[A study among teenagers in Falkenberg: frightening abuse of anabolic steroids].
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Adolescent↗
Biomedical subjects
S Nilsson
Publications and source records attributed to S Nilsson.
Estramustine potentiates the radiation effect in human prostate tumor transplant in nude mice.
In this study, we have investigated the combined effect of estramustine treatment and external beam radiation on human prostatic cancer tumor cells (DU 145) transplanted in nude mice. The treatment was given according to two different schedules. In the first treatment regimen, estramustine was administered intraperitoneally (i.p.) intermittently for 20 days. The radiation therapy, which was started on day 9, was given with 6 Gy fractions during an 11-day-long period to a total dose of 36 Gy. The combination treatment (estramustine + radiation) resulted in a significant tumor growth retardation as compared to the control group. This pronounced effect was seen neither with radiation alone nor with estramustine alone. In order to further extend the radiation treatment time, a second therapy regimen was employed. In this part of the study, estramustine was administered i.p. intermittently for 26 days. The radiation therapy, which was started on day 6, was given with 4 Gy fractions during a 21-day-long period to a total dose of 40 Gy. Under these conditions, a significant tumor growth retardation was disclosed, when comparing the combination treatment (estramustine + radiation) with radiation alone. The tumors were analyzed for content of necrosis and proliferative activity. The largest proportion of necrosis was seen in the combination (estramustine + radiation) treatment group. Also, the tumors from this group expressed a decreased proliferative activity. The data indicate that estramustine acts as a radiosensitizing agent in human prostatic cancer cells in vivo. The radiosensitizing properties of the drug encourage further studies with respect to clinical application.
Animals↗
Evaluation of a new tumor marker for cytokeratin 8 and 18 fragments in healthy individuals and prostate cancer patients.
The serological results from apparently healthy individuals and prostate cancer patients were evaluated with a new assay called TPAcyk ELISA. This assay has a biochemical specificity for fragments of cytokeratins 8 and 18, and exhibits a low within- and between-assay imprecision. The data indicate a significant difference between the results of males and females, but no significant age-dependent relation was found. The cut-off value (95% specificity) for healthy individuals was estimated to be 1.27 ng/mL (n = 190) for males and 0.95 ng/mL (n = 81) for females. When using a cut-off value of 1.27 ng/mL, we found a sensitivity for prostate cancer patients with T2-3 N0M0 of about 20%. For patients with metastatic disease, a sensitivity of 75% was found. A higher sensitivity was obtained with patient sera analyzed with PSA than with TPAcyk, particularly in patients with early stages of the disease. We conclude that the results from this new TPAcyk assay were significantly elevated in patients initially diagnosed with poorly differentiated tumors, that patients with localized tumors exhibited low concentrations, and that patients with metastatic disease showed, on average, 8 times higher concentrations than patients with localized disease. The combination of the TPAcyk and PSA results increased the sensitivity for prostate cancer, particularly in patients with metastatic disease.
Adult↗
Elevated expression of estramustine binding protein (EMBP) in prostatic intraepithelial neoplasia (PIN) compared with malignant and benign prostatic epithelia.
The expression of estramustine-binding protein (EMBP) was studied immunohistochemically in whole-mount prostate sections. Specimens were taken from the prostates of 15 patients who had undergone total prostatectomy due to localized (TOd-T2 NO MO) prostatic cancer (PC). Almost all the examined whole-mount sections displayed areas with prostatic intraepithelial neoplasia (PIN). PIN is regarded as the main precursor of invasive PC. High- and low-grade PIN expressed EMBP. The average positively stained areas accounted for averages of 69.2% and 48.7%, respectively. High-grade PIN contained the highest EMBP levels of all the investigated (benign and malignant) epithelia, followed by moderately differentiated PC. With regard to areas with PC, the highest levels of EMBP expression (61.3%) were observed in moderately differentiated PC; poorly differentiated PC came second. Of all the examined epithelia, EMBP levels were lowest in well-differentiated PC (25.8%). Normal prostatic epithelia and hyperplasia were characterized by low EMBP expression, although somewhat higher than well-differentiated PC. A moderate expression (45%) was observed in the seminal vesicles. According to these results, EMBP was expressed mainly in the diseased peripheral zone (PZ), where PIN and prostatic cancer have their highest prevalence.
Aged↗
Positive cervical smear with subsequent normal colposcopy and histology--frequency of CIN in a long-term follow-up.
From a total of 1466 new cases of cervical smears suggesting cervical intraepithelial neoplasia (CIN) II or worse, all examined with colposcopy and biopsies, 328 cases (22.4%) were initially examined with vaginal and cervical colposcopy, directed biopsies of portio, and endocervical curettage (ECC) with normal results. Patients were followed-up with regular colposcopy and cervical smear for an average of 10.6 years (2-19 years). In 72 cases (22%) a CIN occurred, in general more than 1 year (mean 2.96 years) after entering the study. Possible explanations are discussed and careful monitoring of this group of patients is recommended.
Adolescent↗
Patients with renal cancer have a larger proportion of high-density blood monocytes with increased lucigenin-enhanced chemiluminescence.
The production of oxygen metabolites is probably important in cancer cell killing. The production of the superoxide anion, O2-, can be measured by lucigenin-enhanced chemiluminescence (Cl). Previous studies have shown that whole-blood lucigenin-enhanced Cl is increased in cancer patients and that this increase is related to blood monocyte activity. The present investigation confirmed these findings and showed that whole-blood lucigenin-enhanced Cl was elevated in 17 patients with renal cell adenocarcinoma (P < 0.001). The activity of the monocytes was studied more in detail, whereby monocytes were separated into different populations based upon differences in densities, i.e., high-density and low-density monocytes. The cancer patients had a significantly larger proportion of high-density monocytes (P < 0.05) than controls. The lucigenin-enhanced Cl of purified high-density monocytes in controls was significantly higher than that of low-density monocytes (P < 0.01). The authors conclude that the increase in the lucigenin-enhanced Cl of whole blood observed in cancer patients may partly reflect the increased activity of a larger proportion of high-density monocytes in these patients.
Acridines↗
Hemostasis profile and lipid metabolism with long-interval use of a desogestrel-containing oral contraceptive.
Thirty healthy women, aged 18 to 37, were randomly allocated to treatment with a desogestrel-containing oral contraceptive, with 20 women using a nine-week on, one-week off regimen, and 10 women using the traditional regimen. At 0, 3 and 12 months, blood samples were drawn for liver proteins, lipoproteins and hemostatic variables. No significant changes were observed between the two regimens. Sex hormone binding globulin (SHBG) and corticosteroid binding globulin (CBG, transcortin) were increased two- to four-fold, as a measure of estrogenicity. Minimal changes occurred within the lipoprotein cholesterol fractions, whereas there were some increases within the lipoprotein triglyceride fractions. Among the hemostatic variables, there were significant increases of fibrinogen, factor VII and thrombin/antithrombin III (TAT) complex. The coagulation inhibitors, antithrombin III, protein C and protein S, were essentially unchanged. A decrease of both tissue plasminogen activator antigen (t-PA) and tissue plasminogen activator inhibitor activity (PAI activity) of the fibrinolytic system was observed. A nine-week regimen does not seem to alter lipid metabolism and coagulation more than a three-week regimen.
Adolescent↗
Measurement of magnetic susceptibility and MR contrast agent concentration.
This paper describes an MR imaging method for determining magnetic susceptibility constants of solutions containing paramagnetic contrast agents. The method's validity is demonstrated on Gd(DTPA) and Dy(DTPA) water solutions. The method can be used for measurement of the volume magnetic susceptibility or concentration of contrast agents in biological tissues.
Animals↗
Effect of alpha 1-adrenoceptor blockade on maximal VO2 and endurance capacity in well-trained athletic hypertensive men.
The effect of alpha 1-adrenoceptor blockade (doxazosin, 4 mg daily) on maximal VO2 and physical endurance capacity in 16 mildly hypertensive, athletic men was investigated in a randomized, placebo-controlled, double-blind, two-period of 4 weeks, cross-over study. The maximal workload obtained during graded bicycle ergometer exercise and the corresponding maximal VO2 were reduced by 16 +/- 3 W (mean +/- SE), (P = .00003) and 3 +/- 1 mL/(kg.min) (P = .0004), respectively, on doxazosin compared with placebo. The running time on a 5000 m track increased by 43 +/- 12 sec on doxazosin (P = .04). Heart rate was unchanged during the running session. Systolic blood pressure was reduced by 9 +/- 4.1 mm Hg (P = .04) immediately after finishing 5000 m. Six subjects reported side effects from doxazosin (headache, fatigue, and leg pain). Thus, antihypertensive treatment with alpha 1-selective adrenoceptor blockade moderately, but significantly, reduces maximal O2 consumption and high intensity physical endurance capacity in mildly hypertensive athletic men. Significantly reduced systolic blood pressure and unchanged heart rate immediately after running, combined with unchanged heart rate during the race may, however, suggest a safer exercise performance.
Adrenergic alpha-Antagonists↗
The relation of coronary and peripheral arterial disease to the severity of femoral atherosclerosis in hypercholesterolaemia.
OBJECTIVES: The extent of atherosclerosis in the superficial femoral artery and the severity of arterial disease in the aorto-iliac and femoro-popliteal arterial districts were related to clinical diagnosis of coronary and peripheral atherosclerosis in hypercholesterolaemic patients. DESIGN: The study constitutes baseline cross-sectional data of a randomized double-blind clinical trial on Probucol, using both computer based and visual estimations of angiographies as endpoints. SUBJECTS: Two hundred and ninety men and women (mean age 54 years) with hypercholesterolaemia. MAIN OUTCOME MEASURES: Atherosclerosis was estimated with arteriographies. Lumen volume and edge roughness (vessel inner wall irregularity) of a 20 cm segment of the femoral artery were estimated by computer. A visual atherosclerosis score of the abdominal aorta to the popliteal arteries was made on both sides. RESULTS: Patients with peripheral arterial disease had significantly more advanced disease according to all three angiographic variables than those without symptoms of peripheral vascular disease. Both men and women with coronary artery disease had significantly lower femoral lumen volume and higher roughness values than patients without. Men with previous myocardial infarction had significantly higher mean visual scores of atherosclerosis than those without, while lumen volume and roughness did not differ in either sex. CONCLUSIONS: Femoral atherosclerosis is an expression of a generalized disease, associated with clinical symptoms of coronary artery disease. Femoral atherosclerosis is often accompanied by atherosclerosis also in the coronary arteries.
Adult↗
Germline-encoded IgG antibodies bind mouse cartilage in vivo: epitope- and idiotype-specific binding and inhibition.
Autoantibodies specific for type-II collagen (CII) occur in mice and rats with collagen-induced arthritis (CIA). The binding in vitro and in vivo of mouse monoclonal antibodies (MoAbs) specific for separate epitopes in CII have been investigated. Two-day-old mice were injected intraperitoneally (i.p.) with the anti-CII antibody CIID3 in both unlabelled and biotinylated form. It was found that antibodies binding to the same epitope in CII in vivo can inhibit others from binding in an epitope-specific fashion. The binding in vivo and in vitro of anti-CII antibodies could be inhibited also by an anti-idiotypic rat antiserum produced against the D3 antibody. The anti-idiotypic antiserum inhibited the binding of the antibody D3 and the idiotypically related antibody C2. The cDNA's of anti-CII antibodies D3, C2, and F4 were sequenced and found to contain germline encoded V-genes, apparently without somatic mutations. The variable heavy chain of D3 and C2 both expressed the same VH rearrangement, confirming that they share idiotypes. This report demonstrates that CII-specific germline-encoded IgG autoantibodies bind specifically to normal cartilage in vivo via their combining site.
Amino Acid Sequence↗
The Gothenburg study of perioperative risk. I. Preoperative findings, postoperative complications.
The Gothenburg study of Perioperative Risk is a prospective clinical-epidemiological study designed to elucidate factors affecting the perioperative risk in unselected adult patients undergoing elective general or orthopaedic surgery. In this report reference data regarding preoperative characteristics and postoperative complications are presented. 1770 adult patients scheduled for elective general, urological, peripheral vascular or orthopaedic operative procedures were invited to a preoperative clinic. 81% agreed to participate and were assessed in a standardised way by means of questionnaires, interview, physical examination and laboratory screening. 82% had a previous or present condition in the medical history of some concern to the assessor. 71% had a finding of significance on physical examination. In 8% the assessment prompted further investigations or precautions. Throughout their hospital stay, all the 1361 participating patients were visited daily by an especially trained nurse with the task of registering the occurrence of complications. In 30% an untoward event occurred postoperatively--in 1% a severe one, in 21% a mild event, and in 8% an intermediate one. The complication rate was higher in vascular surgery (69%) than in orthopaedic (33%) and general/urological surgery (26%). Not only the severe and intermediate but also the mild complications affected the number of days in hospital.
Adult↗
Positron emission tomography with L-methyl-11C-methionine in the monitoring of therapy response in muscle-invasive transitional cell carcinoma of the urinary bladder.
OBJECTIVE: To investigate whether positron emission tomography (PET) with L-methyl-11C-methionine as a tracer could be used for diagnostic purposes and for evaluation of therapy in patients with varying stages of urinary bladder cancer treated with chemotherapy. PATIENTS AND METHODS: PET was employed in 44 separate examinations involving 29 patients (24 men and five women with a median age of 68 years [mean 66, range 47-78]) with localized or metastatic transitional cell carcinoma of the urinary bladder. In four patients PET examinations were performed prior to the commencement of chemotherapy, and after one course and after three courses. RESULTS: The diagnostic accuracy of PET was poor. The technique did not monitor the therapeutic effect of neoadjuvant chemotherapy, producing results that correlated with therapy outcome. PET identified those patients who responded less successfully to therapy. CONCLUSION: PET with L-methyl-11C-methionine demonstrates alterations in tumour metabolism long before visible changes appear on computed tomography or magnetic resonance imaging. Further work is required to develop more specific tracers.
Aged↗
Neuropeptides in the Australian lungfish Neoceratodus forsteri: effects in vivo and presence in autonomic nerves.
The Australian lungfish Neoceratodus forsteri is one of the few extant species of a phylogenetically ancient group. Immunohistochemistry showed the presence of galanin-, vasoactive intestinal polypeptide (VIP)-, neurotensin-, substance P-, and calcitonin gene-related peptide (CGRP)-like immunoreactivities in nerve fibers in the heart, lung, and gut, with a coexistence of VIP-, galanin-, and somatostatin-like immunoreactivity in the lung and galanin- and somatostatin-like immunoreactivity in the gut. About 20% of the substance P-immunoreactive fibers in gut and lung contained CGRP-like material. Major vessels showed a sparse innervation. In free-swimming unanesthetized fish, neurotensin (1 nmol/kg), galanin (1 nmol/kg), and bombesin (10 nmol/kg) reduced the heart rate. In two specimens tested, the effect of neurotensin was partially antagonized by atropine. Galanin and bombesin reduced and cholecystokinin 8 (CCK-8-S) increased blood flow to the lung. Neurotensin decreased, CCK-8-S increased, and substance P had no effect on dorsal aortic pressure, and all three decreased flow to the gut. It can be concluded from the present study that the general vertebrate pattern of cardiovascular and visceral nervous control by several neuropeptides is present also in Neoceratodus.
Animals↗
BLOOD PRESSURE CONTROL IN THE ANTARCTIC FISH PAGOTHENIA BORCHGREVINKI
The mechanisms of cardiovascular control in the Antarctic fish Pagothenia borchgrevinki were investigated during rest and swimming exercise using pharmacological tools to reveal the nature of the control systems involved. Simultaneous and continuous recordings of ventral and dorsal aortic blood pressure, heart rate and ventral aortic blood flow (cardiac output) were made using standard cannulation procedures and a single-crystal Doppler flowmeter. Exercise produced a clear and consistent decrease in dorsal aortic blood pressure caused by a decrease in systemic vascular resistance. At the same time, ventral aortic blood pressure increased owing to the combined effects of a markedly increased cardiac output (by about 80 %) and branchial vasoconstriction. Judged from the effects of the alpha-adrenoceptor antagonist prazosin, control of the branchial vasculature involves an alpha-adrenoceptor-mediated vasoconstriction, in addition to more traditional cholinergic vasoconstrictor and ss-adrenoceptor-mediated dilatory mechanisms. The range of heart rates is large, from 3-4 beats min-1 in individual fish during hypertensive bradycardia to about 28 beats min-1 after atropine treatment. Both chronotropic and inotropic effects are responsible for a marked increase in cardiac output during exercise. The increase in blood pressure caused by adrenaline injection was due largely to an increase in cardiac output, while direct effects on the systemic vasculature were small and transient. The increase in cardiac output, in turn, was due solely to an adrenergic stimulation of stroke volume. A barostatic bradycardia, often seen in other vertebrates in response to adrenaline injection, was absent and it is possible that a decrease in heart rate was offset by direct adrenergic stimulation of the heart. Angiotensin II (Ang II) produced consistent hypertension by systemic vasoconstriction. In contrast to the effects of adrenaline injection, the hypertension caused by Ang II was accompanied by a marked bradycardia. This could be abolished by atropine, suggesting a cholinergic vagal reflex of the type found in other vertebrates. Angiotensin I also caused an elevated blood pressure, and this effect was abolished by the angiotensin converting enzyme inhibitor enalapril, demonstrating elements of an angiotensin-related cardiovascular control system.
Journal Article↗
EVIDENCE OF REGULATORY MECHANISMS FOR THE DISTRIBUTION OF BLOOD BETWEEN THE ARTERIAL AND THE VENOUS COMPARTMENTS IN THE HAGFISH GILL POUCH
Of the extant vertebrate animals, the hagfishes are generally considered to be the group which diverged first from the ancestral vertebrate lineage, although molecular sequence analysis has recently suggested that they form a monophyletic group with lampreys (Stock and Whitt, 1992). The circulatory system of hagfishes has features that have been described as 'primitive' (Burggren et al. 1985), but their gills are effective gas exchangers. The gills are contained within discrete muscular pouches, and the anatomy of the blood system and ventilatory ducts has an ideal countercurrent arrangement (Mallatt and Paulsen, 1986; Elger, 1987). Reite (1969) first reported effects of catecholamines and other drugs on the branchial vasculature of hagfish. Recent studies of both perfused gills in situ and of blood flow in vivo have suggested that blood flow through the gills of hagfish is under tonic control by catecholamines (Axelsson et al. 1990; Forster et al. 1992). In teleosts, several studies have shown that adrenergic control mechanisms are involved in the distribution of blood between the arterio-arterial and the arterio-venous pathways of the gill vasculature (see Nilsson, 1983). Anatomical and ultrastructural studies have demonstrated the existence of similar pathways in hagfish (Cole, 1925; Mallatt and Paulsen, 1986; Elger, 1987). The experiments reported here demonstrate that, in the hagfish gill pouch, both adrenaline and isoprenaline can increase the proportion of fluid leaving via the efferent arterial route, at the expense of the venous outflow. Hagfish (Eptatretus cirrhatus Forster) were collected off Motunau, North Canterbury, New Zealand, and held in seawater aquaria until used. The masses of the 11 animals used in these experiments ranged from 680 to 1720 g with a mean of 1140±110 g (s.e.m.). Animals were anaesthetized in a 0.4 % solution of benzocaine in sea water. The hagfish were opened ventrally to expose the gills and their blood supply. Individual gill pouches were prepared for perfusion studies.
Journal Article↗
[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↗
Comparison of excess costs of care and production losses because of morbidity in diabetic patients.
OBJECTIVE: To assess and compare excess costs of care and production losses because of morbidity in diabetic patients and the general population of a Swedish community. RESEARCH DESIGN AND METHODS: Costs of production losses were calculated from medical and social insurance records on sickness benefit days (short-term illness) and premature retirement (permanent disability) in people with diabetes and in the entire population of the community (a municipality comprising a town and rural surroundings, with 28,000 inhabitants). Care costs included those of consultations and inpatient care, as well as costs of insulin, oral antidiabetic medications, other drugs, test material, and treatment devices, and they were obtained from patient records, the health care administration, and the statistics of community pharmacy sales. RESULTS: Of the diabetic patients < 65 years of age, above which both diabetic and nondiabetic people get retirement pension, and sickness benefits cease, 62% of those on insulin treatment in each gender had insulin-dependent diabetes mellitus (IDDM). All insulin-treated non-insulin-dependent diabetes mellitus (NIDDM) patients were > 40 years of age. Both the insulin-treated and the non-insulin-treated diabetic patients were prematurely retired twice as often as the average population and had twice as many inpatient days. The insulin-treated subjects also had twice as many sickness benefit days. The excess costs of production losses as a result of morbidity in people with diabetes were about $7,000 per individual and year. The corresponding excess costs of inpatient care were $800. The therapeutic expenditures for control of diabetes were about $600 per individual and year. If converted to U.S. conditions, the costs of lost production as a result of excess morbidity (< 65 years of age) would be $12 billion and $9 billion for people with insulin-treated and non-insulin-treated diabetes, respectively. CONCLUSIONS: If improved metabolic control by intensified treatment would reduce excess morbidity in both IDDM and NIDDM, the predominant costs of production losses imply that intensified antidiabetic treatment might save costs.
Adult↗