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T Tønnesen

Publications and source records attributed to T Tønnesen.

At least 19 recordsLinked to original sources
PubMed1997

Highly effective second-line anti-Helicobacter pylori therapy in patients with previously failed metronidazole-based therapy.

BACKGROUND: In this study we compared the cure rates of two clarithromycin-based regimens in patients in whom anti-Helicobacter pylori therapy had previously failed. METHODS: Thirty-three patients were randomized to receive either regimen OAC (20 mg omeprazole, 750 mg amoxicillin, and 250 mg clarithromycin) or BTC (240 mg bismuth subcitrate, 750 mg oxytetracycline, and 250 mg clarithromycin), all twice daily for 10 days. A further 28 patients were all treated with OAC. Previously failed therapy included combinations of bismuth (B), omeprazole (O), tetracycline (T), metronidazole (M), amoxicillin (A), or clarithromycin (C) in BTM (n = 48), OAM (n = 13), OA (n = 7), OCM (n = 2), or BCM (n = 1). H. pylori infection was confirmed by culture of biopsy specimens, and antimicrobial susceptibility testing was performed with the E test. RESULTS: H. pylori infection was cured in all patients (n = 18) with OAC and in 8 patients (53%) with BTC (P = 0.001) in the randomized group and in 27 patients (96%) receiving OAC in the open-label group. CONCLUSIONS: Ten-day OAC is highly effective and superior to BTC in patients in whom metronidazole-based treatment has previously failed.

Adult↗
PubMed1997

Identification of point mutations in 41 unrelated patients affected with Menkes disease.

Genomic DNA of 41 unrelated patients affected with the classical severe form of Menkes disease was investigated for point mutations in the ATP7A gene (previously designated as the "MNK" gene). Using SSCP analysis and direct sequencing of the exons amplified by PCR, we identified 41 different mutations, including 19 insertions/deletions, 10 nonsense mutations, 4 missense mutations, and 8 splice-site alterations. Approximately 90% of the mutations were predicted to result in the truncation of the protein (ATP7A). In 20 patients the mutations were within exons 7-10, and half of these mutations affected exon 8. Furthermore, five alterations were observed within the 6-bp sequence at the splice-donor site of intron 8, which would be predicted to affect the efficiency of splicing of exon 8. Although a specific function has not been attributed to the protein region encoded by this exon, this region may be important in serving as a "stalk" joining the metal-binding domains and the ATPase core. The present findings not only help us in understanding the underlying genetic defect but are invaluable data especially for carrier detection and prenatal diagnosis of this lethal disorder.

Adenosine Triphosphatases↗
PubMed1995

Characterization of the exon structure of the Menkes disease gene using vectorette PCR.

The gene defective in Menkes disease, an X-linked recessive disturbance of copper metabolism, has been isolated and predicted to encode a copper-binding P-type ATPase. We determined the complete exon-intron structure of the Menkes disease gene, which spans about 150 kb of genomic DNA. The gene contains 23 exons, and the ATG start codon is in the second exon. All of the exon-intron boundaries were sequenced and conformed to the GT/AT rule, except for the 5' splice site of intron 9. A preliminary comparison demonstrated a striking similarity between the exon structures of the Menkes and Wilson disease genes, giving insight into their evolution.

Adenosine Triphosphatases↗
PubMed1995

Effects of naloxone on glucagon and insulin concentrations after injection of endotoxin in rats.

OBJECTIVE: To find out how infusions of endotoxin and endotoxin plus naloxone affected glucose, glucagon, and insulin concentrations in rats. DESIGN: Random control study. SETTING: University hospital, Norway. MATERIAL: 27 Male Wistar rats. INTERVENTIONS: 8 Rats were given Escherichia coli endotoxin 0.25 mg in saline; 5 were given a naloxone infusion (0.4 ml of 0.04 mg/ml for the first half hour and continued at a rate of 0.4 ml/hour for a total of 80 minutes) starting 10 minutes before the same dose of endotoxin; 6 were given saline alone for 70 minutes, and 8 saline alone for 10 minutes. Blood was taken for analysis after 70 minutes in the first three groups and at the end of the infusion in the 10 minute group. MAIN OUTCOME MEASURES: Serum concentrations of glucose, glucagon, and insulin compared with baseline (10 min group). RESULTS: Median (interquartile) concentrations of all three substances rose significantly 70 minutes after the injection of endotoxin compared to basal values: 9.8 (8.2-10.9) compared with 6.0 (4.8-7.5) mmol/l for glucose (p < 0.01); 53.1 (44.6-56.0) compared with 3.6 (3.1-5.1) ng/l for glucagon; and 39.4 (38-50.4) compared with 16.7 (11.2-25.5) pmol/l for insulin. When naloxone was combined with endotoxin glucagon and insulin concentrations were significantly lower: 24.3 (23.9-37.5) ng/l (p < 0.01), and 30.6 (24.5-31.6 pmol/l (p < 0.05), respectively. The concentration of glucose in venous blood was unchanged. CONCLUSIONS: The rise in glucagon and insulin concentrations after endotoxin infusions may be partly mediated by opioids. Naloxone in the dose given did not abolish the increase in glucagon after endotoxin. The high glucagon:insulin ratio after both endotoxin alone and endotoxin plus naloxone may be important in the aetiology of the hyperglycaemia seen.

Animals↗
PubMed1994

Morphine effects on the release of glucagon, insulin and somatostatin from the isolated, perfused rat pancreas.

The pancreatic glands from six male Wistar rats weighing between 200 and 250 g were isolated and perfused. After 30-min equilibration and 20-min basal periods, perfusion with 0.2 mg/ml of morphine for 20 min resulted in a significant (P < 0.05) increase in insulin release, with no changes in release of gucagon or somatostatin. After a recovery period of 20 min, a higher morphine concentration of 2 mg/ml was introduced for another 20-min period. With this morphine dose there were significant increases in release of insulin (P < 0.05), glucagon (P < 0.01) and somatostatin (P < 0.05). This shows that morphine induces the release of insulin, glucagon and somatostatin from pancreas in a dose-dependent way, and that release of insulin and glucagon is not primarily affected by regulation of somatostatin levels.

Animals↗
PubMed1994

First trimester prenatal diagnosis of Menkes disease by DNA analysis.

Menkes disease is an X linked recessive disorder of copper metabolism characterised by neurological symptoms and connective tissue manifestations. The defective gene in Menkes disease has recently been isolated and the gene product is predicted to be a copper transporting ATPase. The diagnosis of Menkes disease has hitherto been performed by biochemical analysis, based on intracellular accumulation of copper. Cloning the gene opened up the possibility of establishing precise and reliable carrier and prenatal diagnosis by defining the molecular defect. In this report we describe the partial deletion of the Menkes gene in a patient who had inherited the mutation from his phenotypically normal mother. This information enabled us to perform prenatal diagnosis by direct mutation analysis of the mother's sixth pregnancy and we detected the same deletion, indicating that the male fetus was affected. This first prenatal diagnosis of Menkes disease by direct mutation analysis shows some advantages of DNA analysis compared to biochemical diagnosis.

Abortion, Induced↗
PubMed1994

Haemorrhage-induced increases in glucose, glucagon and insulin levels are blocked by naloxone in rats.

OBJECTIVE: To find out if the opioids that are liberated during bleeding influence the concentrations of glucagon, insulin, somatostatin, corticosterone and glucose in rats, and if naloxone has any regulatory effect. DESIGN: Laboratory study. SETTING: University hospital. MATERIAL: 56 Male Wistar rats. INTERVENTIONS: Removal of blood corresponding to 2% of body weight through a catheter in the internal jugular vein. Before bleeding (n = 8), and at 5, 15 and 30 minutes afterwards (n = 16 at each time point, half of which had received naloxone 0.04 mg/ml, 0.7 ml/hour, for 10 minutes before bleeding and up to 30 minutes afterwards) rats were killed and samples of heart blood taken. MAIN OUTCOME MEASURES: Concentrations of glucose, glucagon, insulin, somatostatin, and corticosterone in heart blood. RESULTS: In the control group (saline) concentrations of glucose, glucagon and insulin increased significantly after bleeding, and had returned to baseline concentration by 30 minutes. Naloxone blocked the increases in the treated group. CONCLUSION: Endogenous opioids, possibly endorphin, may be important in the acute regulation of blood glucose, glucagon and insulin concentrations after haemorrhage.

Animals↗
PubMed1993

Clinical and biochemical consequences of copper-histidine therapy in Menkes disease.

Menkes disease (MD) is an X-linked recessively inherited neurodegenerative disorder of copper (Cu) metabolism leading to death in early childhood. Symptoms are attributed to deficient activity of Cu-dependent enzymes. Limited experience has been reported concerning clinical and biochemical consequences of parenteral treatment with copper-(histidine)2-complex (Cu-His) in MD. Cu-His was administered in a 13-week-old boy with MD by daily intramuscular injections. After 6 weeks of therapy, Cu and caeruloplasmin in serum and Cu in CSF were normalized. The excessive dopamine level in CSF was corrected after 3 months of treatment. After 6 weeks of Cu supplementation, complete reduction of epileptic discharges, improved muscular tone and increased motor activities were observed. Developmental regression stopped and was replaced by a slight progression. Death at the age of 19 months was caused by septicaemia due to a fulminant urinary tract infection; there was no evidence of chronic Cu toxicity. These findings suggest that Cu-His supplementation may be a promising palliative treatment in MD.

Bone and Bones↗
PubMed1993

Comparison of the modifying effects of somatostatin and propranolol on morphine-induced changes in glucose, glucagon and insulin levels in fed rats.

Twenty-eight rats in four different groups were used. Catheters were implanted in the carotid artery and jugular vein one week before the experiments were performed. The rats were trained to the experimental situation daily, and allowed food and water ad libitum. One group of rats was used to establish control values; a second was injected with morphine (10 mg/ml, 1 ml/kg); a third group got morphine injection (10 mg/ml, 1 ml/kg) combined with somatostatin infusion (0.01 mg/ml, 1 ml/h); and the fourth group was injected with morphine (10 mg/ml, 1 ml/kg) combined with propranolol (0.4 ml, 1 mg/ml). Blood samples for venous glucose and arterial insulin and glucagon were drawn 15 min after start of stimulation. Glucose, insulin and glucagon levels were significantly higher in morphine treated than in control rats. When morphine was combined with somatostatin, the increase in glucose, insulin and glucagon was significantly reduced. However, after the morphine and propranolol stimulation the increase in glucose and glucagon was significantly reduced, whereas the insulin levels were as high as when morphine was given alone. The combined reduction of both glucagon and glucose after somatostatin or propranolol treatment in morphine exposed rats, points to glucagon as a potential link between opioid stimulation and hyperglycemia. Beta-receptor stimulation seems to contribute to the glucagon but not to the insulin release after morphine.

Animals↗
PubMed1993

Isolation of a candidate gene for Menkes disease that encodes a potential heavy metal binding protein.

Menkes disease is a lethal-X linked recessive disorder associated with copper metabolism disturbance. We have recently mapped two chromosome breakpoints related to this disease in a 1 megabase yeast artificial chromosome contig at Xq13.3. We now report the construction of a phage contig and the isolation of candidate partial cDNAs for the Menkes disease gene. The candidate gene expresses an 8 kb message in all investigated tissues, and deletions were detected in 16% of 100 unrelated Menkes patients. The deduced partial protein sequence shared the GMTCXXC motif with bacterial metal resistance operons, suggesting a potential heavy metal binding protein. These findings should lead to more accurate prenatal diagnosis of this severe disease and a better understanding of the cellular homeostasis of essential heavy metals.

Adenosine Triphosphatases↗
PubMed1993

Morphine and morphine/naloxone modification of glucose, glucagon and insulin levels in fasted and fed rats.

In rats weighing 200-250 g catheters were placed in the internal jugular vein and carotid artery. After 1 week of accommodation the training for the experimental situation, morphine (10 mg kg-1) was injected intravenously alone or in combination with naloxone (0.04 mg ml-1, 0.8 ml h-1). Otherwise no form of anaesthesia was used during the experiments. In control fed and fasted rats, there were no significant differences in blood glucose. In fed rats, morphine increased blood glucose as compared to control rats (p < 0.001). This was not seen in the fasted rats. The morphine induced increase in blood glucose in the fed rats was abolished by naloxone (p < 0.001). Glucagon was significantly higher in fasted than in fed control rats (p < 0.01). It was significantly increased after morphine in fed (p < 0.05), but not in fasted rats. The morphine induced increase in glucagon in fed rats was abolished by naloxone (p < 0.01). Insulin was significantly higher in fed than in fasted control rats (p < 0.05). Morphine increased insulin levels significantly in fed and fasted rats (p < 0.001), p < 0.01). The morphine induced increase in insulin in the fed rats was abolished by naloxone treatment. It is concluded that morphine stimulates glucose and glucagon release in fed but not fasted rats, and that these increases are caused by opioid action. Insulin increases after morphine were proved to be opioid-mediated only in the fed state.

Animals↗
PubMed1993

Compound heterozygosity for metachromatic leukodystrophy and arylsulfatase A pseudodeficiency alleles is not associated with progressive neurological disease.

Several allelic mutations at the arylsulfatase A (ASA) locus cause substantial deficiencies of this lysosomal enzyme. Depending on the genetically determined degree of the deficiency, the clinical outcome may be very different--either metachromatic leukodystrophy (MLD), a lethal lysosomal storage disorder affecting the nervous system, or, more frequently, the so-called pseudodeficiency (PD), which has no apparent clinical consequence. Because of compound heterozygosity for MLD and PD, 1/1,000 individuals in the population have low residual enzyme activities, which are intermediate between those of MLD patients and those of PD homozygous normal individuals. In order to assess whether PD/MLD compound heterozygotes bear a health risk, we examined clinically and biochemically 16 individuals with this genotype. Of these subjects, two had neurological symptoms and two showed lesions, without clinical symptoms, in magnetic resonance imaging of the brain. None of these symptoms was progressive, nor did they resemble those of MLD. Nerve conduction velocities were normal in these probands, and they secreted only low amounts of sulfatide in the urine. We conclude that the observed neurological symptoms are unrelated to the ASA genotype and that PD/MLD compound heterozygotes are not at an increased risk for developing progressive nervous system diseases.

Adolescent↗
PubMed1992

Mapping of the Menkes locus to Xq13.3 distal to the X-inactivation center by an intrachromosomal insertion of the segment Xq13.3-q21.2.

During a systematic chromosomal survey of 167 unrelated boys with the X-linked recessive Menkes disease (MIM 309400), a unique rearrangement of the X chromosome was detected, involving an insertion of the long arm segment Xq13.3-q21.2 into the short arm at band Xp11.4, giving the karyotype 46,XY,ins(X) (p11.4q13.3q21.2). The same rearranged X chromosome was present de novo in the subject's phenotypically normal mother, where it was preferentially inactivated. The restriction fragment length polymorphism and methylation patterns at DXS255 indicated that the rearrangement originated from the maternal grandfather. Together with a previously described X;autosomal translocation in a female Menkes patient, the present finding supports the localization of the Menkes locus (MNK) to Xq13, with a suggested fine mapping to sub-band Xq13.3. This localization is compatible with linkage data in both man and mouse. The chromosomal bend associated with the X-inactivation center (XIC) was present on the proximal long arm of the rearranged X chromosome, in line with a location of XIC proximal to MNK. Combined data suggest the following order: Xcen-XIST(XIC), DXS128-DXS171, DXS56-MNK-PGK1-Xqter.

Adult↗
PubMed1992

Increments in glucose, glucagon and insulin after morphine in rats, and naloxone blocking of this effect.

In awake rats adapted to experimental conditions and allowed food ad libitum, hyperglycemia was induced by the administration of morphine 10 mg/kg through indwelling catheters in the external jugular vein. High glucose values were measured at 5, 15 and 25 min. Glucagon values were high at 5 and 15 min, and again at basal level at 25 min. Insulin was increased after morphine both at 5, 15 and 25 min, whereas somatostatin levels did not change after morphine. When morphine was administered together with naloxone after an initial 10 min period of naloxone administration, there was no increment in glucose, insulin or somatostatin values; neither at 5, 15 or 25 min. There was a remarkable glucagon decrease after naloxone and morphine remaining from 5 to 25 min. Then, one of the possible mechanisms for the hyperglycemic response after morphine may be an opioid effect on pancreas, stimulating glucagon and thereby causing hepatic glucose output.

Animals↗
PubMed1992

Characterization of a 1.0 Mb YAC contig spanning two chromosome breakpoints related to Menkes disease.

Menkes disease, an X-linked recessive disorder of copper metabolism, has recently been mapped to Xq13.3 by two Menkes patients carrying chromosome rearrangements within this region. The breakpoints have been investigated by nonisotopic in situ suppression hybridization using YACs isolated from this region with the flanking markers DXS56 and PGK1. Three YACs were extending over the breakpoints at Xq13.3 and were shown to be overlapping by partial digest restriction maps, IRS-PCR fingerprinting and by the presence of common cosmid clones. These cosmids were subcloned and one of the single copy probes detected both breakpoints using rare-cutting restriction enzyme digests of the patients. All the results together localize the breakpoints to about 100 kb within the overlapping region of the YACs. Mapping of both breakpoints in a 1 Mb YAC contig implies that these YACs contain at least partially, the gene responsible for Menkes disease.

Chromosome Aberrations↗