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E Jellum

Publications and source records attributed to E Jellum.

At least 37 records · Page 2Linked to original sources

A prospective, seroepidemiological study of the role of human papillomavirus in esophageal cancer in Norway.

Infection with the human papillomavirus (HPV), notably HPV type 16, has been associated with esophageal cancer in seroepidemiological studies. To evaluate the consistency of the association, we performed a nested case-control study of HPV seropositivity and risk of esophageal cancer within a prospectively followed cohort of 300,000 Norwegian men and women who had donated blood samples to a serum bank. The data file of the serum bank was linked with the nationwide Cancer Registry of Norway to identify esophageal cancers diagnosed after donation of the serum sample. Fifty-seven cases and 171 matched controls were analyzed for antibodies to specific microorganisms, and odds ratios for developing esophageal cancer were calculated. There was an increased risk of developing esophageal cancer among HPV 16-seropositive subjects (odds ratio = 6.6; 95% confidence interval, 1.1-71) but not among Chlamydia trachomatis-seropositive subjects. Adjustment for the presence of serum cotinine, a marker of smoking habits, did not affect the estimates substantially. The seroepidemiological association between HPV 16 and esophageal cancer seems to be consistent in different countries.

Adult↗

Prospective seroepidemiological study of role of human papillomavirus in non-cervical anogenital cancers.

OBJECTIVE: To evaluate the association between infection with the major oncogenic types of human papillomavirus and the risk of developing non-cervical anogenital cancers in a cohort followed up prospectively. DESIGN: Data from two large serum banks to which about 700,000 people had donated serum samples were followed up for a mean of 8 years. People who developed non-cervical anogenital cancers during follow up were identified by registry linkage with the nationwide cancer registries in Finland and Norway. Within this cohort a nested case-control study was conducted based on the serological diagnosis of infection with human papillomavirus types 16, 18, and 33. SUBJECTS: 81 cases and 240 controls matched for sex, age, and storage time of serum samples. MAIN OUTCOME MEASURES: Odds ratios of developing non-cervical anogenital cancers in presence of IgG antibodies to specific micro-organisms. RESULTS: Subjects seropositive for human papillomavirus type 16 had an increased risk of developing non-cervical anogenital cancers (odds ratio 3.1 (95% confidence interval 1.4 to 6.9)). Subjects seropositive for type 33 also had an increased risk (odds ratio 2.8 (1.0 to 8.3)) but not significantly after adjustment for infection with type 16. Seropositivity for human papillomavirus type 16 was associated with an increased risk of developing vulvar and vaginal cancers (odds ratio 4.5 (1.1 to 22)) and a strongly increased risk of developing preinvasive vulvar and vaginal lesions (odds ratio infinity (3.8 to infinity)). Seropositivity for human papillomavirus type 18 increased the risk of developing preinvasive lesions (odds ratio 12 (1.2 to 590)). High, but non-significant odds ratios for types 16 and 33 were seen for penile cancers. CONCLUSIONS: This study provides prospective seroepidemiological evidence that infection with human papillomavirus type 16 confers an increased risk of developing non-cervical genital cancers, particularly vulvar and vaginal cancers.

Adult↗

Prospective seroepidemiologic study of human papillomavirus infection as a risk factor for invasive cervical cancer.

BACKGROUND: Major risk factors for invasive cervical cancer include infection with human papillomavirus (HPV), infection with other sexually transmitted pathogens (e.g., Chlamydia trachomatis), and smoking. Since exposures to these risk factors can be related, the contribution of any single factor to cervical carcinogenesis has been difficult to assess. We conducted a prospective study to define the role of HPV infection in cervical carcinogenesis, with invasive cancer as an end point. METHODS: A nested case-control study within a joint cohort of 700,000 Nordic subjects was performed. The 182 women who developed invasive cervical cancer during a mean follow-up of 5 years were matched with 538 control women on the basis of age and time of enrollment. Serum samples taken at enrollment were analyzed for evidence of tobacco use (i.e., cotinine levels); for antibodies against HPV types 16, 18, and 33; and for antibodies against C. trachomatis. Relative risks (RRs) were estimated by use of conditional logistic regression. RESULTS: Presence of antibodies against HPV in serum (seropositivity) was associated with an increased risk of cervical cancer, and adjustment for smoking and for C. trachomatis seropositivity did not affect this finding (RR = 2.4; 95% confidence interval [CI] = 1.6-3.7). HPV16 seropositivity was associated primarily with an increased risk of squamous cell carcinoma (RR = 3.2; 95% CI = 1.7-6.2). In contrast, risk associated with HPV18 seropositivity tended to be higher for cervical adenocarcinoma (RR = 3.4; 95% CI = 0.8-14.9). In populations with a low prevalence of antibodies against C. trachomatis, the HPV16-associated risk of cervical cancer was very high (RR = 11.8; 95% CI = 3.7-37.0); in contrast, in populations with a high prevalence of antibodies against C. trachomatis, no excess risk was found. CONCLUSION: Past infection with HPV16 increases the risk of invasive cervical squamous cell carcinoma, most clearly seen in populations with a low prevalence of sexually transmitted diseases.

Adenocarcinoma↗

Prediagnostic level of fatty acids in serum phospholipids: omega-3 and omega-6 fatty acids and the risk of prostate cancer.

Ecological and case-control studies have demonstrated a positive correlation between consumption of fat and the risk of prostate cancer. Two recent human studies have focused on alpha-linolenic acid as a risk factor for prostate cancer. Animal experiments have shown that dietary omega-6 polyunsaturated fatty acids have generally stimulated tumour development, whereas omega-3 polyunsaturated fatty acids have diminished it. The aim of our study was to investigate the association between these fatty acids and the subsequent risk of prostate cancer. Blood donors to the Janus serum data bank in Norway, who later developed prostate cancer, were matched to blood donors without prostate cancer (141 matched sets); the proportional level of fatty acids measured before diagnosis in the donors' serum was examined. The risk of later prostate cancer was analysed by conditional logistic regression. Increasing risk for prostate cancer was found with increasing quartiles of palmitoleic, palmitic and alpha-linolenic acid. An inverse risk association was found with increasing levels of tetracosanoic acid, for the ratios of linoleic to alpha-linolenic acid and arachidonic to eicosapentaenoic acid. There was no clear association between the risk effect of total omega-3 and total omega-6 fatty acids. There were no indications of a relationship between fatty acids and more aggressive cancers. Our results verify recent findings of a positive association between alpha-linolenic acid and a negative association between the ratio of linoleic to alpha-linolenic acid and the risk of prostate cancer.

Case-Control Studies↗

Diagnostic applications of chromatography and capillary electrophoresis.

Capillary electrophoresis (CE) equipped with a diode-array detector, and GC-MS have been used to determine diagnostic metabolites occurring in urine of patients with various metabolic disorders. The urine samples were injected directly onto the CE instrument without any pretreatment. GC-MS required extraction and derivatisation before separation. Identification of abnormal metabolites was based on migration times and characteristic diode-array spectra, or mass spectral library search when GC-MS was used. The CE method has previously been shown capable of diagnosing several metabolic diseases, and was now used on more difficult cases. CE readily diagnosed glyceric aciduria and the secondary metabolite in lysinuric protein intolerance, orotic acid. Methylmalonic aciduria required pressure elution in addition to high voltage to accomplish diagnosis. In mevalonic aciduria the characteristic metabolite had weak light absorption and the mevalonate peak also co-eluted with endogenous aromatic acids making diagnosis difficult. Both in the latter case and with the disorders glutaric aciduria I and glyceroluria, GC-MS was the method of choice. A possible role of CE in the routine system for diagnosing metabolic disorders, might be to use this method for pre-testing all urine samples. Samples with abnormal CE-profiles would subsequently be given high priority for more elaborate analysis with GC-MS and amino acid analyzer. In a different project a CE instrument designed for serum protein analysis was used to study sera from patients with myelomatosis. The method also allowed identification of the various immunoglobulins using immunosubtraction. Samples collected after diagnosis as well as many years prior to disease were available through the Janus-bank. This large serum bank comprises samples collected since 1973 at intervals from nearly 300000 blood donors. It was found that the monoclonal immunoglobulins characteristic of the disease started to appear in serum up to 15 years before clinical diagnosis.

Acidosis↗

Capillary electrophoresis for diagnosis of metabolic disease.

Capillary electrophoresis (CE) equipped with a diode-array detector have been used to determine diagnostic metabolites occurring in urine of patients with various diseases. The urine samples were injected directly onto the CE instrument without any pretreatment. Identification of abnormal metabolites was based on relative migration times and characteristic diode-array spectra. The CE-method readily diagnosed alkaptonuria, neuroblastoma and liver failure due to galactosemia. The simple and automated CE method appears to be suitable for implementation as a screening test in analytical systems aimed at diagnosis of metabolic disorders.

Alkaptonuria↗

Risk for gastric lymphoma in persons with CagA+ and CagA- Helicobacter pylori infection.

Infection with Helicobacter pylori increases the risk for gastric non-Hodgkin's lymphoma (GNHL). Strains that express CagA protein are thought to be particularly virulent. It was determined whether CagA+ H. pylori infection increased the risk for GNHL more than CagA infection. Thirty-two cases and 130 controls previously tested for H. pylori antibodies were tested for CagA antibodies by ELISA. The risk for GNHL was compared among CagA+, CagA-, and uninfected persons by use of conditional logistic regression. CagA+ subjects had 8.2 times the risk for GNHL than uninfected persons (95% confidence interval [CI], 2.5-26.7). CagA- subjects had 4.4 times the risk for GNHL than uninfected persons (95% CI, 1.2-16.5). Among infected subjects only, CagA+ infection was not associated with significantly increased risk for GNHL when compared with CagA- infection (odds ratio, 2.1; 95% CI, 0.8-5.4). This study does not support a major role for CagA in lymphomagenesis.

Antibodies, Bacterial↗

Androgens in serum and the risk of prostate cancer: a nested case-control study from the Janus serum bank in Norway.

We tested the hypothesis that serum levels of testosterone (T), dihydrotestosterone (DHT), and the DHT metabolite 3 alpha,17 beta-androstanediol glucuronide are positively associated with the risk of prostate cancer. This nested case-control study was based on the cohort of men who donated blood to the Janus serum bank at Oslo University Hospital (Oslo, Norway) between 1973 and 1994. Cancer incidence was ascertained through linkage with the Norwegian Cancer Registry. The study included sera from 59 men who developed prostate cancer (cases) subsequent to blood donation and 180 men who were free of any diagnosed cancer (controls) in 1994 and were of similar age (+/- 1 year) and had similar blood storage time (+/- 6 months) to the cases. Neither T, DHT, nor the ratio T:DHT was associated with risk of developing prostate cancer. Compared to the bottom quartile, the odds ratio (OR) associated with the top quartile of T was 0.83 [95% confidence interval (CI), 0.36-1.93]; the OR for the top (compared to the bottom) quartile of DHT was 0.83 (95% CI, 0.36-1.94), and the equivalent OR for T:DHT was 1.31 (95% CI, 0.58-2.97). Similarly, 3 alpha,17 beta-androstanediol glucuronide showed no association with prostate cancer risk; the OR for the top (compared to the bottom) quartile was 1.10 (95% CI, 0.41-2.90). These results showed no association, positive or negative, between androgens measured in serum and the subsequent risk of developing prostate cancer.

Adult↗

Capillary electrophoresis for clinical problem solving: analysis of urinary diagnostic metabolites and serum proteins.

Many clinical laboratories employ gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) to detect abnormal compounds occurring in urine and serum due to disease. The methods, particularly GC-MS, often require laborious sample pre-treatment, and separation times may exceed an hour. We describe the use of capillary electrophoresis (CE) equipped a with a diode-array detector in an attempt to improve the efficiency of an analytical system routinely used for diagnosis of human metabolic disease. It was found that urine samples could be injected directly onto the CE instrument without any pre-treatment, and over 50 metabolites were separated in 15 min. Identification of abnormal metabolites was based on migration times and characteristic diode-array spectra. The method readily diagnosed adenolysuccinase deficiency, 5-oxoprolinuria, propionic acidemia and disorders have orotic acid as diagnostic metabolite (e.g. the HHH-syndrome). The results show that CE may become a useful additional tool for diagnosis of metabolic disease. In a different project CE was used to study sera from the Janus-bank. This large serum bank comprises samples collected at intervals from nearly 300,000 blood donors. As the sera are stored at -25 degrees C and not at a lower temperature, a major concern has been the stability of the specimens. GC-MS, 2D-protein electrophoresis, certain immunological assays and enzyme measurements have previously been used to evaluate the stability of the sera. We can now also show that the protein profile, as determined by CE, is remarkably stable even after 22 years of storage. The results moreover confirmed that the CE-method and traditional gel electrophoresis gave almost identical results, except for small amounts of fibrinogen which did not show up on the CE-pattern.

Blood Proteins↗

Changes in amino acids, ammonium, and coagulation factors after transcervical resection of the endometrium with a glycine solution used for uterine irrigation.

OBJECTIVE: Transcervical resection of the endometrium with the use of 1.5% glycine for irrigation is associated with postoperative nausea in some patients. This could be because of hyponatremia or toxic effects of glycine and its metabolites. Moreover, 1.5% glycine is hypoosmolar, and hemolysis and fibrinolysis are possible. Changes in plasma factors related to these potential complications of transcervical resection of the endometrium were measured. STUDY DESIGN: In 101 patients undergoing transcervical resection of the endometrium sodium, ammonium, and coagulation factors were measured preoperatively and postoperatively at intervals. In the initial 30 patients glycine and 28 other amino acids were measured at the same intervals. The results were correlated with the patients' clinical status and operative parameters. RESULTS: Glycine and nine other amino acids and ammonia showed increased postoperative plasma levels; these changes were correlated with the absorption of the irrigating glycine solution and the development of hyponatremia. Minor activation of fibrinolysis and hemolysis was also seen. CONCLUSION: Nausea after transcervical resection of the endometrium with 1.5% glycine for irrigation may be partly explained by toxic effects of glycine and its secondary metabolites in addition to the effects of water intoxication and hyponatremia. Minor, clinically insignificant changes in the coagulation system may also occur. Studies on alternatives to glycine for creation of near-isotonic irrigating solutions are encouraged.

Adult↗

Atypical methylmalonic aciduria with progressive encephalopathy, microcephaly and cataract in two siblings--a new recessive syndrome?

Two siblings with atypical methylmalonic aciduria and progressive encephalopathy are reported. Initial symptoms were failure to thrive and growth retardation from the first year of life, progressing to severe mental retardation, microcephaly, dystonia, spasticity and cataracts. The amount of methylmalonic acid excreted in the urine was substantially lower than in classical methylmalonic acidemia and was not reduced by vitamin B12 therapy. The activity of methylmalonyl-CoA mutase and the overall assay of propionic acid metabolism in cultured fibroblasts were normal. The primary defect in this probably new autosomal recessive disorder associated with methylmalonic aciduria is currently not known.

Adult↗

Experiences of the Janus Serum Bank in Norway.

The ongoing JANUS project was started in 1973. The serum bank comprises 424,938 serum samples consolidated from 293,692 donors. The specimens are stored at -25 degrees C. From 1 to 13 consecutive samples are available from each donor. Up to October 1993 about 14,000 of the donors had developed some form of cancer. Frozen serum samples collected from a few months to 19 years prior to clinical recognition of their disease are available for research purposes. The principle aim of the JANUS project is to search in the premorbid sera for chemical, biochemical, immunological or other changes that might be indicative of cancer development at early stages. Gas chromatography-mass spectrometry and two-dimensional protein electrophoresis have been used to evaluate the stability of the frozen sera. Some recent findings are: CA-125 may be elevated months prior to the diagnosis of ovarian cancer; serum thyroglobulin may be a preclinical tumor marker in subgroups of thyroid cancer; low levels of selenium in serum reflects increased risk of thyroid cancer; raised antibodies in serum against Epstein-Barr virus is a risk factor for development of Hodgkins disease; prostate-specific antigen may be elevated years prior to clinical diagnosis of prostate cancer; and linoleic acid in serum phospholipids is inversely related to breast cancer risk. The serum bank is, in principle, suitable for environmental studies, e.g., human exposure assessment. The steering committee of the JANUS project is open to suggestions for collaborative research on this topic.

Biomarkers, Tumor↗

Studies on the haemostatic defect in a complicated syndrome. An inverse Scott syndrome platelet membrane abnormality?

The Stormorken syndrome is a multifacetted syndrome including a bleeding tendency. No deviations were found in the coagulation- or fibrinolytic systems. Platelet number was low normal, and size abnormal, whereas EM findings were unremarkable. Survival time was half normal. Clot retraction was initially rapid, but clearly decreased, whereas prothrombin consumption was also initially rapid, but complete. Membrane GP's were normal, so was AA metabolism, PI-cycle, granule storage and secretion, and c-AMP function, whereas 5-HT uptake and storage was decreased. Optical platelet aggregation was low normal with all physiological agonists. The only clearly abnormal finding was that coagulant activity was present on non stimulated platelets at the same level as kaolin-stimulated normal platelets. This indicated a platelet abnormality which should lead to a thrombogenic, not to a haemorrhagic trait. This paradox may have its origin in rheology, because when challenged with in vivo shear rates in an ex vivo perfusion chamber, platelet cohesion was abnormally low. Further studies to better delineate the membrane abnormality are underway.

Blood Platelet Disorders↗

[Slow replenishment of carnitine level after long-term treatment with pivampicillin/pivmecillinam].

Long-term treatment with pivampicillin and pivmecillinam for 6-24 months in five adults and one child reduced the total serum carnitine concentrations to 3.7-14.0 mumol/l (reference value 25-66 mumol/l). The muscle carnitine was reduced to 0.3-0.7 mumol/g wet weight (reference value 3-5 mumol/g) in two cases. All patients had asthenia and muscle symptoms with weakness and pain. One showed signs of carnitine depletion in the liver, with increased secretion of dicarboxylic acids (C6, C8, C10) in urine and limited ketone body formation during prolonged fasting (32 hours). The serum carnitine increased slowly after cessation of therapy and reached normal concentrations after 6-12 months. All symptoms caused by carnitine depletion disappeared after the serum carnitine reached 20 mumol/l. This was achieved on a normal diet without carnitine supplement.

Adult↗

Helicobacter pylori infection and gastric lymphoma.

BACKGROUND: Helicobacter pylori infection is a risk factor for gastric adenocarcinoma. We examined whether this infection is also a risk factor for primary gastric non-Hodgkin's lymphoma. METHODS: This nested case-control study involved two large cohorts (230,593 participants). Serum had been collected from cohort members and stored, and all subjects were followed for cancer. Thirty-three patients with gastric non-Hodgkin's lymphoma were identified, and each was matched to four controls according to cohort, age, sex, and date of serum collection. For comparison, 31 patients with nongastric non-Hodgkin's lymphoma from one of the cohorts were evaluated, each of whom had been previously matched to 2 controls. Pathological reports and specimens were reviewed to confirm the histologic type of the tumor. Serum samples from all subjects were tested for H. pylori IgG by an enzyme-linked immunosorbent assay. RESULTS: Thirty-three cases of gastric non-Hodgkin's lymphoma occurred a median of 14 years after serum collection. Patients with gastric lymphoma were significantly more likely than matched controls to have evidence of previous H. pylori infection (matched odds ratio, 6.3; 95 percent confidence interval, 2.0 to 19.9). The results were similar in both cohorts. Among the 31 patients with nongastric lymphoma, a median of six years had elapsed between serum collection and the development of disease. No association was found between nongastric non-Hodgkin's lymphoma and previous H. pylori infection (matched odds ratio, 1.2; 95 percent confidence interval, 0.5 to 3.0). CONCLUSIONS: Non-Hodgkin's lymphoma affecting the stomach, but not other sites, is associated with previous H. pylori infection. A causative role for the organism is plausible, but remains unproved.

Aged↗

Characterization of in-vitro-translated human regulatory and catalytic subunits of cAMP-dependent protein kinases.

Full-length human cDNAs for all the different regulatory (R) and catalytic (C) subunits of cAMP-dependent protein kinases (PKA) were transcribed and translated in a cell-free in vitro system. The resulting proteins were characterized with respect to molecular size, isoelectric focusing, immunoreactivity, cAMP binding, and to what extent the RII protein subunits revealed mobility shifts upon phosphorylation by catalytic subunit of PKA. We were able to express cDNAs for all the human R (RI alpha, RI beta, RII alpha and RII beta) and C (C alpha, C beta and C gamma) subunits in a wheat-germ extract. [35S]Methionine-labelled in-vitro-translated products were analyzed by SDS/PAGE and revealed distinct protein bands with apparent molecular masses of 49 (RI alpha), 54-55 (RI beta), 51 (RII alpha) and 53 kDa (RII beta) for the R subunits. In vitro transcription/translation of the cDNAs for the C subunits of PKA gave proteins with molecular masses of approximately 40 kDa for all the different C subunits. Phosphorylation of RII alpha and RII beta by the C subunit of PKA, revealed a distinct mobility shift of the RII alpha subunit on one-dimensional SDS/PAGE (51-54 kDa), but not of RII beta (53 kDa). Further characterization of the R subunits by two-dimensional SDS/PAGE revealed that RI alpha was more acidic than RI beta, with pIs of 6.1-6.0 and 6.4-6.2, respectively. Furthermore, the RII alpha protein was more basic than RII beta, with pIs of approximately 5.4-5.3 and 5.3-5.1, respectively. All the in-vitro-translated R subunits could be photoaffinity labelled by the cAMP-analog 8-azido-[32P]cAMP and were also detected by immunoprecipitation with subunit-specific antibodies.

Affinity Labels↗

Dystonia and dyskinesia in glutaric aciduria type I: clinical heterogeneity and therapeutic considerations.

Glutaric aciduria type I (GA-I) is an inborn error in the degradation of lysine, hydroxylysine, and tryptophan due to a deficiency of glutaryl-CoA dehydrogenase. Glutaric, 3-OH-glutaric, and glutaconic acids are excreted in the urine, particularly during intercurrent illness. The enzyme may be assayed in leukocytes, cultured fibroblasts and chorionic villi. Twelve new cases, 9 months-16 years of age, are reported, comprising all known cases of GA-I in Sweden and Norway. Ten had a severe dystonic-dyskinetic disorder, one had a mild hyperkinetic disorder, and one was asymptomatic. Two children died in a state of hyperthermia. Carnitine deficiency and malnutrition developed in patients with severe dystonia and dysphagia, which necessitated substitution and gastrostomy. A slowly progressive dyskinetic disorder developed in spite of adequate early dietary treatment in one subject. Macrocephaly was found in three. Computed tomography and magnetic resonance investigations in 10 showed deep bitemporal spaces in 7. Neuropsychological testing of 8 of 12 subjects demonstrated receptive language function to be superior to expressive language and motor function. Cognitive functions were obviously less affected than motor functions. A review of 57 pooled cases showed that a severe dystonic syndrome developed in 77%, a mild extrapyramidal syndrome in 10%, and 12% were asymptomatic. This disorder may pass undetected in the cerebral palsy and mentally retarded child and adult populations. Repeated urine examinations of organic acids in the urine and enzyme assay may be necessary to confirm GA-I.

Adolescent↗

Longchain serum fatty acids and risk of thyroid cancer: a population-based case-control study in Norway.

Epidemiologic studies have shown an association between seafood consumption and risk of thyroid cancer. Fish meals increase the serum concentrations of the longchain fatty acids, eicosapentaenoic acid (20:5,n-3) (EPA) and docosahexaenoic acid (22:6,n-3) (DHA), for days. The hypothesis that serum concentrations of fatty acids may be associated with thyroid cancer risk therefore was tested in a population-based case-control study with 74 cases and 221 matched controls. Seventy-three cases with sera in the Norwegian serum bank (JANUS) were identified in the Norwegian Cancer Registry and matched with three controls, also in JANUS, on age, gender, place of residence, and time of blood sampling. One [corrected] case was matched with two controls. Serum concentrations of 11 longchain fatty acids were determined blindly by gas chromatography for all subjects. Controls were divided into three groups with increasing serum fatty acid concentrations, and odds ratios between cases and controls were estimated relative to the group with lowest serum level by univariate and multivariate analyses. The main finding was a significant inverse relation between the sum of arachidonic acid (20:4,n-6) (AA) and DHA serum concentrations and thyroid cancer risk. The significance of this association was weakened when the analyses were restricted to the papillary type of thyroid carcinoma. It was of the same order of magnitude whether the period between blood sampling and diagnosis was greater than eight years, or eight or less years. High EPA/AA ratio, indicating consumption of fish fat, was not associated significantly with increased thyroid-cancer risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗