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Biomedical subjects

L Kager

Publications and source records attributed to L Kager.

At least 55 records · Page 3Linked to original sources

Concentrations of ampicillin plus sulbactam in serum and intestinal mucosa and effects on the colonic microflora in patients undergoing colorectal surgery.

Ampicillin and sulbactam were administered intravenously in 2 g and 1 g doses respectively every 8 h for two days to ten patients undergoing colorectal surgery. Drug concentrations were determined in serum, intestinal mucosa and faeces. The first dose was given at induction of anesthesia. The serum half-life was 2.1 h for ampicillin and 2.0 h for sulbactam on the first day. The concentrations in intestinal mucosa were in most cases 50% or more of the serum concentrations and there was no statistical difference between the two drugs. Faecal concentrations of both drugs were found in eight patients: a mean of 10.5 micrograms/g for ampicillin and a mean of 7.5 micrograms/g for sulbactam. Faecal samples were also collected during the investigation period for culture of aerobic and anaerobic bacteria. Among the aerobic bacteria enterococci, streptococci and enterobacteria decreased markedly during the prophylaxis period. Anaerobic bacteria were also suppressed significantly during the same period. The changes in colonic microflora were related to the concentrations of ampicillin and sulbactam in the intestinal mucosa and faeces. Overgrowth of yeasts was observed in six patients and overgrowth of Pseudomonas fluorescens in two others. These strains were resistant to the combination ampicillin and sulbactam. The microflora normalized in all patients after two weeks. No postoperative infections occurred.

Aged↗

Clinical significance of mucosal inflammation of the vermiform appendix.

In 942 emergency appendectomies, the clinical data of 77 patients with inflammatory changes confined to the mucosa of the vermiform appendix were compared with data from 622 patients with diffuse acute appendicitis and 243 patients without evidence of inflammation in the appendix. In all cases, routine histologic sections of the specimens were reviewed. Of the 77 patients with mucosal appendiceal inflammation, 50 were female and 50% were under 17 years of age. In several clinical aspects, such as incidence of nausea, vomiting, migration of pain, and localized muscular rigidity, there existed significant differences between patients with mucosal inflammation and patients with diffuse appendicitis. Conversely, no statistically significant differences were found between patients with mucosal inflammation and patients without evident appendiceal inflammation. These results in addition to the frequent finding of histologically indistinguishable changes in appendices removed incidentally suggest that the condition is not responsible for the actual complaint.

Adolescent↗

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 microU/ml of insulin, respectively (P less than 0.01). Responsiveness of the antilipolytic effect of insulin was threefold higher in the subcutaneous than in the omental region (P less than 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.

Adipose Tissue↗

Reduction of catheter-associated thrombosis in parenteral nutrition by intravenous heparin therapy.

A prospective trial was carried out to test the hypothesis that therapy with intravenous (IV) heparin sodium reduces the incidence of thrombotic complications related to the use of central venous catheters for parenteral nutrition. The patients studied were randomly allocated either to a group given heparin sodium, at a dosage of 5,000 IU/6 hr, or to a control group that received no heparin prophylaxis. The heparin group comprised 23 catheter periods (22 patients), and the control group 26 catheter periods (25 patients). In five of the 23 catheters in te heparin group and 14 of the 26 in the control group, catheter phlebography revealed thrombus formation in association with the catheter when this was removed. The results indicated that the use of IV heparin as prophylaxis against thrombosis reduced the risk of thrombus formation on the central venous catheter.

Adult↗

Morphine glucuronidation in human fetal and adult liver.

The glucuronyltransferase activity towards morphine was measured in microsomes isolated from liver specimens obtained from human fetuses and cancer patients. All the fetal livers investigated had measurable UDP-glucuronyltransferase activity towards morphine. There was no correlation between the gestational age (15 to 27 weeks) and the glucuronidation rate. The mean value of the enzymatic activities was higher in fetal livers obtained by hysterotomy (0.20 nmoles x min-1 x mg-1) than in livers obtained after induced abortion (0.11 nmoles x min-1 x mg-1). The average rate of glucuronidation in microsomes from adult liver (mean 1.15 nmoles x min-1 x mg-1) was 6 to 10 times higher than in the fetal liver microsomes. Together with previous investigations on human adult and fetal liver glucuronidation, the present results support the theory of heterogeneity of human UDP-glucuronyltransferase.

Adult↗

Impact of different betalactam antibiotics on the normal human flora, and colonization of the oral cavity, throat and colon.

Phenoxymethylpenicillin was given orally in doses of 800 mg twice daily for seven days to six patients, and bacampicillin was given in doses of 400 mg three times per day for seven days to another six patients. Saliva, throat and faecal specimens were taken for cultivation of aerobic and anaerobic bacteria. Only small changes in the normal saliva and throat flora were observed, and no changes in the faecal flora were noticed during the observation period. Cefoxitin was administered parenterally in doses of 2 g at 6 h intervals for 12 h to six other patients. Pronounced changes in the colon flora occurred. Of the aerobic bacteria, enterobacteria decreased and cefoxitin-resistant enterococci increased in number; of the anaerobic bacteria, gram-negative rods decreased in number. At the end of the administration period, all cefoxitin-resistant strains decreased, and suppressed enterobacteria and bacteroides increased in number.

Adult↗

Glucuronidation of morphine in human liver and interaction with oxazepam.

Morphine is primarily metabolized through glucuronidation by a microsomal UDP-glucuronyltransferase. With the use of 14C-morphine the activity of this enzyme was measured in hepatic microsomes from ten kidney transplant donors with total cerebral infarction and four icteric patients with pancreatic carcinoma. In the former livers the rate of glucuronidation varied from 1.08 to 8.67 nmol per mg microsomal protein per min, with a mean value of 3.83. These values were somewhat higher than in the liver biopsies from the four cancer patients. Oxazepam, at 1/10 the concentration of morphine, inhibited the morphine glucuronidation by 35%. The inhibition was competitive. Salicylamide also inhibited the morphine glucuronidation but only at concentrations considerably higher than morphine. The relevance of the in vitro data for the in vivo situation is unclear, since the concentrations employed in this study are several-fold higher than those encountered in the plasma of patients treated with these drugs.

Drug Interactions↗

Effects of ampicillin plus sulbactam on bowel flora in patients undergoing colorectal surgery.

The influence of a combination of ampicillin and a beta-lactamase inhibitor, sulbactam, on colonic bacterial flora was studied in patients undergoing colorectal surgery. Drug concentrations were determined in serum, intestinal mucosa, and feces. The results of the drug concentrations were correlated with changes in the numbers of aerobic and anaerobic bacterial bowel flora. Ampicillin and sulbactam were given intravenously to 21 patients in 500-mg doses of each drug every 8 h for 2 days. The first dose was given when anesthesia was begun. The concentrations of ampicillin in serum were significantly higher (0.01 greater than P greater than 0.001) than those of sulbactam. In contrast, at all time intervals, the concentrations of sulbactam in intestinal mucosa were significantly higher than those of ampicillin (0.05 greater than P greater than 0.01). The serum half-life of the two drugs was the same at 2.2 h. After one dose of the antibiotics, sulbactam was detectable in the feces of four patients, and ampicillin was detectable in the feces of 11 patients. During the 2 days of ampicillin and sulbactam prophylaxis, no measurable decrease occurred in the anaerobic flora of the bowel; a mean decrease of 3 logs occurred in the anaerobic bowel flora. The results of this study show that ampicillin and sulbactam prophylaxis had a greater effect on the anaerobic bowel flora than on the aerobic bowel flora. In light of the in vitro spectrum of ampicillin and sulbactam activity, it was surprising that bowel aerobic flora was unchanged.

Aged↗

The normal human anaerobic microflora.

Anaerobic bacteria are prevalent among the bacterial populations of the human body, particularly on mucous membrane surfaces. The major sites with a rich anaerobic normal microflora are the mouth, the gastrointestinal tract and the female genital tract. The oral cavity harbours more than 300 different bacterial species. The concentrations of bacteria in saliva are 10(8) to 10(9) colony forming units/ml and anaerobic bacteria outnumber aerobic bacteria by 10:1. On the tooth surfaces, the concentrations of bacteria are 10(10) to 10(11) cfu/ml with a predominance of anaerobes. Bacterial concentrations in gingival scrapings are 10(11) to 10(12) cfu/ml with anaerobic bacteria outnumbering aerobic bacteria by 1000:1. In the saliva and on the tongue surface, the predominant anaerobic bacteria are cocci, while in the gingival crevice large concentrations of gram-negative rods are recovered. Microorganisms found in the upper intestinal tract are different from those in the lower intestinal tract. In the stomach and the proximal small bowel, the microorganisms found as normal flora are a reflection of the oral flora. Bacterial concentrations in this region are 10(2)-10(5) cfu/ml intestinal content. In the colon, bacterial concentrations of 10(11)-10(12) cfu/g faeces are found. About 500 different bacterial species are recovered in the lower intestine. The most common anaerobic microorganisms are bifidobacteria, lactobacilli and bacteroides. Recent studies have used quantitative techniques for analyses of the vaginal flora and it has been found that anaerobic bacteria outnumber aerobic bacteria in the vagina by approximately 10:1. The most prevalent bacteria are peptococci, present in counts of 10(7)-10(8) cfu/ml. Lactobacilli, corynebacteria, eubacteria and bacteroides are also isolated.

Anaerobiosis↗

(Gln4)-neurotensin changes the motility pattern of the duodenum and proximal jejunum from a fasting-type to a fed-type.

The effect of (Gln4)-neurotensin on the motor activities of the duodenum and small proximal jejunum was investigated in 8 healthy volunteers who fasted for at least 8 h. Motor activity was monitored by measuring the intraluminal pressure at three levels. The proximal site for pressure recording was in the first part of the duodenum, the middle was at the angle of Treitz, and the distal was 25 cm further down. Under control conditions the median time between the migrating motility complexes was 106.3 min. (Gln4)(-Neurotensin, 3 or 6 pmol/kg . min, infused intravenously for 200 min inhibited the migrating motor complexes for 220.4 min (median time) and they were replaced by irregular pressure waves with a frequency of 4-7 waves/min. The plasma concentration of neurotensinlike immunoreactivity increased from 13 +/- 2.8 pM to 131 +/- 6 pM and 231 +/- 16 pM, respectively. Ingestion of fat (55 ml 20% Intralipid) inhibited the migrating motor complex for 196.1 min (median time) and the migrating motor complexes were replaced by irregular pressure waves. The data show that (Gln4)-neurotensin alters the motility pattern in the duodenum and proximal jejunum in man from a fasting- to a fed-type. They further support the contention that neurotensin may function as an endocrine hormone participating in the postprandial regulation of intestinal motility.

Adult↗

The role of Bacteroides fragilis in the pathogenesis of acute appendicitis.

The predominant bacteria from 50 inflamed human appendices were isolated. Anaerobic bacteria were isolated more frequently than aerobic bacteria ( 141 versus 96 isolates). E. coli was the most common aerobic genus (47 out of 50 patients). Bacteria belonging to the B. fragilis groups (B. Fragilis, B. ovatus, B. distasonis, B. thetaiotaomicron, B. vulgatus and B. uniformis) were the most frequently isolated anaerobic microorganisms (87 of 141 strains), and B. fragilis predominated within this group (24 out of 87 strains). There were no significant differences in the numbers and types of bacteria found in three patients groups (Group A--19 phlegmonous; Group B--19 gangrenous; and Group C--12 perforative appendicitis cases). Serological investigations of the humoral antibody responses (IFL) against the predominant bacteria in the three patient groups showed that a doubling, or more, of the titer was observed in the following cases: against B. fragilis, 3 out of 8 patients (Group A); 5 out of 7 patients (Group B); and 7 out of 7 patients (Group C). The corresponding figures for E. coli were 4 out of 18, 3 out of 17, and 5 out of 12 patients. Only minor responses against the remaining aerobic and anaerobic isolates were measured. From the bacteriological and immunological results we conclude that (1) the B. fragilis group were the predominant bacteria in diseased appendices; (2) that significant antibody responses were only observed against B. fragilis; (3) that the response increased with the degree of organ destruction and the length of time elapsed from the onset of the symptoms; (4) that B. fragilis is likely to play an important role in the pathogenesis of acute appendicitis, provided that other predisposing factors, such as a deterioration of the blood circulation in the appendiceal wall, are present.

Acute Disease↗

The incidence of acute appendicitis and appendectomy. An epidemiological study of 971 cases.

The incidence of acute appendicitis was studied in a well defined population. Results from 971 appendectomies performed on suspicion of appendicitis, comprising 955 primary and 16 interval operations, were collected over a four-year period. Appendicitis was diagnosed in 657 cases and the mean yearly incidence was 1.16 per thousand. The incidence in males was 1.33 per thousand versus 0.99 for females. The difference was statistically significant (p = 0.0002). The mean yearly incidences of appendectomies were 1.72 per thousand for males and 1.71 for females. The highest incidences of both appendicitis and appendectomies for both sexes occurred in the second decade of life (2.34/1,000 and 3.63/1,000 per annum, respectively). Slight increases in the frequencies of appendicitis and appendectomies were noticed in the very old patients. There were no differences between the results of this study and other recent comparable reports. Compared with earlier studies there was no marked decline in the incidence of appendicitis.

Acute Disease↗

Obstruction of appendix vermiformis causing acute appendicitis. An experimental study in the rabbit.

In an experimental model using the rabbit, the role of obstruction in the pathogenesis of acute appendicitis was studied. Twenty-one animals were anaesthesized and underwent laparotomy. The appendices were obstructed by a balloon catheter introduced via a caecostomy. Pressures inside the obstructed appendices were measured by a balloon at the tip of the catheter. The abdominal cavity was closed, anaesthesia was continued, and pressure were registered regularly up to 12 hours afterwards in those animals which remained alive during this period. The animals were then sacrificed, and at autopsy evidence of obstruction, distention and inflammatory changes, both gross and microscopic, was registered. In a total of 15 rabbits, experimental obstruction of the appendix resulted in inflammatory changes in the wall of the appendix, which histologically in all respects were similar to appendicitis in man. In the remaining 6 rabbits, either spontaneous release of obstruction or death early during the experiment occurred. Our experimental data suggest that obstruction is an important agent in the causation of acute appendicitis.

Acute Disease↗