

Production of extracellular slime by coryneforms colonizing hydrocephalus shunts.

Corynebacterium spp. are responsible for an important minority of cases of colonization of cerebrospinal fluid shunts used for the treatment of hydrocephalus. In common with coagulase-negative staphylococci, they present a serious therapeutic problem because they are often resistant to multiple antibiotics. We studied the morphologies of coryneforms in colonized hydrocephalus shunts removed from patients and observed extracellular slime similar in appearance to that seen in coagulase-negative staphylococci. We also studied a series of such isolates from other cases of hydrocephalus shunt colonization using an established laboratory model and consistently observed slime production in these shunts as well. We propose that this might be a further reason for failure to eradicate these organisms without shunt removal as well as a factor in their pathogenesis in device-related infections.

Adult

Rural motor vehicle crash mortality: the role of crash severity and medical resources.

We did a retrospective case control study to examine the relationship between the risk of dying for Michigan motor vehicle crash (MVC) drivers and the type of county (rural/nonrural) of crash occurrence, while adjusting for crash characteristics, age, sex, and the medical resources in the county of crash occurrence. The 1987 Michigan Accident Census was used to obtain data regarding all MVC driver nonsurvivors (733) and a random sample of all surviving drivers (2,483). County of crash occurrence was defined as rural or nonrural. The crash characteristics analyzed were vehicle deformity, seat belt use, and drivability of the vehicle from the scene. Age and sex of the driver were also analyzed. Medical resource characteristics for the county of crash occurrence were measured as the number of resources per square mile for each of the following: ambulances, emergency medical technicians (EMT), acute care hospital beds, and operating rooms, surgeons and emergency physicians. Also considered were the number and level of emergency rooms in the county of crash occurrence along with the maximum level of prehospital care available (basic life support versus advanced life support) in a county. Before adjusting, the relative risk (RR) for rural MVC drivers dying, compared to their nonrural counterparts, was 1.96. Adjustment for crash characteristics, age, and sex (using logistic regression) decreased the RR to 1.51. An attempt to add medical resource variables to the model resulted in high correlation with the rural/nonrural variable, as well as with each other. This multi-collinearity prevented us from providing a simple explanation of the role of medical resource variables as predictors of survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Traffic

c-Ki-ras mutations in dysplastic fields and cancers in ulcerative colitis.

A sensitive restriction fragment length polymorphism assay and DNA sequencing were used to detect c-Ki-ras mutations in 56 specimens of colonic epithelium from 18 patients with chronic ulcerative colitis. Mutations were not detected in biopsy specimens that were negative or indefinite for dysplasia. In 4 of 8 patients with high-grade dysplasia, a c-Ki-ras codon 12 or 13 mutation was detected. In three colectomy specimens, a wide area of dysplastic cells (greater than 10 cm2) contained a specific ras mutation. In two of these specimens, an invasive cancer contained a c-Ki-ras mutation identical to that found in adjacent dysplastic epithelium. These studies indicate that mutations of c-Ki-ras may be an excellent molecular genetic marker to map dysplastic fields and invasive cancer in ulcerative colitis.

Base Sequence

Macrocystic serous cystadenoma of the pancreas: a morphologic variant differing from microcystic adenoma.

The term "microcystic adenoma" of the pancreas has gained nearly universal acceptance among pathologists owing to the characteristic gross and microscopic features of this tumor. The possible existence of macrocystic variants of serous cystadenoma has been largely ignored in the literature. We report five cases of macrocystic serous cystadenoma of the pancreas, two of which were of the unilocular type. These tumors exhibited distinctly different macroscopic features from microcystic adenoma, which created diagnostic difficulties for both the radiologist and pathologist. Computed tomography scans on all five cases were thought to represent either mucinous cystic neoplasms or pseudocysts and the tumors were misclassified in two of three cases on which intraoperative frozen sections were performed. In our opinion, microcystic and macrocystic serous tumors represent morphologic variants of the same benign pancreatic neoplasm and we suggest that the term "serous cystadenoma" be used to encompass all variants of this benign neoplasm.

Adenoma

Adverse effect of therapeutic vasoconstrictors in experimental acute pancreatitis.

Alpha-adrenergic drugs commonly are used to treat hypotension resulting from severe acute pancreatitis. It was shown previously that although systemic arterial pressure is increased by phenylephrine, pancreatic microcirculatory perfusion is decreased. Because inadequate tissue perfusion may be critical in the progression of edematous pancreatitis to parenchymal necrosis, it was hypothesized that vasoconstrictors might be harmful in pancreatitis. Therefore the effect of phenylephrine on cerulein-induced mild pancreatitis were studied. Sprague-Dawley rats (n = 54) were randomly allocated to 6 experimental groups and subjected to the following infusion regimens: (1) cerulein (cae) + phenylephrine (phe), (2) cae + saline (NS), (3) NS + phe, (4) cae + phenoxybenzamine (pbz) + phe, (5) NS + pbz + phe, and (6) NS. Initial and terminal hematocrit, serum amylase activity, and blood ionized calcium concentration were determined. The animals were killed 9 hours after starting the infusion. Macroscopic and histologic changes were scored by a 'blinded' pathologist. Phenylephrine increased the severity of cerulein-induced pancreatitis as manifested by statistically significant adverse changes in serum amylase, hematocrit, ionized calcium, peripancreatitic soap formation, and acinar cell vacuolization. These changes were antagonized by alpha-adrenergic receptor blockade with phenoxybenzamine. It is concluded that phenylephrine is deleterious in acute experimental pancreatitis, the first demonstration of such an effect by a pharmacologic vasoconstrictor, and suggested that microcirculatory changes may be important in the transition of mild to severe pancreatitis. Caution in the use of vasoconstrictor drugs in patients with acute pancreatitis is recommended.

Acute Disease

Sarcomas of the gastrointestinal tract. Separation into favorable and unfavorable prognostic groups by mitotic count.

The authors reviewed the Massachusetts General Hospital experience with primary malignant stromal tumors of the gastrointestinal tract since 1962. Fifty-one of fifty-five lesions were leiomyosarcomas, and the most common anatomic location was the stomach (47%), followed by small intestine (24%), rectum (11%), colon (7%), duodenum (5%), and esophagus (5%). Most patients presented with gastrointestinal bleeding. There were peaks in age incidence in the fourth and sixth decades. All patients underwent surgery initially, and 40 of 55 had resections with "curative intent." Radiation therapy and chemotherapy were employed to a lesser extent, mainly in a palliative setting. The authors found that using number of mitoses per high-power field as the sole determinant of tumor grade yielded two very distinct clinical populations. Patients curatively resected with low-grade lesions had a better than 80% disease-free survival at 8 years, compared with a mean disease-free interval of only 18 months for high-grade lesions. In resectable disease, tumor grade appears to be the single most important prognostic factor. For gastric lesions there was no apparent advantage in extended resections compared with lesser resections encompassing all gross disease. Because of limited numbers of patients, no benefit could be demonstrated for adjuvant radiotherapy.

Adolescent

MR imaging of blood-borne liver metastases in mice: contrast enhancement with Fe-EHPG.

To determine whether iron(III)ethylenebis-(2-hydrophenylglycine) (Fe-EHPG), a prototype hepatobiliary magnetic resonance imaging agent, can enhance the liver-to-tumor contrast-to-noise ratio (C/N) in models of liver tumors in mice, two types of cell inoculation were used: intrahepatic implantation of M5076 sarcoma and intrasplenic injection of colon tumor (C-26) or M5076 sarcoma. Significant enhancement of the liver-to-tumor C/N and/or improved visualization of small lesions was consistently observed on T1-weighted images obtained after injection of the contrast material. For intrahepatic implants, the C/N on postinjection T1-weighted images was superior to that on T1- and T2-weighted preinjection images. For the C-26 metastatic liver lesions of larger diameter (greater than 5 mm), the C/N on postinjection T1-weighted studies was superior to that on preinjection T1-weighted images but was comparable to that on preinjection T2-weighted images. However, higher C/N after administration of Fe-EHPG improved visualization of medium-sized (3-5 mm) and small (1-3-mm) metastatic lesions in both M5076 and C-26 models. These results demonstrate that MR imaging with appropriate hepatobiliary agents appears promising for early detection of liver metastases.

Animals

Aneuploidy in pancreatic insulinomas does not predict malignancy.

Nuclear deoxyribonucleic acid (DNA) ploidy studies with paraffin embedded archival material from 14 pancreatic insulinomas were performed by flow cytometry. Clinical follow-up (2 to 17 years; mean, 8 years) was obtained for all patients. Half of the tumors had a normal DNA histogram and half exhibited an abnormal DNA profile consistent with DNA aneuploidy. Six of the seven patients with aneuploid tumors are alive and disease free (2 to 5 years postresection), and one is alive with metastatic disease. Of the seven patients with tumors showing normal DNA profiles, five are alive and disease free, one is dead of disease, and one is alive with metastatic disease. These data suggest that DNA ploidy analysis is unlikely to provide useful prognostic information for patients with insulinomas.

Adolescent

Hypocalcemia in experimental pancreatitis occurs independently of changes in serum nonesterified fatty acid levels.

Hypocalcemia and lipid abnormalities commonly occur in acute pancreatitis. Experimentally, increased plasma concentrations of free fatty acids (NEFA) can lower the serum calcium (Ca). We hypothesized that changes in blood-ionized calcium might parallel changes in NEFA concentration in pancreatitis. This hypothesis was tested in a model of severe necrotizing pancreatitis and a model of mild edematous pancreatitis. Adult male Sprague-Dawley rats (300-400 g) were randomized to receive: 100 microL sodium glycodeoxycholic acid (GDOC 34 mmol/L) infused into the pancreatic duct to produce severe necrotizing pancreatitis (Group 1); 100 microL 0.9% NaCl (NS) infused into the pancreatic duct (Group 2); Sham laparotomy (Group 3); A 6 h IV infusion of cerulein (5 mucg/kg/h) to produce mild edematous pancreatitis (Group 4); and a 6 h IV infusion of NS (Group 5). A significant time dependent decrease in blood-ionized Ca concentration, compared to normal rats, was observed in both GDOC-pancreatitis (0.836 +/- .057 vs 1.069 +/- .038 mmol/L p less than 0.001) and cerulein pancreatitis (0.988 +/- .028 vs 1.069 +/- .038 p less than 0.05), which was maximal 24 h after induction of pancreatitis. The degree of hypocalcemia correlated with the severity of pancreatitis (GDOC 0.836 +/- .057 vs cerulein 0.988 +/- .028 p less than .001). Hypocalcemia was not observed in any of the control groups. All experimental and control groups had significantly increased baseline NEFA concentrations compared with normal rats (p less than 0.001); however, no further increase in NEFA concentration occurred in conjunction with the observed time-dependent decline in ionized calcium concentrations. Although the NEFA concentrations observed in these experiments were comparable to those measured in human acute pancreatitis (exclusive of hyperlipemic pancreatitis), the time course of the changes suggests that increases in serum NEFA concentrations in experimental pancreatitis are not the primary factor mediating hypocalcemia.

Acute Disease

Benign smooth muscle tumors of the gastrointestinal tract. A 24-year experience.

Between 1963 and 1987, 131 patients with benign gastrointestinal stromal tumors, primarily leiomyomas, were treated at the Massachusetts General Hospital. Eighty per cent of tumors were located in stomach or small intestine. Two thirds of the tumors were discovered in symptomatic patients before operation by a variety of diagnostic studies. A mitotic index (MI) was determined for each tumor, defined as the number of mitoses per 50 high-power microscopic fields. Only gastric and small intestine tumors had MIs more than 2. Tumors were treated by conservative excision in 67% and radical excision in 33%. At a median follow-up of 6 years there were no local recurrences. No patient with a tumor discovered incidentally has recurred. Three symptomatic patients have died of metastatic liver disease. Each patient with recurrence had a tumor with MI of 2 or more, which represents a recurrence rate of 16% in this group. We conclude that symptomatic gastric and small intestine tumors having two or more mitoses per 50 high-power fields carry a significant risk for recurrence, and that routine pathologic assessment of MI may identify a subset of patients who would potentially benefit from close follow-up and consideration for further therapy.

Adult

Cultured porcine epithelial grafts: an improved method.

An improved method of in vitro cultivation of porcine keratinocytes by which keratinocyte sheets suitable for grafting can be generated rapidly is described. Epidermis from split-thickness porcine skin is enzymatically separated from dermis with 0.25% Dispase solution (37 degrees C) within 3 h, and trypsinized to a single cell suspension. Keratinocytes are grown in Dulbecco-Vogt modified Eagle medium supplemented with 20 ng/ml hydrocortisone, 100 micrograms/ml penicillin, 100 micrograms/ml streptomycin, and 20% (cells from six-month-old pigs) or 10% fetal calf serum (cells from two-month-old pigs). Freshly isolated keratinocytes are plated at a density of 1.25 X 10(6) cells/ml since their plating efficiency is about 15 times lower than that of human keratinocytes grown under comparable conditions. Primary keratinocytes plated on plastic grow to confluence faster than those plated on lethally irradiated 3T3-J2 feeder layer cells. Porcine keratinocytes grown on plastic reach senescence in the third passage but, when subsequently cultivated on a lethally irradiated 3T3-J2 feeder layer, can be passaged up to seven times. Nevertheless, plating efficiency of second-passage porcine keratinocytes is only about 5%-7%, whereas that of human newborn foreskin keratinocytes is 20%-30%. Confluent stratified primary cultures grown on plastic, or secondary cultures grown on feeder layers, are used for grafting. The sheets are detached with Dispase solution and stapled to vaseline gauze to facilitate handling. Epidermal regeneration from porcine grafts produced by this method has been demonstrated after transplantation to full-thickness wounds excised to muscle fascia in donor animals.

Animals