Positron-emission tomography as a radiological technique in neuroendocrine gastrointestinal tumors.
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5-Hydroxytryptophan↗
Biomedical subjects
B Eriksson
Publications and source records attributed to B Eriksson.
The clinical use of interferons in the management of neuroendocrine gastroenteropancreatic tumors.
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Carcinoid Tumor↗
Effects of GABAB activation and inhibition on vestibulo-ocular and optokinetic responses in the pigmented rat.
The effects of the GABAB agonist baclofen and the GABAB antagonist CGP 35348, given separately or simultaneously, on the central vestibular system of pigmented rats have been evaluated. Drugs were administered either intramuscularly or intracerebroventricularly. Eye movements were recorded during vestibular, optokinetic and combined visual-vestibular stimulation. Activation of the GABAB receptors by baclofen caused a dose related disturbance of the system, manifested by (1) a decrease of the optokinetic gain, (2) a reduced ability to suppress nystagmus during conflicting vestibular and visual input, and (3) a disability to maintain the eccentric eye position upon a spontaneous saccade. All these effects could be inhibited in a dose-dependent fashion by CGP 35348, suggesting that the findings are specifically related to the GABAB receptor. Given separately, the antagonist did not affect the mentioned parameters. During horizontal acceleratory/deceleratory stimulation in darkness baclofen caused a biphasic pattern in the dose-response curves. Small amounts of baclofen caused an increase of the gain and of the duration of poststimulatory nystagmus, while high doses had a depressive action on the same parameters. The stimulating effect of baclofen could be inhibited or even reversed by CGP 35348, which has a depressive effect per se, similar to the effects of baclofen given in the upper range of doses.
Animals↗
[Reform of medical education. A new curriculum at the Karolinska Institute].
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Curriculum↗
Different splice variants of CD44 are expressed in gastrinomas but not in other subtypes of endocrine pancreatic tumors.
Endocrine pancreatic tumors are neuroendocrine neoplasms with malignant potential and give rise to varied clinical syndromes due to excessive secretion of multiple hormones. In this study 22 endocrine pancreatic tumors and 11 carcinoid tumors were examined for the expression of CD44 using a monoclonal antibody. CD44 gene activity of 11 endocrine pancreatic tumor tissues and five carcinoid tumor tissues was also studied by amplifying messenger RNA with the polymerase chain reaction followed by electrophoresis and blot hybridization. Strong immunoreactivity was detected on all gastrinomas examined (P < 0.001), and in two non-functioning endocrine pancreatic tumors. Such immunoreactivity was not observed in other subtypes of endocrine pancreatic tumors. In the normal human pancreas, the acinar portion and ductal epithelial cells stained strongly positive but pancreatic islet cells did not show any significant immunostaining. Furthermore, in endocrine pancreatic tumors with metastatic disease, CD44-positive tumors had a tendency to metastasize to lymph nodes (P = 0.005), as compared with CD44-negative tumors which were locally invasive or metastasized to the liver. Although, in this limited material and short follow-up, we were not able to show any statistical significance, patients with CD44-negative endocrine pancreatic tumors had prolonged survival time compared with patients with CD44-positive tumors (73% versus 59% at 5 years; P = 0.7). Of 10 carcinoid tumors examined, all three foregut carcinoids and one midgut carcinoid stained strongly positive, whereas all other midgut carcinoids were negative. Analysis of CD44 splice variants showed that in all five gastrinomas there was overproduction of alternatively spliced larger molecular variants as compared with other types of endocrine pancreatic tumors and carcinoid tumors. The band pattern from one case of carcinoid tumor with a fulminant clinical course was similar to that of gastrinomas, whereas other carcinoid tumors expressed the epithelial form of CD44. The earlier identified splice variants which confer metastatic behavior on a pancreatic tumor cell line were not expressed in neuroendocrine tumors. Our data indicate that CD44 expression in endocrine pancreatic tumors correlates with the ability to give rise to lymph node metastases and may play a vital role in determining the fate of metastasizing cells. Moreover, because gastrin is not detectable in the normal human pancreas, the pancreatic ductal cell positivity for CD44 strengthened the ductal origin concept of gastrinomas. The band pattern of CD44 splice variants suggests that the previously described splice variants conferring metastatic behavior do not accompany metastatic activity of neuroendocrine tumors.
Adult↗
On the analysis of life tables for dependent observations.
Applying methods assuming independence when observations are positively correlated means that confidence intervals become too short and significance levels of statistical tests are less extreme. This paper discusses elements of life-table analysis based on the standard product-limit estimator and a modified Greenwood formula for its variance to be used for dependent observations. An application from oral surgery is given. Erroneously assuming independence in the analysis of a life table could have serious consequences. It is demonstrated in a simulation study that the confidence levels can be much too low. The proposed modification of the Greenwood formula for the variance of the estimated survival function most often results in confidence levels not too much below the required level. Using the upper bound for the variance will give conservative confidence intervals but also larger standard errors. Averaging individual group survival curves should only be considered for situations with large groups.
Computer Simulation↗
An open clinical and biochemical study of ritanserin in acute patients with schizophrenia.
The effect of the selective serotonin-2 antagonist ritanserin was investigated in an open study of patients with schizophrenia. The patients were in an acute psychotic state considered to require neuroleptic medication. No neuroleptic drug was allowed during the study or during the last month preceeding the study. Oxazepam or nitrazepam were allowed for sedation or sleep inducement. Safety, tolerability, potential antipsychotic effect, and drug effects on monoamine metabolites in serum and CSF and prolactin in serum were evaluated. Central D2-dopamine receptor occupancy was determined by positron emission tomography. Ten male patients (mean age 32.4) fulfilling DSM-III-R criteria for schizophrenia were included in the study. Nine of these patients completed 4 weeks' treatment with ritanserin 10 mg b.i.d. The clinical effect was evaluated by means of CPRS and SANS and significant improvement was seen after 4 weeks' treatment both in positive and negative symptoms. Ritanserin was well tolerated and no extrapyramidal symptoms or akathisia were seen. Concentrations of monoamine metabolites and prolactin did not change during treatment. Ritanserin did not occupy D2-dopamine receptors. Thus, no indications of any D2-dopamine-antagonistic activity were obtained. All patients had expected ritanserin levels in plasma during the whole study. This first study of a selective serotonin-2 antagonist in the treatment of acute schizophrenic patients demonstrated significant clinical effects. However, the open design of the study does not allow us to conclude with any certainty that the patients' improvement was due to a specific blockade of serotonin-2 receptors or unspecific factors, although a direct D2-dopamine blockade could be ruled out.
Acute Disease↗
Ten-year follow-up of a prospective, randomized trial of selective proximal vagotomy with ulcer excision and partial gastrectomy with gastroduodenostomy for treating corporeal gastric ulcer.
Between 1975 and 1980, 30 patients with type I corporeal gastric ulcer were randomly allocated to undergo selective proximal vagotomy with ulcer excision or partial gastrectomy with gastroduodenostomy. Sixteen patients underwent selective proximal vagotomy (1 was excluded from the follow-up since microscopic examination of the excised ulcer revealed an early gastric cancer) and 14 underwent partial gastrectomy. No significant differences in the clinical results were found 3 years after surgery. During a median follow-up of 10 years, ulcer recurred in 3 patients after selective proximal vagotomy and in 2 after partial gastrectomy. One patient in each group had recurrent ulcer without symptoms and received no treatment. Two selective proximal vagotomy patients and three partial gastrectomy patients had epigastric pain with or without ulcer. One patient with selective proximal vagotomy underwent a second operation because of epigastric pain and recurrent ulcer. Bowel habits remained unchanged in all but one patient in each group, and mild or moderate dumping was recorded for two patients in each group. Very good or good results (modified Visick scale) were recorded for 11 of 15 patients after selective proximal vagotomy and for 10 of 14 patients after partial gastrectomy. Except for one patient in each group who had moderate dumping, patients classified as Visick III or IV had no symptoms during treatment with antacids or H2-blockers, or had asymptomatic ulcers and needed no treatment. Selective proximal vagotomy reduced the median acid response to insulin hypoglycemia and to pentagastrin by 100% and 80%, respectively, for at least 3 to 5 years, and partial gastrectomy reduced the median acid response to pentagastrin by 97%. In our opinion, selective proximal vagotomy with ulcer excision is an alternative to partial gastrectomy for surgically treating type I gastric ulcer.
Duodenostomy↗
Chromogranin A and B in neuronal elements in Hirschsprung's disease: an immunocytochemical and radioimmunoassay study.
Chromogranin A and B (CAB) occur in several peptide hormone-producing cells and in neurons of the brain. The aim of the present study was to investigate the possible neuronal localization of these chromogranins in the ganglionic and aganglionic bowel in Hirschsprung's disease by immunocytochemistry and radioimmunoassay, using antibodies recognizing either chromogranin A or both chromogranin A and B. Further, the coexistence of chromogranins and other neuronal constituents was studied. CAB were found in nerve fibers and occasionally in nerve cell bodies of submucous and myenteric ganglia in the ganglionic bowel, indicating that at least a population of chromogranin-immunoreactive nerve fibers is intrinsic in origin. CAB-immunoreactive fibers were numerous in the muscle layers of the aganglionic segment. These fibers contained tyrosine hydroxylase (TH), which indicates that they are adrenergic, in both ganglionic and aganglionic bowel. In the muscle layers of aganglionic (but not ganglionic) bowel, chromogranin A coexisted with galanin, neuropeptide Y (NPY), and vasoactive intestinal peptide (VIP). The concentration of CAB in smooth muscle specimens was higher in the aganglionic bowel than in the ganglionic bowel. Thus, chromogranins are present in the human enteric gut hyperinnervating the aganglionic bowel of Hirschsprung's disease.
Chromogranin A↗
Health benefits from a layman intervention in the primary health care.
In order to make a necessary life-style change, it is of the utmost importance that a sound motivation is created and the best help a person can get in the process of change is social support. The aim of this study was to locate people having physical symptoms of ill-being and to evaluate the work of a primary prevention programme, especially with regard to health benefits. The sample for the study was made up of 134 consecutive patients who went to see a health care professional because they had subjective complaints. The patients were offered a keep-fit exercise programme, i.e. a layman intervention of an educative-supportive nature, which consisted of ten assignments in a fitness club. The assignments comprised both physical exercise and psychosocial instructions. Two self-rated questionnaires were to be filled in; one at the beginning of the intervention and the other 1 year after its completion. Demographic data focused the attention on a female, manual, middle-aged worker, having symptoms bearing on the musculoskeletal system. The intervention definitely affected the life-style, thus favourably changing physical, psychosocial, and behavioural variables (e.g. increased physical well-being t-test: P < 0.001; decreased stress, t-test: P < 0.001; increased physical events, t-test: P < 0.01). In plain language, the use of the said intervention can result in the patients taking less time on sick-relief. Therefore, if many more people could be encouraged to take part in intervention programmes, the national medical cost would most likely be reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Neonatal treatment with monoclonal natural antibodies restores a normal pattern of VH gene utilization in the non-obese diabetic mouse.
The utilization of individual VH7183 genes in the autoimmune non-obese diabetic (NOD) mouse and the normal C57BL/6 mouse, both carrying the IgHb haplotype, was investigated. Nucleotide sequence analyses of a large number of VHDJH rearrangements utilizing VH7183 gene segments allowed us to identify 10 individual members of this family in the IgHb haplotype. Eight of these members were isolated from both C57BL/6 and NOD mice, whereas two were found only in NOD mice. Analysis of polymerase chain reaction libraries derived from genomic DNA revealed that > 50% of the VH7183 rearrangements isolated from both neonatal and adult NOD mice were functional. In contrast, the frequency of functional rearrangements decreased from 61% in neonatal to 9% in adult splenic B cells of C57BL/6 origin. These observations suggested that adult NOD mice retained a neonatal pattern of VH7183 gene utilization. Most interestingly, the deviation from the normal pattern of VH7183 utilization observed in the adult NOD mouse could be 'normalized' by neonatal treatment with a natural mAb previously demonstrated to inhibit the development of diabetes in the NOD mouse. These data demonstrate that certain 'natural' mAbs can influence the development of T cell mediated autoimmunity in the NOD mouse and suggest that the B cell/Ig compartment may play an important role in this process.
Animals↗
Virus validation of plasma-derived products produced by Pharmacia, with particular reference to immunoglobulins.
Important factors to assure the safety of plasma-derived products manufactured on an industrial scale are initial screening of the source material and validation of the manufacturing process in accordance with issued EEC guidelines and US [Points to Consider'. Pharmacia's manufacturing process for immunoglobulins contains a specific virucidal step, in which lipid-enveloped viruses are effectively inactivated with a solvent/detergent (SD) combination consisting of 0.3% tri(n-butyl)phosphate and 1% Tween 80. Results from virus validation studies of scaled-down versions of Pharmacia's manufacturing process for immunoglobulins demonstrated extensive removal of relevant and model viruses. More than 5.0 logs of human immunodeficiency virus type 1 (HIV-1) were inactivated in the SD step and, in total, more than 31 logs of HIV-1 were eliminated in the steps studied. Comparison between SD treatment and heating at 60 degrees C of lipid-enveloped viruses in different protein solutions demonstrated that SD treatment is the superior procedure. Polio virus is a model often used in virus validation studies to predict effects on non-enveloped viruses. Because polio virus is more sensitive to heat than are hepatitis A virus (HAV) and human parvovirus B19, thermal inactivation studies with polio virus may result in an overestimation of the effects on HAV and B19.
Animals↗
Diagnostic potential of chest pain characteristics in coronary care.
OBJECTIVES: To characterize and quantitate the experience of presenting chest pain in coronary care patients in terms of intensity, quality, localization and extension of pain. DESIGN: Localization of presenting chest pain at a body figure and estimation of intensity according to the Borg CR-10 scale of five qualities related to pain: (i) aching, (ii) burning, pricking, (iii) pressing, throbbing, (iv) dyspnoea, suffocation and (v) anxiety were done within 24 h from onset of symptoms. SETTING: Coronary care unit (CCU). SUBJECTS: Eighty consecutive patients of which 40 suffered from acute myocardial infarction (AMI). RESULTS: The AMI and non-AMI groups did not differ with regard to (i) the intensity of chest pain being mainly of moderate degree and (ii) the mean number of qualities of the presenting chest pain that were between 3 and 4. Patients with AMI reported extension of chest pain over a wider body area than patients in the non-AMI group (P < 0.0001). A second type of chest pain in addition to the major type of chest pain was reported by only 25% of the patients with AMI compared to 68% in the non-AMI group (P < 0.0001). CONCLUSIONS: Intensity, quality and localization of presenting acute chest pain in patients admitted to the CCU do not differentiate between patients with or without AMI. Extension of pain over a major part of the chest-related body surface and the absence of secondary pain appear to identify at least half of the patients with ongoing AMI.
Adult↗
Four-year study of caries inhibition of intensive Duraphat application in 11-15-year-old children.
The purpose of the study was to evaluate the caries preventive effect and cost of an intensive application of Duraphat varnish, added to the regular preventive program for 11-15-yr-old children in a Swedish Dental Community Clinic. In 1987, the 134 11-yr-old children in Floda were divided into two groups, every second child to each. Children with fixed orthodontic appliances were excluded. The test group received three applications of Duraphat varnish during 1 week, once a year, by a dental nurse. The control group received one application at the annual check-up. Both groups were included in the regular preventive program at the clinic. The total time cost for the clinic was estimated and used to calculate the cost per hour for dentists and nurses. The caries increment and progression were estimated both by routine diagnosis and by a careful study of radiographs taken at the beginning and end of the study period. There was a small caries increment and progression in the test group as compared to the control group. The difference was statistically significant for all aspects studied. The costs were about the same in both groups but more time was used in the test group. The administrative effort for the staff was considerable for the intensive Duraphat application.
Adolescent↗
Interferons alone or in combination with chemotherapy or other biologicals in the treatment of neuroendocrine gut and pancreatic tumors.
The treatment of malignant neuroendocrine gut and pancreatic tumors provides a therapeutic challenge. Surgery as well as medical treatment rarely cure the patient at this stage. Symptoms related to secretory products from the tumor might be life-threatening or at least reduce the quality of life considerably. Interferons (IFNs) have demonstrated an antitumor effect in multiple tumor diseases and were introduced by our group in 1982 for the treatment of carcinoids. Today, more than 300 patients with various neuroendocrine tumors and who receive alpha-IFN have been reported in the literature. Treatment of midgut carcinoid tumors at doses of 3-9 MU 3-7 times per week subcutaneously has achieved biochemical responses in 44% of the patients with significant tumor reduction in 11%. Subjective improvement has been obtained in around 65% of the patients. A median survival from start of treatment in patients with carcinoid syndrome of 80+ months has to be compared with 8-12 months on chemotherapy (streptozotocin plus 5-FU). Treatment of endocrine pancreatic tumors with alpha-IFN at doses of 5-6 MU 3-5 times per week achieved biochemical responses in 51% of the patients and tumor responses in 12%. The median duration of response was 20 months (range 2-96). Combining alpha-IFN with the somatostatin analogue octreotide in patients with malignant tumors resistant to octreotide alone got biochemical responses in 77% with 18% complete biochemical remissions. No significant reduction of tumor size was noticed, but stabilization of the disease was obtained for a median of 15 months.(ABSTRACT TRUNCATED AT 250 WORDS)
Antineoplastic Agents↗
[111In-DTPA-D-Phe1]octreotide scintigraphy in patients with carcinoid tumours: the predictive value for somatostatin analogue treatment.
This study was performed to evaluate whether the presence or absence of somatostatin receptors in malignant carcinoid tumours detected by [111In-DTPA-D-Phe1]octreotide scintigraphy can be used to predict response to somatostatin analogue treatment. Thirty patients were investigated, 28 with midgut carcinoid tumours and two with foregut carcinoid tumours. Twenty-seven patients showed pathological uptake in tumour lesions at scintigraphy; of these, 22 responded to somatostatin analogue treatment using octreotide, somatuline or octastatin, while five patients failed to respond. None of the three patients displaying negative scintigraphic investigations responded to treatment with somatostatin analogues. These results show a good correlation between the somatostatin receptor status and the patients' ability to respond to somatostatin analogue treatment (p = 0.014). We conclude that somatostatin receptor scintigraphy using [111In-DTPA-D-Phe1]octreotide can be used to select patients with malignant carcinoid tumours suitable for somatostatin analogue treatment and exclude those that will not benefit from such medication.
Aged↗
[Only the teachers are in favour for grades].
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Education, Medical↗
Quality of life among children in the Nordic countries.
Quality of life (QOL) is a concept with no generally accepted definition. Most clinical studies have had an individual approach where demographic and socio-economic population aspects have not been considered. QOL has hardly ever been used in studies of children. In this study QOL is defined as the essential resources of a child population, expressed in external, inter-personal and personal conditions. Both objective conditions and the corresponding subjective perceptions are included. A model for an empirical application is demonstrated on a random sample of 15,000 children in the five Nordic countries. The data were collected in a questionnaire mailed to the families of the children. The QOL was analysed in a normative way, where a base value was defined for each variable and the conditions of the children were compared to a Nordic standard for children's QOL. The results showed that children in the Nordic countries have a high QOL. The differences between the countries were rather small. Children in Sweden had the highest QOL, closely followed by children in Denmark and Norway, while children in Finland were in an intermediate position and the Icelandic children had the lowest QOL, mainly due to a lower level of satisfaction. This study can be considered as a base line study which later can be used in studies of time trends or in comparisons of groups of children such as children with special needs.
Adolescent↗