Lars Kager

Differences at the Receptor and Postreceptor Levels Between Human Omental and Subcutaneous Adipose Tissue in the Action of Insulin on Lipolysis

The possible existence of regional differences in the antilipolytic action of insulin in human adipose tissue was investigated in vitro. Insulin-induced inhibition of glycerol release and insulin binding, measured in terms of receptor number, receptor affinity, and dissociation rates, were determined in omental and subcutaneous adipose tissue segments and isolated fat cells of 16 nonobese subjects who were undergoing elective abdominal surgery but were otherwise healthy. The sensitivity of the antilipolytic effect of insulin was higher in subcutaneous than in omental adipose tissue; the half-maximal effect was obtained with 1 and 3 μU/ml of insulin, respectively (P < 0.01). Responsiveness of the antilipolytic effect of insulin was threefold higher in the subcutaneous than in the omental region (P < 0.005). Insulin receptor affinity was significantly higher in subcutaneous than in omental fat cells, but there was no difference in receptor number (about 300,000 sites/cell). 125I-insulin dissociated more rapidly from omental than from subcutaneous adipocytes in both the absence and the presence of excess native insulin. The data suggest that significant regional differences exist in the antilipolytic action of insulin in man; omental fat being less responsive than subcutaneous fat. The difference involves the insulin receptor affinity, which is caused at least partly by variations in the insulin dissociation rate but is also due to differences in insulin action at the postreceptor level.

Regional differences in the control of lipolysis in human adipose tissue

Omental fat cells were 30% smaller than those in subcutaneous regions. In omental fat cells with a mean diameter of 95 mu, the basal cAMP concentration was 50% lower, but the basal rate of glycerol release was three times as rapid as in subcutaneous (epigastric) fat cells of identical size. Added at maximal effective concentration, noradrenaline increased the level of cAMP and the rate of glycerol release more markedly in the omental than in the subcutaneous adipocytes, whereas the response to isopropyl noradrenaline was similar. Before starvation the lipolytic effects of noradrenaline and isopropyl noradrenaline, respectively, were identical in the two regions of subcutaneous adipose tissue investigated (femoral and hypogastric). The findings were well related to the tissue levels of cAMP induced by the two agents. During starvation noradrenaline and isopropyl noradrenaline increased the cAMP level and the rate of lipolysis in fat cells obtained from the hypogastric region, whereas noradrenaline decreased these parameters in femoral adipocytes. Starvation was associated with a more prominent inhibitory effect of phenylephrine on basal and isopropyl-noradrenaline-induced lipolysis in femoral than in hypogastric adipose tissue. In conclusion, differences exist between different regions of adipose tissue in their lipolytic responsiveness to noradrenaline, which seems related to the balance between alpha- and beta-adrenergic receptor response.

Antibiotic Prophylaxis with Cefoxitin in Colorectal Surgery: Effect on the Colon Microflora and Septic Complications—A Clinical Model For Prediction of the Benefit and Risks in Using a New Antibiotic in Prophylaxis

Cefoxitin was administered parenterally in doses of 2 g, every six hours for two days, to 20 patients undergoing colorectal surgery. Blood and fecal specimens were obtained for five days for analysis of cefoxitin concentrations. Tissue samples from the gut wall were obtained at surgery. The maximum serum concentrations during surgery varied between 25 and 100 μg/ml, and the cefoxitin concentrations for the fecal samples were 1.5–35 μg/g and for the tissue samples, 2.0–50 μg/g. Fecal samples for cultivation of aerobic and anaerobic bacteria were also obtained daily during the first five days, and after 14 days after operation. Pronounced changes in the microflora occurred during the investigation period. Among the aerobic bacteria, cefoxitin-sensitive Escherichia coli and other entero-bacteria decreased markedly while cefoxitin-resistant enterococci, Pseudomonas and Enterobacter proliferated during the antibiotic prophylaxis period. Among the anaerobic bacteria, Bacteroides fragilis and other Gram-negative bacteria decreased significantly. However, after the antibiotic administration period, all cefoxitin-resistant strains decreased while the suppressed E. coli and B. fragilis strains increased. In one patient, a minor postoperative infection caused by a cefoxitin-resistant strain of Pseudomonas aeruginosa was observed.

The combustion of triolein-1-14C and its inhibition by alcohol in man

Abstract In the present investigation monitoring of expired 14CO2 in man has been used in order to determine the immediate effect of alcohol on the formation of 14CO2 from 14C-labelled oleic acid administrated as triolein. From the output of 14CO2 a picture of the rate of oxidation of the labelled substrate could be obtained. Labelled triolein was given perorally or intravenously to male volunteers, and the excretion of 14CO2 in expired air was registered. The same experiment was repeated in the next day, but, in addition, alcohol was given perorally or intravenously. There was then a significant depression of the 14CO2 excretion. In the same volunteers 4-methylpyrazole, administered intravenously, prevented to a variable extent the inhibitory effect of alcohol on the fatty acid oxidation. The results suggest that ethanol inhibits β-oxidation of the fatty acids in the liver in man.

Studies on the ethanol-induced decrease of fatty acid oxidation in rat and human liver slices.

Abstract In order to elucidate the mechanisms involved in the acute ethanol-induced liver triglyceride accumulation, the oxidation, esterification and β-keto acid formation have been studied in rat and human liver slices after incubation with albumin bound, long chain fatty acids (palmitic. oleic and linoleic acids). The addition of alcohol to rat and human liver slices depressed the formation of 14 CO 2 from palmitic acid-1- 14 C, oleic acid-1- 14 C and linoleic acid-1- 14 C. The esterification to triglycerides and phospholipids was increased and the formation of β-keto acids was decreased by alcohol. Addition of 4-methylpyrazole, an inhibitor of liver alcohol dehydrogenase, almost prevented the alcohol effect on the lipid metabolism of the liver slices. The oxidation of alcohol is thus obligatory for the decreased β-oxidation of fatty acids, the increased esterification and for the decreased formation of β-keto acids. The results suggest that ethanol oxidation inhibits β-oxidation of fatty acids and that this primary effect leads to accumulation of liver triglycerides by increased esterification of plasma free fatty acids.

Microbial colonization of tumors in relation to the upper gastrointestinal tract in patients with gastric carcinoma.

The microbial colonization of the oropharynx, the esophagus, the stomach, and the duodenum was studied in relation to the microbial flora found on tumor and gastric mucosal biopsies in 23 patients with gastric carcinoma. The tumor was colonized in all patients, and the stomach, the esophagus, the duodenum, and the gastric mucosa were colonized in 96%, 87%, 83%, and 78% of the patients, respectively. The most common microorganisms isolated were streptococci, bifidobacteria, lactobacilli, and Bacteroides species, belonging to the normal oropharyn-geal flora. Microbial colonization with gram-negative rods, Clostridium species or yeasts, was present in at least one site in 91% of the patients. Clostridium species were isolated from 57% of the patients. The total numbers of microorganisms recovered from the tumor biopsies did not vary with the intra-luminal gastric pH. A relation between the gastric pH and the total number of microorganisms in the gastric juice existed. Significant higher numbers of different strains of microorganisms (p < 0.005) colonized the tumor compared to the gastric mucosa. Anaerobic microorganisms colonized the tumor significantly more often than the mucosa (p < 0.001). Antibiotic agents used as prophylaxis in gastric cancer surgery should cover both aerobic and anaerobic microorganisms, including B. fragilis.

Transferability of a computer system for medical history taking and decision support in dyspepsia. A comparison of indicants for peptic ulcer disease.

The transferability of a British data base for differential diagnosis of dyspepsia using data obtained by computer interrogation was tested in 467 Swedish patients. The diagnostic value for peptic ulcer disease of symptoms such as frequent night pain relieved by food or antacids, smoking, family history of ulcer, food relief pain, male sex, and episodic pain was shown to be reproducible. However, for a number of symptoms their value for the diagnosis of peptic ulcer disease could not be reproduced in Swedish patients. The combined value of indicants was tested using a computer based algorithm for calculating diagnostic probabilities. The performance of this algorithm was poor when British data were applied to Swedish patients but reclassification of the Swedish patients on their own data base showed promising results. Crean and colleagues in Glasgow have developed a computer system for automated interrogation of patients with dyspepsia. The system utilises a large number of questions to obtain information regarding a maximum of 160 diagnostic indicants. The symptoms elicited from a patient can be compared with those of a large number of previously examined patients and the probabilities of ten different diagnoses can be calculated. The calculation of diagnostic probabilities is based on scores reflecting the diagnostic value of different symptoms in different diseases. After careful translation of questions the system has been transferred for use in Sweden. The present report is based on data from patients seen during the first two years with the system at a Swedish hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of aztreonam on the colon microflora in patients undergoing colorectal surgery

SummaryAztreonam was given intravenously at a dose of 1 g at induction of anaesthesia, followed by subsequent doses of 1 g at eight hour intervals during 48 hours to 20 patients undergoing colorectal surgery. A series of serum and faecal specimens were taken for analysis of aztreonam concentrations. Tissue samples from the gut wall were taken at surgery. The maximum serum concentrations (mean value 114.7 mg/l) during surgery were reached 15 minutes after aztreonam administration. The aztreonam concentration in the tissue samples varied from 4.1–28.3 mg/kg and the concentration in the faecal samples from 0.4–34.4 mg/kg. Faecal samples were also collected during the investigation period for cultivation of aerobic and anaerobic bacteria. Enterobacteria were suppressed significantly during the prophylaxis period and there was a significant increase of staphylococci in ten of the patients. Three of these patients developed postoperative wound infections with staphylococci. Among the anaerobic bacteria, only minor changes were observed during the same period. After two weeks, the microflora was normalized in all patients. Five postoperative infections including an anastomose dehiscence in one patient occurred.ZusammenfassungAztreonam wurde bei Einleitung der Anästhesie in einer Dosis von 1 g an 20 Patienten, bei denen colorektale Operationen durchgeführt wurden, intravenös appliziert; im Abstand von acht Studen wurden 48 Stunden lang jeweils weitere 1 g-Dosen verabreicht. Zur Bestimmung der Aztreonam-Konzentrationen wurde eine Reihe von Serum- und Stuhlproben gewonnen. Unter der Operation wurden Gewebeproben vom Darm entnommen. 15 Minuten nach Aztreonam-Gabe wurden unter der Operation die höchsten Aztreonam-Serumkonzentrationen erreicht (Mittelwert 114,7 mg/l). In den Gewebeproben fanden sich Aztreonam-Konzentrationen von 4,1–28,3 mg/kg, in den Stuhlproben von 0,4–34,4 mg/kg. Zur Anzüchtung aerober und anaerober Bakterien wurden im Untersuchungszeitraum ebenfalls Stuhlproben gewonnen. Während der Prophylaxephase war eine erhebliche Suppression der Enterobakterien festzustellen, gleichzeitig stiegen bei zehn Patienten die Staphylokokken signifikant an. Bei drei dieser Patienten traten postoperative Wundinfektionen mit Staphylokokken auf. Die anaerobe Bakterienpopulation änderte sich im selben Zeitraum nur geringfügig. Nach zwei Wochen hatte sich bei allen Patienten die Mikroflora normalisiert. Insgesamt traten fünf postoperative Infektionen auf, einschließlich einer Anastomosendehiszenz bei einem Patienten.

Septic complications in relation to factors influencing the gastric microflora in patients undergoing gastric surgery.

Postoperative septic complications and micro-organisms found in primary infections were studied in 750 gastric operations performed between 1972 and 1986. The overall rate of primary infections was 23%. The infection rates were related to the diagnosis and to factors that could influence the colonization of the stomach. No significant differences in the rates of postoperative infections were found between patients who had received preoperative antibiotic prophylaxis and those who had not. In all groups of patients, aerobic and anaerobic gram-positive and gram-negative bacteria and yeasts were isolated in primary infections. Enterobacteriaceae, enterococci and Bacteroides fragiis were more frequent in patients with gastric bleeding or carcinoma.

Effects of antimicrobial prophylaxis on colonization resistance

The effect of antimicrobial agents on the intestinal microflora of patients undergoing colorectal surgery was examined. Two narrow spectrum agents, clindamycin and aztreonam, disturbed colonization resistance. This was preserved with the broad spectrum compound, imipenem. Ecological effects are difficult to predict and clinical studies of new antibiotics should include investigations of their impact on the normal human intestinal flora.