Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 18 de 18
Filter
Add more filters










Publication year range
1.
J Pediatr Surg ; 30(7): 1042-4; discussion 1044-5, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7472929

ABSTRACT

Children with Beckwith-Wiedemann syndrome (BWS) have an increased risk of developing Wilms' tumors, hepatoblastomas, and adrenal tumors. This study evaluates disease-free survival in children with BWS and intraabdominal tumors. Sixteen tumors occurred in 13 children with BWS (8 boys, 5 girls). Diagnoses included Wilms' tumor (10) (2 bilateral, 20%), hepatoblastoma (2), bladder rhabdomyosarcoma (1), and adrenal cortical tumor (1). In the 10 children with Wilms' tumor, the average age at diagnosis was 3.5 years (range, 7 months to 5 years). Nine of 10 had initial tumor resection, chemotherapy, and radiation therapy (when indicated). One child with bilateral disease had tumor biopsy, chemotherapy, and partial nephrectomy. Tumors were classified as stage I (5), stage II (2), stage IV (1) and stage V (2), all with favorable histology. Disease-free survival rate was 100% with median follow-up of 9 years (range, 4 to 22 years). One patient had a left adrenal tumor detected during screening sonography 11 years after Wilms' tumor resection. Two infants with advanced-stage hepatoblastoma responded to chemotherapy, allowing subsequent complete hepatic resection. Both tumors had unfavorable histology. Both completed postoperative chemotherapy and have no evidence of disease (NED) with normal alpha-fetoprotein levels at 21 and 12 months, respectively, after tumor detection. One patient with stage III (group 3) bladder rhabdomyosarcoma underwent partial cystectomy following chemoradiation and is alive (NED) after 20 months. Children with BWS should be screened at regular intervals (every 3 to 6 months) for renal, adrenal, and hepatic tumors. The exact duration of screening is not yet determined.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Abdominal Neoplasms/complications , Abdominal Neoplasms/therapy , Beckwith-Wiedemann Syndrome/complications , Adrenal Cortex Neoplasms/complications , Adrenal Cortex Neoplasms/therapy , Adrenal Gland Neoplasms/complications , Adrenal Gland Neoplasms/therapy , Child, Preschool , Combined Modality Therapy , Disease-Free Survival , Female , Follow-Up Studies , Hepatoblastoma/complications , Hepatoblastoma/therapy , Humans , Infant , Kidney Neoplasms/complications , Kidney Neoplasms/therapy , Liver Neoplasms/complications , Liver Neoplasms/therapy , Male , Neoplasm Staging , Neoplasms, Second Primary/pathology , Rhabdomyosarcoma/complications , Rhabdomyosarcoma/therapy , Risk Factors , Survival Rate , Treatment Outcome , Urinary Bladder Neoplasms/complications , Urinary Bladder Neoplasms/therapy , Wilms Tumor/complications , Wilms Tumor/therapy , alpha-Fetoproteins/analysis
2.
J Pediatr Surg ; 30(2): 317-21, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7738757

ABSTRACT

The ability to accurately assess tumor size and orientation to surrounding vital structures is an important consideration during preoperative evaluation. The authors report on nine children with solid tumors (hepatoblastoma [1], neuroblastoma [2], adrenal cortical carcinoma [2], liver adenoma [1], primitive neuroectodermal tumor [PNET] [1], and stage V Wilms' tumor [2]) for whom tumor resectability was questioned because of the tumors' close proximity to major blood vessels (noted through conventional radiographic imaging). The children had scanning with spiral volumetric acquisition computerized tomography, (CT) which obtains images during continuous rotation of the x-ray source while the patient moves at a constant velocity through the gantry. This technique is rapid (18 to 30 seconds), and is similar with respect to radiation exposure; little or no sedation is required, and the contrast dose is lower than that of conventional CT. Three-dimensional reconstruction of spiral CT imaging provided useful information that allowed successful resection in all nine cases. The authors suggest that spiral CT may become an important imaging modality in the preoperative evaluation of pediatric solid tumors and that further evaluation of this new methodology is warranted.


Subject(s)
Image Processing, Computer-Assisted , Neoplasms/diagnostic imaging , Tomography, X-Ray Computed/methods , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Motion , Radiographic Image Enhancement , Time Factors , Tomography, X-Ray Computed/economics
3.
J Pediatr Surg ; 30(2): 336-40, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7738761

ABSTRACT

Recognition of pancreatic injuries is frequently delayed, and optimal treatment is often controversial. The use of endoscopic retrograde cholangiopancreatography (ERCP) has allowed accurate delineation of pancreatic ductal injuries; however, the small size of children and the concern with inducing pancreatitis and/or lesser sac contamination have limited its use in children. In 1988, the authors began using ERCP for selected pancreatic injuries. This report describes their experience with this technique and examines the role of ERCP in pediatric pancreatic injuries. Six children with pancreatic transections resulting from blunt trauma were treated between 1988 and 1993. The age range was 2 1/2 to 8 years, and the weight range was 13.6 to 27.9 kg. The average period from injury to referral to the hospital was 14 days (range, 2 to 30 days). All six children presented with chemical evidence of pancreatitis and had an initial computed tomography (CT) scan; five scans were interpreted as being normal. Five of the six patients had subsequent CT scans, which showed lesser-sac fluid collection. Three patients were treated with drainage (2 percutaneous, 1 open [outside hospital]), and when this failed, ERCP was performed, at 13.6 days (average) after presentation. These three patients underwent ERCP relatively early in the course (an average of 3 days after presentation). All six children had major ductal transections documented through ERCP. After ERCP, the serum amylase level remained elevated in three, increased in one, and normal in one. (It was not measured in one of the recent cases taken for immediate operation.)(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Cholangiopancreatography, Endoscopic Retrograde , Pancreas/injuries , Wounds, Nonpenetrating/diagnosis , Abdominal Pain/etiology , Child , Child, Preschool , Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Cholangiopancreatography, Endoscopic Retrograde/instrumentation , Drainage , Humans , Pancreas/surgery , Pancreatectomy , Pancreatic Ducts/injuries , Pancreatic Ducts/surgery , Wounds, Nonpenetrating/complications , Wounds, Nonpenetrating/therapy
4.
JPEN J Parenter Enteral Nutr ; 19(1): 9-14, 1995.
Article in English | MEDLINE | ID: mdl-7658609

ABSTRACT

BACKGROUND: Endotoxemia is characterized by a marked increase in the uptake of amino acids by the liver, but the regulation of this response has not been fully elucidated. In the current study, we investigated the potential role of prostaglandins as mediators of this response. We examined the in vivo effects of the anti-inflammatory agent ketorolac, a cyclo-oxygenase inhibitor that blocks prostaglandin synthesis, on hepatic amino acid transport activity in endotoxin-treated rats. METHODS: We assayed the activities of the Na(+)-dependent transport systems A and N in hepatic plasma membrane vesicles prepared from endotoxemic rats that were pretreated with ketorolac or vehicle. Hepatic plasma membrane vesicles were prepared by differential centrifugation, and the transport of [3H]glutamine (system N) and [3H]2-methylamino-isobutyric acid (system A) was assayed. Hepatic plasma membrane vesicles were also prepared from normal rats that received prostaglandin E2, and glutamine and MeAIB transport were measured. RESULTS: Endotoxin treatment resulted in a twofold to threefold increase in Na(+)-dependent amino acid transport activity in hepatic plasma membrane vesicles secondary to an increase in the transport Vmax, which was consistent with the appearance of increased numbers of corresponding transporter proteins in the hepatocyte plasma membrane. Pretreatment with ketorolac almost completely abrogated the endotoxin-induced increase in hepatic amino acid transport. Administration of prostaglandin E2 to normal rats resulted in a statistically significant increase in glutamine and alanine transport by hepatic plasma membrane vesicles prepared from these animals. CONCLUSIONS: Prostaglandins play a key role in mediating the accelerated hepatic amino acid transport that occurs during endotoxemia.


Subject(s)
Amino Acids/metabolism , Cyclooxygenase Inhibitors/pharmacology , Endotoxins/pharmacology , Liver/metabolism , Sodium/pharmacology , Alanine/metabolism , Animals , Biological Transport/drug effects , Cell Membrane/metabolism , Dinoprostone/pharmacology , Glutamine/metabolism , Ketorolac , Kinetics , Liver/drug effects , Male , Rats , Rats, Sprague-Dawley , Tolmetin/analogs & derivatives , Tolmetin/pharmacology , beta-Alanine/analogs & derivatives , beta-Alanine/metabolism
5.
Ann Surg Oncol ; 1(4): 283-9, 1994 Jul.
Article in English | MEDLINE | ID: mdl-7850526

ABSTRACT

BACKGROUND: Gastrointestinal tumors are relatively uncommon in infants and children, and the histologic diagnoses differ from those seen in an adult practice. Furthermore, the clinical presentation of such tumors is quite variable. METHODS: We reviewed the records of 39 pediatric patients who had been treated for tumors of the alimentary tract at our hospital over the past 20 years. The symptoms, physical findings, treatments, and outcomes are tabulated and discussed. RESULTS: Non-Hodgkin's lymphoma was the predominant diagnosis. It was found in 22 children, and the survival rate was 60%. Other malignant tumors found in this pediatric series included colorectal carcinoma in four patients and gastric leiomyosarcoma in one. The outcomes of these patients were poor; four of the children have died, and one girl remains alive with extensive disease. Benign lesions included neurogenic tumors (n = 5), inflammatory pseudotumors (n = 3), hemangiomas (n = 2), teratoma and carcinoid (n = 1 each). These tumors were ultimately cured, with one exception, after surgical resection. CONCLUSIONS: Gastrointestinal tumors in children cover a broad spectrum of benign and malignant varieties and stem from conditions that differ significantly from those observed in adults. While treatment varies according to diagnosis, most patients respond best to complete resection of the primary tumor.


Subject(s)
Gastrointestinal Neoplasms , Adolescent , Adult , Child , Child, Preschool , Female , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/surgery , Humans , Infant , Lymphoma, Non-Hodgkin/diagnosis , Lymphoma, Non-Hodgkin/pathology , Lymphoma, Non-Hodgkin/surgery , Male , Retrospective Studies , Treatment Outcome
6.
Ann Surg ; 216(3): 353-61; discussion 361-2, 1992 Sep.
Article in English | MEDLINE | ID: mdl-1329681

ABSTRACT

Human growth hormone (GH) has been shown to improve nitrogen balance in surgical patients and to decrease urea production. This has been thought to be due primarily to an increase in protein synthesis in skeletal muscle. Little attention has focused on the liver as a possible site where GH may modulate amino acid uptake and thereby divert nitrogen away from urea-genesis. The authors hypothesized that GH regulates amino acid transport in hepatocytes at the plasma membrane level. They studied hepatic amino acid transport in 20 healthy surgical patients that received saline, low-dose GH (0.1 mg/kg/day), or high-dose (0.2 mg/kg/day) GH for 3 days before operation. At operation, a 5- to 10-g wedge biopsy of the liver was obtained, and hepatocyte plasma membrane vesicles were prepared by Percoll density gradient centrifugation. Vesicle transport of [3H]-MeAIB, a highly selective system A substrate, and [3H]-glutamine, a selective system N substrate, was measured, employing a rapid mixing/filtration technique. Hepatocyte plasma membrane vesicles were also prepared from 14 rats treated with saline or one of three different GH treatment regimens: (A) 12 hours after chronic GH treatment (6 mg/kg every 12 hours x 4 doses); (B) 4 hours after acute (1 dose) GH treatment; and (C) 4 hours after chronic GH treatment. In human liver vesicles, low-dose GH resulted in a 13% decrease in system A activity (p = not significant), whereas high-dose GH caused a marked 79% decrease (6.7 +/- 1.7 pmol/mg protein/10 seconds in control patients versus 1.4 +/- 0.7 in GH, p less than 0.05). System N was unaffected. Kinetic analysis of MeAIB transport by vesicles from high-dose GH patients showed the reduction in transport to be due to a 63% decrease in the Vmax (maximal transport velocity) with no alteration in the transport Km (carrier affinity). Vesicles from rats treated chronically with GH using a protocol similar to that used for human subjects exhibited decreased system A transport activity (10.4 +/- 0.4 pmol/mg pro/10 seconds in controls versus 7.5 +/- 0.2 in GH, p less than 0.05) secondary to a 59% reduction in the transport Vmax. Chronic growth hormone treatment decreases the activity of system A in both human and rat hepatocytes. This may be one mechanism by which GH diminishes hepatic urea-genesis and spares amino acids for peripheral protein synthesis.


Subject(s)
Glutamine/metabolism , Growth Hormone/pharmacology , Liver/metabolism , beta-Alanine/analogs & derivatives , 5'-Nucleotidase/metabolism , Adult , Aged , Animals , Biological Transport/physiology , Cell Membrane/metabolism , Glucose-6-Phosphatase/metabolism , Humans , Male , Middle Aged , NADPH-Ferrihemoprotein Reductase/metabolism , Rats , Rats, Sprague-Dawley , Reference Values , Sodium/metabolism , beta-Alanine/metabolism
7.
J Surg Res ; 51(1): 82-6, 1991 Jul.
Article in English | MEDLINE | ID: mdl-2067363

ABSTRACT

Despite the attenuated skeletal muscle proteolysis that occurs following hypothermic anesthesia and open heart surgery, blood amino acid levels are maintained, suggesting enhanced amino acid release by another organ. To investigate the role of the lung in this response, we determined the release of glutamine (Gln) and alanine by the lung, since these two amino acids transport two-thirds of circulating amino acid nitrogen. Three groups of patients were studied: (a) preoperative non-stressed controls; (b) postoperative general surgical patients; and (c) postoperative cardiac surgical patients studied on Postoperative Day 1 following open heart surgery requiring cardiopulmonary bypass and hypothermic anesthesia. In preoperative controls the lung was an organ of glutamine and alanine balance. These exchange rates were unaffected by the stress of an abdominal surgical procedure despite a mild increase in pulmonary blood flow. However, lung Gln release in the cardiac surgical patients was significantly increased (-0.6 +/- 1.2 mumole/kg/min in controls vs -6.5 +/- 1.3 mumole/kg/min in postoperative hearts, P less than 0.05) and was due exclusively to an increase in the pulmonary artery-systemic arterial concentration difference. Alanine release by the lungs was also increased in the postoperative cardiac surgical patients. The mechanism by which this augmented pulmonary glutamine release occurs following open heart surgery is unclear, but the lungs appear to play a central role in maintaining amino acid homeostasis. This metabolic role of the lungs following hypothermic anesthesia and cardiopulmonary bypass has not been previously described.


Subject(s)
Cardiac Surgical Procedures , Glutamine/metabolism , Lung/metabolism , Amino Acids/blood , Amino Acids/metabolism , Humans , Osmolar Concentration , Postoperative Period , Pulmonary Artery , Pulmonary Circulation
8.
J Invest Surg ; 4(1): 81-6, 1991.
Article in English | MEDLINE | ID: mdl-1863590

ABSTRACT

We have developed a simple, accurate, and relatively inexpensive method of measuring pulmonary blood flow in the anesthetized rat using a modification of the dye dilution technique. The method is attractive because it allows for the measurement of pulmonary blood flow and also the determination of pulmonary substrate flux. Using rats with a catheter in the carotid artery and a doubly cannulated right ventricle (RV), a constant infusion of [14C]P-aminohippurate ([14C]PAH) is begun via the distal RV catheter. After steady state is obtained the infusion of [14C]PAH is then stopped and blood is immediately withdrawn from the proximal RV cannula. This maneuver insures that [14C]PAH from the infusate is not sampled through the proximal RV catheter. Obtaining the blood from the proximal RV catheter within 5 s after clearing the infusion catheter insures that no dilution of [14C]PAH in the right ventricle (from recirculating blood) occurs. Catheter position is verified at autopsy. Calculations are performed to determine pulmonary blood flow. In 20 normal rats studied, the pulmonary blood flow was 24 +/- 1 mL/100 g body wt min-1 and in 12 endotoxin-treated rats (10 mg/kg body wt) the pulmonary blood flow was 32 +/- 2 mL/100 g body wt. These values are similar to values obtained with other methods used to measure total pulmonary blood flow.


Subject(s)
Pulmonary Circulation , Anesthesia , Animals , Blood Flow Velocity , Indicator Dilution Techniques , Male , Rats , Rats, Inbred Strains , p-Aminohippuric Acid/blood
9.
JPEN J Parenter Enteral Nutr ; 14(6): 569-73, 1990.
Article in English | MEDLINE | ID: mdl-2273530

ABSTRACT

The relative contributions of skeletal muscle and the pulmonary bed in maintaining amino acid homeostasis were studied. Inasmuch as more than 60% of whole blood amino acid nitrogen is transported as glutamine and alanine, the flux of these two amino acids across the lungs (n = 20) and hindquarter (n = 20) was determined in the postabsorptive adult rat. Both skeletal muscle and the lungs released net amounts of glutamine and alanine in the postabsorptive state. Blood flow to the hindquarter was approximately 16% of cardiac output (3.8 +/- 0.3 cc/100 g BW/min), while pulmonary blood flow (cardiac output) was 23.7 +/- 1.7 cc/100 g BW/min. Thus, despite a lower glutamine concentration difference across the lungs (-32 +/- 6 mumol/liter) compared with the hindquarter (-59 +/- 10 mumol/liter (p less than 0.01), the lungs released significantly more glutamine (741 +/- 142 nmol/100 g BW/min) than the hindquarter (208 +/- 39 nmol/100 g BW/min) (p less than 0.01) because of the significantly higher pulmonary blood flow. Similarly, the concentration difference for alanine across the lungs was less than that of the hindquarter (-24 +/- 8 mumol/liter vs -60 +/- 12 mumol/liter, p less than 0.01) but the lungs released significantly more alanine than the hindquarter (553 +/- 159 nmol/100 g BW/min vs 221 +/- 41 nmol/100 g BW, p less than 0.01. Compositional studies demonstrated that the hindquarter comprises 40% of total body muscle mass in the rat; thus both total skeletal muscle mass and the lungs contribute approximately equally to the maintenance of blood glutamine and alanine levels.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Alanine/metabolism , Glutamine/metabolism , Lung/metabolism , Alanine/blood , Animals , Cardiac Output , Glutamine/blood , Homeostasis/physiology , Male , Muscles/metabolism , Rats , Rats, Inbred Strains
10.
Surgery ; 108(2): 213-8; discussion 218-9, 1990 Aug.
Article in English | MEDLINE | ID: mdl-2382221

ABSTRACT

The role of the glucocorticoid hormones as possible mediators of the accelerated lung glutamine and alanine release that occurs during critical illness was investigated. Studies were done in adult rats receiving dexamethasone (0.6 mg intramuscularly/100 gm body weight/day for 2 consecutive days; n = 24) or saline solution (controls; n = 20). Measurements were made in the postabsorptive state and amino acid flux was calculated by multiplying pulmonary blood flow by the right ventricular-arterial concentration difference for glutamine and alanine. Lung glutamine release was 703 +/- 184 nmol/100 gm body weight/min in control rats. This release rate doubled in the dexamethasone-treated rats (1476 +/- 256; p less than 0.05). The activity of the glutamine synthetase enzyme increased by 33% in the dexamethasone-treated animals and there was a 50% decrease in lung glutamine content (p less than 0.01). Likewise, dexamethasone accelerated the release of alanine by the lungs twofold (559 +/- 173 nmol/100 gm body weight/min in controls vs 1113 +/- 184 nmol/100 gm body weight/min in dexamethasone-treated rats; p less than 0.05). The increased release of both amino acids was caused by a significant increase in the concentration difference across the lungs and not a change in pulmonary blood flow. Glucocorticoids appear to be key mediators of the accelerated lung amino acid release that characterizes catabolic diseases.


Subject(s)
Alanine/metabolism , Dexamethasone/pharmacology , Glutamine/metabolism , Lung/metabolism , Alanine/blood , Amino Acids/metabolism , Animals , Arteries , Glutamine/blood , Male , Osmolar Concentration , Rats , Rats, Inbred Strains
11.
Arch Surg ; 125(8): 1040-5, 1990 Aug.
Article in English | MEDLINE | ID: mdl-2378557

ABSTRACT

The healing effects of glutamine given orally for 8 days as a single amino acid nutrient after treatment with whole abdominal radiation (10 Gy) were studied. Rats received isonitrogenous and isovolumic diets containing 3% glutamine or 3% glycine. Control rats were not irradiated but were given identical diets. In irradiated animals, survival was 100% in animals receiving glutamine compared with 45% in animals receiving glycine. Glutamine ingestion diminished bloody diarrhea and the incidence of bowel perforation. Arterial glutamine level was higher in animals receiving glutamine in the diet, as were gut glutamine extraction (35% +/- 8% vs 12% +/- 7%) and intestinal glutaminase activity. These metabolic improvements were associated with a marked increase in villous height, villous number, and the number of mitoses per crypt in rats receiving glutamine. Glutamine was not beneficial in control nonirradiated animals. The data demonstrated that provision of oral glutamine after abdominal radiation supported gut glutamine metabolism, improved mucosal morphometrics, and decreased the morbidity and mortality associated with this abdominal radiation model.


Subject(s)
Enteritis/drug therapy , Glutamine/therapeutic use , Intestine, Small/pathology , Radiation Injuries, Experimental/drug therapy , Administration, Oral , Analysis of Variance , Animals , Disease Models, Animal , Enteritis/metabolism , Enteritis/pathology , Glutamine/administration & dosage , Glutamine/metabolism , Glycine/therapeutic use , Intestinal Mucosa/pathology , Intestine, Small/metabolism , Jejunum/pathology , Male , Radiation Injuries, Experimental/metabolism , Radiation Injuries, Experimental/pathology , Rats , Rats, Inbred Strains
12.
JPEN J Parenter Enteral Nutr ; 14(4 Suppl): 68S-70S, 1990.
Article in English | MEDLINE | ID: mdl-2205734

ABSTRACT

The role of the lungs in maintaining amino acid homeostasis has only recently been studied. The data suggest that the lungs play a key role in glutamine flow in both normal and catabolic states. Further studies are necessary to clarify the regulation of lung glutamine at the whole organ and cellular level.


Subject(s)
Glutamine/metabolism , Lung/metabolism , Animals , Biological Transport, Active , Glutamine/blood , Glutamine/pharmacokinetics , Homeostasis , Humans , Muscles/metabolism , Rats
13.
Cancer ; 66(1): 62-8, 1990 Jul 01.
Article in English | MEDLINE | ID: mdl-2354410

ABSTRACT

Glutamine may be an essential dietary component, especially for the support of intestinal mucosal growth and function. This study evaluated the effects of a glutamine-enriched elemental diet, administered before whole-abdominal radiation on gut glutamine metabolism, mucosal morphometrics, and bacterial translocation. Rats were randomized to receive a nutritionally complete elemental diet that was glutamine-enriched or glutamine-free for 4 days. The animals were then subjected to a single dose of 1000 cGy x-radiation to the abdomen. After irradiation, all animals received the glutamine-free diet. Four days later the animals underwent laparotomy for sampling of arterial and portal venous blood, culture of mesenteric lymph nodes, and removal of the small intestine for microscopic examination. There was no difference in arterial glutamine or gut glutamine extraction between the two groups, but body weight loss was significantly diminished in the glutamine-fed rats. Rats receiving the glutamine-enriched elemental diet before radiation had a significant increase in jejunal villous number, villous height, and number of metaphase mitoses per crypt. Scanning electron microscopy confirmed the presence of an intact gut epithelium in eight of eight rats receiving prophylactic glutamine compared to one of eight animals in the glutamine-free group. Three of eight rats fed glutamine had culture positive mesenteric lymph nodes compared with five of seven rats receiving the glutamine-free diet. Glutamine exerts a protective effect on the small bowel mucosa by supporting crypt cell proliferation effect on accelerate healing of the acutely radiated bowel.


Subject(s)
Glutamine/therapeutic use , Intestinal Diseases/prevention & control , Intestinal Mucosa/radiation effects , Radiation Injuries/prevention & control , Animals , Glutamine/blood , Intestinal Mucosa/anatomy & histology , Jejunum/anatomy & histology , Male , Organ Size/drug effects , Radiation-Protective Agents , Rats , Rats, Inbred Strains
14.
Ann Surg ; 211(5): 543-9; discussion 549-51, 1990 May.
Article in English | MEDLINE | ID: mdl-2339916

ABSTRACT

The effects of sepsis on gut glutamine (GLN) metabolism were studied to gain further insight into the regulation of the altered glutamine metabolism that characterizes critical illnesses. Studies were done in laboratory rats and in hospitalized patients. The human studies were done in seven healthy surgical patients (controls) and six septic patients who underwent laparotomy. Radial artery and portal vein samples were obtained during operation and were analyzed for GLN and oxygen content. Despite no reduction in arterial glutamine concentration in the septic patients, gut glutamine extraction was diminished by 75% (12.0% +/- 1.6% in controls vs. 2.8% +/- 0.8% in septic patients, p less than 0.01). Similarly gut oxygen extraction was diminished by nearly 50% in the septic patients (p less than 0.05). To further investigate these abnormalities, endotoxin (10 mg/kg intraperitoneally) or saline (controls) was administered to adult rats 12 hours before cannulation of the carotid artery and portal vein. The arterial GLN concentration was increased by 13% in the endotoxin-treated animals (p less than 0.05) but gut glutamine uptake was diminished by 46% (526 +/- 82 nmol/100 g BW/minute in controls vs. 282 +/- 45 in endotoxin, p less than 0.01). Simultaneously gut glutaminase activity was diminished by 30% (p less than 0.01) and intestinal glutamate release fell by two thirds. Blood cultures were negative in control animals (0 of 20), but were positive in 25% of endotoxemic animals (6 of 24) for gram-negative rods (p = 0.019). Sepsis and endotoxemia impair gut glutamine metabolism. This impairment may be etiologic in the breakdown of the gut mucosal barrier and in the development of bacterial translocation.


Subject(s)
Endotoxins/blood , Glutamine/metabolism , Infections/metabolism , Intestinal Mucosa/metabolism , Adolescent , Adult , Aged , Animals , Glutaminase/metabolism , Glutamine/blood , Humans , Infections/physiopathology , Intestines/blood supply , Male , Middle Aged , Models, Biological , Oxygen/blood , Portal Vein , Rats
15.
J Surg Res ; 48(4): 383-91, 1990 Apr.
Article in English | MEDLINE | ID: mdl-2187115

ABSTRACT

In the critically ill surgical patient a variety of therapeutic maneuvers is required to maintain a "healthy gut." Provision of adequate amounts of glutamine to the gastrointestinal mucosa appears to be just one of these maneuvers. Other methods utilized to protect the gut from becoming a wound include: (a) minimizing additional systemic insults (such as hypotension, sepsis, multiple operative procedures); (b) aggressive pulmonary care; (c) the judicious use of antibiotics; and (d) aggressive enteral or parenteral feedings. The concept that the gut is an organ of quiescence following surgical stress merits reconsideration. The intestinal tract plays a central role in interorgan glutamine metabolism and is a key regulator of nitrogen handling following surgical stress. Critically ill patients are susceptible to developing gut-origin sepsis, the incidence of which will be diminished by instituting measures and providing treatments which support intestinal structure, function, and metabolism. Provision of glutamine-enriched diets to such patients may be one of these therapies.


Subject(s)
Glutamine/physiology , Infections/metabolism , Intestinal Diseases/metabolism , Intestines/physiology , Animals , Glutamine/metabolism , Humans , Intestinal Mucosa/metabolism , Intestines/injuries , Reference Values , Stress, Physiological/metabolism , Wounds and Injuries/metabolism
16.
J Surg Res ; 48(4): 319-23, 1990 Apr.
Article in English | MEDLINE | ID: mdl-2338817

ABSTRACT

Glutamine is a principal fuel utilized by rapidly growing tumors. Advanced malignant disease results in muscle glutamine depletion and weight loss. Concern exists about providing dietary glutamine to the host with cancer since it may stimulate tumor growth. This study examined the effects of oral glutamine on muscle glutamine metabolism and tumor growth. Twenty-four rats with large sarcomas were pair fed a glutamine-enriched or glutamine-free elemental diet. Diets were isonitrogenous and isocaloric. After 6 days of feeding, the animals were anesthetized and arterial glutamine, hindquarter glutamine flux, muscle glutamine content, tumor weight, tumor DNA content, tumor glutaminase activity, and number of metaphase mitoses/high power field (HPF) in the tumor were determined. There was no difference in arterial glutamine between the two groups, but provision of a glutamine-enriched diet increased muscle glutamine content by 60% (2.31 +/- 0.21 mumole/g tissue vs 1.44 +/- 0.22 mumol/g tissue, P less than 0.05), which supported muscle glutamine release. There were no differences among tumor DNA content, tumor glutaminase activity, or tumor weight and there was no difference histologically in the number of metaphase mitoses/HPF. Glutamine-enriched oral diets may replete host glutamine stores and support muscle glutamine metabolism without stimulating tumor growth.


Subject(s)
Diet , Glutamine/administration & dosage , Muscles/metabolism , Sarcoma, Experimental/pathology , Animals , Glutamine/metabolism , Glutamine/pharmacology , Male , Rats , Sarcoma, Experimental/metabolism
17.
Arch Surg ; 125(1): 57-61, 1990 Jan.
Article in English | MEDLINE | ID: mdl-1967211

ABSTRACT

Amino acid flux across the lungs was studied in humans to gain further insight into the altered nitrogen metabolism that characterizes catabolic disease states. Lung flux of glutamine, glutamate, and alanine was determined in three groups of surgical patients with indwelling pulmonary artery catheters: (1) preoperative controls (n = 14), (2) postoperative elective general surgical patients (n = 10, and (3) hyperdynamic septic surgical patients (n = 17). In controls the lung was an organ of amino acid balance. These exchange rates did not change in general surgical patients. In the septic group, glutamine release by the lung increased markedly from a control value of 0.80 +/- 0.99 mumol/kg per minute to 6.80 +/- 1.32 mumol/kg per minute. This accelerated release rate was secondary to both an increase in total pulmonary blood flow and an increase in the pulmonary artery-systemic arterial concentration difference. The lung also became an organ of significant alanine release in septic patients. The lung plays an active metabolic role in the processing of amino acids and may be a key regulator in interorgan nitrogen flux after major injury and infection.


Subject(s)
Alanine/pharmacokinetics , Bacterial Infections/metabolism , Glutamine/pharmacokinetics , Lung/metabolism , Alanine/blood , Ammonia/blood , Cardiac Output , Catheterization, Swan-Ganz , Glutamates/blood , Glutamic Acid , Glutamine/blood , Humans , Postoperative Period , Surgical Procedures, Operative
18.
Cancer Res ; 43(7): 3108-11, 1983 Jul.
Article in English | MEDLINE | ID: mdl-6682699

ABSTRACT

The intent of this study was to determine whether or not local control and/or cure of rabbits bearing the VX-2 carcinoma could be achieved with regional hyperthermia and chemotherapy. A model of isolation-perfusion used cis-diamminedichloroplatinum(II) (DDP). Five different experimental groups were studied, each group receiving progressively smaller tumor inocula and shorter treatment intervals. Although local control and cure improved as the tumor inocula became smaller and treatment interval became shorter, there was no benefit demonstrated when compared to sham-operated animals. DDP appeared to be well tolerated in animals perfused as normothermic temperatures. However, animals perfused at hyperthermic temperature with DDP experienced necrosis of normal as well as neoplastic tissue, resulting in early demise of the animal. This final observation suggests that the amount of DDP utilized in clinical isolation-perfusion should be approached with caution.


Subject(s)
Carcinoma/therapy , Cisplatin/therapeutic use , Hot Temperature/therapeutic use , Animals , Carcinoma/pathology , Cell Line , Cell Survival , Chemotherapy, Cancer, Regional Perfusion , Cisplatin/administration & dosage , Neoplasm Transplantation , Neoplasms, Experimental/therapy , Rabbits , Thigh
SELECTION OF CITATIONS
SEARCH DETAIL
...