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Biomedical subjects

S Nilsson

Publications and source records attributed to S Nilsson.

At least 181 records · Page 10Linked to original sources

Does surgical repair of a rectocele improve rectal emptying?

PURPOSE: This study was undertaken to assess results of surgical repair of rectocele and to identify possible determinants of outcome from patient's history and preoperative defecography. Another aim was to evaluate how surgery affects rectal evacuation. METHOD: Thirty-four women with constipation and rectal emptying difficulties underwent surgery with a transanal technique. A preoperative defecography was performed in each patient. They were followed up after a median of 10 (range, 2-60) months with a questionnaire (n = 34) and a defecography (n = 31). Computer-based image analysis of defecographies was used to evaluate rectal evacuation. RESULTS: In 27 patients (79 percent), the result of surgery was good with subjectively improved emptying. The need for vaginal or perineal digitation preoperatively was related to a good result (P < 0.05), whereas a previous hysterectomy (P < 0.01) and a large rectal area on defecography (P < 0.01) related to a poor result. Preoperative use of enemas, motor stimulants, or several types of laxatives also related to a poor outcome (P < 0.05). Surgical treatment resulted in reduction of the rectocele (P < 0.001), an elevated position of the anorectal junction (P < 0.05), and improved rectal evacuation on defecographies (P < 0.001). CONCLUSIONS: Surgical repair reduces the size of the rectocele and improves rectal emptying. These changes are accompanied by a symptomatic improvement in the majority of patients. Preoperative patient data and defecography may help in selecting patients for surgery.

Adult↗

Sexual risk behavior in women with cervical human papillomavirus infection.

In a study of 972 women, sexual characteristics of 66 women with a cervical human papillomavirus infection (CHPI) were compared to the remaining study population. Among a number of sexual variables that were significantly correlated with CHPI were number of lifetime sexual partners, short partnerships, many recent partners, infidelity, casual travel sex, sexual début abroad, oral and anal sex, and sexual abuse. In multifactorial analyses four variables remained significantly correlated with CHPI, i.e., number of lifetime sexual partners, casual travel sex, sexual début abroad, and infidelity. It is concluded that CHPI shows most of the epidemiological characteristics of a sexually transmitted disease.

Adolescent↗

Retention and processing of the monoclonal anti-prostate E4 antibody after binding to prostatic adenocarcinoma DU 145 cells.

Cellular retention and processing of a radiolabelled monoclonal anti-prostate antibody were evaluated after binding to prostatic adenocarcinoma DU 145 cells. An endocytosis assay revealed that the rate of release of radioactivity from the cells had an initially rapid phase within the first hours after antibody incubation, which was presumably due to release of monovalently bound antibodies. This was followed by a slower phase, with the possible release of intact bivalently bound antibodies and excretion of degraded internalized antibodies. The relative amount of released radioactivity of high molecular mass was high, indicating that the major part of the antibodies were released without being internalized and degraded. However, when only the radiolabelled antibody that remained cell-associated after 2 h and longer was considered, a substantial part was found to be internalized and radioactive degradation products were excreted. About 30% of the initially cell-associated radioactivity still remained associated with the cells after 48 h, indicating a rather slow antibody processing, which is favourable if the antibody is to be used for targeted radiotherapy. The retention of cell-associated radioiodine was very similar irrespective of whether the antibodies were radiolabelled with the direct chloramine-T method or the indirect ATE (succinimidyl based reagent) method. Since the ATE method can be used to form stable antibody constructs with the therapeutically relevant alpha-emitting radionuclide, astatine-211, this was an interesting finding that will be further evaluated in the future.

Adenocarcinoma↗

Development of femoral atherosclerosis in relation to flow disturbances.

Angiography and post-mortem studies have indicated that disturbed blood flow may promote atherogenesis. Our aim was to demonstrate flow disturbances in vivo and correlate them to the subsequent development of atherosclerosis. The femoral arteries of 17 patients with early atherosclerosis were studied with cineangiography. The films are digitized and analyzed with an image analysis computer. From the time-intensity curves, the arrival time of the contrast medium at each pixel was calculated. In the resulting parametric images, the computer identified zones of delayed contrast filling, (ZDF) which have been shown to correspond to disturbed flow. The progression or regression of atherosclerosis was followed with another angiography 3 years later by computing changes in edge roughness. Arterial segments without flow disturbances (defined as ZDF) showed a more marked decrease in edge roughness than those with flow disturbances (p < 0.05). In addition, the edge roughness tended to increase more in segments with larger ZDF area. Angiographic studies of fluid mechanics and atherogenesis are feasible, but larger patient materials are needed.

Adult↗

Mutant p53 protein as a predictor of survival in endometrial carcinoma.

The expression of mutated p53 protein was studied in paraffin-embedded, formalin-fixed tumour specimens from 183 women with endometrial carcinoma. Fifty-five per cent of the specimens were negative, whereas the staining intensity was weak, moderate or strong in 15, 2 and 28% of cases, respectively. Strong p53 expression (> 75% of the cells stained) was more common in uterine papillary serous cancers and clear cell cancers than in other tumour subtypes (P < 0.001), as well as in poorly differentiated tumours (P < 0.01) and in tumours with nuclear grade 3 (P < 0.0001). Strong p53 expression was also more frequently found in aneuploid tumours (P < 0.0001) and in tumours with a high S-phase fraction (P < 0.001). Strong p53 expression was highly predictive of poor survival in the univariate analysis (P = 0.006) and in the Cox multivariate analysis which included age, stage and grade. However, it lost most of its impact when the strongly prognostic nuclear grade and ploidy were added to the multivariate models.

Adult↗

Monocyte activation in patients with non-seminomatous germ cell tumour of the testis before and after tumour eradication.

AIMS: To investigate the kinetics of normalisation of monocyte oxidative activity following tumour eradication. METHODS: Whole blood lucigenin enhanced chemiluminescence was studied in patients with non-seminomatous germ cell tumours. Group 1 comprised 14 patients who had been "cured" of their cancer (the term "cured" as used in this report denotes a relapse free period of at least three years). Group 2 comprised 15 patients who were followed from diagnosis to up to two years after the start of treatment. RESULTS: Lucigenin enhanced chemiluminescence of whole blood in the "cured" patients was similar to that of controls and lower than that in patients who had not yet received chemotherapy (group 2). After treatment, chemiluminescence decreased slowly and did not normalise until 18 months after the start of treatment. Tumour necrosis factor alpha (TNF alpha) concentrations were normal in "cured" patients but were raised in those who had not yet received treatment. TNF alpha was normalised 12 months after start of treatment. Alpha-fetoprotein concentrations were raised in most patients but normalised rapidly after tumour eradication. CONCLUSIONS: The activity of blood monocytes, as measured by whole blood lucigenin enhanced chemiluminescence, is increased in cancer. This activity may be a consequence of the presence of tumour cells. Immunocompetent cells remain active for over a year after eradication of the tumour.

Adolescent↗

Nervous control of the spleen in the red-blooded Antarctic fish, Pagothenia borchgrevinki.

The mechanisms of splenic control in the Antarctic fish, Pagothenia borchgrevinki, were investigated using isolated spleen and mesenteric artery strips in vitro and perfused spleen preparations in situ. Splenosomatic index (SSI) [100 x (spleen wt/body wt)] and hematocrit were determined in animals treated with atropine and phentolamine. Atropine injection increased the SSI from 0.60 +/- 0.06 to 0.89 +/- 0.04, whereas phentolamine decreased SSI to 0.45 +/- 0.03. In atropine-injected fish, hematocrit was 18.6 +/- 1.4 before and 6.6 +/- 0.8% 3 h after injection. Electrical stimulation of the splenic nerves produced biphasic flow responses. In 11 of 12 tested preparations, atropine (3 x 10(-7) to 10(-6) M) abolished the response, suggesting a major cholinergic component in the splenic innervation. Isolated spleen strip preparations contracted in response to carbachol, a response that was antagonized by atropine. The response to acetylcholine was markedly enhanced by the specific cholinesterase inhibitor BW-284c51. Catecholamine effects were somewhat irregular, and maximal contraction force with epinephrine and norepinephrine was 41 and 56%, respectively, of the carbachol response. The results suggest a mainly, if not solely, cholinergic autonomic control of the borch spleen, and a major function of the cholinergic innervation in the control of hematocrit in this species.

Animals↗

Myocardial cell death in reperfused and nonreperfused myocardial infarctions. MR imaging with dysprosioum-DTPA-BMA in the pig.

PURPOSE: To investigate whether Dy-DTPA-BMA-enhanced MR imagining would permit identification of myocardial cell death, myocardial infarction was induced in 12 domestic pigs. MATERIAL AND METHODS: In 6 pigs with irreversible cell damage, Dy-DTPA-BMA (1.0 mmol/kg b.w.) was administered i.v. 70 min after coronary occlusion. In 6 other pigs, the infarctions were reperfused 80 min after the occlusion, followed by injection of Dy-DTPA-BMA after 30 min of reperfusion. In 4 additional pigs, the hearts were reperfused after 2 min of occlusion. All 16 pigs were sacrificed 10 min after the injection of Dy-DTPA-BMA. The hearts were excised and imaged with MR. RESULTS: Reversibly injured myocardium could not be distinguished from adjacent nonischaemic myocardium after the administration of Dy-DTPA-BMA. Reperfused, infarcted myocardium demonstrated a high signal intensity in the proton-density- and T2-weighted sequences, despite a 5-fold higher Dy concentration compared with both nonreperfused infarcted and nonischaemic myocardium. CONCLUSION: This lack of susceptibility effect in infarcted myocardium, due to a homogeneous distribution of Dy, indicates the usefulness of Dy as a marker of tissue viability.

Animals↗

Double-contrast MR imaging of reperfused porcine myocardial infarction. An experimental study using Gd-DTAA and Dy-DTPA-BMA.

PURPOSE: Myocardial infarctions were induced in 12 pigs to investigate whether a double-contrast method, combining a positive and a negative MR contrast agent, could improve the visualization of reperfused myocardial infarctions. MATERIAL AND METHODS: All 12 pigs were subjected to 80 min of occlusion followed by reperfusion. In the double-contrast group (6 pigs), Gd-DTPA-BMA (0.3 mmol/kg b.w.) and Dy-DTPA-BMA (1.0 mmol/kg b.w.) were administered i.v. after 30 min of reperfusion. In the remaining 6 pigs, a single injection of Gd-DTPA-BMA (0.3 mmol/kg b.w.) was given after 30 min of reperfusion. All pigs were sacrificed 10 min post-contrast injection, corresponding to a reperfusion time of 40 min. The hearts were excised and imaged with MR. The concentrations of GD and Dy were measured in infarcted and nonischaemic myocardium using ICP-AES. RESULTS AND CONCLUSION: Contrast media concentrations were more than 4-fold higher in infarcted compared with nonischaemic myocardium. The infarctions were best shown on T1-weighted images, and there were no differences between the double and single contrast groups. In the T2-weighted images, the infarctions were significantly better visualized in the double-contrast group, due to a Dy-induced signal intensity loss in nonischaemic myocardium.

Animals↗

Positron emission tomography in the diagnosis and staging of urinary bladder cancer.

PURPOSE: Evaluation of positron emission tomography (PET) using (18)fl 18F-2-fluoro-2-deoxy-D-glucose (18FDG) and L-methyl-11C-methionine in the diagnosis and staging of urinary bladder carcinoma. MATERIAL AND METHODS: Twenty-three patients with biopsy-proven urinary bladder carcinoma were examined with PET after intravenous injection of 11C-methionine; 2 were also examined with 18FDG. The results from the PET investigations were compared with CT or MR findings and TNM classification before and after treatment. RESULTS: The urinary excretion of 18FDG prevented distinction of the primary tumour from the surrounding tracer. With 11C-methionine it was possible to detect 18/23 primary tumours. A trend was seen, suggesting that the higher the uptake values of 11C-methionine in the tumour, the greater the tumour stage. CONCLUSION: It is possible to visualize urinary bladder tumours larger than 1 cm in diameter with PET using (11)C-methionine, but the value of the method in the staging of the lesions is not superior to conventional methods.

Aged↗

Dynamic anatomical study of cardiac shunting in crocodiles using high-resolution angioscopy

Prolonged submergence imposes special demands on the cardiovascular system. Unlike the situation in diving birds and mammals, crocodilians have the ability to shunt blood away from the lungs, despite having an anatomically divided ventricle. This remarkable cardiovascular flexibility is due in part to three anatomical peculiarities: (1) an 'extra' aorta (the left aorta) that leaves the right ventricle and allows the blood from the right ventricle to take an alternative route into the systemic circulation instead of going to the lungs; (2) the foramen of Panizza, an aperture that connects the right and left aortas at their base immediately outside the ventricle; and (3) a set of connective tissue outpushings in the pulmonary outflow tract in the right ventricle. Using high-resolution angioscopy, we have studied these structures in the beating crocodile heart and correlated their movements with in vivo pressure and flow recordings. The connective tissue outpushings in the pulmonary outflow tract represent an active mechanism used to restrict blood flow into the lungs, thus creating one of the conditions required for a right-to-left shunt. We observed that the foramen of Panizza was obstructed by the medial cusp of the right aortic valve during most of systole, effectively differentiating the left and right aortic blood pressure. During diastole, however, the foramen remained open, allowing pressure equilibration between the two aortas. Contrary to current theories, we found that the left aortic valves were unable to cover the foramen of Panizza during any part of the cardiac cycle, supporting the reversed foramen flow hypothesis. This would ensure a supply of blood to the coronary and cephalic circulation during a complete shut-down of the left side of the heart, such as might occur during prolonged submergence.

Journal Article↗

Effects of preload and afterload on the performance of the in situ perfused portal heart of the New Zealand hagfish Eptatretus cirrhatus

The portal heart of the New Zealand hagfish (Eptatretus cirrhatus) was perfused in situ. Stroke volume, cardiac output and power output increased in response to increased preload, in accordance with Starling's law of the heart. A positive chronotropic effect was found when the input pressure increased from 0.05 to 0.1 kPa. Increased afterload decreased stroke volume and cardiac output. Power output peaked at an output pressure of 0.22 kPa, after which it decreased. There was no change in heart rate in response to increased afterload. In unanaesthetized resting animals, the pressure in the supraintestinal vein, which supplies the portal heart, ranged from 0.025 to 0.07 kPa (mean 0.040&plusmn;0.005 kPa). The beta-adrenoceptor antagonist sotalol did not affect the response to different input and output pressures. Sotalol produced a significant decrease in heart rate and abolished the pressure-sensitive increase in heart rate. Bolus injections of adrenaline produced a transient increase in portal heart rate. The negative chronotropic response to sotalol and the response to adrenaline indicate the presence of an endogenous beta-adrenergic tonus on the portal heart.

Journal Article↗

Adverse effects after radical external beam radiotherapy of localized prostatic adenocarcinoma using two-dimensional dose-planning and a limited field technique.

Adverse effects were assessed after definitive limited field, 2-dimensional CT-planned radiation treatment of localized prostatic adenocarcinoma. In 66 surviving patients, out of a total of 176 treated patients, personal interviews were performed and self-administered questionnaires distributed. The average follow-up was 6.6 years. Adverse effects with regard to bowel function and micturition were investigated, and graded 0-4 with increasing severity and impact on performance status, essentially according to the RTOG toxicity scoring system. Sexual functions were registered on visual analogue scales. The majority of adverse effects were considered minor (grade 1) and did not require any treatment. Late adverse effects on bowel and bladder or urethra that required treatment (grade 2-4) were reported in up to 8% (n = 5) of cases respectively. Late bowel side-effects that interfered with life style (grade 3-4) occurred in up to 3% (n = 2) of patients; the majority were rectal complications. Corresponding urinary side-effects were registered in up to 6% (n = 4) of the patients. Major surgical interventions were not required. Sexual functions were substantially affected in 60% of cases not administered endocrine treatment. Multivariate analyses could not identify patient or treatment risk factors related to complications.

Adenocarcinoma↗

Estramustine-binding protein (EMBP) in renal cell carcinoma immunohistochemistry, immunoscintigraphy and in vitro estramustine effects.

The present report shows that the human renal cell carcinoma (RCC) cell lines, A498 and CAKI-2, express the estramustine-binding protein (EMBP). The RCC cell lines investigated were highly sensitive for estramustine, with cell arrest in atypical metaphase. In vitro experiments using a fluorimetric cytotoxicity assay (FMCA) showed a pronounced cytotoxic effect mediated by estramustine. Immunohistochemical analysis of tumour specimens from patients with RCC showed positive staining for EMBP in 12/16 cases. Immunoscintigraphy was performed in an experimental system in nude mice, heterotransplanted with the CAKI-2 cell line. A radiolabelled monoclonal anti-EMBP antibody was used. The results show a specific uptake of the antibody in the RCC tumour, expressed as a percentage of the injected dose per gram tissue, which ranged from 4.03 to 6.9. The results obtained form the basis for clinical studies on the feasibility of utilizing estramustine in the management of RCC. Immunoscintigraphy using the monoclonal anti-EMBP antibody is of potential use for in vivo characterization of the malignancy and in the selection patients suitable for treatment with estramustine.

Adult↗

99mTc-dextran-antibody conjugates. Labelling procedures.

Dextran forms stable chelates with 99mTc, a radionuclide with ideal properties for planar scintigraphic and tomographic imaging. This study investigates some of the factors of importance to the formation of 99mTc-dextran. The complex was used for the technetium labelling of a monoclonal antibody. Two radiolabelling methods were studied: direct dextran labelling with the reductant dissolved in HCI and labelling via a weak 'transfer' chelator (tartaric acid) with the reductant dissolved in ethanol. Different conditions during the labelling reaction were studied. Finally, dextran was coupled to a monoclonal anticytokeratin antibody and the conjugate was subsequently radiolabelled with 99mTc. Gel filtration (GFR) and thin layer chromatography (TLC) were compared as methods for estimation of the labelling efficiency. When using 10-500 microM of ligand, 5-100 microM SnCl2 with 10-500 MBq of technetium at pH 7 incubated for 10-15 min, the radiolabelling seemed optimal (70-75% labelling efficiency). It was found that 100 microM tartaric acid used as a weak intermediate chelator with SnCl2 dissolved in ethanol improved the reproducibility of the labelling. The labelling efficiency was not affected by either the presence of oxygen or the addition of an oxygen scavenger during the labelling incubation. In general, TLC showed higher labelling efficiencies than GFR, indicating inadequate separation of the different moieties.

Antibodies, Monoclonal↗

Functional results after abdominal suture rectopexy for rectal prolapse or intussusception.

OBJECTIVE: To assess the functional outcome after suture rectopexy in patients with rectal prolapse or intussusception. DESIGN: Retrospective study. SETTING: University hospital, Sweden. SUBJECTS: 33 patients with rectal prolapse and 19 patients with intussusception treated by abdominal suture rectopexy 1969-1992. MAIN OUTCOME MEASURES: Bowel function evaluated by a questionnaire a median of 97 months after operation. RESULTS: 10/33 patients (30%) reported less constipation after rectopexy in the prolapse group compared with 3/19 (16%) in the intussusception group (p = 0.33). Rectal emptying improved in 14/33 (42%) and 1/19 (5%), respectively (p = 0.005), and incontinence in 12/33 (36%) and 3/19 (16%), respectively (p = 0.20). Seventeen patients (52%) with prolapse and 3 (16%) with intussusception described the result of operation as excellent or good (p = 0.02). CONCLUSION: There is a reasonable chance of improved rectal emptying and continence in patients undergoing suture rectopexy for rectal prolapse, whereas bowel symptoms commonly worsen postoperatively in patients treated for intussusception.

Adult↗

Vanilloid (capsaicin) receptors in the rat: distribution in the brain, regional differences in the spinal cord, axonal transport to the periphery, and depletion by systemic vanilloid treatment.

Vanilloid (capsaicin) receptors were visualized by [3H]resiniferatoxin (RTX) autoradiography in the brain of newborn as well as adult (both control and colchicine-treated) rats. Specific labelling was seen in the brain stem only, in the nucleus of the solitary tract extending into the area postrema and the spinal sensory nucleus of the trigeminal nerve. Also, a strong signal was seen in the dorsal horn, dorsal root, trigeminal and nodose ganglia. Membranes obtained from the cervical, thoracic, and lumbar segments of the spinal cord showed similar affinities for RTX and likewise for capsaicin and capsazepine; maximal receptor density was similar in the cervical and thoracic segments (approximately 70 fmol/mg protein) but was twice as high in the lumbar segment. 24 h after ligation of the vagal or the sciatic nerves, a strong accumulation of specific RTX binding sites was observed mainly proximal to the ligature, implying intraaxonal receptor transport from the nodose and dorsal root ganglia, respectively, to the periphery. Systemic (s.c.) vanilloid treatment depleted specific [3H]RTX binding sites from the brain stem, the sensory (dorsal root as well as trigeminal) ganglia, and the spinal cord. RTX was approximately 200-fold more potent than capsaicin for eliminating vanilloid receptors from the spinal cord. The present results suggest a discrete expression of vanilloid receptors in the brain stem (sensory nuclei); although intrinsic vanilloid receptor-expressing neurons are though to exist in the rat brain, they remain undetected by the present [3H]RTX autoradiography methodology.

Animals↗

Labeling of polypeptides with technetium-99m using a dextran spacer.

Radioimmunoscintigraphy and other forms of scintigraphy are becoming increasingly important as tools in detection and evaluation of cancer diseases. Several radionuclides can be considered as radiolabel; however, 99mTc may be the most suitable because of easy availability and near ideal physical properties. This study describes how dextran is coupled to a monoclonal anticytokeratin antibody, epidermal growth factor, and somatostatin through stable amine bonds. The dextran moiety could then be labeled with 40-62 MBq of 99mTc. The labeling efficiency was 60-94%, determined by gel filtration or TLC. The specific binding could be considerably preserved after the dextranation, the antibody retained > 90% of its activity, epidermal growth factor bound with > 90% specificity to receptor-expressing tumor cells, and somatostatin showed approximately 40% specific binding to rat adrenal homogenates. Because somatostatin only has a transient half-like in vivo, the in vivo plasma half-life of somatostatin-dextran was tested in normal female Sprague-Dawley rats. The result showed a strong enhancement of the plasma half-life that was dependent on two compartments, 4 and 8 h.

Animals↗