[Organ-specific in vivo dipeptide (alanylglutamine, glycylglutamine) values in catabolic dogs].
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Biomedical subjects
Publications and source records attributed to J Karner.
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We carried out metabolic investigations of 26 patients with severe forms of acute pancreatitis which were evaluated by an organ score. We formed six groups from this data: survivors and deceased in the first week, the second week, and after a further two weeks of illness. The amino acid patterns in plasma and muscles deviated considerably from normal at all times in both the surviving and the deceased patients. In particular, changes in the concentrations of branched-chain amino acids and glutamine in the muscle tissue have a prognostic value. In the range two to four (normal range: above 20), the factor glutamine/VAL+LEU+ILE characterizes a prefinal condition in non-survivors. This factor increased in patients recovering from the illness from 6 to values over 20. Non-survivors (NS) had higher plasma levels of glucose and glucagon compared to surviving patients. Plasma glucagon concentrations in NS reached levels up to 4,000 pg/mL at admission, which declined gradually to normal range during the course of the illness.
The metabolic derangement of sepsis leads to changes of the plasma and muscle amino acid (AA) pattern. In this study the influence of a septic process on liver AA pattern was investigated. In seven patients with abdominal sepsis, liver AA concentrations were determined during surgery and compared with those of four patients who had undergone cholecystectomy. In sepsis lowered AA levels were found for most of the AAs. Outstanding decreases exhibited the levels of the gluconeogenetic AAs (especially threonine and alanine), the branched chain AAs, lysine, and taurine. In the patients who did not survive the septic process, the depletion of these AAs was even amplified. Slightly increased AA levels were analyzed for P-ethanolamine, cystathionine, citrulline, beta-alanine, tyrosine, and phenylalanine. The results indicate a disturbed free AA pattern of the septic liver. Despite the increased flux of gluconeogenetic AA from muscle to liver in sepsis, as reported by several authors, no accumulation of these AAs occurs in the liver.
Nosocomial pneumonia is a major risk for long term ventilated ICU patients. The infection route may be hematogenic or via inhalation or aspiration of microorganisms. The source of aspiration is the oropharynx. This prospective study intended to study the role of the stomach as a reservoir of bacteria in ICU patients treated with cimetidine. Gastric juice and bronchial secretion from 34 patients ventilated for more than 4 days were examined bacteriologically. 72,8% of the gastric (G) and 79,1% of the bronchial aspirates (B) revealed significant bacterial growth (more than 10(4) microorganism/ml). Pseudomonas, Klebsiella, and Candida spp. were found in 56,7% (B) and 51,8% (G) of the positive cultures as an effect of selection caused by antibiotics. Organisms of intestinal origin were found in 17,8% (B) und 15,5% (G), respectively. In 32,5%, identical organisms or patterns of organisms were found in the gastric and bronchial aspirates. 7 of the 34 patients (20,6%) developed pneumonia; in 6 of these 7 cases, the same organisms could be identified at the same and/or at the last examination before developing pneumonia in gastric content and bronchial secretion. The pH-value of the sterile aspirates was lower than of the colonized aspirates (5,39 vs 5,99). During enteral nutrition, 31,4% of the aspirates were sterile, whereas during parenteral nutrition only 24,3% of the gastric aspirates were sterile. Therefore, enteral nutrition should be started as soon as possible, the pH-value should be checked frequently and should not exceed 4 in order to reduce bacterial overgrowth in the stomach. A further consequence is to use as few antibiotics as possible.
We measured amino acid concentrations in plasma and skeletal muscle of three groups of patients with acute hemorrhagic pancreatitis: (a) patients without secondary organ lesions, (b) patients also suffering from kidney damage, and (c) patients in whom the pancreatitis was accompanied by sepsis and multiple organ failure. In all three groups, especially the third group, the amino acid concentrations in both plasma and muscle were below normal. Glutamine was only 14% of normal in muscle tissue of the third group. Onset of renal insufficiency was indicated by increasing values for 3-methylhistidine and cystathionine; multiple organ failure, by increased concentrations of methionine and phenylalanine in plasma. The low amino acid concentrations of patients with acute pancreatitis can be explained as a combined effect of semistarvation and hypercatabolism. Changes in the plasma concentrations of amino acids did not reflect necessarily the concentrations in muscle tissue.
In this study the effect of p-bromophenacylbromide (p-BPAB), an inhibitor of phospholipase A, was studied in acute pancreatitis in an experimental rat model. Acute pancreatitis was produced by instillation of 0.4 ml bile into the pancreatic duct. p-BPAB was injected i.p. in a dosage of 0.25 micrograms/g b.wt. 30 min before, 30 min after, or 4h after the onset of pancreatitis. Prophylactic and early administration of p-BPAB inhibited severe morphological changes, such as necrosis and hemorrhages. Moreover, during administration of the inhibitor, decreased plasma concentrations of serum lipase and amylase (P less than 0.001) were monitored and compared with untreated animals. These therapeutic effects of p-BPAB were not seen in rats in which the inhibitor was injected 4 h after the onset of pancreatitis. As a result the phospholipase inhibitor, p-BPAB, reduces the clinical and morphological manifestations of acute pancreatitis. The effect of p-BPAB is dependent on the time of administration.
In this study the influence of a severe catabolic situation (scalding and nitrogen deprivation) on amino acid (AA) metabolism was investigated in an experimental rat model. Scalding of 25 per cent of the total body surface area (TBSA) and hypocaloric alimentation (5.6 kcal per 100 g rat per day, no nitrogen) resulted in mean daily nitrogen losses of -0.27 +/- 0.3 g. Compared to anabolic growing rats this nitrogen catabolism significantly reduced the total free AA content of muscle (-47 per cent, P less than 0.001) and liver (-39 per cent, P less than 0.001). The total plasma AA concentrations were slightly increased in catabolic rats (+10 per cent). In catabolic rats muscle glycine concentrations dropped significantly (-79 per cent, P less than 0.001), while glutamine concentrations decreased by 22 per cent, which was not significant. Branched chain AA and phenylalanine were significantly elevated both in muscle and in plasma. Scalding and nitrogen depletion in rats leads to characteristic changes in plasma, muscle and liver AA concentrations, which are comparable to the results obtained in catabolic patients. However, the low muscle glycine concentrations in burned rats differ from the clinical observations where glutamine rather than glycine concentrations in muscle tissue are reduced. The rat model seems to be well suited for studying the influence of various therapeutic approaches such as different forms of parenteral nutrition or hormonal substitution on nitrogen catabolism.
In a randomised study the influence of 3 different amino acids (AA) solutions on nitrogen balance, plasma protein synthesis, and plasma and urine AA pattern was investigated in postoperative (p.o.) cancer patients. The patients in group I received a balanced AA solution designed especially for p.o. patients with 10 percent branched chain amino acids (BCAA), those in group II a solution with 60 percent BCAA and those in group III a solution with 67 percent alanine. All patients received the same amount of nitrogen (0.16 g/kg BW/day) and energy (2.p.o. day: 80 kJ/kg BW/day; 3.-5. p.o. day: 160 kJ/kg BW/day) with a 3:1 ratio of carbohydrate to fat calories. No difference was observed between the three groups for mean daily nitrogen balances, however, the cumulative nitrogen balance of group I (-4.5 +/- 3.6 g) was significantly (p less than 0.05) improved compared to group II (-12.2 +/- 4.2 g). The p.o. decreased concentrations of short-life plasma proteins (prealbumin, transferrin, retinol-binding protein) increased until the end of the study period without any statistic differences between the three groups. On the 2nd p.o. day especially the gluconeogenetic AA were decreased in all patients, but were nearly normal in all patients on the 5th p.o. day. In conclusion the increased administration of BCAA neither improved nitrogen retention nor plasma protein synthesis and does not seem advantageous in the postoperative total parenteral nutrition.
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The possible role of poly(C)RNase serum activity and CEA serum level for early detection and differentiation of pancreatic carcinoma and its specificity and valuability were critically analyzed: Serum RNase (median, min-max) with polycytidin as substrate was determined in 13 "normal" patients (14.6 E/ml, 4.3--29.8 E/ml), 16 patients with pancreatic cancer (T3 or metastases) (17.6 E/ml, 6--49-9 E/ml), 15 patients with chronic pancreatitis (9.5 E/ml, 4.9--26.5 E/ml), 7 patients with acute pancreatitis (14.2 E/ml, 5.5--67.3 ng/ml), and 13 patients with other types of malignomas (15 E/ml, 4.3--42.5 E/ml). Serum CEA level was evaluated in 18 "normal" patients (1.15 ng/ml, 0--4.3 ng/ml), 12 patients with pancreatic carcinoma (T3 or metastases) (6.5 mg/ml, 2--456.5 ng/ml), 13 patients with chronic pancreatitis (2.3 ng/ml, 0--8.5 ng/ml), 8 patients with acute pancreatitis (2.7 ng/ml, 0.1--4.6 ng/ml) and 5 patients without operative verification of suspected pancreatic carcinoma (0.9 ng/ml, 0--1.7 ng/ml). The serum RNase activity in pancreatic cancer patients did not show any significant increase in comparison to the other groups, and these patients could not be distinguished from those with the other diseases when excluding other factors influencing serum RNase level such as: Renal insufficiency, nutrition, age, sex. Their CEA level was significantly higher in comparison to the other groups (p less than 0.05). Using 2.5 ng/ml as the limit, the sensitivity was found to be 80% (10/12 of pancreatic carcinomas positive) and the specificity being 70.5% (31/44 of other groups without malignant diseases negative). The presented study and data in the literature show that poly (C) RNase measurement is not useful in early detection of pancreatic carcinoma, but the CEA test could be helpful in the differential diagnosis of pancreatic diseases due to its specificity (70.5%) and seems to be valuable in detection of residual and in monitoring for recurrent pancreatic carcinoma in view of its sensitivity and correlation with the stage of cancer.
UNLABELLED: An alanine infusion (90 mg/kg/h) for eight hours was administered to seven patients after cholecystectomy in order to investigate the influence of elevated plasma alanine levels on the postoperative metabolism. The following metabolites and hormone concentrations were analysed in plasma: glucose, urea, free fatty acids, ketone bodies, amino acids, insulin and glucagon. Compared to the pre-infusion values on the 1. postoperative day after an overnight fasting, the following changes were monitored. The plasma glucose concentrations reached a maximum after four hours of infusion (p less than 0.05). Of the amino acids, significant elevated levels were found for alanine (300%, p less than 0.001), glutamine (36%, p less than 0.05), and alpha-aminobutyrate (61%, p less than 0.01). The free fatty acids and ketone bodies concentrations decreased immediately after the onset of the infusion of alanine (p less than 0.05), the increased again during the last four hours of infusion. The secretion of insulin and also the secretion of glucagon were stimulated by the increased alanine levels. The stimulation of insulin reached a maximum after only five minutes, but the glucagon levels increased continuously until the end of the infusion. During the administration of alanine a nitrogen homeostasis was achieved, which was a significant improvement (p less than 0.001) when compared to saline infusions before and after the alanine infusion. CONCLUSIONS: (1) Postoperative increased plasma levels of alanine stimulate gluconeogenesis and reduce the plasma levels of lipolytic metabolites. The induced stimulation of insulin and glucagon is dependent on the duration of the alanine infusion for during extended infusion of alanine the insulin stimulation diminishes while the glucagon secretion continuously increases. (2) Alanine is a potent anabolic substrate in the immediate postoperative situation.
Levels of free amino acids were analysed in plasma and muscle tissue of nine patients with acute hemorrhagic necrotising pancreatitis and compared with date from healthy volunteers. In the patient group the concentrations of threonine, serine, glutamine (p less than 0.001) and tyrosine (p less than 0.01) in plasma were found to be significantly lower than in the volunteers group, while increased plasma levels were found for 3-met-histidine (p less than 0.05). In muscle tissue the cytoplasmatic levels of glutamate, glutamine and histidine (p less than 0.001) and also of lysine, ornithine and arginine (p less than 0.,01) showed decreased concentrations. However tyrosine and phenylalanine had increased intracellular concentrations (p less than 0.05). It is concluded that (1) the patients in this study had a severely disturbed amino acid metabolism with extremely reduced levels of free glutamine in muscle tissue and (2) that the disturbed amino acid metabolism results from an acute catabolic situation of the patients, in which the reduced levels of free amino acids may indicate an impaired nutritional state.
1. 20 patients before surgery received enteral nutrition for three days (12 g nitrogen, 1800 Kcal). Nitrogen and urea excretions in urine during the second and third day were determined. Eleven patients had a negative nitrogen balance (-2,7 and -2,4 g/day). In these patients urea production rates were 21,1 and 20,1 g/day. An urea production rate exceeding 15 g urea/day is probable an indication for a protein catabolism. The reason for this catabolic state seems to be a decreased protein utilisation (49 and 47 percent) as the result of a metabolic stress situation. This metabolic stress was determined according the stress index (Bistrian). The patients were in a stress situation comparable to postoperative stress (+3,7 and +3,9). The determination of urea production rate and catabolic index seems a suitable tool for defining a catabolic state. 2. 3-met-histidine excretion in urine were measured in seven patients postoperatively. In different periods saline or aminoacids solutions (5% alanine) were infused. During alanine administration protein (+49%)--and 3-met-histidine excretions (+50%) increased. It is not possible to state a catabolic situation out of the 3-met-histidine excretion, because an increased excretion may result from a stimulated protein synthesis in muscle tissue or from an increased muscleprotein wasting. 3. Free amino acid pools in plasma and muscle tissue were analysed in patients with severe illness of liver and pancreas. The free amino acid pattern differed from healthy volunteers. In patients with liver disease significantly increased concentrations of phenylalanine, tyrosine and methionine were found. In patients with acute pancreatitis highly abnormal pattern of intracellular amino acids occurred with decreased concentrations of glutamine, cysteine, histidine, lysine, arginine and ornithine. The highly significant decreased concentrations of glutamine (p less than 0,01) indicate a catabolic situation of these patients. A quantification of the severity of the catabolic state out of amino acid concentrations is not possible.
This study set out to investigate the effect of three different parenterally administered diets on the free amino acid (AA) levels in the plasma, muscle, and liver of scalded rats. Diet I consisted of AA (1.4 g/100 g weight) and a high glucose dose (6 g/100 g weight), diet II consisted of AA and a low glucose dose (1.4 g/100 g weight) and in diet III only a low glucose dose was infused. Parenteral nutrition was started on the 3rd day posttraumatically. Sampling was performed on the 7th day posttraumatically. Nitrogen balances were significantly different in all three groups, being lowest in group III. Scalded rats fed isonitrogenously, but with different amounts of glucose showed only minor changes in AA concentrations. However scalded rats fed with a nitrogen-free diet exhibited significantly reduced total muscle and liver AA levels. These decreased AA levels were due to a drop of glycine in the muscle tissue (74%) and liver (49%). Contrary to the clinical catabolic situation in scalded and starved rats, it was not intracellular glutamine but glycine which was considerably influenced by catabolism and starvation.
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Seventy-three institutionalized patients suffering from probable dementia of the Alzheimer type (DAT) were surveyed for the presence of eating difficulties. Among 71 patients fed by natural means four different groups emerged: (1) patients who fed themselves (n = 17, 23.9%), (2) patients who had to be fed but posed no other eating problem (n = 13, 18.3%), (3) patients who refused food although they were able to swallow it (n = 18, 25.4%), and (4) patients who choked on liquid and/or solid food, some of whom also refused food (n = 23, 32.4%). Patients who fed themselves were in a less advanced stage of the disease than those who did not, and their average body weight was equal to the ideal weight. The remaining three groups, ie, those with different eating problems, did not differ in mean severity of DAT, and their body weights were significantly lower. The mortality rate during 2 years following the survey was similar in all four groups of patients, although tube feeding was used in only one case. The mortality rate was also similar in patients whose body weights were 20% or more below the median weight for their age, and in patients whose relative body weight was higher. The results of this study suggest that eating difficulties occur in a majority of institutionalized DAT patients, but can be managed without resorting to tube feeding.
A randomized prospective study comparing PTFE-Y and Dacron-Y-grafts with regard to function rate, morphology, hemodynamic differences along the proximal anastomosis and body of the graft, complications and quality of material was performed. Between March 1983 and February 1987, 112 patients were admitted to the study. Randomization including the criteria of age, sex, indication to operation (chronic occlusive disease, aneurysm) run-off, diabetes, nicotine consumption and operative approach (transperitoneal, retroextraperitoneal) followed the methods of adaptive randomization developed by Pocock and Simon and was well balanced. Function rate and complications as well as morphological alterations showed no significant differences in either group. During a mean observation period of 24 months, Group I yielded a 97% and Group II a 95% function rate (Kaplan-Meier). In all patients but one in each group with limb graft occlusions (n = 5) function was regained by successful thrombectomy and profundaplasty. With respect to Doppler ultrasound differences in flow pattern, in four patients with enlarged proximal side-end anastomosis and adequate--not to large--incision is recommended performing the proximal anastomosis.