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B Eriksson

Publications and source records attributed to B Eriksson.

At least 73 records · Page 4Linked to original sources
PubMed1999

Summing up 15 years of somatostatin analog therapy in neuroendocrine tumors: future outlook.

Neuroendocrine gastrointestinal tumors express somatostatin receptors (ssts) in 80%-90% of cases and somatostatin analogs have become increasingly important in the management of these patients. Most of the presently available somatostatin analogs (octreotide, RC-160, and lanreotide) bind to the sst2 and sst5, and in higher doses to sst3 of the ssts 1-5 described. Clinical improvement during somatostatin analog therapy is mainly mediated via a direct inhibitory effect on hormone production from the tumors, seen in 30%-70% of the patients. Also indirect non-tumor mediated effects on peripheral target organs contribute to the subjective improvement, achieved in 30%-70% of patients. Recently, significant improvement of quality of life has been demonstrated with long-acting depot formulations. There is little or no effect on tumor growth during octreotide therapy; tumor shrinkage has been reported in 10%-20% of patients, but stabilization of tumor growth can be achieved in about half of the patients with a duration of 8-16 months. Recently, induction of apoptosis has been described with high doses of lanreotide (12 mg/d). Eventually, however, all patients escape from somatostatin analog therapy with regard both to hormonal production and tumor growth, and the mechanism behind the tachyphylaxis is not yet known. Studies of optimal dosage and modes of administration, development of new slow release formulations, the potential value of high-dose somatostatin analog therapy and novel somatostatin receptor subtype specific analogs are important directions for the use of somatostatin analogs in the future. In addition, assessment of somatostatin receptor status for each patient and studies of tumor biology, e.g., inhibition of exocytosis, antiproliferative effects and induction of apoptosis during treatment will help to optimize treatment and provide new insights into mechanisms of action of somatostatin analogs.

Animals↗
PubMed1999

Streptococcal DNase B is immunologically identical to superantigen SpeF but involves separate domains.

The previous suggestion that streptococcal superantigen SpeF might be identical to DNase B was confirmed in this study. Polyclonal SpeF-specific antisera were able to inhibit depolymerization of methyl-green DNA by DNase B. However, T-cell mitogenicity and nuclease activity appear to involve separate immune epitopes on SpeF, since sera with the capacity to neutralize the mitogenic activity of SpeF did not always inhibit the DNase activity.

Animals↗
PubMed1999

Suggested minimal effective dose of risperidone based on PET-measured D2 and 5-HT2A receptor occupancy in schizophrenic patients.

OBJECTIVE: Multicenter trials with the novel antipsychotic risperidone have suggested a standard dose of 6 mg/day. However, a dose producing the highest response rate in fixed-dose studies is likely to exceed the minimal effective dose in most patients. The aim of this positron emission tomography (PET) study was to suggest a minimal effective dose of risperidone based on measurements of dopamine D2 and serotonin 5-HT2A receptor occupancy. METHOD: Eight first-episode or drug-free schizophrenic patients were treated with risperidone, 6 mg/day, for 4 weeks and then 3 mg/day for 2 weeks. PET was performed after 4 and 6 weeks, with [11C]raclopride to measure D2 receptor occupancy and [11C]N-methylspiperone to measure 5-HT2A receptor occupancy. RESULTS: Seven patients completed the study and responded to treatment with risperidone. No patient had extrapyramidal side effects at the time of inclusion in the study. At the 6-mg/day dose, mean D2 receptor occupancy was 82% (range = 79%-85%), 5-HT2A receptor occupancy was 95% (range = 86%-109%), and six patients had developed extrapyramidal side effects. After dose reduction to 3 mg/day, D2 receptor occupancy was 72% (range = 53%-78%), and 5-HT2A receptor occupancy was 83% (range = 65%-112%). Three patients had extrapyramidal side effects at this time. CONCLUSIONS: Treatment with risperidone, 6 mg/day, is likely to induce unnecessarily high D2 receptor occupancy, with a consequent risk of extrapyramidal side effects. High 5-HT2A receptor occupancy did not prevent extrapyramidal side effects completely. The authors previously suggested an optimal interval for D2 receptor occupancy of 70%-80%. To achieve this, resperidone, 4 mg/day, should be a suitable initial dose for antipsychotic effect with a minimal risk of extrapyramidal side effects in most patients.

Adult↗
PubMed1999

Efficacy and safety of prolonged-release lanreotide in patients with gastrointestinal neuroendocrine tumors and hormone-related symptoms.

PURPOSE: To evaluate the prolonged release (PR) of the long-acting somatostatin analog lanreotide in patients with gastrointestinal neuroendocrine tumors and its effect on hormone-related symptomatology, tumor markers, tumor size, tolerability, and quality of life (QOL). PATIENTS AND METHODS: Eligible patients had the following substantial daily symptoms: for patients with carcinoid tumors, three or more stools and/or 1.5 or more flushing episodes; for patients with gastrinoma, greater than 50% elevated basic acid output; and for patients with vasoactive intestinal peptide-secreting tumors (VIPomas), four or more stools and/or a stool volume of >/= 800 mL, a measurable tumor, and an elevated biochemical tumor marker (>/= two times the upper limit of the normal reference range). Lanreotide PR was administered intramuscularly every 14 days at 30 mg for 6 months. We measured efficacy by studying symptoms, tumor markers, tumor size, and QOL. Side effects were scored according to the National Cancer Institute's toxicity grading system and ultrasound examination of the gallbladder. RESULTS: Fifty-five patients were included in the study (48 patients with carcinoid tumors, six patients with gastrinoma, and one patient with VIPoma). Symptomatic improvement (> 50% reduction) occurred in 38% of the assessable patients with carcinoid tumors, in 67% of the gastrinoma patients, and in the VIPoma patient. Tumor markers normalized in two of 45 assessable patients, 19 patients exhibited a reduction (> 50%), 19 patients exhibited no change, and tumor markers rose by more than 50% in five patients. Tumor size was reduced in two of 31 assessable patients and remained stable in 25 patients; four patients experienced progression. QOL assessments after 1 month showed improvements in emotional and cognitive function, and diminished fatigue, sleeping disorders, and diarrhea. Eight of 30 assessable patients developed gallstones. CONCLUSION: Lanreotide PR is a well-tolerated somatostatin analog with significant clinical, biochemical, and antitumor effects that bring about a significant improvement in QOL for patients with neuroendocrine tumors.

Adult↗
PubMed1999

Plasma chromogranin A in patients with multiple endocrine neoplasia type 1.

Plasma chromogranin A (CgA) has been claimed to be a sensitive marker for neuroendocrine tumors, but its role in the early diagnosis of multiple endocrine neoplasia type 1 (MEN 1) pancreatic endocrine tumors has not been evaluated. We measured CgA in 36 patients with MEN 1, of whom 9 lacked pancreatic involvement, 20 had biochemical evidence of pancreatic endocrine tumors, and 7 displayed radiologically detectable pancreatic tumors. CgA was also analyzed in 25 patients with sporadic pancreatic endocrine tumors, 39 subjects with inflammatory bowel disease, 7 patients harboring nonendocrine pancreatic disease, and 19 healthy controls. Four of 9 of the MEN 1 patients without pancreatic involvement had elevated CgA. Furthermore, 60% with biochemically unequivocal tumors and all with a radiologically visible tumor showed elevations. All 25 patients with sporadic pancreatic endocrine tumor had increased CgA, as had 28% of patients with inflammatory bowel disease and 57% with nonendocrine pancreatic disease. Mean day to day CgA variation was 29% (range, 0-113%) in the neuroendocrine tumor patients and 21.0% (range, 0.0-47%, within reference range) among healthy controls. In summary, nonendocrine diseases may cause elevation of CgA, and its spontaneous variation can be considerable. Plasma chromogranin A is the most sensitive of the basal markers for neuroendocrine tumors, but cannot replace other established measures when screening for early pancreatic involvement in MEN 1.

Adult↗
PubMed1999

Longer delays in tuberculosis diagnosis among women in Vietnam.

SETTING: Study conducted in 23 randomly selected districts in four provinces of Vietnam. OBJECTIVE: To describe and compare health seeking behaviour between men and women and to measure delays in tuberculosis (TB) diagnosis. DESIGN: All patients (n = 1027) aged 15-49 years with new smear-positive pulmonary TB detected in the selected districts during 1996 were interviewed using a structured questionnaire. RESULTS: Mean total delay to TB diagnosis was 13.3 weeks (95% confidence interval [CI] 11.5, 15.1) for women and 11.4 weeks (95% CI 10.6, 12.2) for men, including a patient's delay of 7.9 weeks (95% CI 6.5, 9.3) and 7.6 weeks (95% CI 6.9, 8.3) respectively. Doctor's delay was significantly longer among women (5.4 weeks, 95% CI 4.2, 6.6) than among men (3.8 weeks, 95% CI 3.3, 4.3). Women did not start seeking care later than men, nor did they have a different health seeking pattern. Women visited more health care providers than men (1.7 and 1.5 providers, respectively, P = 0.02). CONCLUSION: Patient's delay is unacceptably long for both men and women. Women do not receive a diagnosis of TB by doctors or other health care providers as quickly as men once they seek health care. The reasons for this gender difference warrant further investigations.

Adolescent↗
PubMed1999

Genetic alterations on 3p, 11q13, and 18q in nonfamilial and MEN 1-associated pancreatic endocrine tumors.

Pancreatic endocrine tumors occur sporadically and as part of the multiple endocrine neoplasia type 1 (MEN 1) and von Hippel-Lindau (VHL) syndromes. The MEN1 locus on 11q13 and a candidate tumor suppressor locus on 3p are known to be hemi- or homozygously mutated in a subset of these tumors. Chromosome arm 18q harbors the SMAD4/DPC4 tumor suppressor gene that is frequently deleted and inactivated in tumors of the exocrine pancreas. We have analyzed 22 nonfamilial and 16 MEN 1-associated pancreatic endocrine tumors for loss of heterozygosity (LOH) at 3p, 11q13, and 18q. LOH at 3p was revealed in 45% and 36% of tumors from 31 patients with nonfamilial and MEN 1-associated disease, respectively. The corresponding proportions for 11q13 were 55% and 91%, and for 18q 27% and 25%, respectively. A striking relation between LOH at 11q13 and 3p and a malignant phenotype was found for the nonfamilial tumors. None of the six benign tumors (all of them insulinomas) had allelic loss at 3p or 11q13, whereas 92% (P < 0.01) of the malignant tumors (including malignant insulinomas) had such deletions. Besides the 11q13 abnormality, more than half of the MEN 1-associated tumors had additional genetic lesions affecting 3p or 18q. LOH analysis of several tumors from two MEN 1 patients suggested different clonal origin of the lesions. Sequencing of the SMAD4/DPC4 gene did not identify mutations in coding regions or at exon/intron boundaries in tumors with LOH at 18q. The data indicate involvement of tumor suppressor genes on 3p and 18q, in addition to the MEN1 gene at 11q13, in the tumorigenesis of both nonfamilial and MEN 1-associated pancreatic endocrine tumors.

Biomarkers, Tumor↗
PubMed1999

Tumour markers in neuroendocrine tumours.

Most of the neuroendocrine tumours produce and secrete a large number of peptide hormones and amines. Each of these substances cause a specific clinical syndrome: carcinoid, Zollinger-Ellison, hyperglycaemic, glucagonoma and WDHA syndrome. Specific markers for these syndromes are basal and/or stimulated levels of: urinary-5-HIAA, serum or plasma gastrin, insulin, glucagon, and VIP, respectively. About 1/3 of neuroendocrine tumours belong to the so-called "non-functioning" tumours. Therefore, general markers such as chromogranin A, pancreatic polypeptide, serum neuronspecific enolase and subunit of glycoprotein hormones have been used for screening purposes in patients without distinct clinical hormone related syndromes. Among these general tumour markers chromogranin A, although its precise function is not yet established, has been shown to be a very sensitive and specific serum marker for various types of neuroendocrine tumours. This is because it may also be increased in many cases of less well differentiated tumours of neuroendocrine origin that do not secrete known hormones. Then chromogranin A is considered the best general neuroendocrine serum or plasma marker available at the moment and is increased in 50-100% of patients with various neuroendocrine tumours. Chromogranin A serum or plasma levels reflect tumour load and may be an independent marker of prognosis in patients with midgut carcinoids.

Biomarkers, Tumor↗
PubMed1999

Positron emission tomography in neuroendocrine tumours.

Positron emission tomography is an in vivo tracer and imaging technique that utilizes short-lived positron emitting radionuclides (11C, 15O, 13N, 18F) with half-lives ranging between 2 min and 2 hours. These radionuclides are interesting from the labelling viewpoint since they are natural constituents of most biologically active compounds. The short half-life is an advantage with regard to the irradiation dose to the patient but it is also a limitation since it requires the production of these radionuclides in close vicinity to the positron emission tomography camera.

Female↗
PubMed1998

Transgenic Cre recombinase expression in germ cells and early embryogenesis directs homogeneous and ubiquitous deletion of loxP-flanked gene segments.

We report on the establishment of a transgenic mouse line expressing Cre recombinase under control of the c-kit promoter. Expression of Cre recombinase was only observed in late spermatogenesis and oogenesis, however, Cre-mediated deletion of floxed gene segments occurred at this stage as well as in early embryogenesis. As a consequence of this, a chimeric distribution of loxed alleles was found in a large fraction of these mice. The chimerism was very homogeneous in different organs and tissues of the same individual but varied between different individual offspring. The potential uses for this mouse line are discussed.

Alleles↗
PubMed1998

Effects of the GABA agonists baclofen and THIP on long-term compensation in hemilabyrinthectomised rats.

Horizontal eye movements, elicited by sinusoidal rotation in darkness, were recorded with a magnetic search coil technique in pigmented rats, hemilabyrinthectomised 8-12 weeks before the investigation. Separate gains during rotation towards the lesioned side (LS) and the intact side (IS) were calculated by a computer program, demonstrating an asymmetry. Systemic single administration of the GABAB agonist baclofen caused a dose-related temporary rebalancing of the compensatory eye movements to the LS and the IS. At an optimal dose of 14 micromol/kg b.wt symmetry was achieved by excitation of eye movements during rotation to the LS and depression during rotation to the IS. Administration of the GABAA agonist THIP did not obviously reduce the asymmetry. It is suggested that stimulation of GABAB receptors modifies the tonic imbalance between the bilateral vestibular nuclei and/or the central processing of the input from the peripheral sensory organs.

Animals↗
PubMed1998

Limited tumor involvement found at multiple endocrine neoplasia type I pancreatic exploration: can it be predicted by preoperative tumor localization?

Radiologically demonstrable pancreatic endocrine tumors are a frequent requirement for exploration in patients with multiple endocrine neoplasia type I (MEN-I). Such delayed intervention is accompanied by a 30% to 50% incidence of pancreatic endocrine metastases. This study explores biochemical tumor markers and operative findings in relation to preoperative pancreatic radiology in 25 MEN-I patients. They underwent pancreatic surgery with (n = 19) or without (n = 6) radiologic signs of primary tumor and absence of metastases upon conventional examination, including OctreoScan testing (n = 10). Biochemical diagnosis required an increasing elevation of at least two independent pancreatic tumor markers. Tumor diameters averaged 1.1 cm (0-5 cm) and 0.9 cm (0.2-1.5 cm) in the patients with and without positive preoperative radiology, respectively. These investigations never displayed more than one of the consistently multiple tumors, and the results were falsely positive in 26%. Preoperatively unidentified regional or hepatic metastases were found at surgical exploration in 26% of patients with radiologic localization and in none of the others. Limited pancreatic tumor involvement necessitated intraoperative absence of metastases and pancreatic lesions </= 1 cm in diameter on palpation, intraoperative ultrasonography, and microscopy. It occurred in 37% and 50% of the patients with and without radiologic tumor localization, respectively. The number of positive tumor markers was similar for patients with limited and major disease (2.3 vs. 2.7), whereas four or more such markers were found in all those with malignancies. The mean marker level was higher in patients with radiologically demonstrable tumors and lower in those with limited disease, but with a substantial overlap. OctreoScan testing was negative in all cases with limited disease and was the single most sensitive method (75%) in the others. Limited pancreatic disease could not be identified preoperatively, and the present means of biochemical pancreatic tumor identification invariably involved the presence of at least one lesion >/= 7 mm in diameter. Conventional pancreatic imaging is insensitive and nonspecific for recognizing even substantial pancreatic tumors associated with MEN-I.

Adult↗
PubMed1998

Selective effects of somatostatin analogs on human drug-metabolizing enzymes.

Pharmacologic or surgical manipulation with growth hormone secretion or with the physiologic release of somatostatin and growth hormone-releasing hormone affects some rat liver enzymes, especially the sex-differentiated ones. We investigated the effects of two somatostatin analogs on several enzyme functions in six patients with carcinoid syndrome, using codeine as a probe drug. Codeine was given intravenously and its N- and O-demethylation, as well as 6-glucuronidation catalyzed by CYP3A, CYP2D6, and uridine diphosphate-glucuronosyltransferase, respectively, were studied before and during treatment with somatostatins. After 3 days of treatment with somatostatins the partial metabolic clearance of codeine by N-demethylation decreased by 21% to 64% in all patients (mean change, 44%; p < 0.05), and the clearance by O-demethylation was decreased by 20% to 69% in five of the patients (mean change in all patients, 35%; p < 0.05). In contrast, the partial clearance by 6-glucuronidation and the total systemic clearance of codeine were unchanged. Our results may be caused by the inhibition of growth hormone secretion induced by the somatostatins, inasmuch as direct metabolic interactions with these peptide drugs are improbable. The decline in CYP3A4 and CYP2D6 activity might have clinical implications when substrates of these enzymes with low therapeutic indices are combined with somatostatin analogs. Because the formation of morphine from codeine was altered, the analgesic effect of this drug may be reduced during concomitant treatment with somatostatins.

Adult↗
PubMed1998

Pharmacokinetics of 14C-delmopinol in the healthy male volunteer.

1. The absorption and excretion of delmopinol, an inhibitor of plaque formation and gingivitis, were studied in healthy male volunteers. Each subject received a single dose of a 10-ml aqueous solution of 14C-delmopinol at 2 mg/ml as a 1-min mouth rinse (the intended route of administration; n=6) or as an oral dose (n=6). 2. After mouth rinsing, 72% of the dose was expectorated. The retained portion of the dose was rapidly absorbed and eliminated. Of the dose, 25% was recovered in the urine. Renal excretion was predominant also after oral administration with 92% of the dose excreted in the urine. The total recovery of 14C-activity after 6 days was 99% (rinsing) and 95% (oral) with the bulk, 20% (rinsing) and 80% (oral), of the dose excreted already within 8 h. 3. Peak plasma levels of 14C-labelled compounds were attained at 1.5 h after rinsing and 0.5 h after oral administration; total concentrations were approximately 200 and 3000nmol/l, respectively. For parent delmopinol, peak plasma levels of 49 nmol/l (rinsing) and 8 nmol/l (oral) occurred after 1.5 and 1.3 h, respectively. After rinsing, the concentration of delmopinol declined with a half-life of 2.4 h. The plasma level of 14C-labelled compounds declined multiphasically. In the terminal elimination phase (after 72 h) remaining radioactivity, < 2% of dose (rinse) and < 5% of dose (oral), decreased with a half-life of approximately 130 and 160 h, respectively. 4. Results indicate a very low bioavailability (1-3%) due to extensive first-pass metabolism of delmopinol after oral administration. A high plasma clearance (> 60 l/h) and a large volume of distribution (> 200 l) were also indicated. 5. The results of rapid and almost complete recovery in the urine support that delmopinol can safely be used in the treatment of patients with plaque or gingivitis.

Administration, Oral↗
PubMed1998

Life events, mood, mental strain and cardiovascular risk factors in Swedish middle-aged men. Data from the Swedish part of the Renault/Volvo Coeur Study.

The associations between life events, mood, mental strain and cardiovascular risk factors were investigated in the Renault/Volvo Coeur Study. About 1,000 men, blue-collar and white-collar workers, were asked by means of interview-administered questionnaires about life events experienced during the year preceding the screening, about mood and mental strain and about smoking, alcohol consumption and exercise habits. Blood pressure, concentration of serum lipids and blood glucose, and anthropometric measures were determined in a screening procedure. Negative life events, especially work-related, were associated with depressed mood and mental strain but not with elevation of biological risk factors such as elevated blood pressure and serum lipids. Depressed mood and mental strain were related to increased tobacco consumption in blue-collar workers and increased alcohol consumption in white-collar workers.

Adult↗
PubMed1998

Long-term neurological dysfunction and neonatal hypoglycaemia after diabetic pregnancy.

AIM: To determine if children born to mothers with diabetes mellitus during pregnancy, who subsequently developed neonatal hypoglycaemia, experienced long-term neurological dysfunction. METHODS: Thirteen children with, and 15 without, neonatal hypoglycaemia (blood glucose < 1.5 mmol/l) were randomly selected from a larger cohort and investigated at the age of 8 years. They were also compared with 28 age matched healthy controls. RESULTS: Children with neonatal hypoglycaemia had significantly more difficulties in a validated screening test for minimal brain dysfunction than controls and were also more often reported to be hyperactive, impulsive, and easily distracted. On psychological assessment, they had a lower total development score than normoglycaemic children born to diabetic mothers, and control children. CONCLUSIONS: Neonatal hypoglycaemia in diabetic pregnancy was associated with long-term neurological dysfunction related to minimal brain dysfunction/deficits in attention, motor control, and perception.

Adult↗