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Biomedical subjects

L Domellöf

Publications and source records attributed to L Domellöf.

At least 19 recordsLinked to original sources
PubMed2001

Helicobacter pylori, N-methyl-N'-nitro-N'-nitrosoguanidine, and bile modulate gastric cell kinetics in experimental cancer.

Helicobacter pylori infection is a risk factor for gastric cancer. How the bacterium contributes to this process is still unclear. We present a new Wistar rat model that was used to evaluate the effect of H. pylori on early preneoplastic events as judged from epithelial cell turnover and histopathological changes. One hundred and four rats were colonized with H. pylori and exposed MNNG (N-methyl-N'-nitro-N'-nitrosoguanidine) and/or taurocholic acid. Inflammation, goblet cell-like metaplasia, atrophy, dysplasia, and adenocarcinoma were scored in a blinded manner. Apoptotic cells were counted after staining with terminal uridine deoxynucleotidyl nick end labeling, and epithelial cell proliferation was determined by means of the Ki-67 labeling index. No early tumor enhancement with H. pylori could be found in ordinary histology. However, H. pylori significantly enhanced the epithelial cell proliferation compared with the control group, and the combination with taurocholic acid appeared to have a synergistic effect. MNNG significantly increased the normal gastric epithelial apoptosis. This increase was reduced in antral mucosa with H. pylori infection. The findings suggest that H. pylori, especially when combined with bile. has an influence on cell kinetics, contributing to the development of gastric cancer. The reduced apoptosis of MNNG also observed in infected animals indicates a dual function of H. pylori.

Adenocarcinoma↗
PubMed2001

Effects of Helicobacter pylori and bile on N-methyl-N'-nitro-N'-nitrosoguanidine exposed antral mucosa of C57BU6 mice.

The aim of this study was to evaluate the early influence of Helicobacter pylori infection on cell kinetics in the antral mucosa of mice exposed to N-methyl-N'-nitro-N'-nitrosoguanidine (MNNG) and bile alone or in combinations. Four hundred and one C57BL/6 male and female mice were assigned into seven treatment groups and one non-treated control group. The gastric antrums were assessed by histology and immunohistochemistry for studies of cell proliferation and apoptosis at 32 and 44 weeks. One female and one male mouse had developed dysplastic adenomas in the pylorus mucosa and one male animal had dysplastic proliferation in the antrum. Only one of these lesions occurred in a H. pylori colonized animal. H. pylori infection significantly increased the cell proliferation at 32 weeks and promoted the cell proliferation in the MNNG and bile group at 44 weeks. Female mice showed less increase in cell proliferation than did the males. No change in apoptosis was seen in any of the groups. Bile had no promotional effect on cell proliferation. These results indicate that H. pylori infection has the potential to alter epithelial cell kinetics as well as antrum mucosa of an animal species that is regarded as resistant to MNNG. However, this change is not sufficient to promote the early development of neoplastic lesions.

Adenoma↗
PubMed1998

Biliary-intestinal bypass in the treatment of obesity: long term follow up.

OBJECTIVE: To evaluate the long term outcome after biliary-intestinal bypass for morbid obesity. DESIGN: Retrospective study. SETTING: County hospital, Sweden. SUBJECTS: 120 consecutive patients operated on between 1977 and 1990. INTERVENTIONS: A variation of jejunoileal bypass in which the excluded bowel was anastomosed to the gallbladder. MAIN OUTCOME MEASURES: Weight, concentrations of blood lipids and glucose in blood, results of liver function tests, reversal rates, and complications. RESULTS: The mean body mass index was reduced by 39% (from 42 kg/m2 to 26 kg/m2), serum cholesterol and triglyceride concentrations by more than 30%, and fasting blood glucose concentrations by 1 1%. There were no cases of irreversible hepatic failure, diabetes, deaths related to the operation, or progressive renal failure. The incidence of renal calculi increased by a ratio 2.3. The reversal rate/year was 2% (n = 20). CONCLUSION: We conclude that biliary-intestinal bypass may be used to treat cases of obesity associated with seriously high blood lipid concentrations and where gastric restrictive operations are less suitable.

Adult↗
PubMed1997

Mutagenicity from neutrophils after challenge with Helicobacter pylori and bile.

OBJECTIVE: To study some mechanisms involved in Helicobacter pylori (H. pylori)-induced gastric carcinogenesis. DESIGN: In vitro study. SETTING: Medical centre hospital, Sweden. INTERVENTIONS: Mutagenicity in Ames' test of neutrophils challenged for 2 hours or more by two different strains of H. pylori. One strain designated NCTC 11637 by the National College of Type Cultures activated neutrophils to an oxidative burst and producing vacuolating cytotoxin, the other strain C-7050 lacked these abilities. Mutagenicity was also studied with sterile human gall bladder bile alone added to neutrophils or in combination with both neutrophils and H. pylori. RESULTS: There was no increase in the number of revertants with the crude suspension or the supernatant of neutrophils challenged for 1 hour or less with H. pylori, bile, or the combination of both. However, in 5 out of 19 experiments there was significant mutagenicity after challenge of neutrophils for 2 hours or more with either strain of H. pylori, bile, or the combination of the two. The strongest mutagenicity was obtained after challenge over night (18 hours) with the combination of H. pylori and bile. CONCLUSION: Mutagenicity occurs when neutrophils are challenged with H. pylori and bile. Factors other than reactive oxygen metabolites seem to be responsible.

Bile↗
PubMed1994

Prognosis of chronic pancreatitis: an international multicenter study. International Pancreatitis Study Group.

OBJECTIVES: The aim of this study was to determine which factors predict mortality in a cohort of patients with chronic alcoholic and nonalcoholic pancreatitis. Patients with chronic pancreatitis are known to have a reduced life expectancy, but the quantitative relationship between various clinical features and survival is unclear. METHODS: We evaluated survival among 2015 subjects with chronic pancreatitis treated at seven centers located in six countries. RESULTS: Mean age at diagnosis was 46 +/- 13 yr and mean duration of follow-up was 7.4 +/- 6.2 yr. Overall survival at 10 yr was 70% (95% confidence interval (CI), 68-73%) and at 20 yr was 45% (95% CI, 41-49%). Survival was significantly less than in the background population. There were 559 deaths observed among those with chronic pancreatitis compared with an expected number of 157.4, yielding a standardized mortality ratio (SMR) of 3.6 (95% CI, 3.3-3.9). Older subjects and those with alcoholic pancreatitis had a significant reduction in survival. In a multivariate analysis, mortality of middle-aged and older subjects was 2.3 (95% CI, 1.8-2.8) and 6.3 (95% CI, 4.7-8.3) times greater than subjects less than 40 yr at diagnosis. Smoking (hazard ratio, 1.4; 95% CI, 1.0-1.9), drinking (hazard ratio, 1.6; 95% CI, 1.2-2.2), or development of cirrhosis (hazard ratio, 2.5; 95% CI, 2.0-3.2) increased the risk of death during the observation period, but we observed no survival difference in operated vs. nonoperated patients. CONCLUSIONS: Age at diagnosis, smoking, and drinking are major predictors of mortality in patients with chronic pancreatitis.

Age of Onset↗
PubMed1993

Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group.

BACKGROUND: The results of case-control studies and anecdotal reports suggest that pancreatitis may be a risk factor for pancreatic cancer, but there have been no studies of sufficient size and power to assess the magnitude of the relation between these two diseases. METHODS AND RESULTS: We undertook a multicenter historical cohort study of 2015 subjects with chronic pancreatitis who were recruited from clinical centers in six countries. A total of 56 cancers were identified among these patients during a mean (+/-SD) follow-up of 7.4 +/- 6.2 years. The expected number of cases of cancer calculated from country-specific incidence data and adjusted for age and sex was 2.13, yielding a standardized incidence ratio (the ratio of observed to expected cases) of 26.3 (95 percent confidence interval, 19.9 to 34.2). For subjects with a minimum of two or five years of follow-up, the respective standardized incidence ratios were 16.5 (95 percent confidence interval, 11.1 to 23.7) and 14.4 (95 percent confidence interval, 8.5 to 22.8). The cumulative risk of pancreatic cancer in subjects who were followed for at least 2 years increased steadily, and 10 and 20 years after the diagnosis of pancreatitis, it was 1.8 percent (95 percent confidence interval, 1.0 to 2.6 percent) and 4.0 percent (95 percent confidence interval, 2.0 to 5.9 percent), respectively. CONCLUSIONS: The risk of pancreatic cancer is significantly elevated in subjects with chronic pancreatitis and appears to be independent of sex, country, and type of pancreatitis.

Adult↗
PubMed1990

Adjuvant chemotherapy with 5-fluorouracil, vincristine and CCNU for patients with Dukes' C colorectal cancer. The Swedish Gastrointestinal Tumour Adjuvant Therapy Group.

A prospective controlled randomized trial testing adjuvant postoperative combination chemotherapy (5-fluorouracil, lomustine (CCNU) and vincristine) versus no adjuvant therapy in patients operated on for Dukes' C colorectal cancer is reported. In total 334 patients aged less than 70 years were recruited: 205 patients with colonic and 99 with rectal cancer, but there were three protocol violations and these cases are excluded from further consideration. Twenty-seven patients had a limited resection of their cancer. After 5 years' follow-up there was no significant difference in the tumour-free survival rate or in the survival rate between the treated and control groups. Twenty-nine of the 147 patients who started chemotherapy discontinued this treatment because of side-effects, mainly from the gastrointestinal tract. In 30 patients treatment was discontinued because of recurrent disease. The conclusion is that systemic administration of combination chemotherapy for colorectal cancer after operation is not worthwhile in routine clinical practice.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Effect of therapeutic concentrations of anthracyclines on monocyte phagocytosis of yeast cells.

The effect of therapeutic concentrations of doxorubicin, epirubicin, and mitoxanthrone on mature leukocyte function has been examined by measuring phagocytosis of yeast cells by surface-bound monocytes, using a fluorescence-quenching method. There was a 10% inhibition of monocyte phagocytosis by doxorubicin, but epirubicin and mitoxanthrone had no effect on monocyte phagocytosis. Anthracyclines may have a major immunosuppressive effect due to bone marrow depression. The lack of interference with mature monocyte function by epirubicin and mitoxanthrone provides a potential advantage in comparison with the parent compounds.

Antibiotics, Antineoplastic↗
PubMed1989

Gallstone growth, size, and risk of gallbladder cancer: an interracial study.

To investigate gallstone size, growth, and the relation between stone size and gallbladder cancer we have used cholecystectomy reports from 1676 female subjects (169 Whites, 531 Blacks, and 976 Native American Indians). Although the prevalence of gallstones differs markedly in these groups it appears that the estimated growth rate of gallstones in younger subjects, 2.0 mm per year (95% confidence interval: 1.7-2.3 mm) is homogeneous for all three groups. In both Indian and non-Indian populations the proportion of small stones diminished and the proportion of large stones increased over time. We found a strong relationship between gallstone size and gallbladder cancer. Large stones (greater than or equal to 3 cm) were found in 40% of patients with gallbladder cancer but in only 12% of all subjects of similar age. The relative risk for gallbladder cancer in subjects with stones greater than or equal to 3 cm was 9.2 compared with subjects with stones less than 1 cm. (95% confidence interval: 2.3-37). We estimate that one-third of all gallbladder cancers in subjects with calculi will be associated with large (greater than or equal to 3 cm) stones. We believe that stone size might be used to determine the risk of gallbladder cancer in patients with gallstones.

Adult↗
PubMed1989

Pharmacokinetics and central haemodynamic effects of doxorubicin and 4'epi-doxorubicin in the pig.

The relationship between the cardiotoxicity and the haemodynamics/pharmacokinetics of clinical concentrations of doxorubicin and 4'epi-doxorubicin was studied. Twelve pigs were randomized to receive i.v. infusions of either drug of 50 mg/m2 over 3.0 min. Aortic, pulmonary arterial, coronary sinus and central venous plasma concentrations of the agents were determined until 180 min after the infusion. The V5 ECG, left ventricular dP/dT, aortic, pulmonary arterial and right atrial pressures were recorded continuously, cardiac output and coronary sinus blood flow were recorded intermittently. No haemodynamic changes were recorded after administration of either drug. Pharmacokinetic data indicated myocardial extraction, followed by myocardial release of both drugs. This release was higher after administration of 4'epi-doxorubicin than after doxorubicin, within the range 2-4 min and 20-40 min after the infusion. The tendency of greater myocardial release of 4'epi-doxorubicin may explain its lower cardiotoxicity.

Animals↗
PubMed1989

Pharmacokinetics of intra-arterial mitomycin C with or without degradable starch microspheres (DSM) in the treatment of non-resectable liver cancer.

The effects of degradable starch microspheres (DSM) on mitomycin C pharmacokinetics and bone marrow toxicity were studied in a phase II multicenter study. Sixty-three patients with non-resectable primary or secondary liver cancer were randomized to receive either i.a. mitomycin C 15 mg/m2 first, followed 5 weeks later by mitomycin C 15 mg/m2 plus DSM 360 mg administered into the hepatic artery (group I) or the same treatments in the opposite sequence (group II). In 36 out of 47 patients who received at least 2 treatments, peripheral venous blood samples were analyzed for mitomycin C pharmacokinetics on a minimum of 2 paired courses. In all patients, the area under the concentration time curve (AUC) was significantly lower when the drug was co-administrated with DSM, but the terminal half-life (t1/2) of mitomycin C was unchanged. In group I the addition of DSM resulted in a significantly lowered AUC, but not in group II. The discrepancy between the 2 groups is probably due to differences in DSM-induced intra-hepatic shunting. The addition of DSM resulted in significantly higher platelet nadir values, but unchanged white blood cell count nadir value. In conclusion, DSM reduce the systemic exposure of mitomycin C and seem to lessen the haematologic toxicity judged from a less pronounced decrease in platelets.

Adult↗
PubMed1989

Cystadenocarcinoma of the pancreas 9 years after a pancreatic cyst operation: report of a case.

A patient case with cystadenocarcinoma of the pancreas in a middle-aged woman is described. Nine years prior to the pancreatic malignancy she underwent cystogastrostomy due to a pancreatic cyst presumed to be of non-neoplastic nature. The malignancy occurred at the site of the previous cystogastrostomy and was radically resected. Five years later the patient was well without signs of recurrence. The possibilities of incorrect primary diagnosis or development of a rare pancreatic malignancy in a previous cystogastrostomy are discussed.

Cystadenocarcinoma↗
PubMed1988

Cardiopulmonary hemodynamics and pharmacokinetics after hepatic intraarterial infusion of 5-fluorouracil (5-FU). An experimental study in the pig.

Reported 5-FU-induced cardiac side effects may be explained by drug-induced hemodynamic changes and/or by direct myocardial toxicity due to regional drug uptake. This question was studied in 11 animals given constant infusions and 6 animals given bolus 5-FU infusions into the hepatic artery. Six animals, which received normal saline infusion, served as controls. A second aim was to study possible pulmonary drug clearance. Aortic, pulmonary arterial, and coronary sinus plasma 5-FU concentrations were determined during constant and after the bolus infusions of 5-FU. The V5 ECG, aortic, pulmonary arterial, and right atrial pressures were recorded continuously, and cardiac output and coronary sinus blood flow were recorded intermittently in all animals. No significant alterations in hemodynamic variables were seen during constant infusion. After the bolus infusion, an increased arterio-mixed venous oxygen content difference was recorded. Pharmacokinetic data after 3-min infusions indicated pulmonary drug uptake and release; during constant infusions, the data indicated myocardial drug uptake. As there were no alterations in myocardial oxygen demand or supply or in systemic hemodynamics during this myocardial drug uptake, it is likely that the cardiotoxicity is related to the direct effects of the drug on cardiac myocytes.

Animals↗
PubMed1988

A cytostatic drug (taxol) which does not inhibit monocyte phagocytosis.

Taxol is a new cytotoxic agent which arrests cell division in the G2 and the M phases, due to its unique property of inhibiting microtubule function by stabilization. In contrast to other microtubule antagonists except griseofulvin, taxol did not inhibit monocyte phagocytosis. It is suggested that lack of interference with the function of mature leukocytes may reduce the immunosuppression induced by a cytotoxic agent.

Alkaloids↗
PubMed1988

Therapeutic concentrations of melphalan do not affect yeast cell phagocytosis by monocytes.

The effect of melphalan on monocyte phagocytosis was assessed by studying the uptake of fluorescent yeast cells by glass-adherent monocytes (a fluorescence-quenching technique). In contrast to several other cytotoxic agents, melphalan did not inhibit monocyte phagocytosis. Although the main immunosuppressive side effect of most cytotoxic drugs appears to be due to bone marrow depression with reduction of leukocyte counts, it is reasonable to assume that lack of interference with the function of mature leukocytes is a favourable feature of an antineoplastic drug.

Humans↗