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Biomedical subjects

R G Tompkins

Publications and source records attributed to R G Tompkins.

At least 163 records · Page 9Linked to original sources
PubMed1989

Occult gastrointestinal bleeding: newer techniques and diagnosis and therapy.

Complex problems occur concerning the diagnosis and treatment of GI bleeding. How often can the exact cause and site of the bleeding be determined? What are the advantages and complications of various forms of treatment? There are no universal answers, applicable to all situations. Nevertheless, certain assumptions seem to be justified. Diagnosis of the cause of severe bleeding, often suggested by the patient's history, is confirmed most effectively by selective angiography, which should give an answer in over 95% of cases. The causes of slow, persistent bleeding, manifested either by gross blood or by positive tests for blood in the stools, are diagnosed in about the same percentage of cases by endoscopy. It is when the bleeding is intermittent and of minimum or moderate severity that determination of the site of origin is the most difficult; angiography cannot help in the majority of cases, and endoscopy can miss tiny lesions that are not bleeding at the time of examination. However, laparotomy, especially when it is combined with intraoperative enteroscopy or angiography, should reduce the number of unsolved diagnoses to under 5% of the total. Surgery is the primary method of therapy in many cases. Primary control of bleeding also can be obtained in approximately 80% of cases of severe bleeding by endoscopy, by the use of coagulation or laser, or by selective arterial infusion of pitressin. Recurrences must be treated by surgery, except in some instances where selective embolization by the angiographer may result in a cure. The surgeon must attempt to cure the hemorrhage and to prevent recurrence at a later date by such measures as gastric resection and vagotomy for bleeding duodenal ulcers to prevent stomal ulcers, or by subtotal rather than segmental colectomy for widespread colonic diverticulosis. There will be an irreducible percentage of lesions that continue to develop in other sections of the GI tract after successful primary treatment of the original cause of bleeding; AVMs, angiodysplasia, and vasculitis are examples. Fortunately, such diseases are relatively rare. It is not unreasonable today to expect that the measures discussed herein will cure bleeding in 95% of cases; if death occurs it rarely is due to hemorrhage, but to some type of organ failure.

Gastrointestinal Hemorrhage↗
PubMed1988

Increase of sialyltransferase activity in the small intestine following thermal injury in rats.

The acute phase protein response following inflammation is associated with an increased total protein-bound carbohydrate content in plasma in the form of glycoproteins. Glycosyltransferases in liver may serve as a regulator of this increased glycosylation activity in the plasma and may also serve as a marker for the acute phase response. Sialyltransferase is an example of a glycosyltransferases in which sialic acid is transferred to oligosaccharides of glycopeptides in the Golgi prior to glycopeptide secretion. In this study, sialyltransferase activities were determined in plasma, liver, and intestinal mucosa following a standardized 25% body surface area thermal injury in the rat. A statistically significant increase in sialyltransferase activity was found in liver and small intestine which were maximal at 24 hours after the injury. These increased sialyltransferase activities were accompanied by a statistically significant 2 to 4 fold elevation in plasma sialyltransferase activity at 24 hours. The plasma and liver elevations in these activities were similar to elevations seen in other models of acute inflammation using turpentine injections and bacterial infections. The increased sialyltransferase activity within the rat intestine was comparable to increases in intestinal sialyltransferase activity following colchicine treatment and may represent a similar mechanism(s).

Animals↗
PubMed1988

Significant reductions in mortality for children with burn injuries through the use of prompt eschar excision.

During the past 19 years, mortality due to burn injuries has markedly declined for children at the Boston Unit of the Shriners Burns Institute (SBI), dropping from an average of 9% of SBI admissions during 1968-1970 to an average of 1% during 1981-1986. Detailed statistical analysis using logistic regression was necessary for determining whether this decline in mortality was explained by changes in patient characteristics, such as age or burn size, which are known to strongly influence the outcome of burn injuries. This dramatic decline in mortality during the past 19 years was not the result of change in the age of the patients or their burn sizes; rather, it may be attributed to improvements in burn care. Results of this statistical analysis indicated that, for burn injury patients whose ages ranged from 11 days to 19 years, age had no demonstrable effect on survival from a burn injury. Children survived burn injuries at least as well if not better than the young adult (20-29 years of age). Also, infants (less than 1 year old) survived as well as other children (2-19 years old). Dramatic improvement in survival occurred in patients with burns covering more than 50% of the body surface area. Since 1979, mortality has been essentially eliminated for patients with burn sizes less than 70% of the total body surface area (of 296 patients with burns covering 15-69% of the total body surface area, only two patients died). During the period 1979-1986, 29 of 37 patients (78%) survived an 80% or greater total body surface area thermal injury.

Administration, Topical↗
PubMed1988

Rectal necrosis after pelvic crush injury.

A case is described in which transmural necrosis of the rectum occurred following a severe pelvic crush injury in an obese man. The necrosis presumably resulted from occlusion of both internal iliac arteries, disruption of the pelvic collateral circulation, and as a result of direct rectal contusion.

Adult↗
PubMed1988

Redistribution of blood flow after thermal injury and hemorrhagic shock.

Diminished mucosal mass and a diminished rate of DNA synthesis by the intestinal mucosa have been identified in the rat after thermal injury. Because these changes may be associated with ischemia, the distribution of intestinal blood flow was studied after a thermal injury and compared with the blood flow distribution after hemorrhagic shock. For the thermal injury, anesthetized animals received a standardized 20% body surface area, full-thickness injury and were given intraperitoneal saline resuscitation. By the use of 46Sc- or 141Ce-labeled microspheres, no changes in intestinal and hepatic blood flow occurred after thermal injury. In contrast, a marked redistribution of blood flow was identified after hemorrhagic shock in which a decrease in arterial blood flow was identified to the stomach and to the small and large intestine. Although clinical shock was not present, the cardiac output decreased to a comparable degree in the hemorrhagic shock and the thermal injury. These studies indicate that although physiological changes in intestinal mucosa can be demonstrated after burn injury, these changes are not due to decreases in mesenteric arterial blood flow.

Animals↗
PubMed1988

Measurement of 125I-low density lipoprotein uptake in selected tissues of the squirrel monkey by quantitative autoradiography.

A recently developed technique of absolute quantitative light microscopic autoradiography of 125I-labeled proteins in biologic specimens was used to measure 125I-low density lipoprotein (125I-LDL) concentration levels in various tissues of the squirrel monkey after 30 minutes of in vivo LDL circulation. Liver and adrenal cortex exhibited high 125I-LDL concentrations, presumably because of binding to specific cell surface receptors and/or internalization in vascular beds with high permeability to LDL. High tissue concentrations of LDL were associated with the zona fasciculata and reticularis of the adrenal cortex and the interstitial cells of Leydig in the testis; significantly lower levels of 125I-LDL were observed in the adrenal medulla, the zona glomerulosa, and germinal centers of the testis. Contrary to previous reports, low 125I-LDL concentrations were observed throughout the gastrointestinal tract and in lymph nodes. In addition, multiple arterial intramural focal areas of high 125I-LDL concentrations were identified in arteries supplying the adrenal gland, lymph node, small bowel, and liver.

Adrenal Glands↗
PubMed1986

Burn therapy 1985: acute management.

Mortality occurs from a burn injury because of infections which result from the metabolic and bacterial consequences of a large open wound, depression of the host's resistance, and both protein and total caloric malnutrition. Systemic antibiotics, topical wound therapy, and gentle wound debridement constitute traditional burn therapy. The systemic antibiotics and topical wound therapy do not solve problems presented by large open wounds and the related protein and caloric deprivation. A more rational approach uses antibiotics and topical wound therapy only as adjuncts to a program of early operative removal or excision of the devitalized, burned tissue and immediate closure of the wound. The excised wound is normally closed with available autograft, but in massive burn injuries, donor skin is insufficient. In these massive injuries, artificial skin can provide that immediate wound closure. As long as devitalized, burned tissue remains present in the setting of depressed host resistance, cross infection tends to colonize those remaining devitalized burn wounds with more virulent organisms than those that were already present. Bacterial controlled nursing units (BCNU) provide strict protection against that cross infection. Though inevitably a catabolic response occurs with massive injury, intensive nutritional support provides the calories necessary for the response to injury to avoid a prolongation of that negative nitrogen balance.

Administration, Topical↗
PubMed1986

Prompt eschar excision: a treatment system contributing to reduced burn mortality. A statistical evaluation of burn care at the Massachusetts General Hospital (1974-1984).

Mortality at the Adult Burn Center of the Massachusetts General Hospital (MGH) has declined from 24% in 1974 to an average of 7% for 1979-1984. From 1974 to 1976, prompt eschar excision and immediate wound closure therapy was initiated and standardized. After 1976, this therapy was the standard treatment. Detailed statistical analysis is necessary to determine the influence of this treatment on the improved survival. Therefore, logistical regression analysis was used to examine the influence of variables such as burn size, age, and treatment on mortality for 1103 patients during 1974-1984. Survival rates during the treatment development phase (1974-1977) were compared to the survival rates of the last 5 years of standardized excisional treatment (1979-1984). Survival rates for the standardized excisional treatment were also compared to the results of previously published studies from this hospital that were probit analyses of burn mortality for 1939-1955 and 1955-1970. This latter comparison provided 45 years' experience with burn mortality at a single institution. Results of the statistical analysis of the survival data from 1974 to 1984 indicate that mortality strongly depends on burn size, age, and treatment (p less than 0.001 for each independent variable). In addition, length of stay (LOS) for the total group decreased significantly from 32 to 22 days. The improved survival for 1974-1984 occurred independently of changes in the annual distributions of burn size, age, or sex. Comparison of survival rates shows improved survival during standardized excisional treatment when compared to the treatment development phase. The most extensive increases in survival during 1974-1984 were seen in the treatment of elderly patients and patients with massive burn injuries. Survival for the period 1974-1984 was markedly improved as compared to the 1939-1970 published experiences.

Adolescent↗
PubMed1985

Improved management of the perineal wound after proctectomy.

In an effort to avoid the failures of perineal wound healing that are common after proctectomy, 57 patients who had abdominoperineal resection of the rectum or total proctocolectomy for ulcerative colitis (35 patients), Crohn's colitis (12), or carcinoma (10) had primary closure of the levator muscles and perineal tissues. No attempt was made to approximate the pelvic peritoneum. The small bowel was allowed to fill the pelvic space, which was also drained by suction catheters brought out through the lower abdominal wall. The skin and subcutaneous tissues were allowed to heal by secondary intention in seven patients who had excessive preoperative perineal sepsis from fistulas, deep fissures, and abscesses. All seven wounds healed within 2 months. Of the other 50 patients, whose wounds were closed to the skin, 48 were discharged with completely healed perineal wounds. Two patients had sterile pelvic hematomas that drained through the perineum and delayed wound healing 1 month and 2 months. There were no postoperative perineal, pelvic, or intraabdominal abscesses. Immediate postoperative ambulation was allowed. There was no increased short-term or long-term incidence of small bowel obstruction related to this procedure, nor did perineal hernia occur after long-term observation (mean: 5.3 years). This method of accomplishing perineal wound healing is simpler, safer, more comfortable, and remarkably effective in eliminating the prolonged morbidity of an unhealed perineal wound. It is superior to any other reported method of managing the perineal wound in patients with inflammatory bowel disease and may be applicable to the treatment of cancer without compromising the chances for cure.

Colectomy↗
PubMedDate not supplied

Progress in burn treatment and the use of artificial skin.

Recently improved survival from thermal injuries has been demonstrated both in children and adults. This increase in burn injury survival rates is the result of multiple changes in treatment; probably the most important changes are, first, a more aggressive management of the wound with prompt excision of devitalized tissues and immediate closure of the wound, and, second, a better understanding and management of metabolic, immunologic, and nutritional aspects of the injured patient. Artificial skin is a very important additional treatment modality that has more recently become available and promises to contribute significantly to improvements in wound management and survival rates by its ability to physiologically close a burn wound immediately after its excision.

Adult↗
PubMedDate not supplied

Burn wound closure using permanent skin replacement materials.

Over the past decade, very significant advances in the development of clinically useful, permanent skin replacement materials have taken place. The most prominent and successful approaches to the physiological closure of an open wound have been either by creating a totally artificial dermal matrix material, by using culture techniques to expand cell populations for autologous transplantation, or by using a combination of these methods. As a result of substantial early progress in this field, permanent skin replacement materials as a treatment modality promise significant contributions to improved wound management and increased survival rates for patients with devastating soft tissue destruction such as massive burn injuries.

Artificial Organs↗
PubMedDate not supplied

Melanin in the rat brain.

Melanin was measured in various parts of the rat brain by a spectrophotofluorometric assay. This method could detect natural, Sepia melanin as well as melanin synthesized from L-DOPA. Contrary to published expectations of other investigators, measurable amounts of melanin were found in the brain of albino as well as pigmented rats. The highest concentrations of melanin occurred in the pons-medulla and midbrain, but all regions within the blood-brain barrier contained greater concentrations than samples from many other tissues in the body. No significant change in the melanin content was found after various endocrine manipulations such as removal of the pituitary, pineal, adrenals, thyroid, testes, or ovaries, exposure to constant illumination or darkness, and daily injection for 5 weeks of alpha-MSH, Pro-Leu-Gly-NH2 (MIF-I) or melatonin. As expected, retinal tissue from black-hooded rats contained extremely high levels of melanin whereas that from albino rats contained no melanin. It is thought that the presence of melanin in the brain of albino and pigmented rats may have a function which is still unknown.

Albinism↗
PubMedDate not supplied

Preparation and characterization of immunoconjugates for antibody-targeted photolysis.

Monoclonal antibody (MAb)-dextran-tin(IV) chlorin e6 (SnCe6) immunoconjugates were prepared by a new technique involving the use of reducing, terminal-modified dextran carriers and site-specific modification of the Fc oligosaccharide moiety on the antibodies. Dextran carriers were synthesized to increase the number of SnCe6 molecules attached to a MAb. The dextran carriers were coupled to the MAb via a single, chain-terminal hydrazide group to prevent aggregation of MAbs. Conjugates were prepared with antimelanoma MAb 2.1 containing up to 18.9 SnCe6 molecules per MAb. Under neutral conditions, no hydrolysis of the hydrazone bond between the MAb and the dextran carrier could be detected, and the hydrazone was not stabilized by reduction with NaCNBH3 or NaBH4. Analysis of the purified immunoconjugates showed that approximately two dextran carrier chains were attached to a MAb regardless of the number of SnCe6 molecules linked to a dextran carrier. Site-specific covalent attachment of the SnCe6-dextran chains to the MAb was confirmed by SDS-PAGE. HPLC analysis of the conjugates gave a single species eluting in the range of 200-240 kDa. As determined by a competitive inhibition radioimmunoassay using viable SK-MEL-2 human malignant melanoma cells, the conjugates showed excellent retention of antigen-binding activity relative to unconjugated MAb.

Antibodies, Monoclonal↗
PubMedDate not supplied

Long-term in vitro function of adult hepatocytes in a collagen sandwich configuration.

In an effort to reconstruct the cellular polarity normally found in the liver, adult rat hepatocytes were sandwiched between two layers of hydrated rat tail tendon collagen matrix. Functionally, sandwiched hepatocytes maintained the secretion of albumin, transferrin, fibrinogen, bile acids, and urea for at least 6 weeks, whereas cells cultured on a single layer of collagen gel ceased such secretion in 1-2 weeks. After 1 week of culture on a single layer of collagen gel, hepatocytes could still recover these lost functions when a second layer of collagen gel was applied. The exact nature of the substrate for constructing the sandwich system appeared to be unimportant as long as it allowed cellular attachment. Hepatocytes cultured in the sandwich system appeared to maintain a distribution of actin filaments similar to the in vivo state, whereas cells cultured on a single layer of collagen gel showed abnormal formation of stress fibers. These studies suggest that simple manipulations of the configuration of extracellular elements can dramatically alter the behavior of cultured hepatocytes.

Actins↗
PubMedDate not supplied

Intracellular ice formation during the freezing of hepatocytes cultured in a double collagen gel.

During freezing, intracellular ice formation (IIF) has been correlated with loss in viability for a wide variety of biological systems. Hence, determination of IIF characteristics is essential in the development of an efficient methodology for cryopreservation. In this study, IIF characteristics of hepatocytes cultured in a collagen matrix were determined using cryomicroscopy. Four factors influenced the IIF behavior of the hepatocytes in the matrix: cooling rate, final cooling temperature, concentration of Me2SO, and time in culture prior to freezing. The maximum cumulative fraction of cells with IIF increased with increasing cooling rate. For cultured cells frozen in Dulbecco's modified Eagle's medium (DMEM), the cooling rate for which 50% of the cells formed ice (B50) was 70 degrees C/min for cells frozen after 1 day in culture and decreased to 15 degrees C/min for cells frozen after 7 days in culture. When cells were frozen in a 0.5 M Me2SO + DMEM solution, the value of B50 decreased from 70 to 50 degrees C/min for cells in culture for 1 day and from 15 to 10 degrees C/min for cells in culture for 7 days. The value of the average temperature for IIF (TIIF) for cultured cells was only slightly depressed by the addition of Me2SO when compared to the IIF behavior of other cell types. The results of this study indicate that the presence of the collagen matrix alters significantly the IIF characteristics of hepatocytes. Thus freezing studies using hepatocytes in suspension are not useful in predicting the freezing behavior of hepatocytes cultured in a collagen matrix. Furthermore, the weak effect of Me2SO on IIF characteristics implies that lower concentrations of Me2SO (0.5 M) may be just as effective in preserving viability. Finally, the value of B50 measured in this study indicates that cooling rates nearly an order of magnitude faster than those previously investigated could be used for cryopreservation of the hepatocytes in a collagen gel.

Animals↗
PubMedDate not supplied

Antibody-targeted photolysis: in vitro immunological, photophysical, and cytotoxic properties of monoclonal antibody-dextran-Sn(IV) chlorin e6 immunoconjugates.

A set of anti-melanoma immunoconjugates were prepared which contained chlorin e6: antibody molar ratios of 18.9:1, 11.2:1, 6.8:1, and 1.7:1. All immunoconjugates retained antigen binding activity regardless of the chromophore:antibody substitution ratio that was attained. In contrast, the ground-state absorption spectra of the immunoconjugates showed features which appeared to be dependent on the chromophore:antibody molar ratio. In addition, the quantum yield of singlet oxygen generated by the conjugated chromophores was observed to be significantly less than that observed with the unbound dye. Time-resolved absorbance spectroscopy of the chromophore excited triplet state indicated that the loss of singlet oxygen quantum yield resulted from diminished chromophore triplet yield. Analysis of data obtained from in vitro photolysis of target melanoma cells, in combination with that obtained from the immunochemical and photochemical studies, indicates that the observed immunoconjugate phototoxicity can be reasonably quantitatively represented by (1) the ability of the immunoconjugate to bind SK-MEL-2 cell surface antigen, (2) the amount of chromophore localized at the target cells by immunoconjugate binding, (3) the delivered dose of light at 634 nm, and (4) the singlet oxygen quantum yield of the antibody-bound photosensitizer. Though these data argue strongly for photolysis by the cumulative dosage of singlet oxygen at the cell membrane, nonetheless, the concurrent photoinduced release of other cytotoxic agents should not be ruled out.

Antibodies, Monoclonal↗
PubMedDate not supplied

A stable long-term hepatocyte culture system for studies of physiologic processes: cytokine stimulation of the acute phase response in rat and human hepatocytes.

Prior studies on the in vitro hepatic acute phase response have involved either hepatoma cell lines or conventional short-term cultures of primary hepatocytes. No data are available on the response of primary hepatocytes in stable long-term culture systems. In this study, the acute phase response of rat and human hepatocytes in a new long-term culture system was examined in response to interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF-alpha). The cultured cells were sandwiched between two layers of collagen in a (double-gel) configuration which has been shown to preserve both hepatocyte function and morphology over prolonged periods of time. The stability of this culture configuration enabled us to investigate, for the first time, the temporal aspects of the response in addition to the effects of the mediators on protein secretion. Exposure of rat hepatocytes to IL-6 after culture for 16 days resulted in a 2-fold reduction of albumin secretion and a 15-fold increase in the secretion rates of fibrinogen and alpha 2-macroglobulin. In all instances, the peak response occurred at 48 h after IL-6 exposure, and all protein secretion rates returned to pretreatment values within 5 days posttreatment. Changes in the mRNA levels of these proteins in response to IL-6 corresponded with those changes seen with the secreted products, indicating pretranslational regulation. Administration of IL-1 beta to rat hepatocyte produced a similar decline of albumin secretion and a 5-fold increase of fibrinogen secretion, whereas alpha 2-macroglobulin secretion remained undisturbed.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Reaction↗