Biomedical subjects

R I Inculet

Publications and source records attributed to R I Inculet.

28 records · Page 2Linked to original sources

PubMed1987

Altered leucine metabolism in noncachectic sarcoma patients.

Leucine and whole body protein metabolism were quantitated in 26 human subjects (6 sarcoma patients, 20 age-matched normal controls) using a primed, continuous infusion of [13C]leucine. Plasma samples were analyzed every 15 min for enrichment of [13C]leucine. Plateau enrichment levels were then used to calculate whole-body protein turnover, synthesis, and breakdown rates. Exhaled gas samples were analyzed every 15 min for enrichment of 13CO2, and plateau enrichment levels (as well as CO2 production rates) were used to calculate leucine oxidation rates. Fasting plasma amino acid levels, serum albumin, and total protein levels were also determined. The 6 patients were otherwise healthy but had a large, localized high-grade sarcoma which had not been previously treated. No patient had weight loss. Amino acid, albumin, and total protein levels were equivalent in patients and controls. Whole-body protein turnover rates were significantly greater in sarcoma patients than age-matched controls (15%). Increased protein turnover rates resulted in increased whole-body protein synthesis and breakdown rates in sarcoma patients compared to controls. Leucine oxidation rates were not different in the 2 groups. The results suggest that in humans with high-grade sarcomas leucine metabolic abnormalities are specific to tumor growth and not malnutrition because abnormalities of turnover, synthesis, and breakdown occur prior to any weight loss or measurable change in blood amino acid or protein level.

Adult↗

PubMed1987

Gluconeogenesis in the tumor-influenced rat hepatocyte: importance of tumor burden, lactate, insulin, and glucagon.

In an attempt to define the relationship between tumor burden (cachexia) and host hepatocyte gluconeogenesis, the following experiments were performed with the use of an F344 male rat bearing a transplantable sarcoma. Food intake of tumor-bearing (TB) rats was constant until day 24 following implant and a tumor burden of 18 +/- 5.2% (mean +/- SD), at which time food intake progressively declined daily. Tumor burden was arbitrarily divided at 12.8% to determine if any measured changes occurred prior to or following the approximate time when a significant decline in food intake occurred. Plasma glucose levels decreased with tumor burden. Whole-blood lactate levels increased with tumor burden. Fasting plasma alanine levels decreased with tumor burden. Plasma 3-methylhistidine levels increased with tumor burden. Plasma glucagon levels increased with tumor burden, whereas plasma insulin levels decreased. Hormone changes were noted at small tumor burdens prior to a decline in food intake. Viable hepatocytes were isolated from 4 groups: non-tumor-bearing (NTB), small tumor burden [(STB) 3.5% total body weight (TBW)], moderate tumor burden [(MTB) 14% TBW], and large tumor burden [(LTB) 23% TBW]. As expected in NTB rats, hepatocytes produced significantly more glucose with 20 mM lactate than 20 mM alanine or than Hanks' balanced salt solution (HBSS) alone. Hepatocytes from STB rats demonstrated the same basic relationship for lactate, alanine, and HBSS, but they produced significantly more glucose from lactate and HBSS alone than NTB hepatocytes. With alanine as substrate, the rates of glucose production by hepatocytes were not affected by the presence or size of tumor. However, with lactate as substrate, hepatocytes from MTB and LTB rats produced progressively less glucose as tumor burden increased (r = -0.85, p less than .001), which may partly explain the reduction in blood glucose and elevation in blood lactate levels observed. Elevated gluconeogenesis in TB rats occurred early prior to a decline in food intake. The key precursor appeared to be lactate. The balance between glucagon and insulin appeared to promote the abnormal host carbohydrate metabolism observed.

Amino Acids↗

PubMed1987

Resting energy expenditure and body cell mass alterations in noncachectic patients with sarcomas.

Resting energy expenditure (REE), body cell mass (BCM), and body fat (BF) were measured in six male and seven female volunteers and in a homogeneous group of noncachectic patients with sarcoma, (n = 7). The patients all had large localized tumors, no history or clinical evidence of decreased food intake or weight loss, and had received no prior treatment for cancer. Indirect calorimetry (for REE), K40 analysis (for BCM), and anthropometric measurements (for BF) were performed in accordance with established methods. Physical activity and nutritional status were also assessed. As expected, female control subjects had 50% greater percent BF (p less than 0.001) and 13% less percent BCM (p less than 0.01) than male controls. Male patients with sarcoma had equivalent percent BF, but significantly less percent BCM than controls matched for age, sex, and body surface area (BSA) (p less than 0.05). The REE corrected for BSA was similar in male and female controls but was 25% greater in male sarcoma patients than in male controls (p less than 0.05). This difference was doubled when REE was corrected for BCM (p less than 0.01). In patients with sarcomas, REE/BSA varied inversely with percent BCM (r = -0.782; p less than 0.05) while a similar relationship was not observed in healthy volunteers. We conclude that both REE and vital, functional BCM can be significantly altered in sarcoma patients before any overt signs of cachexia develop. The results support the contention that sarcoma alters host energy metabolism and causes abnormal body composition.

Adult↗

PubMed1986

Major operative trauma increases peripheral amino acid release during the steady-state infusion of total parenteral nutrition in man.

The effect of major operative trauma on skeletal muscle metabolism was examined in nine patients receiving a constant infusion of calories (1460 kcal/m2/day) and protein (75 gm of amino acids/m2/day) for 5 days before and 4 days after an operation. Compared with the preoperative state, 72 hours after the operation there was a significant rise in arterial levels of glucagon, cortisol, norepinephrine, and inactive triiodothyronine and a drop in concentrations of insulin, active triiodothyronine, and amino acids. Forearm blood flow increased, as well as the efflux from forearm muscle of lactate, taurine, serine, glycine, valine, methionine, isoleucine, leucine, phenylalanine, lysine, arginine, and total amino acid nitrogen (440%). This loss of muscle protein after trauma is associated with increased muscle proteolysis, as measured by increased urinary 3-methylhistidine excretion (83%), and accounts for increased nitrogen loss (54%) from the body. Increased activity of the sympathetic nervous system is manifested by increased levels of epinephrine and norepinephrine, a relative lack of insulin, and increased levels of glucagon. This hormonal milieu plays an important role in the production of hypoaminoacidemia, increased efflux of amino acids and lactate from muscle, and negative nitrogen balance observed in these traumatized patients.

Aged↗

PubMed1986

Insulin decreases muscle protein loss after operative trauma in man.

Seventy-two hours after major operative trauma, nine patients receiving a constant infusion of calories (1460 kcal/m2/day) and protein (75 gm of amino acid/m2/day) showed a negative nitrogen balance, increased muscle catabolism, as measured by 3-methylhistidine excretion, increased amino acid efflux from muscle, and decreased circulating levels of insulin. When 5 U of insulin/hr were added to the infusate, arterial insulin levels rose significantly from 39.7 +/- 4.1 microU/ml to approximately the pretrauma levels (74.6 +/- 7.7 microU/ml). Despite this normalization of insulin levels, excretion of nitrogen and 3-methylhistidine and the efflux of amino acids from forearm muscle fell but did not return to pretraumatic levels, suggesting some insulin resistance. Visceral gluconeogenesis from amino acids appeared to decrease, since insulin infusion decreased the efflux of alanine from skeletal muscle with no change in its arterial level. Insulin also significantly reduced the efflux of isoleucine, tyrosine, phenylalanine, glutamine, and total amino acid nitrogen from forearm muscle. These findings, along with the partial reduction in the excretion of 3-methylhistidine and nitrogen, suggest that insulin, in combination with infused calories and protein, decreases the loss of muscle protein after trauma.

Aged↗

PubMed1985

Evaluation of noninvasive tests for the preoperative staging of carcinoma of the esophagus: a prospective study.

A prospective study was undertaken to define the usefulness of conventional full-lung linear tomography, radionuclide liver plus spleen and bone scans, and thoracic and abdominal computed tomography for the preoperative staging of carcinoma of the esophagus. Thirty-three patients with carcinoma of the esophagus were studied. The computed tomographic (CT) scan of the thorax and upper abdomen was the single most accurate noninvasive study. With computed tomography, the relationship of the tumor to the tracheobronchial tree was the feature most useful in predicting local resectability. In all patients with the finding of tracheobronchial compression by the tumor, the tumor could not be resected completely. The predictive value of this CT finding in patients with locally unresectable tumor was high (0.83), indicating its usefulness in assessing unresectability. The CT finding of visible separation between tumor mass and tracheobronchial tree was present in 10 of 14 patients with locally resectable tumor (predictive value, 0.63). However, tumor abutting the tracheobronchial tree without compression was a poor predictor of unresectability (predictive value, 0.36). The radionuclide bone scan was the only other noninvasive study to demonstrate a metastasis not evident by CT scan. The combination of chest and abdominal CT scan, bone scan, and bronchoscopy before operation will accurately stage the majority of patients with esophageal cancer but no noninvasive test is of sufficient reliability to exclude patients from operative resection if otherwise indicated.

Adenocarcinoma↗

PubMed1982

Immune response to transplanted pancreas in pigs.

Segmental allografts of the body and tail of the pancreas have been carried out in pigs using an open duct technique. Diabetes was induced by total pancreatectomy. Control animals on no immunosuppression survived an average of 17 days while animals receiving CyA survived 30 days. In the CyA group those with adequate serum levels of CyA survived 46 days while those with low levels survived 18 days. Once the animal became diabetic rejection was not reversible. In this model complement dependent cytotoxicity was more useful than lymphocyte mediated cytotoxicity in predicting rejection. However the rejected pancreas showed intensive mononuclear infiltration. Malabsorption resulting from total pancreatectomy used to induce diabetes may have contributed to the erratic CyA absorption. Prolonged and relatively normal pancreatic allograft function is possible, but adequate CyA levels must be achieved and maintained. Monitoring of serum levels is essential.

Animals↗

PubMedDate not supplied

Minithoracoscopy for pleural effusions.

The current management of pleural disease often requires direct visualization and biopsy of the pleural space using thoracoscopy. A diagnostic and therapeutic approach to pleural disease is described that uses a new 2 mm rigid thorascope. The technique allows complete visualization, biopsy and drainage of the pleural space with rapid recovery and minimal pain.

Endoscopes↗

PubMedDate not supplied

Water-soluble vitamins in cancer patients on parenteral nutrition: a prospective study.

Forty-three patients with mild weight loss were studied prospectively to determine whether the parenteral water-soluble vitamin doses in a commercially available preparation (MVI concentrate; USV Laboratories, Tarrytown, NY) maintained serum, red blood cell (RBC), and urinary concentrations of water-soluble vitamins in stressed cancer patients receiving total parenteral nutrition (TPN). Patients were divided into three groups: (1) oral diet, no intravenous vitamins given; (2) TPN plus 5 ml MVI; and (3) TPN plus 10 ml MVI. Vitamins C, B1, B2, B3, B6, and niacin were measured initially and weekly during a 6-week study period. Caloric and nitrogen balances were quantified. Most of the patients in all three groups had normal blood or urine levels of all water-soluble vitamins. No clinical evidence of vitamin deficiency or MVI toxicity was detected. The recommended parenteral dosages of vitamin C (100 mg/day) and B3 (15 mg/day) provided measurably adequate levels in all patients. Levels of vitamins B1, B2, B6, and niacin that were less than the normal range were noted in 4-40% of patients receiving the recommended daily dosages of 3 mg, 3.6 mg, 4 mg, and 40 mg, respectively. These deficiencies appeared to improve in group III patients who received twice the recommended parenteral vitamin dosages, although they did not completely disappear. Niacin deficiency appeared to be the most prevalent, occurring in 40% of patients studied. Since intravenous doses of B1, B2, B6, and niacin are safe and well tolerated, it appears that increased daily amounts of these vitamins should be given to cancer patients on parenteral nutrition.

Adolescent↗

PubMedDate not supplied

A model for in vivo serial investigation of hepatic metabolism using 31P nuclear magnetic resonance spectroscopy.

We have developed an animal model which allows serial, in vivo, evaluation of high energy phosphate metabolism in rat liver, using 31P nuclear magnetic resonance spectroscopy (MRS). In seven rats, the left lobe of the was surgically relocated into a subcutaneous position. The animals recovered quickly from the surgery and continued to thrive. Localization of the liver was obtained using simple surface coil technology. Typical MRS data acquisition times were less than 45 minutes. After the 28 days, the livers showed both normal histology and 31P metabolic measures.

Aging↗