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Biomedical subjects

S Nilsson

Publications and source records attributed to S Nilsson.

At least 109 records · Page 6Linked to original sources

Water-gymnastics reduced the intensity of back/low back pain in pregnant women.

OBJECTIVE: To investigate if water-gymnastics during pregnancy may reduce the intensity of back/low back pain and the number of days on sick-leave. METHODS: A prospective, randomized study. One hundred and twenty-nine women were randomized to participate in water-gymnastics once a week during the second half of pregnancy and 129 were randomized to a control group. The women in both groups filled in questionnaires in gestational weeks 18, 34 and within the first postpartum week. Every day from week 18 to labor they assessed the intensity of back/low back pain. RESULTS: Back pain intensity increased during pregnancy. No excess risk for the pregnancy associated with water-gymnastics was observed. The women participating in water-gymnastics recorded a lower intensity of back/low back pain. The total number of days on sick-leave because of back/low back pain was 982 in the water-gymnastics group (124 women) compared with 1484 in the control group (120 women). After weeks 32 33, seven women in the water-gymnastics group compared with 17 in the control group were on sickleave because of back/ low back pain (p=0.031). CONCLUSIONS: Intensity of back/low back pain increased with advancing pregnancy. There was no excess risk for urinary or vaginal infections associated with water-gymnastics. Water-gymnastics during the second half of pregnancy significantly reduced the intensity of back/ low back pain. Water-gymnastics decreased the number of women on sick-leave because of back/low back pain. Water-gymnastics during pregnancy can be recommended as a method to relieve back pain and may reduce the need for sick-leave.

Absenteeism↗

Elevated activity of semicarbazide-sensitive amine oxidase in blood from patients with skeletal metastases of prostate cancer.

The semicarbazide-sensitive amine oxidases constitute a group of copper-containing enzymes whose physiological function is unclear. The enzymes are present in various tissues, including blood plasma. At present, the source of the plasma enzyme in humans is not known. Results of a recent study suggested that semicarbazide-sensitive amine oxidase is expressed in the skeleton, e.g. in the spine. Using an indirect autoradiographic method in mice, we provide evidence that semicarbazide-sensitive amine oxidase is present in high abundance in bone tissue. Specific activities of semicarbazide-sensitive amine oxidase were estimated in blood samples from subjects with femoral bone fractures. Moreover, enzyme activities were also measured in patients suffering from prostate cancer with skeletal metastases. The level of specific semicarbazide-sensitive amine oxidase activity in serum was significantly elevated in patients with skeletal metastases compared with both healthy controls and patients having prostate cancer without signs of skeletal metastases. Based on the results of the present study, we propose that semicarbazide-sensitive amine oxidase in blood plasma may originate, at least in part, from the skeleton.

Aged↗

Ion exchange tumor targeting: a new approach.

Connective tissues are distinguished by the types, concentrations, and organizations of material in the extracellular matrix. Many physiological functions are determined largely by the nature and organization of the extracellular components. The components are characterized by their content and distribution of charged, mostly anionic groups. The distinct roles played by the charges are sometimes modeled by analogy to the transport theory of ion exchange resins. The intent of this study was to investigate whether the properties of the tumor matrix could be used for selective, charge-dependent accumulation of charge-modified dextran. Ten patients with diagnosed superficial urinary bladder carcinoma were included in the study. They received intravesical instillations of technetium-99m-labeled charge-modified dextran derivatives (approximately 0.1-1 mg; approximately 50 MBq in saline; 30-min incubation). After treatment and resection, samples were taken from normal and diseased tissue. The result clearly demonstrated a charge-dependent difference in the quotient of radioactive uptake in tumor tissue: normal tissue. Instillations of cationic dextran yielded a high quotient, up to 3000. Normal tissue had background activity. Anionic dextran yielded a low quotient, 1.8-2, with increased background (i.e. uptake in normal tissue). Neutral dextran gave a quotient of up to 90. No radioactivity could be detected in blood. The tumors in this study apparently displayed cation-exchanging properties. We will continue this investigation and determine whether this is a general property of bladder carcinomas and whether other carcinomas display ion exchange properties. If this is the case, the finding could have important implications for the local treatment of several cancers.

Dextrans↗

Affinity capillary electrophoresis: important application areas and some recent developments.

Affinity capillary electrophoresis (ACE) is a broad term referring to the separation by capillary electrophoresis of substances that participate in specific or non-specific affinity interactions during electrophoresis. The interacting molecules can be found free in solution or can be immobilized to a solid support. Every ACE mode has advantages and disadvantages. Each can be used for a wide variety of applications. This paper focuses on applications that include purification and concentration of analytes present in diluted solutions or complex matrices, quantitation of analytes based on calibration curves, and estimation of binding constants from direct and derived binding curves based on quantitation of analytes or on analyte migration shifts. A more recent chemicoaffinity strategy in capillary electrophoresis/capillary electrochromatography (CE/CEC) termed molecular imprinting ('plastic antibodies') is discussed as well. Although most ACE studies are aimed at characterizing small-molecular mass analytes such as drugs, hormones, and peptides, some efforts have been pursued to characterize larger biopolymers including proteins, such as immunoglobulins. Examples of affinity interactions that have been studied are antigen-antibody, hapten-antibody, lectin-sugar, drug-protein, and enzyme-substrate complexes using ultraviolet, laser-induced fluorescence, and mass spectrometer detectors. This paper also addresses the critical issue of background electrolyte selection and quantitation of analytes. Specific examples of bioaffinity applications are presented, and the future of ACE in the biomedical field is discussed.

Electrophoresis, Capillary↗

Sample enrichment in a single levitated droplet for capillary electrophoresis.

This paper describes sample enrichment in a single levitated droplet for capillary electrophoresis (CE) analysis. The droplet was trapped in an acoustical field. The minute sample volumes needed for the enrichment procedure were precisely handled using a piezoelectric flow-through liquid microdispenser. Droplets with a volume of 65 pl were ejected from the device at a repetition rate ranging from one single droplet up to several hundreds per second. By counting the number of droplets ejected and accumulated in the levitated drop the sample volume was controlled. Through solvent evaporation the analytes were enriched in the diminishing droplet. The droplet was then injected into a CE capillary and the analytes, dansyl-Gly and dansyl-Val dissolved in ethanol, were separated in a 100 mM borate buffer (pH 9.0) utilising UV-absorption detection at 200 nm near the capillary outlet. Enrichment of 36000 sample droplets (2.3 microl) through solvent evaporation in the levitated drop resulted in a concentration limit of detection (CLOD) of 15 nM for the dansylated amino acids as compared to a CLOD of 2.5 microM which was achieved using standard hydrodynamic injection without preconcentration.

Electrophoresis, Capillary↗

Expression of epidermal growth factor receptor in urinary bladder cancer metastases.

Bladder cancers frequently exhibit an increased number of epidermal growth factor receptors (EGFR) in comparison to normal urothelium. The EGFR could potentially be a target for toxic conjugates. The aim of our study was to compare the expression of EGFR in metastases with concurrent or primary tumour in the urinary bladder using immunohistochemical techniques and a monoclonal antibody. Tumour material from 20 patients was investigated. The majority (13/20) of the metastases were homogeneously stained and showed a moderate to strong membranous staining for EGFR. The expression of EGFR in primary bladder tumours and metastases was similar. There was no indication that tumour tissue exposed to chemotherapy or radiation had a decreased number of EGFR. Targeting of the EGFR thus seems potentially applicable to metastatic disease.

Aged↗

Synergistic activation of RLD-1 by agents triggering PKA and PKC dependent signalling.

RLD-1 and OR-1 are closely related orphan nuclear receptors that can be activated by certain oxysterols. To obtain cells stably expressing RLD-1 or OR-1, CHOK1 cells were successively transfected with a DGRE2-ALP reporter and GR-RLD-1 or GR-OR-1 chimeric constructs. The selected cell clones that showed low background activity of the reporter and maximum fold induction by 22R(OH)cholesterol were used for subsequent experiments. Treatment of the cells with PGE2, TPA, or 8-bromo-cAMP alone did not transactivate the reporter. However, the induction of the reporter by 22R(OH)cholesterol was markedly enhanced in the presence of PGE2, TPA, 8-bromo-cAMP, or forskolin in cells expressing GR-RLD-1. The enhancement was inhibited by H-89 and bisindolylmaleimide, both inhibitors of protein kinases. These results suggest that transactivation by ligand-activated RLD-1 may be further modulated/regulated through other signal transduction pathways involving phosphorylation catalyzed by protein kinases.

8-Bromo Cyclic Adenosine Monophosphate↗

Routine ultrasound screening in pregnancy and the children's subsequent handedness.

OBJECTIVE: To study a possible association between ultrasound screening in early pregnancy and altered cerebral dominance measured by the prevalence of non-right handedness among children, particularly boys. METHODS: Follow-up of 8 to 9 year old children to women who participated in a randomised controlled trial on ultrasound screening during pregnancy in 1985-87. The children were followed up through a questionnaire sent to their mothers. The dominant hand of the child was assessed by eleven questions. The dominant foot by one question. RESULTS: No differences were found in non-right handedness between children in the screening and non-screening group. In separate analyses on ultrasound exposure and non-right handedness among boys a significant difference was found (odds ratio 1.33; 95% confidence interval 1.02-1.74). CONCLUSION: This study could not rule out a possible association between non-right handedness among boys and ultrasound exposure in early fetal life. The association was, however, confined to analyses comparing exposed and non-exposed boys and no associations were found when the comparisons were performed according to the randomised groups.

Child↗

Exploitation of a monoclonal antibody for weak affinity-based separation in capillary gel electrophoresis.

Weak biospecific recognition has been established for affinity separation in high performance liquid chromatography (HPLC). The use of weak affinity chromatography (WAC) has been limited previously by the insufficient separation efficiency achieved, allowing only some 1000 plates/m to be obtained. However, it has been shown that chiral drug separation can be performed with capillary affinity gel electrophoresis (CAGE) at considerably improved efficiency as compared with traditional chromatographic procedures. Our present study demonstrates the potential of weak affinity monoclonal antibodies as a generic method for immunologically based separations in capillary electrophoresis. Monoclonal antibodies were polymerized within a silica capillary and were used for the separation of structurally similar carbohydrate antigens. The results indicate that weak biospecific interactions can be utilized in a CAGE format to produce highly selective separation of the alpha- and beta-forms of p-nitrophenyl-labeled maltose. It remains to be seen, however, how efficient weak affinity separation in CAGE can be compared with affinity HPLC protocols. Details of typical separations and of the preparation of the antibody gel are presented.

Antibodies, Monoclonal↗

Fluorescence imaging of light absorption for axial-beam geometry in capillary electrophoresis.

A new method for investigation of axial-beam absorption detection for improved detection limits in microcolumn separations is reported. The method is based on fluorescence imaging of light absorption along a separation capillary. The probing UV light is introduced at one end of the capillary and shows an exponential fall-off along the capillary. As the UV light propagates through the sample peaks, an additional loss in intensity will be observed. In order to view the absorption profile along the capillary, a background fluorophore is added to the buffer. A charge-coupled device (CCD) detector and imaging optics are placed beside the capillary to view the capillary in a direction perpendicular to the capillary. Signal integration is employed for consecutive exposures as well as for neighboring detector pixels in order to increase the signal-to-noise ratio. Measurements for stilbene 3 with sulforhodamine B as a background fluorophore are presented. The characteristics of the detection method and potential improvements are discussed.

Electrophoresis, Capillary↗

Paradoxical puborectalis contraction is associated with impaired rectal evacuation.

The role of paradoxical puborectalis contraction in the aetiology of constipation and how to best diagnose this condition is controversial. The aims of this study were to investigate whether absolute or relative paradoxical electrical activity during electromyography (EMG) are related to rectal emptying and to compare EMG, defecography and digital examination in the diagnosis of paradoxical puborectalis contraction. Included in the study were 171 consecutive patients with idiopathic constipation; 136 of these cases were also classified as paradoxical or unclear or not paradoxical at digital examination. Absolute amplitudes and a strain/squeeze index were used to grade the EMG activity in the puborectalis and external sphincter muscle. Rectal evacuation was analysed by defecography with image analysis of rectal area. The results showed that 142 patients had paradoxical EMG activity during straining. There was a correlation between rectal evacuation and amplitudes (r = -0.20 to -0.03, P < 0.01) and between evacuation and index (r = -0.34 to -0.39, P < 0.0001). Forty-two patients with an index of > 50 had impaired rectal evacuation compared with those with an index < or = 50 (P < 0.0001). Thirty-three of 34 cases (n = 136) with an index of > 50 also were paradoxical at defecography whereas 19 were diagnosed digitally. In conclusion, paradoxical puborectalis contraction is associated with impaired rectal evacuation. The activity seems to be best reflected by a strain/squeeze index. The best correlation in diagnostic methods was between EMG and defecography.

Adult↗

Synthesis and in vitro evaluation of [carbonyl-11C]estramustine and [carbonyl-11C]estramustine phosphate.

[carbonyl-11C]Estramustine and [carbonyl-11C]estramustine phosphate were synthesized from [11C]phosgene using a one pot procedure. [carbonyl-11C]Estramustine was obtained in 31-43% decay corrected yield based on radioactivity trapped in the reaction vessel. The product was obtained 25 min after the end of radionuclide production with a specific radioactivity of 0.38-1.11 Ci/mumol. A method was developed yielding [carbonyl-11C]estramustine phosphate in 29-45% decay corrected yield based on trapped radioactivity, without purification of the [carbonyl-11C]estramustine intermediate. The product was obtained within 40 min of the end of radionuclide production with a specific radioactivity of 0.59-0.86 Ci/mumol. Results from in vitro experiments suggest that because of their high nonspecific binding, the compounds are unsuitable for positron emission tomography as imaging agents for the estramustine binding protein in cancer.

Animals↗

X-ray crystallographic and functional studies of thyroid hormone receptor.

We have solved several X-ray crystallographic structures of TR ligand-binding domains (LBDs), including the rat (r) TR alpha and the human (h) TR beta bound to diverse ligands. The TR-LBD folding, comprised mostly of alpha-helices, is likely to be general for the superfamily. The ligand, buried in the receptor, forms part of its hydrophobic core. Tight fitting of ligand into the receptor explains its high affinity for the TR, although the structure suggests that ligands with even higher affinities might be generated. The kinetics of 3,5,3'-triiodo-L-thyronine (T3) and 3,5,3',5'-tetraiodo-L-thyronine (T4) binding suggest that folding around the ligand, rather than receptor opening, is rate-limiting for high affinity binding. TR beta mutations in patients with resistance to T3 cluster around the ligand; these different locations could differentially affect on other receptor functions and explain the syndrome's clinical diversity. Guided by the structure, mutations have been placed on the TR surface to define interactions with other proteins. They suggest that a similar surface in the LBD is utilized for homo- or heterodimerization on direct repeats and inverted palindromes but not on palindromes. Coactivator proteins that mediate TR transcriptional activation bind to a small surface comprised of residues on four helices with a well-defined hydrophobic cleft, which may be a target for pharmaceuticals. The coactivator-binding surface appears to form upon ligand-binding by the folding of helix 12 into the scaffold formed by helices 3, 4 and 5. The analysis of most currently used antagonists suggest that although they probably fit into the ligand-binding pocket, they possess a group that may alter proper folding of the receptor, with disruption of the coactivator-binding surface (the 'extension model').

Animals↗

Gill blood flow control.

The arrangement of the fish gill vasculature is quite complex, and varies between the different fish groups. The use of vascular casting techniques has greatly enhanced our knowledge of the anatomy of the branchial microcirculation, not least through the contributions of Pierre Laurent and co-workers at Strasbourg. At different physiological situations, the contact surface between water and blood (functional surface area) varies to balance oxygen uptake against osmotic water flow ("respiratory-osmoregulatory compromise"). This is controlled by nerves and by blood-borne or locally released substances that affect blood flow patterns in the gill. Histochemical techniques have been used to demonstrate neurotransmitter substances in the branchial innervation. In combination with physioly-osmoregulatory compromise" at different physiological situations.

Animals↗

History, clinical findings, sexual behavior and hygiene habits in women with and without recurrent episodes of urinary symptoms.

BACKGROUND: To compare women with and without a history of recurrent symptoms suggestive of a urinary tract infection but a current negative urine culture regarding symptoms and signs of a genital infection, carriership of sexually transmitted agents and vaginal flora changes, sexual behavior and genital hygiene practice. SETTINGS: Contraceptive attendees at family planning and youth clinics. MATERIALS AND METHODS: Two hundred and seventeen women who reported recurrent symptoms of dysuria, frequent micturition, and urgency and had a negative bacterial urine culture were recruited as cases. Seven hundred and ten culture-negative women lacking such symptoms served as controls. A careful record was made including details about gynecological symptoms, sexual behavior and genital hygiene practice. Gynecological signs were noted at gynecological examination. Genital infections, including sexually transmitted diseases, were diagnosed. RESULTS: The mean age of the two groups studied was 26.2 and 25.8 years, respectively. Symptoms, such as dysmenorrhea, vaginal discharge, genital pruritus, abdominal pain and superficial dyspareunia were more frequent in the study group than among the controls. On examination, only erythema was observed more often. However, the cases more often had a history of genital herpes and vulvovaginal candidosis. They used tampons only for menstrual purposes, and soap for genital hygiene, but more often used low-pH solutions and took hot baths less frequently. The women with recurrent urinary symptoms more often masturbated and more often had experience of anal sex and sex during menstruation than the control group. CONCLUSIONS: Sexual behavior and genital hygiene habits may play an etiological role in the lives of women with recurrent episodes of urinary symptoms with a negative bacterial urine culture.

Adult↗

Survival in renal cell carcinoma-a randomized evaluation of tamoxifen vs interleukin 2, alpha-interferon (leucocyte) and tamoxifen.

Metastatic renal cell carcinoma (RCC) has a poor prognosis. Conventional treatment strategies, including chemotherapy and hormonal therapy, have limited value. Although encouraging results have been achieved in terms of objective response using immunological manipulations, no conclusive studies yet exist with a controlled comparative evaluation of survival. Therefore, the present study was undertaken, which compared one of the present (and presumed best) treatments, interleukin 2/interferon-alpha (IL-2/IFN-alpha) and tamoxifen, with a control arm of tamoxifen only. Tamoxifen has been shown to potentiate in vivo anti-tumour activity of IL-2, and because of its non-toxic behaviour it was included in both groups. The study was open, randomized and included seven institutions in Sweden. The patients were stratified according to the different centres involved. An interim analysis was planned when a minimum of 100 patients were evaluable. The 128 patients finally included had a histologically documented metastatic RCC, with a life expectancy of more than 3 months, a performance status WHO 0-2 and no prior chemo- or immunotherapy. Informed consent was obtained from each patient. The patients randomized to the control arm (n = 63) received only tamoxifen 40 mg p.o. daily for at least 1 year or until progression. The patients (n = 65) randomized to biotherapy received subcutaneous recombinant IL-2, leucocyte IFN-alpha in a treatment cycle of 42 days, as well as tamoxifen p.o. In the absence of undue toxicity or disease progression, these patients received one additional treatment cycle of 42 days followed by maintenance treatment, consisting of 5 days therapy every 4 weeks, for 1 year, or until proven progression. Only two patients in the tamoxifen-only group received immunotherapy when the disease progressed, but without any beneficial effect. All patients received appropriate local treatment when indicated. The interim analysis demonstrated no survival advantage for either group, and therefore further inclusion of patients was stopped. The median follow-up was 11 months (range 0.4-48 months). The final survival analysis showed no significant differences between the two treatment arms in so far as comparison from the day of diagnosis of primary disease, from the day of first evidence of metastatic spread, or from the onset of treatment. This was valid both when the evaluation was performed with regard to intention to treat and when the analysis was directed only to patients that managed at least one treatment cycle (42 days) of IL-2/IFN-alpha. The adverse effects were more pronounced in the IL-2/IFN-alpha group. Although the number of patients is limited, the results raise doubt concerning immunotherapy with IL-2 and IFN-alpha as a routine treatment in the management of advanced RCC. The difference in cost of drugs and health care (drug costs per patient: IL-2/IFN-alpha $27000 vs tamoxifen $360) as well as adverse effects caused by IL-2/IFN-alpha are also factors of importance. The study emphasizes the need for more effort to find the 'optimal schedule' of immunotherapy, as well as the need for randomized controlled studies before approval of a new treatment in the routine setting.

Adult↗

Lung aeration and pulmonary gas exchange during lumbar epidural anaesthesia and in the lithotomy position in elderly patients.

We investigated a total of 36 subjects with a mean (SD) age of 65 (13) years, during baseline conditions (supine, before any anaesthesia), and then during one of the following protocols: (1) lithotomy positioning (n = 12), (2) epidural anaesthesia (n = 12), (3) general anaesthesia in the supine position (n = 12). Lung aeration, ventilation/perfusion matching, gas exchange and functional residual capacity were measured. Lung aeration was normal during baseline assessment with almost no regions with poor aeration and no substantial dependent densities. Shunt and perfusion of poorly ventilated regions were minor. Lithotomy positioning did not reduce functional residual capacity and did not affect aeration of the lung or ventilation/perfusion matching. Epidural anaesthesia, in general, had no effect on aeration, ventilation/perfusion matching or gas exchange, regardless of whether the patient was in the supine or lithotomy position. General anaesthesia, however, caused significant increases in poorly aerated lung regions and in dependent densities (interpreted as atelectasis). In conclusion, no or little impairment of lung aeration and ventilation/perfusion matching was caused by the lithotomy position and/or epidural anaesthesia, contrary to the effects seen during general anaesthesia. However, our findings also suggest that being overweight is a factor that may cause impairment of lung aeration.

Aged↗

Hormonal aspects of epithelial ovarian cancer: review of epidemiological evidence.

Epithelial ovarian cancer is fairly common with high rates in Scandinavia, intermediate rates in western Europe and North America and low rates in the developing countries and in Japan. The 5-year survival rate is less than 40%. Increasing parity consistently gives a strong protection against epithelial ovarian cancer. A lesser degree of protection is probably derived from incomplete pregnancies and lactation. Ages at menarche and menopause are most probably weak predictors of epithelial ovarian cancer risk. Ever users of oral contraceptives (OC) have 30% lower risk compared to never users. The protection increases with duration of OC use, being about 50% after 5 years. The reduced risk among past OC users persists for at least 10 years after cessation of use. Results concerning hormone replacement therapy (HRT) and epithelial ovarian cancer risk are conflicting, but most data point to a weak or no association, but as an increasing number of women use HRT it still seems important to resolve any potential effect. Infertility adds to epithelial ovarian cancer risk in nulliparous women, while temporary fertility problems in parous women do not appear to increase risk. A possible independent risk effect of fertility drug use has not been easy to assess and remains unresolved. It has been particularly difficult to separate the effects of fertility drugs from those of infertility. Tubal ligation and hysterectomy convey protection against epithelial ovarian cancer, possibly through a suppressed ovarian hormone production. The causes of epithelial ovarian cancer are poorly understood, but reproductive hormones are thought to be involved in the aetiology. For a long time the 'incessant' and 'gonadotrophin' hypotheses have been promoted in relation to carcinogenesis. Both hypotheses find support in ovarian cancer epidemiology, and recent progress in molecular biology adds to the understanding of possible aetiological mechanisms. Another hypothesis focuses on the retrograde transport of contaminants or carcinogens through the Fallopian tubes. It is important to establish if the same risk factors apply to the various histological types of ovarian cancer, as particularly the mucinous ovarian tumours seem to present with different risk factors. Another question to resolve is if sporadic vs. inherited cases carry distinct risk profiles. As the hypotheses above do not explain all of the results derived from ovarian cancer epidemiology, there is a need to test additional hypotheses to possibly define preventive programmes and to come closer to the cause of ovarian cancer.

Adenocarcinoma↗