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Biomedical subjects

H Jacobsson

Publications and source records attributed to H Jacobsson.

At least 55 records · Page 3Linked to original sources

Malignant human renin producing paraganglionoma-localization with 123I-MIBG and treatment with 131I-MIBG.

A 22-year-old woman presenting severe hypertension and hypokalaemia is described. Initial evaluation showed a large tumour localized at the position of the left adrenal gland. Subsequent surgery temporarily relieved all signs and symptoms caused by the tumour. The symptoms relapsed after a 2-year disease-free interval. At re-evaluation, the tumour was shown to produce an uncontrolled secretion of renin, thus triggering aldosterone-dependent hypertension. This report describes the diagnosis, treatment and clinical course of this unique patient with a malignant paraganglionoma of adrenal origin.

3-Iodobenzylguanidine↗

GLP-1 slows solid gastric emptying and inhibits insulin, glucagon, and PYY release in humans.

The aim of the present study was to assess the effect of glucagon-like peptide-1 (GLP-1) on solid gastric emptying and the subsequent release of pancreatic and intestinal hormones. In eight men [age 33.6 +/- 2.5 yr, body mass index 24.1 +/- 0.9 (means +/- SE)], scintigraphic solid gastric emptying during infusion of GLP-1 (0.75 pmol. kg(-1). min(-1)) or saline was studied for 180 min. Concomitantly, plasma concentrations of C- and N-terminal GLP-1, glucose, insulin, C-peptide, glucagon, and peptide YY (PYY) were assessed. Infusion of GLP-1 resulted in a profound inhibition of both the lag phase (GLP-1: 91.5, range 73.3-103.6 min vs. saline: 19. 5, range 10.2-43.4 min) and emptying rate (GLP-1: 0.34, range 0.06-0. 56 %/min vs. saline: 0.84, range 0.54-1.33 %/min; P < 0.01 for both) of solid gastric emptying. Concentrations of both intact and total GLP-1 were elevated to supraphysiological levels. Plasma glucose and glucagon concentrations were below baseline during infusion of GLP-1 in contrast to saline infusion, where concentrations were elevated above baseline (both P < 0.001). The insulin and C-peptide responses were lower during infusion with GLP-1 than with saline (P < 0.004 and P < 0.001, respectively). Plasma PYY concentrations decreased below baseline during GLP-1 infusion in contrast to saline, where concentrations were elevated above baseline (P = 0.04). Infusion of GLP-1 inhibits solid gastric emptying with secondary effects on the release of insulin, C-peptide, and glucagon, resulting in lower plasma glucose concentrations. In addition, the release of PYY into the circulation is inhibited by GLP-1 infusion, suggesting a negative feedback of GLP-1 on the function of the L-cell.

Adult↗

Pulmonary perfusion is more uniform in the prone than in the supine position: scintigraphy in healthy humans.

The main purpose of this study was to find out whether the dominant dorsal lung perfusion while supine changes to a dominant ventral lung perfusion while prone. Regional distribution of pulmonary blood flow was determined in 10 healthy volunteers. The subjects were studied in both prone and supine positions with and without lung distension caused by 10 cmH2O of continuous positive airway pressure (CPAP). Radiolabeled macroaggregates of albumin, rapidly trapped by pulmonary capillaries in proportion to blood flow, were injected intravenously. Tomographic gamma camera examinations (single-photon-emission computed tomography) were performed after injections in the different positions. All data acquisitions were made with the subject in the supine position. CPAP enhanced perfusion differences along the gravitational axis, which was more pronounced in the supine than prone position. Diaphragmatic sections of the lung had a more uniform pulmonary blood flow distribution in the prone than supine position during both normal and CPAP breathing. It was concluded that the dominant dorsal lung perfusion observed when the subjects were supine was not changed into a dominant ventral lung perfusion when the subjects were prone. Lung perfusion was more uniformly distributed in the prone compared with in the supine position, a difference that was more marked during total lung distension (CPAP) than during normal breathing.

Adult↗

The somatostatin analogue octreotide inhibits neuroblastoma growth in vivo.

Neuroblastoma, a neural crest-derived childhood tumor of the sympathetic nervous system, may in some cases differentiate to a benign ganglioneuroma or regress due to apoptosis. However, the majority of neuroblastomas are diagnosed as metastatic tumors with a poor prognosis despite intensive multimodal therapy. The neuropeptide somatostatin (SOM) has been shown to inhibit neuroblastoma growth and induce apoptosis in vitro. Therapeutic effects of SOM analogues are dependent on tumor expression of high-affinity receptors. In the present study, human neuroblastoma SH-SY5Y cells were grown as xenografts in nude rats. In vivo SOM receptor expression in the xenografts was identified using scintigraphy with 111In-pentetreotide. Rats were randomized to treatment with the long-acting SOM analogue octreotide (10 microg s.c. every 12 h), 13-cis-retinoic acid (4 mg orally every 24 h), or vasoactive intestinal peptide (40 microg s.c. every 24 h) and compared with controls. Tumor volume was assessed every second day and tumor weight after 10-12 d. Octreotide treatment inhibited neuroblastoma growth significantly with reduced tumor volumes at 10 and 12 d compared with untreated controls (mean 3.56 and 4.24 versus 6.48 and 8.01 mL, respectively; p < 0.01). Also, tumor weights after 10-12 d were reduced in octreotide-treated animals (n = 8, median weight 2.90 g, range 1.67-5.57 g) compared with untreated rats (n = 14, 7.54 g, 1.65-10.82 g, p = 0.005). Serum IGF-I decreased significantly over time both in rats treated with octreotide and in untreated controls. It is concluded that treatment with the SOM analogue octreotide may significantly decrease neuroblastoma tumor growth in vivo. Further studies are warranted to establish the role of SOM analogues in the treatment of children with unfavorable neuroblastoma.

Animals↗

Sympathotropic drugs and the distribution of 99mTc-hydroxymethylene diphosphonate. Experimental studies in the mouse.

OBJECTIVE: The uptake of bone-seeking radiopharmaceuticals depends on the blood flow, which is influenced by the sympathetic nervous system. Our aim was to study the effect of sympathomimetic drugs on the distribution of bone-seeking agents. MATERIAL AND METHODS: Various sympathomimetic and beta-blocking drugs were injected in mice at different times in relation to the administration of 99mTc-HDP. Three hours after this, venous blood and various organs were removed and their activities were related to the administered activity. A kinetic study of the whole-body activity retention after administration of terbutaline was also made. RESULTS: The biodistribution of 99mTc-HDP was similar after the administration of sympathomimetics and of beta-antagonists. All drugs gave rise to an increased soft tissue activity and a decreased bone activity, corresponding to a lowered quality of the potential bone scan. Terbutaline gave rise to an increased excretion of 99mTc-HDP. The mechanisms behind the findings cannot be entirely explained. CONCLUSION: Drug interference with the sympathetic nervous system causes undesirable effects on the biodistribution of 99mTc-HDP in the mouse. Studies in humans are necessary to evaluate whether clinical treatment with sympathotropic drugs affects the bone scintigram.

Adrenergic beta-Antagonists↗

Concentration of 123I-metaiodobenzylguanidine in left and right liver lobes. Findings indicate regional differences in function in the normal liver.

PURPOSE: Normal radioactivity in the liver is often shown to be higher in the left lobe than in the right lobe at clinical examination by single photon emission computed tomography (SPECT) with 123I-metaiodobenzylguanidine (123I-MIBG). Our objective was to determine whether this represents a pathological condition. MATERIAL AND METHODS: The distribution of 123I-MIBG in the liver was retrospectively studied in clinical patients who had normal CT examinations of the liver and spleen. In the SPECT sections of 27 123I-MIBG examinations, we determined the activity ratios between the left and right lobes. The control group comprised 33 examinations with (111)In-pentetreotide (OctreoScan) and 23 examinations with 99mTc-antigranulocyte antibody. RESULTS: The mean activity ratio between left and right lobes for 123I-MIBG was 1.24, and for (111)In-pentetreotide 0.87. These figures differed significantly both from each other and from 1.00. The mean ratio for 99mTc-antibody at the early examinations was 0.99, and at the late examinations 0.95. These figures differed significantly from the values for 123I-MIBG and (111)In-pentetreotide. CONCLUSION: The increased concentration of 123I-MIBG in the left lobe of the liver compared to the right lobe is a normal finding. The reason for this cannot be explained. The difference in the way in which the left and right lobes deal with the three radiopharmaceuticals is a new finding and indicates a regional difference in liver function that has not been reported previously.

3-Iodobenzylguanidine↗

Neonatal adrenal haemorrhage at bone scintigraphy: a case report.

We report the case of a girl with known large right-sided and small left-sided neonatal adrenal haematomas who underwent bone scintigraphy 23 days after birth for suspected osteomyelitis. The radionuclide examination showed uptake of bone tracer around the right-sided haematoma, but no abnormality on the left side.

Adrenal Gland Diseases↗

Resting state rCBF mapping with single-photon emission tomography and positron emission tomography: magnitude and origin of differences.

Single-photon emission tomography (SPET), using technetium-99m hexamethylpropylene amine oxime, and positron emission tomography (PET), using oxygen-15 butanol were compared in six healthy male volunteers with regard to the mapping of resting state regional cerebral blood flow (rCBF). A computerized brain atlas was utilized for 3D regional analyses and comparison of 64 selected and normalized volumes of interest (VOIs). The normalized mean rCBF values in SPET, as compared to PET, were higher in most of the Brodmann areas in the frontal and parietal lobes (4.8% and 8.7% respectively). The average differences were small in the temporal (2. 3%) and occipital (1.1%) lobes. PET values were clearly higher in small VOIs like the thalamus (12.3%), hippocampus (12.3%) and basal ganglia (9.9%). A resolution phantom study showed that the in-plane SPET/PET system resolution was 11.0/7.5 mm. In conclusion, SPET and PET data demonstrated a fairly good agreement despite the superior spatial resolution of PET. The differences between SPET and PET rCBF are mainly due to physiological and physical factors, the data processing, normalization and co-registration methods. In order to further improve mapping of rCBF with SPET it is imperative not only to improve the spatial resolution but also to apply accurate correction techniques for scatter, attenuation and non-linear extraction.

Adult↗

Accumulation of FDG in axillary sweat glands in hyperhidrosis: a pitfall in whole-body PET examination.

A diabetic male with severe autonomic neuropathy and recently discovered Hodgkin's disease demonstrated bilateral uptake of [2-18F]-2-fluoro-2-deoxy-d-glucose (FDG) in the axillary sweat glands during profuse sweating caused by hypoglycaemia at positron emission tomography examination. It is not yet clear whether the sweating interfered with the distribution of the radiopharmaceutical. Regardless of the cause or mechanism for the uptake, the finding is clinically relevant. A bilateral symmetrical accumulation of FDG in the axillae of a tumour patient does not necessarily indicate malignant involvement of the lymph nodes.

Adult↗

Distal small bowel hormones: correlation with fasting antroduodenal motility and gastric emptying.

The aim of the present study was to study the interdigestive motor complex (MMC), distal small intestinal hormones, and gastric emptying in normal-weight and obese subjects before and after jejunoileal bypass (JIB). Therefore, fasting antroduodenal motility, gastric emptying, and RIA for motilin (MOT), neurotensin (NT), peptide YY (PYY), and glucagon-like peptide-1 (GLP-1) was performed in nine obese subjects before (BMI 42 +/- 4 kg/m2) and nine months after (BMI 31 +/- 4) JIB, and in two groups of nine age- and sex-matched controls (BMI 23 +/- 1 and 21 +/- 1). The rate of gastric emptying was faster in obese subjects and GLP-1 lower compared to normal-weight controls. After JIB, fewer phase III of the MMC were observed; fasting levels of PYY were elevated during the MMC; postprandial levels of NT, PYY, and GLP-1 were elevated; and gastric emptying was delayed. Our results suggest that there may be an association between an impaired GLP-1 response after food intake and obesity, and after JIB, PYY seems to regulate interdigestive motility while GLP-1 may regulate early gastric emptying.

Adolescent↗

Multidrug resistance phenotype in leukaemic cells from patients with acute myelocytic leukaemia can be detected with 99Tc(m)-MIBI.

The aim of the study was to investigate whether 99Tc(m)-MIBI (Cardiolite), recently shown to be a substrate for P-glycoprotein, has the potential to be used as a marker for mdr1 gene expression and whether cyclosporin A (CyA) can modify its accumulation in vivo. Leukaemic cells from ten patients with acute myelocytic leukaemia (AML) were used, five with undetectable mdr1 gene expression and five with mdr1 mRNA levels ranging from 1.0 to 3.8 mdr1 mRNA transcripts per cell. Cells were incubated with 99Tc(m)-MIBI, or with daunorubicin (Dnr), with and without 3 microM CyA. The median 99Tc(m)-MIBI accumulation (% of added radioactivity) in mdr1-negative cells was 0.89% and in the mdr1-positive cells 0.34%, P = 0.01. In mdr1-negative cells, the median increase in 99Tc(m)-MIBI accumulation with CyA was 30% compared with the mdr1-positive cells with a median increase of 242%, P = 0.009. CyA had no significant effect on Dnr accumulation in four of the mdr1-negative samples. The median increase of Dnr accumulation in the mdr1-positive cells was 40%. The results show that 99Tc(m)-MIBI with a high sensitivity can detect rather low levels of mdr1 gene expression in clinical samples. Consequently, 99T(c)m-MIBI scintigraphy has the potential to be used for monitoring the effect of resistance modifiers on the accumulation and retention of cytostatic drugs in human tumours in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Influence of the phosphate balance on the activity distribution of 99mTc-hydroxy-methylene diphosphonate. Experimental studies in the mouse.

OBJECTIVE: The purpose was to determine whether changes in the phosphate balance have an influence on the distribution of bone-seeking radiopharmaceuticals. MATERIAL AND METHODS: The biodistribution of 99mTc-HDP in mice, intravenously administered under varying conditions, was assessed by removing different organs and estimating their activity in a scintillation counter. Some experiments were also performed with 99mTc-MDP and 99mTc-DPD. RESULTS: After 1 h and 18 h on phosphate-enriched drinking water, the mice showed a strongly increased uptake in all organs/tissues representing background activity and a decrease in the bone uptake. This pattern changed with time. After 6-8 days of phosphate load, we saw a more favourable distribution with a reduction of the background and whole-body activity. Administration of hPTH 1-34 gave rise to an activity distribution similar to that after 6-8 days on phosphate-enriched water. Changing the phosphate balance had less obvious effects on the distribution of 99mTc-MDP and 99mTc-DPD. CONCLUSION: The activity distribution of bone-seeking radiopharmaceuticals in the mouse is affected by the phosphate balance. The mechanism behind this finding is unknown but it may be partially mediated by PTH. It is possible that changes in the phosphate balance, induced by pharmaceuticals or by dietary changes, may affect the image quality at bone scintigraphy.

Animals↗

Use of 99mTc-MIBI scintigraphy in the evaluation of the response of osteosarcoma to chemotherapy.

The use of gamma camera scintigraphy with technetium-99m hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) for assessment of the response of high-grade osteosarcoma to preoperative chemotherapy was evaluated. Twelve patients with osteosarcoma of the extremities underwent planar examination with 99mTc-MIBI before and after preoperative chemotherapy according to the recommendations of the Scandinavian Sarcoma Group. After calculating a quotient for the tumour and the average activity of both extremities and correcting for background activity, the change in uptake between the two examinations was assessed. This was compared with histological examination of the ultimately resected specimen in 11 patients and progressive clinical disease in one. All the 11 tumours undergoing histological examination showed cellular necrosis of between 50% and 100% as well as a reduced uptake of 99mTc-MIBI, while the single progressive tumour showed an increased uptake. There was a correlation between the reduction of radiopharmaceutical uptake and the histological response in the entire series, while the variation was too large to allow conclusions in individual patients. This variation may have biological reasons or may be due to the planar imaging technique, which only allows semiquantitative evaluation. The technique reflects response to therapy but is not yet clinically applicable for the identification of poor responders, which would serve as a basis for alteration of the chemotherapy regimen. In order to evaluate whether such a role could be fulfilled, further studies using single-photon emission tomography with correction for attenuation and scattering of photons are necessary.

Adolescent↗