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Biomedical subjects

Y Fong

Publications and source records attributed to Y Fong.

At least 163 records · Page 9Linked to original sources
PubMed1994

Internal mammary artery is a safe conduit for repeat coronary revascularization.

The safety of repeat coronary revascularization using the internal mammary artery (IMA) as a conduit was examined in patients undergoing repeat revascularization between January 1988 and June 1991. The 71 patients in whom the IMA was used as one of the conduits were compared with 57 patients in whom only vein grafts were used. Patients undergoing IMA grafts were likely to have more vessels revascularized. Nevertheless, there were no significant differences in outcome between the two groups as measured by complications or period of hospitalization. In a multivariate analysis, the only independent predictor of poor outcome was emergency surgical treatment. The current study would indicate that IMA grafts are safe in the setting of repeat coronary revascularization.

Aged↗
PubMed1993

Glucocorticoid therapy alters hormonal and cytokine responses to endotoxin in man.

Previous experimental data have demonstrated that steroid pretreatment regulates endotoxin-elicited cytokine production. The timing of such hypercortisolemia also appears to be a major determinant of both the systemic and the cytokine response to infectious stimuli. Our study was undertaken to further study the in vivo influence of glucocorticoid infusion concurrent with and before endotoxin exposure in man. A total of 23 normal human subjects were given endotoxin (LPS) alone or pretreated with hydrocortisone infusion for 6 h immediately before and concomitant to LPS administration; or rendered hypercortisolemic for a 6-h period waiting 6, 12, or 144 h before LPS administration. LPS administration was followed by significant elevations in temperature (1.9 +/- 0.3 degrees C), pulse (29 +/- 6 bpm), and resting energy expenditure (26.2 +/- 0.4 kcal/kg/day) as well as epinephrine (236 +/- 59 pg/ml), cortisol (296 +/- 29), and C-reactive protein (4.2 +/- .03 mg/dl) as compared with base-line values. Levels of TNF and IL-6 that were not detectable before LPS administration, peaked, respectively, at 90 and 120 min after LPS (155 +/- 4 pg/ml, 12 +/- 1 U/ml). Glucocorticoids when given immediately before and concomitant with LPS significantly attenuated the temperature (0.8 +/- 0.01 degrees C) and pulse rate response (10 +/- 3 bpm) seen after LPS alone as well as suppressing peak levels of epinephrine (78 +/- 14 pg/ml) and C-reactive protein (undetected). TNF remained undetectable in this group although the IL-6 response (14 +/- 1 U/ml) was unchanged. With a 6-h interval between hydrocortisone infusion and LPS challenge, changes in temperature, pulse, resting energy expenditure, and hormone levels were similar to those seen after LPS alone whereas TNF remained undetectable and IL-6 levels were similar to subjects receiving LPS alone. Subjects receiving LPS after 12 or 144 h after hydrocortisone infusion displayed hemodynamic and hormonal responses similar to the LPS alone group, yet mounted significantly greater circulating levels of both IL-6 (117 +/- 14 U/ml, 160 +/- 51 U/ml at 12 and 144 h) and TNF (609 +/- 173, 671 +/- 132 pg/ml at 12 and 144 h) to those observed after LPS alone. We conclude that antecedent periods of hypercortisolemia participate in regulation of the hemodynamic, hormonal, and cytokine responses to endotoxin and that a complex temporal relationship between hypercortisolemia and LPS induced cytokine and systemic responses exists.

Adult↗
PubMed1993

Gallbladder cancer discovered during laparoscopic surgery. Potential for iatrogenic tumor dissemination.

OBJECTIVE: To examine the results of treatment of laparoscopically discovered gallbladder cancer. DESIGN: Retrospective review of clinical data for the 10 patients with laparoscopically discovered gallbladder cancer who were referred to our institution for definitive surgical therapy. SETTING: An oncologic referral center. PATIENTS: All patients in the 24-month period from November 1990 to November 1992 with this entity who were referred for surgical therapy. INTERVENTION: Exploratory laparotomy was performed on all patients. Resection with curative intent was performed when possible. MAIN OUTCOME MEASURES: Resectability and outcome of cancer treatment. RESULTS: In three patients, a subsequent radical resection was performed and as a result, two patients are currently free of disease. Intraperitoneal spread, not present at the original laparoscopy and associated with violation of tumor at laparoscopy, precluded potentially curative resection for four patients. In two of these patients, there was obvious tumor growth within the laparoscopy tracts. CONCLUSIONS: Tumor dissemination is a real hazard of laparoscopic violation of gallbladder integrity in the presence of gallbladder cancer. Modification of management based on awareness of such a hazard is needed to improve resectability and outcome of future cases of laparoscopically discovered gallbladder cancer.

Aged↗
PubMed1993

Inhibition of matrix-induced bone differentiation by advanced glycation end-products in rats.

Glycation of long-lived proteins is an inevitable consequence of aging that is accelerated in patients with diabetes mellitus. Treatment of demineralized bone matrix particles from 35-week-old normal Long-Evans rats with glycoaldehyde, a precursor of advanced glycation end-products, was used to assess the effects of bone-matrix glycation on the process of bone differentiation. Matrix was incubated in phosphate buffered saline alone, phosphate buffered saline containing glycolaldehyde, glycolaldehyde plus the advanced glycation product-inhibitor aminoguanidine, or glycolaldehyde plus the advanced glycation product-inhibitor sodium cyanoborohydride. Glycolaldehyde increased the matrix advanced glycation product content as measured by specific fluorescence more than two-fold, while inhibiting bone differentiation more than 90% as measured by in vivo 45CaCl2 uptake, alkaline phosphatase levels, and histology. In contrast, simultaneous incubation with the advanced glycation product-inhibitor aminoguanidine or sodium cyanoborohydride not only reduced fluorescence to normal, but also restored bone differentiation. Furthermore, the inhibition of bone differentiation by glycolaldehyde was not reversed by subsequent application of recombinant bone morphogenetic protein-2. These observations suggest that formation of advanced glycation products on bone matrix alters its ability to induce bone formation, and probably involves alterations of binding sites for extractable proteins with direct bone inductive properties such as bone morphogenetic protein-2. Decreased bone formation associated with aging and diabetes may result, in part, from advanced glycation product formation on matrix proteins.

Acetaldehyde↗
PubMed1993

Lymph node metastasis from soft tissue sarcoma in adults. Analysis of data from a prospective database of 1772 sarcoma patients.

To examine the natural history of lymph node metastasis from sarcomas and the utility of therapeutic lymphadenectomy, clinical histories of all adult patients identified by a prospective sarcoma database for the 10-year period July 1982 to July 1991 were examined. Of the 1772 sarcoma patients, 46 (2.6%) were identified with lymph node metastasis. Median follow-up of all patients from diagnosis of lymph node metastasis was 12.9 months (range, 0 to 100 months). Median survival for nonsurvivors was 12.7 months (range, 0 to 40.7). The tumor types with the highest incidence of lymph node metastasis are angiosarcoma (5/37 total cases; 13.5%), embryonal rhabdomyosarcoma (ERMS) (12/88 total cases; 13.6%), and epithelioid sarcoma (2/12 total cases; 16.7%). Lymph node metastasis from visceral primary (p = 0.004) and malignant fibrous histiocytomas (p = 0.006) were associated with particularly poor prognosis. Thirty-one patients underwent radical, therapeutic lymphadenectomy with curative intent, whereas 15 patients had less than curative procedures, in most cases biopsy only. Patients not treated with radical lymphadenectomy had a median survival of 4.3 months (range, 1 to 32) whereas radical lymphadenectomy was associated with a 16.3 month median survival and the only long-term survivors (46% 5-year survival by Kaplan-Meier). The authors conclude that lymph node metastases from sarcoma are rare in adults, but vigilance is warranted, especially in angiosarcoma, ERMS, and epithelioid subtypes. Radical lymphadenectomy is appropriate treatment for isolated metastasis to regional lymph nodes and may provide long-term survival.

Adolescent↗
PubMed1993

Multifocal desmoids.

BACKGROUND: This study examines the natural history of patients treated for multifocal desmoids at a referral center for sarcomas. METHODS: Patients with multifocal desmoids seen at Memorial Sloan-Kettering Cancer Center in the 9-year period between 1982 and 1991 were identified through a prospective sarcoma data base. The clinical histories were reviewed. In addition, tumor estrogen and progesterone receptor status were evaluated by immunohistochemistry. RESULTS: This rare condition occurred in six (4.8%) of the 124 patients with desmoid tumors and all occurred in premenopausal women. In each instance the tumors were restricted to one anatomic region of the body and no patient had familial polyposis or Gardner's syndrome. When tested immunohistochemically, the tumors displayed no nuclear reactivity for estrogen or progesterone receptors. CONCLUSIONS: Further investigative work must be undertaken before considering routine use of antiestrogen therapy even in this subset of patients with desmoid tumors.

Adolescent↗
PubMed1992

Tumour location influences local cytokine production and host metabolism.

To determine whether the location of tumour growth influences host cytokine and metabolic responses, experimental subcutaneous (SQ) and liver (LIV) tumours were compared in Buffalo rats. An LIV tumour that was only 1 +/- 1% (P < 0.05 versus SQ) of body weight produced similar anorexia, weight loss, acute phase response, and systemic cytokine responses as are SQ tumour that was 10 +/- 2% of body weight. Neither tumour-bearing group had abnormal liver function tests or evidence of obstructive biliary pathology. Tumour necrosis factor (TNF) was detected by western analysis in both tumour as well as histologically normal liver remote from the tumour in the LIV group but not in livers of animals in freely fed and SQ groups. The proximity of the tumour to competent tissue macrophage populations, such as hepatic Kupffer cells, may be sufficient to induce cachexia. Hence, tumour location may be as important as tumour burden in determining the host's response to cancer.

Animals↗
PubMed1992

Tolerance to endotoxin prevents mortality in infected thermal injury: association with attenuated cytokine responses.

Endotoxin, a lipopolysaccharide (LPS), is a bacterial cell wall product instrumental in producing deleterious host responses to infection. This LPS appears to act, in part, by triggering release of endogenous mediators such as cytokines. Repeated exposures to endotoxin produce attenuated responses to this molecule. To examine the mechanisms and biologic consequences of this tolerance to LPS, Wistar rats were subjected to a 14-day course of LPS administration. Tolerance to LPS with regard to anorexia, weight loss, and acute-phase responses was noted. Attenuation of these physiologic responses was accompanied by abrogation of circulating cytokine appearance in response to endotoxin, suggesting that tolerance to LPS is in part due to a decreased production of cytokines. Tolerance to LPS also diminished the response to a subsequent infected thermal injury, as measured by food intake, body weight, fibrinogen levels, and mortality. Thus, clinical conditions involving repeated exposure to LPS may modify the host's responses to subsequent injury. The attenuated responses to injury accompanying the decreased production of cytokines further implicate cytokines in the pathogenesis of injury and disease.

Acute-Phase Reaction↗
PubMed1992

Recombinant human growth hormone enhances the metabolic efficacy of parenteral nutrition: a double-blind, randomized controlled study.

This multicenter, randomized, double-blind study was performed to investigate whether recombinant GH improves the efficacy of total parenteral nutrition (TPN). Fifteen stable patients requiring parenteral feeding due to gastrointestinal/pancreatic disease were studied. Constant maintenance TPN providing approximately 30 kcal/kg day and approximately 1.6 g protein/kg.day was administered during an initial 7-day baseline period. After randomization, daily sc injections of saline (control, n = 9) or GH (10 mg/day, n = 6) were administered a 14-day treatment period as nutrient intake remained constant. Elemental balances for nitrogen (N), potassium (K), phosphorus (P), and sodium (Na) were determined daily and serial blood indices, vital signs, and other clinical parameters were monitored. Nutrient balances approached equilibrium during the baseline week in both groups. With GH administration, a significant increase in N, K, and P balance occurred; in contrast, nutrient balances did not change significantly from baseline values in control patients. The cumulative change (delta) in nutrient balances from the baseline week was also significantly greater in the GH-treated patients (delta N: control+2 +/- 7 g vs. GH+36 +/- 6. g, P less than 0.005; delta K:+57 +/- 45 mmol vs.+199 +/- 19 mmol, P less than 0.03; delta P: -27 +/- 30 mmol vs. +91 +/- 69 mmol, P less than 0.02). Plasma insulin-like growth factor-I concentrations rose 5-fold and serum cholesterol rose slightly with GH; no other significant change in group mean blood values occurred. One patient receiving GH and chronic prednisone therapy developed moderate hyperglycemia and mild peripheral edema; no other deleterious effects attributable to GH were observed. GH was well tolerated and significantly enhanced nutrient retention compared to standard parenteral feeding alone. GH improves the efficacy of parenteral nutrient utilization in patients requiring TPN.

Adolescent↗
PubMed1992

Prevention of ischemic orchitis during inguinal hernioplasty.

Ischemic orchitis and testicular atrophy remain the most dreaded complications of inguinal hernioplasties. The current study examines these complications in a series of hernia repairs during a period of 20 years. The incidence of the complications in the ten year period from 1971 to 1981 was compared with the experience since 1981, from which time all distal indirect hernia sacs were left in place and increasing experience was gained in properitoneal repairs of recurrent hernias. The incidence of ischemic orchitis in primary hernia repairs was reduced from 0.65 per cent (11 instances in 1,682 repairs) to 0.03 per cent (one in 3,634 repairs). The incidence in recurrent hernia repairs was reduced from 2.25 per cent (seven in 311 repairs) to 0.97 per cent (eight in 827 repairs). These data have led us to emphasize the importance of minimizing cord dissection by leaving intact all significant distal hernia sacs and not dissecting beyond the pubic tubercle. Additionally, properitoneal repairs should be considered for repairs of recurrent hernias not only to reduce further recurrences but also to avoid testicular complications.

Atrophy↗
PubMed1990

Identification of a novel tumor necrosis factor alpha/cachectin from the livers of burned and infected rats.

Tumor necrosis factor alpha (TNF-alpha)/cachectin is a monocyte/macrophage-derived cytokine implicated as a proximal mediator of many of the catastrophic host responses to infection or endotoxin. However, circulating levels of TNF-alpha/cachectin have only been episodically detected in hospitalized patients with life-threatening bacterial infections. In the present report, increased quantities of immune-reactive TNF-alpha/cachectin were recovered from the livers of rats 3 days following a lethal burn and infection. Two species of TNF-alpha/cachectin were detected, one of approximately 29 kd and the other 17 kd, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In murine peritoneal macrophages and rat Kupffer cells stimulated in vitro with endotoxin, a 29-kd cell-associated and 17-kd secreted form were also detected. We conclude that the increased appearance in vivo of a 29-kd form of TNF-alpha/cachectin from the livers of lethally burned and infected rats represents a novel cell-associated form of the protein.

Animals↗
PubMed1990

The biologic characteristics of cytokines and their implication in surgical injury.

Cytokines are integral to normal homeostasis and to the response to injury. The biologic activities and synergistic actions of these proteins continue to be elucidated. In moderate quantities, these proteins likely confer such beneficial effects as myelostimulation, activation of immune cells and reprioritization of metabolic processes to provide substrates important in combating the results of injury. Exaggerated or prolonged production of these proteins, however, may produce detrimental effects that lead to a poor outcome. Specific antagonists against cytokines offer potential therapy in these instances of aberrant cytokine response.

Animals↗
PubMed1990

Serum cachectin/tumor necrosis factor in critically ill patients with burns correlates with infection and mortality.

Serum cachectin/tumor necrosis factor (TNF), a cytokine implicated in the pathogenesis of septic shock, may appear in the circulation during serious infection, but the frequency of detection of elevated serum levels during protracted critical burn injury is unknown. Serial serum samples taken from 43 critically ill patients with burns with and without sepsis were analyzed for TNF using an enzyme-linked immunosorbent assay (ELISA). TNF was detectable (greater than 34 picograms per milliliter) at one or more time points in 69 per cent of the patients with sepsis versus 33 per cent of those without sepsis, in 71 per cent of the patients who died versus only 31 per cent of the survivors and in only one healthy normal control patient (n = 21). The frequency of the appearance of TNF correlated with both infection and mortality rate. Moreover, all three patients with TNF levels greater than 540 picograms per milliliter died. Neither the size of the burn nor injury from inhalation correlated with detection of TNF. A subset of 16 patients was studied longitudinally from admission until resolution of injury and these data demonstrate that TNF appears transiently and repetitively in the circulation of patients during infection and protracted critical burn injury. Also, serum cortisol levels were significantly higher during sepsis and death in the absence of serum TNF, compared with sepsis and death with detectable cachectin, suggesting that cortisol may interact with the production or detection of this cytokine during ongoing infection and lethal injury. In this study, we have demonstrated that serum TNF is detectable with greater frequency and in higher concentration in patients with sepsis and in those who ultimately succumb to the burn injury, that serum TNF appears transiently and repetitively in the circulation during injury and that higher serum cortisol levels are correlated with the absence of serum TNF during sepsis and lethal injury.

Burns↗
PubMed1989

Antibodies to cachectin/tumor necrosis factor reduce interleukin 1 beta and interleukin 6 appearance during lethal bacteremia.

Cytokines secreted in response to invading micro-organisms are important mediators of detrimental hemodynamic and metabolic changes in the host. To test whether cachectin/TNF plays a role in triggering release of other cytokines in the setting of infection, anesthetized baboons were passively immunized against systemic cachectin/TNF before infusion of a LD100 dose of live Escherichia coli. Bacteremia led to significant increases in circulating levels of cachectin/TNF, IL-1 beta, and IL-6. Although bacterial endotoxin/lipopolysaccharide is a potent stimulus for the synthesis and release of IL-1 and IL-6 in vitro, specific neutralization of cachectin/TNF in vivo with mAb pretreatment significantly attenuated both the IL-1 beta and the IL-6 responses despite fulminant overwhelming bacteremia. These data suggest that cachectin/TNF is essential for the initiation or amplification of IL-1 and IL-6 release during lethal gram-negative septic shock syndrome.

Animals↗
PubMed1989

Endotoxemia elicits increased circulating beta 2-IFN/IL-6 in man.

beta 2-IFN/hepatocyte stimulating factor/IL-6 is a cytokine secreted by monocytes, fibroblasts, and endothelial cells in cell culture that possesses diverse biologic activity including the stimulation of acute phase plasma protein synthesis and immunomodulation. The circulating levels of this cytokine in man in response to bacterial LPS (endotoxin) were studied. A single i.v. bolus of endotoxin (20 U/kg) produced a monophasic rise in circulating immunoreactive IFN-beta 2/IL-6 and IFN-beta 2/IL-6 bioactivity (hepatocyte stimulation and B cell differentiation assays) peaking 2 to 4 h after the endotoxin challenge. Peak IFN-beta 2/IL-6 levels ranged from 4.1 to 27.5 ng/ml. Associated with this was a rise in circulating C-reactive protein levels detected 20 h after the endotoxin bolus. Thus, IFN-beta 2/IL-6 is likely one of the endogenous mediators which is triggered in man during bacterial infection and likely participates in the metabolic and immune responses of the infected host.

Adult↗
PubMed1989

Starvation leads to decreased levels of mRNA for myofibrillar proteins.

Malnutrition is a common complicating factor in surgical illness. To investigate the cellular changes and mechanisms responsible for the protein wasting associated with nutritional deprivation, Sprague-Dawley rats were subjected to total protein-calorie starvation for 3 (n = 12) or 5 days (n = 12) and compared to freely fed animals monitored for 3 (n = 8) or 5 (n = 8) days. Gastrocnemius protein and RNA content and levels of mRNA coding for the myofibrillar proteins myosin heavy chain, myosin light chain, and alpha-actin were measured. Starvation resulted in a significant decrease in gastrocnemius mass and protein content, and was associated with decreases in mRNA levels for the three myofibrillar proteins assayed. We conclude that changes in mRNA levels for these proteins likely contribute to the loss of peripheral protein which occurs during total nutritional deprivation. In addition, the changes in mRNA levels for these three structural proteins appear to be coordinate, suggesting that transcription of no single myofibrillar protein is rate-limiting in the regulation of skeletal muscle protein content.

Actins↗