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S Nilsson

Publications and source records attributed to S Nilsson.

At least 145 records · Page 8Linked to original sources

[New glucocorticoids are more selective. Current knowledge can eliminate serious adverse effects].

Glucocorticoids have been used as anti-inflammatory, anti-allergic and immunosuppressive agents since the beginning of the 1940s, and during recent years the mechanisms by which they exert their anti-inflammatory effects have begun to be better understood. Inhibition of inflammatory response is primarily mediated via the glucocorticoid receptor and the two transcription factors, AP-1 and NF kappa B, which are of crucial importance for the expression of pro-inflammatory cytokines and other genes involved in the inflammatory process. Unfortunately, long-term treatment with glucocorticoids is associated with a series of adverse effects such as hypertension, bone fragility, diabetes, dermatrophy and personality changes. However, owing to advances in biotechnology and recent clarification of the molecular mechanisms involved, it is now becoming possible to develop new glucocorticoids with a more selective anti-inflammatory effect without serious side-effects.

Anti-Inflammatory Agents↗

Anemia associated with advanced prostatic adenocarcinoma: effects of recombinant human erythropoietin.

BACKGROUND AND METHODS: Nine patients with hormone-refractory metastatic prostatic adenocarcinoma and anemia were treated with recombinant human erythropoietin (rHuEpo) at a median dose of 150 U/kg BW 3 times a week subcutaneously. Baseline hemoglobin (Hb) ranged from 70 to 116 g/L, and the study duration was 12 weeks (median patient participation period was 8 weeks). RESULTS: Four patients demonstrated a median Hb increase of 20 g/L and were considered responders. Three patients showed a median increase of 17 g/L but required blood transfusion once, and were therefore considered as partial responders. Baseline erythropoietic status showed a significant correlation between serum Epo and Hb. Inadequate Epo production, evaluated by the observed/predicted log Epo ratio, was found in two patients. Defective bone marrow activity, demonstrated by low transferrin receptor (TfR), and hypoferremia in spite of abundant iron stores were also shown. Hemorheological investigations showed elevated plasma viscosity. CONCLUSIONS: Our results indicate that suppression of erythropoiesis can be mainly explained by the depressed marrow activity. The altered hemorheology might contribute to the anemia. This anemia could possibly be corrected with rHuEpo.

Adenocarcinoma↗

Characterization of residual tumor cells following radical radiation therapy for prostatic adenocarcinoma; immunohistochemical expression of prostate-specific antigen, prostatic acid phosphatase, and cytokeratin 8.

BACKGROUND: Our knowledge about the nature and biological activity of tumor cells residing in the prostate gland after radical radiotherapy (RRT) is limited. METHODS: In the present study, residual tumor in core biopsies taken from 37 patients after an average of 6.8 years follow-up after radiation, were investigated with immunohistochemistry for the biochemical markers prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and the epithelial marker, cytokeratin 8 (CK8). RESULTS: Tumor cells were cytokeratin-positive in 33 of 34 evaluable specimens (97%). PSA and PAP were expressed in the tumor cells in 94% (34/36) and 81% (30/37) of cases, respectively. No significant correlation was observed between PSA/PAP expression and tumor grade after treatment. Endocrine treatment administered in addition to RRT in 12 of the 37 patients did not affect the expression of PSA or PAP. The expression of both biochemical markers was reduced after radiotherapy in 10 of the 12 cases for which pre- and post-treatment specimens were available. CONCLUSIONS: Tumor cells retain their epithelial characteristics immunohistochemically after radiation, though their morphology sometimes suggests an altered phenotype after treatment. PSA and PAP reactivity was demonstrated in tumor cells nearly 7 years after radiotherapy, which indicates that these cells maintain their biochemical integrity and protein synthesis to a certain extent. Furthermore, endocrine treatment did not abolish PSA or PAP expression in the tumor cells. Whether PSA and PAP immunoexpression provides independent prognostic information needs to be further investigated.

Acid Phosphatase↗

Binding, internalization and degradation of EGF-dextran conjugates in two human bladder-cancer cell lines.

Bladder carcinomas often have an increased number of epidermal growth factor (EGF) receptors. The EGF receptors can, in these cases, be targets for toxic conjugates. In this study, EGF-dextran conjugates were used as targeting agents with therapeutic potential. The binding, internalization and degradation of 125I-EGF-dextran conjugates in J82 and RT4, 2 different bladder cancer cell lines, were investigated. The behaviour of 125I-EGF was studied as a comparison. The 125I-EGF-dextran showed a continuous increase in binding up to 24 hr, while 125I-EGF exhibited maximum binding after about 90 min. Both cell lines showed similar binding patterns. The binding of 125I-EGF-dextran and 125I-EGF was, on both cell lines, receptor-specific since the binding could be displaced with non-radioactive EGF. Analysis of internalized and membrane-bound 125I activity after administration of 125I-EGF-dextran showed that most of the activity was membrane-bound. A large part of both the internalized and the membrane-bound activity remained cell-associated up to 24 hr. The internalized and membrane-bound activity after administration of 125I-EGF decreased rapidly and only a small fraction remained cell-associated after 24 hr. 125I-EGF-dextran remained cell-associated, with only a limited release of low- and high-molecular-weight radioactivity throughout the 24-hr period, while 125I-EGF was extensively degraded and released into the incubation medium as low-molecular-weight radioactivity during this time. Several qualities of the 125I-EGF-dextran conjugates might be favourable for targeted radiotherapy.

Cell Membrane↗

Three approaches to enantiomer separation of beta-adrenergic antagonists by capillary electrochromatography.

Three different capillary electrochromatographic methods for the enantiomer separation of beta-adrenergic antagonists (acebutolol, alprenolol, atenolol, metoprolol, pindolol, prenalterol, and propranolol) were applied using different cyclodextrins (beta-cyclodextrin, carboxymethyl-beta-cyclodextrin and dimethyl-beta-cyclodextrin) added to the electrolyte, a cross-linked protein-gel (cellobiohydrolase I) and a molecularly imprinted ((R)-enantiomer of propranolol) superporous polymer as chiral selectors. Through use of these different separation strategies, all the beta-adrenergic antagonists studied could be resolved into their enantiomers, although the three methods were carried out without extensive optimization. The protein and molecularly imprinted phases gave the highest selectivities whereas employing cyclodextrins resulted in the highest separation efficiency. Proteins and cyclodextrins are primarily natural products, albeit the cyclodextrins can be derivatized. In contrast, the molecularly imprinted chiral stationary phase can be highly customized when produced.

Adrenergic beta-Antagonists↗

Contraceptive use in women with bacterial vaginosis.

The aim of the study was to investigate if bacterial vaginosis (BV) is associated with use of specific contraceptives. Women at family planning and youth clinics (n = 956), among whom 131 had BV, were subjects for structured in-depth interviews including current and previous contraceptive use. Variables measuring sexual risk-taking were ascertained. Current users of contraceptives were compared with non-users. Both oral contraceptive (OC) and condom use showed a significant protective effect against BV, adjusted for possible confounders (odds ratios were 0.4 and 0.3, respectively). Intrauterine device use (IUD) showed no association with BV. Women with BV had less often used any contraceptives, including condom, at their sexual debut than the women in the comparison group. In this study, OC and condom use seemed to exert a protective effect against BV, whereas no effect for IUD use was found.

Adult↗

Severe alpha1-antitrypsin deficiency (PiZ homozygosity) with membranoproliferative glomerulonephritis and nephrotic syndrome, reversible after orthotopic liver transplantation.

BACKGROUND/AIMS: Nephropathy associated with alpha1-antitrypsin deficiency is assumed to be an unusual entity. We describe the case of a 23-year-old woman with severe alpha1-antitrypsin (PiZ homozygosity) deficiency who developed hepatic cirrhosis in childhood, and glomerulonephritis and nephrotic syndrome in adult life. METHODS/RESULTS: A renal biopsy was consistent with membranoproliferative glomerulonephritis. An immunofluorescence study revealed the presence of alpha1-antitrypsin (PiZ) in the subendothelial region of the glomerular basement membrane. The renal disease was reversible after orthotopic liver transplantation. CONCLUSIONS: The presence of abnormal PiZ protein in the subendothelial region of the glomerular basement membrane may suggest a possible role for this protein in the pathogenesis of glomerulonephritis. The case should add impetus to the search for alpha1-antitrypsin deficiency in any patient presenting with combined liver and renal disease, in the absence of evidence of hepato-renal syndrome, and illustrates that liver transplantation alone may reverse the nephropathy associated with alpha1-antitrypsin deficiency.

Adult↗

Risk-adapted treatment of clinical stage 1 non-seminoma testis cancer.

250 patients with clinical stage 1 non-seminomatous germ cell tumours of the testis (NSGCT 1) were included into a prospective multicentre protocol during 1990-1994 and treated according to three risk strata: patients without tumour cell invasion of vascular structures in the testis (VASC-) and elevated serum AFP levels (AFP+) at orchiectomy were considered low risk (LR) and only observed closely. VASC- and AFP- or VASC+ and AFP+ patients were presumed intermediate risk (IR) and pathologically staged (PS) by retroperitoneal lymph node dissection (RPLND). VASC+ and AFP-patients were regarded as high risk (HR) and received adjuvant chemotherapy (PEB x 3). At a median observation time of 40 (7-68) months, all patients were alive and without evidence of active germ cell cancer. The actuarial relapse rate in the 106 LR patients was 22%, and 70% (14/20) had elevated serum tumour markers at relapse. One of 32 (3%) HR patients relapsed with a resectable retroperitoneal mature teratoma despite adjuvant chemotherapy. Only 14% of the 99 IR patients who underwent RPLND had PS2 disease, and the actuarial relapse rate in 85 PS1 patients was 18%. This multicentre study demonstrated that excellent therapeutic outcome is possible when 18 comparatively small urological and oncological centres follow a strict and formal cancer care programme. The useful prognostic effect of VASC was once again verified. Pathological staging by RPLND in NSGCT1 is, in our opinion, not necessary, with presumed low-risk patients offered surveillance and high-risk patients offered adjuvant chemotherapy.

Biomarkers, Tumor↗

Characterization of the "estrogenicity" of tamoxifen and raloxifene in HepG2 cells: regulation of gene expression from an ERE controlled reporter vector versus regulation of the endogenous SHBG and PS2 genes.

The estrogenic character of tamoxifen and raloxifene was studied on three different genes, an ERE-reporter construct and two endogenous genes, sex hormone binding globulin (SHBG) and pS2, in two variants of the human liver carcinoma cell line HepG2. On the ERE-reporter construct and the pS2 gene both tamoxifen and raloxifene acted as pure estrogen antagonists, whereas on the SHBG gene they functioned as partial estrogens/antiestrogens at concentrations below 1 microM and as full "agonists" at concentrations higher than 1 microM. The fold stimulatory effect of tamoxifen and raloxifene on SHBG protein expression was similar in the estrogen receptor (ER) expressing HepG2 cells (HepER3) and the parental non-ER expressing HepG2 cells at concentrations above 1 microM. In contrast, the 17beta-estradiol analogue moxestrol stimulated SHBG expression only in the HepER3 cells. Both tamoxifen and raloxifene had an additive effect to estrogen receptor-dependent SHBG gene expression in the HepER3 cells in the presence of saturating concentrations of moxestrol. However, a significant difference was observed in that a much higher concentration of moxestrol was required to see an additive effect of raloxifene compared to tamoxifen. The cytokine IL1-beta completely blocked the tamoxifen-dependent induction of SHBG gene expression in HepER3 cells, but only partly blocked the effect of moxestrol mediated by the ER. In conclusion, our results suggest that the mechanism for the liver-selective "estrogenic" character of tamoxifen and raloxifene is mediated by a non-ER dependent pathway.

Alkaline Phosphatase↗

Positron emission tomography (PET) with 11C-5-hydroxytryptophan (5-HTP) in patients with metastatic hormone-refractory prostatic adenocarcinoma.

The discovery of neuroendocrine differentiation in hormone-refractory prostatic adenocarcinoma has opened a potentially new therapeutic approach in this group of patients with a poor prognosis and few effective therapy modalities. Based on previous findings of increased uptake of 11C-5-hydroxytryptophan (11C-5-HTP) in neuroendocrine tumours using the PET technique, this tracer was applied in the study of 10 patients with metastatic hormone-refractory prostatic adenocarcinoma. In three patients, the study was repeated after treatment. An increased uptake of 11C-5-HTP was observed in all investigated skeletal lesions, although the magnitude of the uptake was moderate. The difference between the standard uptake values (SUV) in normal bone and metastatic lesions was significant (p < 0.001). A kinetic analysis of the uptake of 11C-5-HTP demonstrates an increase during the first minutes followed by a wash-out and a stabilization of the tissue/blood ratio at about 2. The Patlak plots demonstrated a gradual increase in the transport rate during the first 20 to 30 min, after which a constant level was observed. The SUV varied between patients and between lesions over time and treatment. The uptake of 11C-5-HTP discriminates metastatic lesions from normal bone and may thus aid in the diagnosis and, potentially, in treatment monitoring of metastatic hormone-refractory prostatic adenocarcinoma. Uptake kinetics are characterized by a wash-out and cannot alone be used as proof of neuroendocrine differentiation in hormone-refractory prostatic adenocarcinoma.

5-Hydroxytryptophan↗

The eosinophil granule proteins in serum, but not the oxidative metabolism of the blood eosinophils, are increased in cancer.

The eosinophil activity in patients with renal cell adenocarcinoma during treatment with interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) was reduced when measured as zymosan-induced lucigenin-enhanced chemiluminescence (CL). Eosinophil cationic protein (ECP), eosinophil peroxidase (EPO) and eosinophil protein-X (EPX) were significantly elevated before and during treatment (P<0.001) when compared with the controls. ECP and EPO were unaffected by the treatment whereas it induced an increased EPX level compared with values measured before treatment (P<0.05). The propensity of eosinophils to secrete their granule proteins may reflect the fact that eosinophils in cancer patients have an enhanced capacity to kill cancer cells.

Adult↗

125I-galanin binding sites in Alzheimer's disease: increases in hippocampal subfields and a decrease in the caudate nucleus.

Using iodinated human galanin and autoradiography, galanin binding sites were studied in cortical and hippocampal areas and in some brainstem nuclei in the brains of eight patients with senile dementia of the Alzheimer type (SDAT) and of nine matched control cases. The highest density of binding sites was found in the substantia nigra with a less intense labeling in the hippocampus and cortical regions. In the SDAT cases a significant increase in number of galanin binding sites was found in some hippocampal areas, a decrease in the caudate nucleus, and no significant changes in frontal and entorhinal cortices. These findings suggest that some central galanin systems may be deranged in SDAT.

Aged↗

Diverticulitis of the sigmoid colon. A comparison of CT, colonic enema and laparoscopy.

PURPOSE: To evaluate the use of laparoscopy, CT, colonic enema (CE), and laboratory tests (white blood cell count (WBC), sedimentation rate (SR), and C-reactive protein (CRP) in diagnosing diverticulitis of the sigmoid colon. MATERIAL AND METHODS: The diagnostic methods were prospectively evaluated in 88 patients, 30 of whom were referred for laparoscopy. RESULTS: Fifty-two patients were found to have sigmoid diverticulitis: 20 patients by laparoscopy, 21 by CT, and 11 by CE combined with one positive laboratory test. Laparoscopy proved to be superior to the other diagnostic methods in diagnosing diverticulitis of the sigmoid colon. CT had a high specificity (1.0; 95% CI: 0.92-1.0) but low sensitivity (0.69; 95% CI: 0.56-0.79) in detecting diverticulitis. CE had a higher sensitivity (0.82; 95% CI: 0.71-0.90) but a lower specificity (0.81; 95% CI: 0.67-0.91) than CT. CONCLUSION: CT was the best method for diagnosing abdominal pathology outside the colon. CT can be recommended as the first examination in seriously ill patients where abscesses and other causes of the symptoms than diverticulitis must first be ruled out. Laparoscopy is probably the most accurate method in diagnosing diverticulitis.

Adult↗

E4, a new monoclonal antibody identifying a human prostatic cell surface antigen

The monoclonal antibody E4 (IgG2a, kappa) was raised by immunizing mice with dispersed cells obtained from human benign prostatic hyperplasia (BPH). The antibody identifies an antigen abundantly expressed in normal prostate epithelial cells, in benign epithelial prostatic cells and in well- and moderately well differentiated adenocarcinomas of the prostate, whereas poorly differentiated prostatic adenocarcinomas display somewhat less expression. Investigation of the human prostatic adenocarcinoma cell line DU 145 revealed E4 immunoreactivity localized to the cell surface. SDS-PAGE analysis under reducing conditions demonstrated an approximate molecular weight of 70,000 for the antigen. The highly specific reactivity with prostate tissue, as well as intense surface staining, especially in well- and moderately well differentiated prostatic adenocarcinomas, makes the E4 antibody a useful immunohistochemical marker and a possible candidate for future immunoscintigraphy and/or targeted radiotherapy.

Journal Article↗

Comparison between transversal SPECT, 3-dimensional rendering and 3-dimensional rendering plus clipping in the diagnosis of somatostatin receptor distribution in malignancies using 111In-DTPA-D-Phe1-octreotide scintigraphy.

Two hundred and seven patients were investigated with [111In-DTPA-D-Phe1]-octreotide Single Photon Emission Computerized Tomography (SPECT) scintigraphy. A comparison was carried out of the diagnostic accuracy of the three display modalities, viz. transversal SPECT (trvSPECT), three dimensional volume rendering (3Dvr) and three dimensional volume rendering plus clipping (3Dvr + c) in the rendered volume. TrvSPECT could visualize a greater number of lesions in 85 (41%) cases when compared with 3Dvr. In 48 (23%) cases, trvSPECT could visualize a greater number of lesions when compared with 3Dvr + c. The differences were caused by radioactivity in intestines and the gallbladder and in lesions shaped like an hour-glass. In conclusion, 3Dvr + c imaging was regarded as the reference since it combines both transversal and volume information. An overall sensitivity of 0.998 was found for trvSPECT and the corresponding value for 3Dvr was 0.75. The specificity was 0.45 for trvSPECT and 0.80 for 3Dvr. The accuracy was 0.87 for trvSPECT and 0.76 for 3Dvr, when compared with 3Dvr + c. The value of 3Dvr is in high-contrast images, where it provides additional anatomical information, whereas in low-contrast images, 3Dvr was found to have low accuracy. In low-contrast images, trvSPECT was found to be almost equal in accuracy to 3Dvr + c imaging. However, in high-contrast images, trvSPECT was found to give more false positives than 3Dvr + c in the assessment of SPECT studies using [111In-DTPA-D-Phe1]-octreotide. The interpretation was that trvSPECT has to be used in conjunction with 3Dvr + c and, in high-contrast images, 3Dvr provides additional value.

Adolescent↗

Sexual behavior risk factors associated with bacterial vaginosis and Chlamydia trachomatis infection.

BACKGROUND AND OBJECTIVES: Few studies have demonstrated that bacterial vaginosis (BV) is associated with sexual behavior risk factors similar to those for other sexually transmitted diseases. The objective of this study was to determine the prevalence of these factors in a multivariate analysis of data from women infected with BV and Chlamydia trachomatis, and noninfected control subjects. GOALS: To study detailed sexual behavior risk factors reported by women with BV versus genital C. trachomatis infection (CT) and by non-BV-infected controls. STUDY DESIGN: A cross-sectional study was conducted with 1,011 women (Swedish Women's Health Study) recruited from family planning and youth clinics in Eskilstuna and Stockholm, Sweden (November, 1989-January, 1991). Participants were evaluated for the presence of BV, CT, Neisseria gonorrhoeae, Treponema pallidum, Trichomonas vaginalis, and human immunodeficiency virus, and interviewed in detail with respect to sexual behaviors. Statistical comparisons were made using chi-square test (Pearson and likelihood ratio), t test, and logistic regression multivariate analysis. RESULTS: Of 956 women eligible for analysis, the prevalence of BV and CT was 13.7% and 8.9%, respectively. The comparison group consisted of the remaining 825 women without BV. After excluding those with concomitant CT infection, there were 118 women with BV who were compared with 72 women with CT infection only. Sexual factors associated with BV versus the comparison group were a short-term relationship before and after sexual debut, high number of lifetime sexual partners, multiple partners during the last month, high orgasm ability, and more frequent history of group sex, sexual abuse, and rape. When the BV group was compared with the CT group, there were no significant differences in sexual activity risk factors, except for a higher frequency of experience of casual sex in the CT group. CONCLUSIONS: Bacterial vaginosis is associated with sexual behavior risk factors similar to those associated with genital CT infection.

Adult↗

Risky behavior in women with history of casual travel sex.

OBJECTIVES: To define epidemiologic and psychosocial characteristics in women with a history of casual travel sex abroad. STUDY DESIGN: The participants consisted of 996 women attending for contraceptive advice, of whom 276 admitted that they had experience of casual travel sex. The remaining women served as a comparison group. In structured interviews, questions were asked about educational level, partnerships, reproductive history, contraceptive and drug use, smoking, and psychosocial factors such as wariness, success, and attractiveness. RESULTS: The women with experience of casual travel sex were more often single, had more often experienced broken relationships, were more often smokers, and used alcohol or cannabis at a higher-frequency. Their educational level was higher and a history of induced abortions was more common. CONCLUSIONS: The results of this study indicate that women with experience of casual travel sex not only take sexual risks, but take other risks that might impose danger to their health.

Adult↗