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Biomedical subjects

E Jellum

Publications and source records attributed to E Jellum.

At least 19 recordsLinked to original sources

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

The JANUS serum bank.

The on-going JANUS project was initiated by the Norwegian Cancer Society in 1973. The serum bank comprises close to 0.5 million serum samples collected from 170,000 donors. From 2-16 consecutive samples are available from each donor. The sera are stored at -25 degrees C. At regular intervals the JANUS-collection is matched against the files of the Norwegian Cancer Registry. From 1973 to 1991 almost 5000 of the donors have developed some form of cancer. Frozen serum samples collected from a few months to 18 years prior to clinical recognition of their disease are consequently available for research purposes. The aim of the JANUS-project is to search in these 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: CA125 is elevated several months prior to diagnosis of ovarian cancer; serum thyroglobulin may be a preclinical tumour marker in subgroups of thyroid cancer; low level of selenium in serum reflects increased risk of thyroid cancer; and raised antibodies in serum against Epstein-Barr virus is a risk factor for development of Hodgkin's disease. On-going research includes trace elements and cancer, and studies on lipid-profiles, diet and cancer. The serum bank may in principle be used for other purposes, e.g. in environmental studies. Analysis of sequential sera may determine chemical substances in the sera that might reflect differences in exposure to environmental pollutants in the period 1973-1991.

Antigens, Tumor-Associated, Carbohydrate

Slow replenishment of carnitine deficiency after cessation of long-term treatment with pivaloyl-containing antibiotics.

Long-term treatment with pivampicillin and pivmecillinam for 6-24 months in five adults and one child reduced the total serum carnitine concentration to 3.7-14 mumol/l (reference value: 25-66 mumol/l). 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 muscle symptoms with weakness, asthenia and pains. 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. Serum carnitine increased slowly after cessation of therapy and reached normal concentrations after 6-12 months. All symptoms caused by carnitine depletion disappeared. This was achieved on a normal diet without carnitine supplementation.

Adult

Polyunsaturated fatty acids in serum phospholipids and risk of breast cancer: a case-control study from the Janus serum bank in Norway.

We have tested the hypothesis that specific polyunsaturated fatty acids (PUFA) of the n-3 and n-6 families, as measured in serum phospholipids, are negatively associated with the risk of breast cancer. The study is based on serum samples from women who have donated blood to the Janus serum bank at the University Hospital in Oslo, Norway. It consists of sera from 87 women who developed breast cancer (cases) subsequent to blood donation and 235 women who were free of any diagnosed cancer (controls), but were of similar age and had similar blood storage time as the cases. We measured fatty acids (monounsaturated, polyunsaturated and saturated) in serum phospholipids, and made comparisons between cases and controls. The results showed that there was an inverse relation between the n-6 PUFA linoleic acid (18:2n-6) and risk of breast cancer, but this association was restricted to women who were 55 years and younger. In this age group, the relative risk (odds ratio) of women in the highest quartile of linoleic acid was 0.4 (95% confidence limits, 0.2 and 1.0) compared with women in the lowest quartile, and there was a negative trend over quartiles of linoleic acid (Mantel's chi for trend = -2.49, P < 0.02). No association was noted between the n-3 PUFA of marine oil origin and breast cancer risk. If the measured concentration of linoleic acid in serum phospholipids reliably reflects dietary intake, these data suggest that linoleic acid in the diet may decrease breast cancer risk among women at premenopausal and perimenopausal age. No similar association with n-3 unsaturated fatty acids was observed. It is noteworthy that none of the measured fatty acids (saturated or unsaturated) showed a positive association with breast cancer risk.

Breast Neoplasms

[Glutaric aciduria type I].

Glutaric aciduria type I is a congenital metabolic disease caused by an enzymatic defect in the degradation of the amino acids lysine and tryptophane. This article presents five Norwegian patients with this condition. Early clinical features may be similar to those of encephalitis. The further clinical course is dominated by choreoathetosis, hyperkinesis and spasticity. The diagnosis is made by tracing enhanced glutaric acid in the urine. The treatment is a low protein diet containing only small quantities of lysine and tryptophane. Four of our patients underwent a neuropsychological examination. Despite the fact that such patients are difficult to test, our examination indicates that the condition has a greater effect on motor than on cognitive functions.

Adolescent

Branched-chain amino acids increase the seizure threshold to picrotoxin in rats.

During infusion of branched-chain amino acids (BCAAs) in humans, changes in ventilatory drive, appetite, and sleep have been reported. The mechanism by which BCAAs exert their effects on CNS remains unclear. Picrotoxin is a proconvulsant drug, acting as an antagonist on the GABA-benzodiazepine receptor complex. Twenty rats were randomized to receive either an IP injection with 4% BCAAs (300 mg/kg; 8 ml/kg) (n = 10) or placebo (saline 8 ml/kg) (n = 10). The mean latency time from injection to onset of seizures was recorded as an indication of the seizure threshold. Latency time was significantly longer for BCAAs than for placebo, 11.2 (+/- 1.9) vs. 8.3 (+/- 1.8) min. Thus, a BCAA injection increased the seizure threshold to picrotoxin (p < 0.03). This suggests that BCAA infusion may exert effects on the GABA-benzodiazepine receptor complex.

Amino Acids, Branched-Chain

Capillary electrophoresis for diagnosis and studies of human disease, particularly metabolic disorders.

High-performance capillary electrophoresis (HPCE) has been used in a multicomponent analytical system designed to diagnose and study human diseases, particularly metabolic disorders. Comparative analyses, using HPCE, high-performance liquid chromatography (HPLC) and an automated amino acid analyser, were carried out on urine and blood samples from patients with homocystinuria, cystinuria, glutathione synthetase deficiency and adenylosuccinase deficiency. HPCE of the sulphur-containing amino compounds, derivatized with monobromobimane and detected by fluorescence spectroscopy, was a quick and simple alternative to classical amino acid analysis. The detection of the characteristic succinylpurines associated with adenylosuccinase defect was equally well achieved with HPLC and HPCE (absorbance detector). Owing to the possible connection between deficiency of taurine (2-amino-1-ethanesulphonic acid) in the heart and the development of cardiomyopathy and heart failure, a simple HPCE method was developed for the determination of taurine in sub-milligram samples of biopsies of the myocardium. The homologue 3-amino-1-propanesulphonic acid was the internal standard, and derivatives of 9-fluorenylmethyl chloroformate and fluorescence detection were used. It is suggested that the potential of HPCE to analyse small volumes should be exploited in biomedicine and clinical diagnosis to analyse sub-milligram samples of tissue biopsies and cells.

Biopsy

Epstein-Barr virus antibody patterns preceding the diagnosis of non-Hodgkin's lymphoma.

Immunosuppressed patients who develop non-Hodgkin's lymphoma (NHL) have abnormal antibody responses against the Epstein-Barr virus (EBV) prior to the diagnosis of malignancy. To see if this is also true of "spontaneous" cases in the general population, we undertook a collaborative serologic case-control study. From 4 serum banks containing specimens from over 240,000 persons, 104 subjects were identified for whom a blood specimen had been stored an average of 63 months before diagnosis of NHL, and 259 controls matched for age, sex, ethnic group and date of serum collection. The relative risks (RR) for subsequent development of NHL associated with elevated levels of IgG and IgM antibodies against viral capsid antigen were 2.5 (95% confidence interval = 1.1-5.7) and 3.2 (1.3-7.5), respectively; these associations increased with age at diagnosis. For the nuclear antigen, the distribution of titers for cases was more restricted than that of controls, with fewer cases having either elevated or low titers, RR = 0.5 (0.2-1.4) and 0.5 (0.2-1.2), respectively. Cases had significantly lower antibody titers against the cytomegalovirus, RR = 0.4 (0.2-0.9). These findings suggest that, at least for some patients, NHL is preceded by an enhanced level of endogenous immunosuppression with resultant EBV activation. This observation supports the role of EBV either directly in the development of NHL or as a primary marker of immune dysfunction.

Adult

Epstein-Barr virus antibody patterns preceding the diagnosis of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) patients have elevated IgG and IgA antibody titers against the Epstein-Barr viral capsid antigen (VCA) and the diffuse component of the early antigen complex (EA-D) at diagnosis. Several studies have implied that the presence of anti-VCA-IgA can be used as a screening marker for early NPC. To evaluate this further, we undertook a serologic case-control study based on four serum banks which together had specimens from over 240,000 persons. Seven cases of undifferentiated or poorly differentiated NPC were diagnosed in the period after serum collection ranging from 26 months to 154 months. Two controls per case matched on serum bank, age, sex, race, and date of serum collection were selected by a predetermined random process. For anti-VCA-IgG, the geometric mean titer for cases (88.3) was significantly higher than that for controls (75.5, P less than 0.05). The difference was greatest among the Asian patients. No significant differences were found for anti-VCA-IgA, anti-EA-D, and anti-EA-R or anti-EBNA. No time effects were evident when titers were plotted against time of blood collection preceding diagnosis. Our results do not suggest EBV activation in the period preceding NPC diagnosis, nor that detectable IgA antibody against VCA is a marker for early disease.

Adult