Biomedical subjects

T J Fahey

Publications and source records attributed to T J Fahey.

At least 37 records · Page 2Linked to original sources

PubMed1995

Diagnosis of follicular thyroid lesions by proton magnetic resonance on fine needle biopsy.

Most thyroidectomies are currently performed for diagnostic purposes. It has been established that proton magnetic resonance spectroscopy (MRS) on excised thyroid tissue can distinguish normal thyroid from invasive carcinomas (P < 0.0001). The purpose of this study was to assess whether the same discrimination could be obtained preoperatively from fine needle biopsy (FNB). This has clinical importance because cytological examination of fine needle aspirates cannot distinguish between benign and malignant follicular thyroid lesions. Here we demonstrate a sensitivity of 95% for proton MRS to correctly identify clinically or histologically proven carcinoma. MRS measurements were made on FNB specimens (containing as few as 10(6) cells) from solitary thyroid nodules. MR assessment of FNB was inconsistent with that of the corresponding tissue in only 6.5% of cases. The discrimination between cancer and normal tissue was based on altered cellular chemistry measured as a one-dimensional spectral ratio of resonances from the amino acid lysine and lipid. Benign follicular lesions were separated into two groups: 67% with a spectral ratio similar to malignant thyroid tumors, and 33% with a spectral ratio comparable to that in normal thyroid tissue. Thus, in contrast with histopathology, MRS offers a method for assessment of FNB of follicular lesions with the potential to identify a biologically benign group, which could avoid thyroid surgery for purely diagnostic purposes.

Adenocarcinoma, Follicular↗

PubMed1994

Adrenalectomy: expanded indications for the extraperitoneal approach.

The adrenal glands can be removed surgically by the anterior transperitoneal approach, or by the extraperitoneal approaches, either posteriorly or posterolaterally. While the extraperitoneal routes have become accepted as the preferred approach to the adrenal glands for small benign cortical adenomas, many authors still recommend the anterior transperitoneal route as the preferred operative approach for phaeochromocytoma, large tumours, adrenal cancers or bilateral hyperplasia. A series of 51 consecutive adrenalectomies performed for a wide range of adrenal disorders is presented, including phaeochromocytoma and large malignant tumours. In 47 cases the tumours were successfully removed through an extraperitoneal approach, with minimal morbidity. The anterior approach had to be employed in only four cases, and in three of these there was pre-operative evidence of tumour invasion into either the major vessels or the liver. The extraperitoneal approach to the adrenal gland is technically simple and can be performed quickly, with a low postoperative morbidity and should be regarded as the routine approach for almost all adrenal procedures.

Adrenal Cortex Neoplasms↗

PubMed1993

Crown architecture of stand-grown sugar maple (Acer saccharum Marsh.) in the Adirondack Mountains.

Leaf and crown morphology of shade-tolerant sugar maple (Acer saccharum Marsh.) were examined to test the hypotheses (1) that leaf area exhibits significant plasticity both within and between crown classes and individual tree crowns and (2) that leaf area is accurately predicted from estimates of crown volume. A total of 18 trees, ranging from 3.3 to 43.4 cm dbh, were felled and dissected into upper, middle, lower, and below-crown layers, for measurements of leaf, bark, and xylem dimensions. For dominant trees only, bark thickness and xylem radii were higher within the crown than below the crown. Cumulative leaf area index increased with decreasing stratum height at similar rates in all trees, except for two trees that were located in the understory. Area leaf weight declined with decreasing stratum height within the crown of all except four overstory trees. These four trees showed an increase with decreasing stratum height, i.e., leaves were heavier per unit area in the lower crown stratum and below the crown than they were at mid-crown. Within-tree leaf area density was usually higher in the upper crown of overstory trees and in the lower crown of understory trees. Total crown volume was the best predictor of whole-tree leaf area, but it was only slightly better than dbh.

Journal Article↗

PubMed1992

Macrophage inflammatory protein 1 modulates macrophage function.

Macrophage inflammatory protein 1 (MIP 1), initially purified from the conditioned medium of endotoxin-stimulated macrophages, is a low m.w. heparin-binding protein doublet comprising two peptides, MIP 1 alpha and MIP 1 beta. Although native doublet MIP 1 has previously been shown to exert pyrogenic, mitogenic, and proinflammatory effects on other cell types, its actions on its cell of origin, the macrophage, have not been well catalogued. Our study reports several aspects of macrophage function that are modulated by MIP 1. MIP 1 was not directly cytotoxic for WEHI tumor cells, but MIP 1-treated macrophage exhibited enhanced antibody-independent macrophage cytotoxicity for tumor targets. MIP 1 treatment stimulated proliferation of mature tissue macrophages, and this effect was enhanced upon costimulations with either CSF-1 or granulocyte-macrophage-CSF. Thioglycollate-elicited peritoneal exudate macrophages incubated with native doublet MIP 1-secreted bioactive TNF and IL-6, as well as immunoreactive IL-1 alpha, and these effects were enhanced significantly when the cells were costimulated with IFN-gamma. Purified preparations of the recombinantly derived MIP 1 alpha peptide alone stimulated the secretion of TNF, IL-1 alpha, and IL-6 by peritoneal macrophages, but MIP 1 beta did not. In fact, as little as eightfold excess MIP 1 beta blocked TNF-induction by MIP 1 alpha to a significant degree. By contrast to these apparent "macrophage activating" properties of MIP 1, the cytokine failed to trigger the macrophage oxidative burst, or to up-regulate the expression of Ia on the macrophage surface. Taken together, these data reveal that MIP 1 peptides act as autocrine modulators of their cells of origin, and raise the possibility that MIP 1 peptides may play a role in modulating macrophage responses to inflammatory stimuli in vivo.

Animals↗

PubMed1992

Effect of cyclosporine on adrenocortical response to injury and infection.

The effects of cyclosporine administration on the adrenocortical response to the severe stress of burn wound sepsis were studied in Wistar rats. Animals were treated with cyclosporine (10 mg/kg/day) or saline by gavage for 10 days, then subjected to 30% scald burns with wound inoculation with Pseudomonas. Animals were sacrificed on Postburn Days (PBDs) 1, 4, and 7 for determination of serum corticosterone and ACTH levels and adrenal weights and histology. Adrenal glands from animals sacrificed on PBD 7 were also analyzed for DNA, RNA, and protein content. Cyclosporine treatment without injury had no significant effect on body weight gain, adrenal mass, or baseline ACTH or corticosterone levels. During sepsis, cyclosporine-treated animals demonstrated a significantly diminished adrenocortical response compared to those given only saline. Serum corticosterone levels in the cyclosporine group were 45, 53, and 62% lower on PBDs 1, 4, and 7, respectively, than in saline-treated controls (P < 0.01 on each day). ACTH levels were 43 and 36% lower in cyclosporine-treated animals on PBDs 4 and 7, respectively, compared to the saline-treated group (P < 0.05 on each day). Adrenal hyperplasia occurred in both groups by PBD 7, but increases in adrenal mass and in histologic changes associated with hyperplasia (lipid depletion, vascular dilation) were less pronounced in cyclosporine-treated animals compared to those receiving saline, while adrenal composition remained similar between the two groups. Thus, cyclosporine administration is associated with an attenuated adrenocortical response to the stress of sepsis due to diminished circulating levels of ACTH.

Adrenal Cortex↗

PubMed1991

Pathophysiologic glucocorticoid levels and survival of translocating bacteria.

Burn wound sepsis in rats results in sustained corticosterone elevations and the prolonged presence of translocated bacteria in the mesenteric lymph nodes (MLNs). To determine if survival of bacteria in the MLNs may be influenced by pathophysiologic corticosterone levels, MLNs were quantitatively analyzed from rats randomized to the following groups: burn wound sepsis (BI); BI with adrenocortical response attenuated by cyclosporine (cyclosporine/BI); or cyclosporine/BI with corticosterone replacement (cyclosporine/BI + P). Although rates of bacterial translocation were similar, corticosterone levels were significantly different among the three groups and correlated with the number of lymphocytes and the number of enteric bacteria present per gram of MLN. Thus, pathophysiologic elevations of corticosterone levels during sepsis may exert an effect that allows survival of translocated bacteria in the MLNs of rats, perhaps due to glucocorticoid-associated alterations in regional immunity.

Administration, Cutaneous↗

PubMed1991

Bacterial overgrowth and intestinal atrophy in the etiology of gut barrier failure in the rat.

Bacterial translocation occurs in animal models of shock, trauma, sepsis, and parenteral or elemental enteral alimentation. Bowel atrophy and cecal bacterial overgrowth have both been implicated in the pathophysiology of bacterial translocation in many of these models. To further define the etiology of bacterial translocation resulting from dietary manipulations, rats were fed a elemental/defined-formula diet (DFD) for 2 weeks ad libitum and then randomized to either intestinal decontamination with a nonabsorbable antibiotic (neomycin) or no antibiotic treatment. Neomycin treatment significantly (p less than 0.01) reduced the incidence of bacterial translocation after DFD, in association with a significant reduction in the number of cecal gram-negative bacteria. Neither loss of bowel mass after DFD nor bowel composition was affected by oral neomycin. Bacterial translocation after DFD would thus appear to be the result of cecal bacterial overgrowth rather than a loss of a physical intestinal barrier due to atrophy.

Animals↗

PubMed1991

Diabetes impairs the late inflammatory response to wound healing.

Diabetes mellitus is recognized as a risk factor for compromised wound healing. This study examines leukocyte infiltration and the appearance of tumor necrosis factor-alpha (TNF) and IL-6 in wound chambers implanted in normal and streptozotocin-induced diabetic mice. Perforated silicone wound chambers containing a strip of polyvinyl alcohol sponge were implanted along the flanks of normal and diabetic mice. Wound fluid aspirated from the chambers 1, 3, and 7 days following implantation was analyzed for the total number of leukocytes and TNF and IL-6 levels. While the number of leukocytes in the wound fluid was similar on Days 1 and 3 following implantation, there were significantly fewer inflammatory cells in wound fluid from diabetic animals (13.8 X 10(6)/ml) than in wound fluid from normal animals (28.5 Z 10(6)/ml) on Day 7 following implantation. TNF levels in the cell-free exudate fluid were similar between the two groups on all days examined. IL-6 levels were similar on Days 1 and 3 following implantation between the two groups, but there was significantly more IL-6 in wound fluid from normal animals (10,998 U/ml) than in wound fluid from diabetic animals (2096 U/ml) on Day 7 following implantation. Histologic evaluation of chambers 8 days following implantation revealed decreased neovascularization and less organization of granulation tissue. These data suggest that delayed healing in diabetes is associated with altered leukocyte infiltration and wound fluid IL-6 levels during the late inflammatory phase of wound healing.

Animals↗

PubMed1991

Differential pathophysiology of bacterial translocation after thermal injury and sepsis.

Bacterial translocation (BT) occurs transiently after thermal injury and may result from an ischemic intestinal insult. To evaluate continued intestinal ischemia in the ongoing BT associated with sepsis after injury, rats were randomized to (1) 30% burn injury with Pseudomonas wound infection (BI), (2) BI + fluid resuscitation (BI + Fluid), (3) BI after allopurinol pretreatment to inhibit xanthine oxidase (BI + Allo), or (4) BI after azapropazone pretreatment to inhibit neutrophil degranulation (BI + Aza). On postburn days (PBD) 1, 4, and 7, animals were studied for evidence of BT and intestinal lipid peroxidation. BI + Fluid, BI + Allo, and BI + Aza significantly (p less than 0.05) reduced rates of BT and ileal lipid peroxidation acutely after thermal injury (PBD 1) compared to BI. All four groups had equally high rates of BT associated with the onset of sepsis (PBDs 4 and 7), without evidence of further intestinal lipid peroxidation. These data indicate that the chronic gut barrier failure associated with sepsis after injury occurs independently of continued intestinal ischemia.

Animals↗

PubMed1991

Splanchnic vasoconstriction and bacterial translocation after thermal injury.

Gut barrier failure and bacterial translocation (BT) after thermal injury may result from splanchnic vasoconstriction and intestinal ischemia. The role of the renin-angiotensin system in intestinal blood flow and BT after thermal injury was studied by pretreatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril in Wistar rats before sham or 30% scald burn. Adequacy of ACE inhibition was documented by the absence of a hypertensive response to angiotensin I, and intestinal blood flow was determined using 51Cr-labeled microspheres. Small bowel blood flow was decreased by 46% at 4-h postburn (P less than 0.05) in untreated burned animals despite maintenance of normal cardiac index but returned to baseline levels by 24 h after injury. Enalapril pretreatment resulted in maintenance of small bowel blood flow after thermal injury and was associated with a significantly reduced incidence of BT (20% vs. 75% in untreated burned animals, P less than 0.01). These findings further implicate intestinal ischemia in the etiology of gut barrier dysfunction after thermal injury, mediated in part by activation of the renin-angiotensin system.

Animals↗

PubMed1990

Cytokine production in a model of wound healing: the appearance of MIP-1, MIP-2, cachectin/TNF and IL-1.

Macrophages are essential for normal wound repair and many of their effects on healing wounds are likely to be mediated by the secretion of cytokines. This study examines the appearance of messenger RNA (mRNA) for cachectin/tumor necrosis factor (TNF), IL 1, and macrophage inflammatory proteins 1 and 2 (MIP-1 and MIP-2), as well as the mature peptides, in a model of wound healing using wound chambers. RNA for all four cytokines can be detected in wound inflammatory cells by polymerase chain reaction amplification throughout the first 7 days. Cachectin/TNF and IL 1 protein levels peaked on the first day after wound chamber implantation, and MIP-1 and MIP-2 were detected only on day 3. The data suggest that these cytokines participate in the early inflammatory response to wounding.

Animals↗

PubMed1990

Interleukin 1 receptor blockade attenuates the host inflammatory response.

Cytokines, including interleukin 1 (IL-1), tumor necrosis factor alpha, and interleukin 6, are often produced in response to tissue injury and contribute to several host responses such as weight loss, anorexia, and acute-phase protein synthesis. However, the role of IL-1 in specific tissue responses is unclear. To test our hypothesis that specific in vivo blockade of IL-1's action might inhibit the catabolic host changes associated with inflammation, mice were passively immunized with a monoclonal antibody directed against the murine IL-1 receptor prior to initiation of a turpentine-induced sterile abscess. This antibody prevents IL-1-mediated proliferation of murine thymocytes in vitro by inhibiting IL-1 alpha and IL-1 beta by way of competition for a common receptor. Weight loss following turpentine challenge was prevented by daily injections of anti-IL-1 receptor monoclonal IgG. Body composition analysis confirmed that lean tissue and fat were preserved by passive immunization. Furthermore, pretreatment with an anti-IL-1 receptor monoclonal antibody significantly attenuated the plasma amyloid P and interleukin 6 responses but did not affect the decline in plasma albumin or the increase in circulating corticosterone. Passive immunization of similar mice with polyclonal antisera against another cytokine, tumor necrosis factor alpha, failed to prevent either the weight loss or hepatic acute-phase protein changes observed in this inflammatory model. These findings suggest that IL-1 orchestrates weight loss and body compositional changes during inflammation and contributes to the induction of interleukin 6 and acute-phase protein synthesis.

Acute-Phase Proteins↗

PubMed1990

Bacterial translocation and intestinal atrophy after thermal injury and burn wound sepsis.

Bacterial translocation (BT) occurs after thermal injury in rodents in association with intestinal barrier loss. Infection complicating thermal injury may also affect the intestine producing bowel atrophy. To study these relationships, Wistar rats received either 30% scald followed by wound inoculation with Pseudomonas; 30% scald with pair feeding to infected animals; or sham injury as controls. On days 1, 4, and 7 after injury animals were killed with examination of the bowel and culture of the mesenteric lymph nodes (MLN), livers, spleens, and blood. All burned animals demonstrated BT to the MLN on day 1 after injury, but only burn-infected animals had continued BT on days 4 and 7, with progression of BT to the abdominal organs and blood. Burn injury and infection also resulted in significant atrophy of small bowel mucosa temporally associated with continued BT. Thus injury complicated by infection results in prolonged and enhanced bacterial translocation, perhaps due to failure to maintain the mucosal barrier.

Animals↗

PubMed1990

Antibiotic prophylaxis diminishes bacterial translocation but not mortality in experimental burn wound sepsis.

Pseudomonas (PSA) burn wound sepsis results in prolonged bacterial translocation (BT) of enteric organisms such as E. coli to the mesenteric lymph nodes (MLN) and organs in rats. Intestinal decontamination with oral antibiotics may improve mortality after burn injury, perhaps due to decreased BT. To determine the effect of oral antibiotic prophylaxis effective against E. coli but not PSA on BT and subsequent mortality in a model of PSA burn wound sepsis, rats were given a 30% scald burn and wound inoculation with 10(8) PSA followed by randomization to either ampicillin (50 mg/kg/d) or saline gavage. Cultures of MLN, organs, blood, and cecal contents were obtained on days 1, 4, and 7 after injury, with additional animals observed for 14-day mortality. Although oral antibiotic prophylaxis resulted in increased cecal colony counts, the incidence of BT was unchanged. The number of organisms present in both the MLN and organs, however, was significantly reduced with prophylaxis, indicating cecal overgrowth by non-translocating bacteria. Reduction of the number of translocating organisms did not result in improved mean survival time after injury, suggesting that mortality from PSA burn wound sepsis occurs independently of bacterial translocation.

Ampicillin↗

PubMed1990

Pathophysiologic glucocorticoid elevations promote bacterial translocation after thermal injury.

Thermal injury results in transient elevations of plasma glucocorticoids and promotes translocation of bacteria from the gut to the mesenteric lymph nodes (MLN) in rats. Translocated organisms are quickly cleared following uncomplicated thermal injury. However, subsequent burn wound infection, in temporal association with sustained pathophysiologic elevations of plasma corticosterone, results in the continued presence of enteric bacteria in the MLN. To study the role of sustained pathophysiologic steroid elevations in the mediation of this prolonged bacterial translocation, Wistar rats were randomly placed in groups receiving one of the following: (i) a 30% total body surface area scald injury with placement of a subcutaneous corticosterone pellet, (ii) a 30% total body surface area scald and a sham pellet implantation, (iii) a sham burn and a corticosterone pellet implantation, or (iv) a sham burn and a sham pellet implantation. The animals were sacrificed on days 1 and 4 after injury, and cultures of the MLN, as well as the liver and spleen, were taken. Implantation of corticosterone pellets resulted in sustained elevations of plasma corticosterone compared with controls not receiving corticosterone pellets, similar to results seen in association with injury and infection. These pathophysiologic elevations were associated with the prolonged presence of organisms in the MLN (90% of burned rats with implanted corticosterone pellets versus 25% of rats with uncomplicated burns on postburn day 4; P less than 0.01), but only in the presence of burn injury. Pathophysiologic glucocorticoid elevations did not lead to progression of translocation to the viscera or blood. Thus, the pathophysiologic glucocorticoid response contributes to the translocation of enteric bacteria and their prolonged presence in the MLN after systemic injury.

Animals↗

PubMed1990

Metabolic effects of cachectin/tumor necrosis factor are modified by site of production. Cachectin/tumor necrosis factor-secreting tumor in skeletal muscle induces chronic cachexia, while implantation in brain induces predominantly acute anorexia.

We have developed a murine model of wasting by injecting intracerebrally cells which continuously secrete h-cachectin/TNF (CHO-TNF) to: (a) determine the effects of cachectin/TNF produced continuously in the central nervous system (CNS), and (b) compare the metabolic effects of cachectin/TNF-secreting tumor in the brain to the cachexia caused by CHO-TNF tumor in peripheral tissue (IM). Intracerebral CHO-TNF tumors produced increased serum h-cachectin/TNF levels with lethal hypophagia and weight loss (mean survival time of 11 d); these changes were not observed in association with nonsecretory control brain tumors. The metabolic consequences of intracerebral cachectin/TNF production were indistinguishable from acute, lethal starvation: whole-body lipid content was decreased significantly but protein was conserved. Although intramuscular cachectin/TNF-secreting tumors caused similar increases of serum h-cachectin/TNF levels, profound anorexia did not develop; wasting developed after a longer period of tumor burden (50 d) with classical signs of cachexia (i.e., anemia and depletion of both protein and lipid). These studies provide a reproducible animal model of site-specific cytokine production and suggest that, regardless of serum levels, cachectin/TNF produced locally in brain influences both the rate of development of wasting and its net metabolic effects.

Animals↗

PubMed1990

Additive effects of thermal injury and infection on the small bowel.

Thermal injury is associated with functional alterations of multiple organ systems, including the gastrointestinal tract. To study the effects of ongoing infection after thermal injury on bowel mass, composition, and blood flow, male Wistar rats were randomized to receive either 30% scald burn, 30% scald burn with Pseudomonas aeruginosa wound inoculation, sham burn, or sham burn with pair feeding to burned and infected animals. On days 3 and 7 after injury, intestinal blood flow was measured with 51Cr-labeled microspheres, and intestinal mass and composition were analyzed. Burned and infected animals demonstrated a chronic loss of small bowel mass not seen in burned animals without infection by day 7 after injury. Compositional alterations of the small bowels of burned and infected animals included protein wasting similar to but occurring earlier than that seen with anorexia alone and significantly decreased deoxyribonucleic acid and ribonucleic acid content, whereas tissue water content remained unchanged. These chronic intestinal alterations in the burned and infected group could not be explained by ongoing ischemia because intestinal blood flow in these animals was not significantly altered at either time point, implying mediation by other pathophysiologic mechanisms.

Animals↗

PubMed1987

Cachectin/tumor necrosis factor induces lethal shock and stress hormone responses in the dog.

Cachectin/tumor necrosis factor has been implicated as a mediator of lethal endotoxemia, but the metabolic and hemodynamic responses to this macrophage-derived peptide have been incompletely characterized. Cachectin was administered by intra-arterial infusion in two groups of beagle dogs at lethal (100 micrograms per kilogram) and sublethal (10 micrograms per kilogram) doses. The infusion produced serum cachectin levels (1 to 50 nanomoles per liter) similar to those achieved after experimental endotoxemia. The lethal response to cachectin was characterized by progressive hypotension, shock and death within three hours. Histopathologic findings included acute inflammation of the pulmonary interstitium, intravascular thrombosis with hemorrhagic necrosis, adrenal medullary necrosis and acute renal tubular necrosis. Cachectin infusion precipitated significant increases of plasma catecholamines, cortisol and glucagon in a dose response manner. Cachectin infused directly into the isolated hindlimb mediated reductions of skeletal muscle resting transmembrane potential and stimulated lactate efflux. Cachectin appears to occupy a crucial role in physiopathologic responses to infection, and likely participates in the mobilization of host energy stores, intravascular depletion and shock after lethal endotoxemia.

Animals↗