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Biomedical subjects

A Magnusson

Publications and source records attributed to A Magnusson.

At least 109 records · Page 6Linked to original sources

Neuroendocrine pancreatic tumours: clinical presentation, biochemical and histopathological findings in 84 patients.

A prospective study has been performed on 84 patients with endocrine pancreatic tumours evaluated at the Medical Department in Uppsala. Available information concerning the patients' presenting symptoms, age at diagnosis, clinical syndrome, tumour location, location of metastases, diagnostic radiology, biochemical and histopathological findings has been analysed. Our results indicate that most patients initially show rather vague and non-specific symptoms, with dyspepsia and pain being the most frequent presenting features. The median delay between appearance of the first symptom and diagnosis was 2 years; the delay was 35 months in sporadic cases and 14.5 months in familial cases. In spite of improvements in diagnostic methods, the median age at diagnosis (53 years) has not been reduced, and most patients are encountered when the tumour has reached an advanced stage. There is a need for a method of screening patients with still uncharacteristic abdominal symptoms for a neuroendocrine tumour. The presence of elevated levels of plasma chromogranin in all patients with a proven tumour suggests that such possibilities exist, and the use of this biochemical marker in the future might reduce the age at diagnosis and thus improve the likelihood of cure and survival of patients with endocrine pancreatic tumours.

Adenoma, Islet Cell↗

Use of cell culture to predict toxicity of solid materials in blood contact.

A comparison was made, for in vitro assessment of toxicity, between six different procedures to extract biomaterials. A new method was developed, with a special insert inside the tissue culture well, that allows relevant contact between cells and material without disturbing physical contact. To predict the toxicity of materials in blood contact, our results suggest that two simple methods ought to be used, one based on water eluates and the other on contact between cells and material.

Animals↗

Preoperative localization of endocrine pancreatic tumours by intra-arterial dynamic computed tomography.

Eleven patients with biochemically confirmed endocrine pancreatic tumours were examined with intra-arterial (i.a.) dynamic computed tomography (CT) and angiography preoperatively. Seven of the patients suffered from the multiple endocrine neoplasia type 1 (MEN-1) syndrome. All patients were operated upon and surgical palpation and ultrasound were the peroperative localization methods. Of the 33 tumours which were found at histopathologic analysis of the resected specimens in the 11 patients, 7 tumours in 7 patients were correctly localized by both i.a. dynamic CT and angiography. Six patients with MEN-1 syndrome had multiple tumours and this group of patients together had 28 tumours, of which 5 (18%) were localized preoperatively by both CT and angiography. I.a. dynamic CT, with the technique used by us, does not seem to improve the localization of endocrine pancreatic tumours, especially in the rare group of MEN-1 patients, as compared with angiography.

Adult↗

Biochemical evidence for the GABA regulation of vasopressin levels in microdissected brain structures after servo-controlled hypotension.

Discrete brain structures were analysed for gamma-aminobutyric acid (GABA) and vasopressin content in normo- and hypotensive rats treated with the glutamic acid decarboxylase inhibitor, 3-mercaptopropionic acid (MPA) and the GABAA agonist muscimol. In the normotensive group treated with MPA only, the concentration of vasopressin increased in the supraoptic nucleus, indicating an inhibitory role for GABA. In the hypotensive group a rise in the vasopressin level in the nucleus of the solitary tract was detected and the GABA level decreased in the supraoptic nucleus. Muscimol decreased the concentration of vasopressin in the nucleus of the solitary tract. The changes in the concentration of vasopressin may be a result of increased or decreased activation of the GABAergic system. The results show that the GABA- and vasopressinergic systems somehow interact although the more precise way of action remains to be clarified.

3-Mercaptopropionic Acid↗

Treatment of malignant carcinoid tumors with recombinant interferon alfa-2b: development of neutralizing interferon antibodies and possible loss of antitumor activity.

Twenty patients with malignant carcinoid tumors were treated for 6 months with recombinant interferon alfa-2b (IFN alpha-2b; Intron-A; Schering Corp., Bloomfield, NJ) at a mean dose of 5.9 megaunits three times per week. Eleven of the 20 patients (55%) had a greater than 50% reduction of tumor markers (urinary 5-hydroxyindoleacetic acid or plasma neuropeptide K), showing objective tumor response. Six patients (30%) had stable disease with no significant change in tumor markers or tumor size, and three (15%) had progressive disease with an increase in tumor markers and size. These results are similar to those reported earlier for treatment with natural leukocyte IFN in patients with carcinoid tumors. Only two patients (35%) had a slight reduction of tumor size after 6 months of treatment. Three patients developed neutralizing antibodies to IFN alpha-2b. Two of these patients initially showed an objective response, which lasted until IFN antibodies developed. In one of these patients, a change to human leukocyte IFN resulted in normalization of antibody titers within 3 months, and the patient had a second objective clinical response. There was no correlation between development of IFN antibodies and development of autoimmune phenomena such as increased titers of antinuclear antibodies or thyroid autoantibodies. IFN alpha-2b seems to be as potent as human leukocyte IFN in the treatment of patients with malignant carcinoid tumors, but it is important to recognize that antibodies neutralizing IFN may develop in some patients, with concomitant loss of antitumor effects. A change to natural leukocyte IFN might be beneficial in these patients.

Aged↗

Fluoroscopic measurement of tibial torsion in adults. A comparison of three methods.

Three methods based on the fluoroscopic technique for measurement of tibial torsion were analyzed. The measurements were performed bilaterally in 100 normal adults. The values for bilateral tibial torsion were recorded and the values for the difference in torsion between the right and left tibia were calculated. The standard error of all investigated methods was found to be lower than published figures for computerized tomography and ultrasonic methods. The method found to be most convenient for routine use also presented the best repeatability. With this method, the standard error of a single determination of tibial torsion was estimated to be 0.7 degrees.

Adolescent↗

A simple method for shell-less cultivation of chick embryos.

The chorio-allantoic membrane of explanted chick embryos can be used for the study of vascular development and of the vascular response to drugs and to tissue implants or tissue extracts. Three different types of vials for shell-less cultivation of chick embryos were compared in terms of short-term survival. Plastic cups with rounded bottoms were superior to Petri dishes and polyethylene film bags, in that they combined a high survival rate of the embryos with a possibility of using a large number of embryos in each experiment. With the use of plastic cups this method is simple, reliable and inexpensive.

Allantois↗

Implantable drug delivery systems in computed tomography and magnetic resonance imaging--a comparison between titanium and stainless steel.

The effect of implantable drug delivery systems on computed tomography (CT) and magnetic resonance imaging (MRI) was investigated in a phantom and in two patients. The implantable systems of identical construction consisted either of medical grade titanium alloy or stainless steel. Images of a phantom showed artefacts of the stainless steel port in both CT and MRI. These artefacts were substantially reduced in images of the titanium port. Similar results were found in situ in two patients.

Catheters, Indwelling↗

Single- and multiple-dose pharmacokinetics of terodiline in geriatric patients.

As a target group, geriataric patients were selected for pharmacokinetic studies with terodiline (Mictrol), an anticholinergic and calcium antagonist drug effective in the treatment of urinary incontinence. The single-dose kinetics in the geriatric patients (mean age 82 years) differed significantly from that previously found (Hallén et al. 1987) in healthy volunteers (mean age 35 years). There were higher peak serum concentrations (110 vs 79 micrograms.l-1), increased half-life (189 vs 60 h), lower renal clearance (4.0 vs 10.9 ml.min-1) and lower total clearance (29 vs 75 ml.min-1). Multiple-doses of 12.5 mg b.d. for 6-8 weeks resulted in a mean steady-state concentration of 642 micrograms.l-1, which was in agreement with the single dose parameters. The studied geriatric patients can be characterized not only as old, but also as frail, bedridden, having several diseases and polymedicated. The differences in pharmacokinetics between younger and elderly subjects can be attributed to a variety of complex factors, which may alter the clearance and/or the volume of distribution.

Aged↗

The value of computed tomography and ultrasound in assessment of pelvic lymph node metastases in patients with clinically locally confined carcinoma of the prostate.

With the aim of detecting any metastases in pelvic lymph nodes, computed tomography (CT) was performed in 42 patients with clinically localized prostatic carcinoma, and ultrasound (US) examination in 35 of them, prior to pelvic lymphadenectomy. CT was positive in only one patient, and US was negative in all examined patients. At lymph node dissection macrometastases were found in four patients and histopathologic examination revealed micrometastases in a further ten patients. It is concluded that in clinically locally confined prostatic carcinoma CT and US are insensitive in diagnosing pelvic lymph node metastases, and that lymph node dissection remains the only method for staging of the regional lymph nodes.

Aged↗

Malignant carcinoid tumors. An analysis of 103 patients with regard to tumor localization, hormone production, and survival.

In a prospective study of 103 patients with carcinoid tumors consecutively referred for medical treatment, the most common sites of the primary tumors were the ileum (73%), bronchi (7%), and jejunum (4%). All patients had local metastases, and 96 (93%) also had liver metastases. The most common initial symptoms were diarrhea (32%), ileus (25%), and flush (23%). The overall frequency of diarrhea was 84% and of flush was 75%. Heart insufficiency caused by cardiac valve disease was seen in 33% of the patients. The carcinoid syndrome, including flush, diarrhea, and elevated urinary 5-hydroxyindole acetic acid (5-HIAA) concentrations, was manifested by 69 patients (67%), 64 of whom (93%) had carcinoid tumors of mid-gut origin. Elevated urinary 5-HIAA was found in 91 patients (88%), of which 89 displayed liver metastases. The plasma concentration of the tachykinin neuropeptide K (NPK) was elevated in 67 patients (66%), 63 of whom had tumors of the mid-gut region. Serum pancreatic polypeptide (PP) and human chorionic gonadotrophin alpha levels were elevated in 43% and 28% of the patients, respectively, and the highest levels were found in patients with metastatic bronchial carcinoid tumors. Thirty-nine of the 103 patients are now dead; 18 died of tumor progression, whereas 14 patients died of heart failure secondary to a carcinoid tricuspidal valve insufficiency. The estimated median survival from the time of histologic diagnosis was 14 years, and from the time of carcinoid syndrome was 8 years.

Adult↗

Regional differences in the changes in rat brain GABA concentrations post mortem and following inhibition of the synthesis and metabolism.

Experimentally induced changes in the concentration of GABA were studied in regions where GABA is present, predominantly in nerve terminals (substantia nigra, pituitary gland) or outside nerve terminals (corpus callosum). Some other regions (cerebellum, cuneate nucleus, corpus striatum, hippocampus) were included where the cellular localization of GABA is less certain. The post mortem increase in GABA was about equal percentage-wise in all regions indicating that it occurs in all locations where GABA is present. The increase in GABA following the GABA alpha-ketoglutaric acid aminotransferase inhibitor gamma-acetylenic GABA was much greater in the corpus callosum than in the other regions indicating that this enzyme is more important for the GABA present outside than inside the GABA nerve terminals. The glutamic acid decarboxylase inhibitor 4-deoxypyridoxine decreased the endogenous concentration of GABA and it inhibited the increase in GABA induced by gamma-acetylenic GABA in the substantia nigra and in the pituitary gland, but not in the corpus callosum, indicating that this compound inhibits the decarboxylase mainly in the GABA nerve terminals.

Alkynes↗

Object size determination at computed tomography.

To investigate whether large differences in attenuation between an object and its background at CT examination alter the apparent size of the object on the image compared with the conditions with a small attenuation difference, phantom experiments were performed. At the same time the influence of large attenuation differences on the geometric resolution was examined. The results show that neither the size reproduction of the object nor the geometric resolution is altered by variations in attenuation differences. Especially with large differences in attenuation between the object and background, however, the window centre setting was of greatest importance for correct reproduction of the object.

Physical Phenomena↗

Treatment of malignant endocrine pancreatic tumors with human leukocyte interferon.

Twelve patients with malignant endocrine pancreatic tumors refractory to cytotoxic treatment were treated with human leukocyte interferon im at daily doses of 3 X 10(6)-6 X 10(6) IU. Ten of 12 patients showed an objective response with a mean duration of 15.2 months, median, 11 months (range, 2-36+). All ten patients had a decrease in tumor markers and an objective reduction in tumor size was also noted in four. Improvement of clinical manifestations was seen in all cases with an objective response. Adverse effects, including influenza-like syndrome, reduction of blood cells, and chemical signs of liver dysfunction occurred, but were reversible or could be circumvented by dose reduction. One patient developed hypothyreosis on an autoimmune basis; another patient developed liver steatosis. Although the number of patients is small, the results are promising. Interferon therapy seems to be as potent as cytotoxic treatment but with far less side effects. This study indicates that further trials with interferon in patients with less advanced stages of malignant endocrine pancreatic tumor should be performed.

Adult↗

Clinical pharmacological evaluation of an assay kit for intoxications with tricyclic antidepressants.

The performance of an enzyme immunoassay kit (EMIT) to diagnose intoxications with tricyclic antidepressants was compared with a high performance liquid chromatography (HPLC) technique in vitro and in vivo. The cut-off reference solution contained in the kit of nominally 1,140 nM nortriptyline varied from 1,250 to 1,600 nM. In vitro addition of antidepressants gave positive results (change in absorbance above the cut-off value) of approximately 1,100 nM for amitriptyline, imipramine, and desmethylimipramine and approximately 1,600 nM for clomipramine and desmethylclomipramine. In contrast, high concentrations of the tetracyclic antidepressant maprotiline (7,000 nM) and the bicyclic zimeldine (2,000 nM) gave negative results. False positive results were obtained with high concentrations of thioridazine (4,000 nM), chlorpromazine (300 nM), and alimemazine (trimeprazine) (5,000 nM). Of 51 patient samples, five gave readings above the cut-off value, consistent with a tricyclic antidepressant intoxication, but two of these were false positives as compared with the specific HPLC analysis. However, no false negative results were obtained with the EMIT. In conclusion, the EMIT kit is likely to detect intoxications with tricyclic antidepressants but miss intoxications with nontricyclic antidepressants. For a screening method, this is a serious drawback, since maprotiline and zimeldine together make up approximately 25% of the total of antidepressants used in Sweden. Users of the kit must also be aware that certain phenothiazines in high therapeutic doses or in intoxication cases could interfere with this test and might lead to the false diagnosis of intoxication with tricyclic antidepressants.

Antidepressive Agents, Tricyclic↗

Treatment of malignant carcinoid tumors with human leukocyte interferon: long-term results.

Thirty-six patients with malignant carcinoid tumors were treated with human leukocyte interferon (IFN) im at doses of 3-6 megaunits/day. The origins of the primary tumors were as follows: mid-gut (29 patients); pulmonary (four); rectal (one); ovarian (one); and unknown (one). Nineteen of the 36 patients had previously been treated with cytotoxic agents, streptozocin plus 5-fluorouracil or doxorubicin, but showed progressive disease. With IFN objective tumor responses were seen in 17 of the 36 patients (47%): in 14 of the 29 patients with mid-gut carcinoids (48%) and in three of the four patients with lung carcinoids (75%). The median duration of response was 34 months. Stable disease was noted in 14 of 36 patients (39%), all presenting mid-gut carcinoids. The median duration of stable disease was 25 months. Progressive disease from the start of IFN therapy was seen in five patients (14%). All responders except one had a greater than 50% reduction of urinary 5-hydroxyindoleacetic acid or alpha-human chorionic gonadotropin, whereas four patients also had a significant reduction of tumor size on computerized tomographic scan or at laparotomy. Two patients achieved complete remission. Improvement of clinical manifestations of the carcinoid syndrome was seen in all patients with objective response. Adverse effects including influenza-like syndrome, reduction of blood cells, chemical signs of liver dysfunction, and disturbed lipid metabolism occurred but were reversible or could be circumvented by dose reduction. Autoimmune phenomena were also noted such as development of thyroid autoantibodies with thyroiditis, SLE syndrome with antinuclear factors, and parietal cell antibodies with pernicious anemia. IFN therapy seems to be very effective in controlling tumor-secreted substances and thus giving relief of clinical symptoms. It also arrests tumor growth for extended time periods (median, 2 years). The adverse effects are surmountable and less severe than with cytotoxic therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Ligament reconstruction of the thumb carpometacarpal joint using a modified Eaton and Littler technique.

A modification of the Eaton and Littler technique for reconstructing ligaments and restoring stability of the carpometacarpal joint of the thumb is described. We use a strip from the flexor carpi radialis tendon, which is split down to the crest of the trapezium. The tendon strip is led beneath the ligaments and the abductor pollicis longus insertion, through a tunnel drilled in the metacarpal base, around the insertion of the flexor carpi radialis tendon and finally back to the dorsum of the base of the metacarpal where it is inserted in the periosteum. This procedure ensures a dynamic fixation of the apical ligament and therefore a better stability.

Adult↗