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Biomedical subjects

L Kager

Publications and source records attributed to L Kager.

At least 19 recordsLinked to original sources

Prognostic impact of chromosomal aberrations in Ewing tumours.

Although greater than 50% of Ewing tumours contain non-random cytogenetic aberrations in addition to the pathognomonic 22q12 rearrangements, little is known about their prognostic significance. To address this question, tumour samples from 134 Ewing tumour patients were analysed using a combination of classical cytogenetics, comparative genomic and fluorescence in situ hybridisation. The evaluation of the compiled data revealed that gain of chromosome 8 occurred in 52% of Ewing tumours but was not a predictive factor for outcome. Gain of 1q was associated with adverse overall survival and event-free survival in all patients, irrespective of whether the tumour was localised or disseminated (overall survival: P=0.002 and P=0.029; event-free survival: P=0.018 and P=0.010). Loss of 16q was a significant predictive factor for adverse overall survival in all patients (P=0.008) and was associated with disseminated disease at diagnosis (P=0.039). Gain of chromosome 12 was associated with adverse event-free survival (P=0.009) in patients with localised disease. These results indicate that in addition to a 22q12 rearrangement confirmation in Ewing tumours it is important to assess the copy number of 1q and 16q to identify patients with a higher probability of adverse outcome.

Adult↗

Chromosomal regions involved in the pathogenesis of osteosarcomas.

The comparative genomic hybridization technique (CGH) was used to identify common chromosomal imbalances in osteosarcomas (OS), which frequently display complex karyotypic changes. We analyzed 13 high-grade primary tumors, 5 corresponding cell lines, 2 primary tumors grade 2, and 1 recurrent tumor from a total of 16 patients. Some of the CGH results have been verified by fluorescence in situ hybridization (FISH) studies. Gains of chromosomal material were more frequent than losses. Most common gains were observed at 8q (11 cases), 4q (9 cases), 7q (8 cases), 5p (7 cases), and 1p (8 cases). The smallest regions of overlap have been narrowed down to 8q23 (10 cases), 4q12-13 (8 cases), 5p13-14 (7 cases), 7q31-32 (7 cases), 8q21 (7 cases), and 4q28-31 (5 cases). These data demonstrate that a number of chromosomal regions and even two distinct loci on 4q and 8q are involved in the pathogenesis of OS, with gain of 4q12-13 chromosomal material representing a newly identified locus. Seven of 16 cases displayed, besides gain of 8q23 sequences, gain of MYC copies in CGH and FISH. Previous CGH reports confined gain of 8q material to 8cen-q13, 8q21.3-8q22, and 8q23-qter, whereas our data suggest that the loci 8q21 and 8q23-24 are affected in the development of OS. In contrast to recent reports, copy number increases at 8q and 1q21 did not have an unfavorable impact on prognosis in the present series. Genes Chromosomes Cancer 28:329-336, 2000.

Adolescent↗

Predictive potential of testing for bone marrow involvement in Ewing tumor patients by RT-PCR: a preliminary evaluation.

EWS/ets-oncogene fusion transcripts can be detected in at least 98% of Ewing tumors [(ET) Ewing sarcoma and peripheral primitive neuroectodermal tumor] by reverse transcriptase-polymerase chain reaction (RT-PCR), thus confirming the histopathologic diagnosis. To detect minimal amounts of tumor cells in the bone marrow (BM), we used an RT-PCR assay with a high sensitivity, revealing one tumor cell in a background of 10(6) normal cells. We examined BM samples from 35 newly diagnosed ET patients (23 with localized and 12 with metastatic disease). At diagnosis, tumor cells in the BM were detected in 7/23 patients with localized disease (30%). Fifty percent of patients with isolated lung metastasis were RT-PCR positive (3/6), whereas 6/6 patients with bone metastases showed positive signals (100%). All patients with initial PCR positivity in the BM became negative during treatment. After a median follow-up of 30 months, relapses were observed in both groups of patients with localized disease (3/7 RT-PCR positive and 2/16 RT-PCR negative). The only recurrence in the group with isolated lung metastases occurred as progressive lung disease in 1 of the 2 RT-PCR-negative patients, whereas among the 6 patients with bone metastases 2 remain in complete remission. So far, RT-PCR screening for BM involvement did not allow prediction of early relapse in ET. To assess better the significance of this test in the evaluation of long-term prognosis and in monitoring the effectiveness of systemic therapy, long observation periods are warranted before it becomes a tool for treatment stratification.

Adolescent↗

The effect of omeprazole and ranitidine on ulcer healing, relief of symptoms, and incidence of adverse events in the treatment of duodenal ulcer patients.

In a Swedish double-blind multicenter study involving 143 patients, the new proton pump inhibitor omeprazole (30 mg taken as a single morning dose) was compared with ranitidine (400 mg b.i.d.). Clinical assessment and laboratory investigations were carried out at 2 and 4 weeks, and again at 6 weeks if patients had not healed earlier. Endoscopy was repeated at two-weekly intervals until the ulcer was healed. The patients in the two treatment groups were well matched prior to treatment. There was a higher ulcer healing rate in the omeprazole group (70%) than in the ranitidine group (55%) after two weeks of treatment. This difference reached statistical significance in 128 patients adhering to the protocol as shown by a logit model analysis with drug, ulcer size and smoking as the prognostic factors (p = 0.04). There were no major differences between the two treatment groups in terms of symptomatic relief. Both drugs were generally well tolerated, and the number of adverse events in the two treatment groups were similar. After healing, 127 patients entered a follow-up study, with endoscopy either after 6 months or on recurrence of symptoms. There was no significant difference between the two treatment groups, with the relapse frequency within 6 months being 39% in the omeprazole group and 47% in the ranitidine group. These results, with a 15 percentage points higher ulcer healing rate for omeprazole as compared with H2-receptor antagonists after two weeks, are in accordance with results reported in other studies.

Duodenal Ulcer↗

Hospital and catchment area antibiotic utilization and bacterial sensitivity in primary infections following gastric surgery in Huddinge, Sweden.

The relationship between hospital and catchment area utilization of antimicrobial agents and the antibiotic sensitivity of bacteria isolated from primary infections has been studied after 750 gastric operations performed between 1972 and 1986 at the Huddinge University Hospital. Over 80% of the antibiotics were used in the catchment area. Penicillins (G and V) overall were the most commonly used drugs and comprised 37% of the total antibiotic consumption in 1977-1986. Narrow-spectrum antibiotics dominated throughout the period under investigation. No change in the bacterial resistance to antimicrobial agents was found over time. Many strains of Klebsiella/Enterobacter and E. coli resistant to ampicillin and tetracyclines were recovered throughout the period under investigation. No aerobic Gram-negative bacteria were resistant to gentamicin. All Bacteroides strains except two were sensitive to cefoxitin. Tetracyclines and ampicillin/amoxycillin were mainly used in the catchment area, and cefoxitin and aminoglycosides were almost exclusively used in the hospital. Antimicrobial agents primarily used for out-patients in the catchment area seemed to have more influence on the susceptibility of microorganisms isolated from post-operative infections than agents primarily used in the hospital.

Anti-Bacterial Agents↗

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.

Adolescent↗

Imipenem concentrations in colorectal surgery and impact on the colonic microflora.

Twenty patients undergoing colorectal surgery were given, as prophylaxis, imipenem-cilastatin intravenously. Ten of them received a dose of 0.5/0.5 g of imipenem-cilastatin at induction of anesthesia, followed by subsequent doses of 0.5/0.5 g every 6 h for 48 h. The other 10 patients were given 1.0/1.0 g imipenem-cilastatin in the same way for 48 h. Samples from serum, intestinal mucosa, and feces were taken for analysis of imipenem concentrations during the day of surgery. The mean concentrations in serum at 1 h after the first imipenem dose were 15.9 +/- 1.7 micrograms/ml for the 0.5-g dose and 68.2 +/- 8.2 micrograms/ml for the 1.0-g dose. The mean half-lives were 1.5 and 1.4 h, respectively, and the mean areas under the serum concentration-time curve were 41.2 +/- 6.0 and 128.3 +/- 13.5 mg.h/liter, respectively. The imipenem concentrations in the intestinal mucosa varied between less than 0.1 and 3.6 mg/kg for the 0.5-g dose and 3.2 and 13.4 mg/kg for the 1.0-g dose. The concentrations in the fecal samples varied between less than 0.1 and 5.0 mg/kg for the 0.5-g dose and 0.7 and 11.3 mg/kg for the 1.0-g dose. Fecal samples were also collected during the investigation period for cultivation of aerobic and anaerobic bacteria. The aerobic bacteria--staphylococci, streptococci, enterococci, and enteroaerobic enterococci, and enterobacteria--were and anaerobic bacteria. The aerobic bacteria--staphylococci, streptococci, enterococci, and enterobacteria--were suppressed significantly during the imipenem prophylaxis period. Among the anaerobic bacteria, cocci, bifidobacteria, eubacteria, lactobacilli, clostridia, fusobacteria, and bacteroides decreased markedly during the same period. The microfloras were normalized after 2 weeks. There were no differences between the patients receiving 0.5-g doses of imipenem and those receiving 1.0-g of imipenem. No postoperative infections occurred.

Adult↗

Antimicrobial activity of dactimicin against aerobic and anaerobic bacteria isolated from intra-abdominal infections.

The in vitro antimicrobial activity of dactimicin against aerobic and anaerobic bacteria isolated from intra-abdominal infections was compared to those of gentamicin and metronidazole. The data obtained show that dactimicin is a promising new aminoglycoside covering aerobic bacteria and that it may be used together with an antianaerobic agent in the treatment of these infections.

Abdomen↗

Impact of Lactobacillus acidophilus on the normal intestinal microflora after administration of two antimicrobial agents.

Twenty healthy volunteers participated in a comparative study concerning the influence of Lactobacillus acidophilus supplements on the normal intestinal microflora after the administration of two antimicrobial agents, enoxacin and clindamycin, respectively. L. acidophilus NCFB 1748 was given as a fermented milk product containing 5 x 10(8)-2 x 10(9) CFU/ml to ten of the volunteers immediately after the administration of the antimicrobial agents. On the seventh day of enoxacin administration enterobacteria were eliminated in nine of ten subjects. Enterococci disappeared or decreased significantly in five subjects. During the L. acidophilus supplementation, there was a significant increase in the number of Escherichia coli in one subject, while enterococci returned to the same level as before enoxacin administration in all subjects.

Adult↗

Effect of ofloxacin on oral and gastrointestinal microflora in patients undergoing gastric surgery.

The effect of ofloxacin on the microflora in saliva, gastric juice, and feces was evaluated in 24 patients undergoing gastric surgery. A single peroral dose of 400 mg ofloxacin was given to each patient 2-4 h before surgery. The concentrations of ofloxacin in serum, saliva, gastric juice, and gastric mucosa tissue were assayed. Only Branhamella cocci were affected in the saliva. In the gastric juice, both the aerobic and anaerobic flora were suppressed on the day of surgery, but increased in number afterwards. There was a significant correlation between gastric pH and the number of microorganisms isolated in the gastric juice on day 0. In faeces, the aerobic and part of the anaerobic flora were suppressed by the administration of ofloxacin. Ofloxacin was well tolerated by the patients. Four of 24 patients developed postoperative complications. Microorganisms isolated from wound sepsis and intraabdominal sepsis (three patients) were Staphylococcus epidermidis, Staphylococcus aureus, hemolytic streptococci group A, Streptococcus sp. and Escherichia coli. All related infections occurred in patients with very low ofloxacin serum concentrations, probably due to impaired absorption. Oral antibiotic prophylaxis is not recommended in patients in whom impaired gastric emptying can be expected.

Adult↗

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.

Adult↗

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 oropharyngeal 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 intraluminal 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 less than 0.005) colonized the tumor compared to the gastric mucosa. Anaerobic microorganisms colonized the tumor significantly more often than the mucosa (p less than 0.001). Antibiotic agents used as prophylaxis in gastric cancer surgery should cover both aerobic and anaerobic microorganisms, including B. fragilis.

Aged↗

Effect of imipenem treatment versus imipenem surgical prophylaxis on the intestinal microflora.

The impact of imipenem treatment versus imipenem surgical prophylaxis on the intestinal microflora was investigated in 40 patients. Ten patients received 0.5 g imipenem four times a day and ten patients 1.0 g imipenem four times a day for four to 11 days for treatment of different infections. The imipenem treatment was associated with minor to moderate changes in the intestinal flora. There was a decrease in the numbers of enterobacteria, anaerobic cocci and bacteroides during treatment, but afterwards the microflora was normalized in all patients. No new colonization with imipenem-resistant bacteria was seen. No concentrations of imipenem in faeces were observed. Twenty patients undergoing elective colorectal surgery participated in the imipenem surgical prophylaxis group. To ten patients, imipenem was given in a dose of 0.5 g at induction of anaesthesia followed by subsequent doses of 0.5 g at 6 h intervals for 48 h. The other ten patients received 1 g imipenem at 6 h intervals for 48 h. The aerobic bacteria - staphylococci, streptococci, enterococci and enterobacteria - were suppressed significantly during the prophylaxis period. Among the anaerobic bacteria, cocci, bifidobacteria, eubacteria, lactobacilli, clostridia, fusobacteria and bacteroides decreased markedly during the same period. The microflora was normalized after two weeks. The imipenem concentrations in the intestinal mucosa varied between 0.1-3.6 mg/kg for the dose of 0.5 g and 3.2-13.4 mg/kg for the dose of 1.0 g, and the concentrations in the faecal samples were between 0.1-5.0 mg/kg and 0.7-11.3 mg/kg respectively.

Adolescent↗

Effect of enoxacin on colonic microflora of healthy volunteers.

Ten healthy volunteers received 400 mg enoxacin orally twice daily for seven days. Fecal specimens were collected at 0, 2, 4, 7, 9, 11, 16 and 21 days to study the effect of enoxacin on the normal colonic microflora. On the seventh day the fecal mean concentration of enoxacin was 348 mg/kg feces. Whereas enterobacteria were strongly suppressed during the administration of enoxacin, the gram-positive and anaerobic microflora was not significantly altered. Two weeks after enoxacin was discontinued, the colonic microflora had returned to normal.

Adult↗

Comparative effects of enoxacin and norfloxacin on human colonic microflora.

Ten healthy volunteers received 400 mg of enoxacin and another ten healthy volunteers received 200 mg of norfloxacin orally twice a day for 7 days. Fecal specimens were collected before, during, and after drug administration to study the impact of enoxacin and norfloxacin on the normal colonic microflora. On day 7, the mean concentrations of enoxacin and norfloxacin were 350 and 950 mg/kg of feces, respectively. Enoxacin and norfloxacin affected the colonic microflora in similar ways. The number of strains of the family Enterobacteriaceae was markedly suppressed during drug administration, whereas the gram-positive and anaerobic microfloras were not significantly altered. Two weeks after withdrawal of the drugs, the colonic microflora had returned to normal.

Adult↗