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Biomedical subjects

S Nilsson

Publications and source records attributed to S Nilsson.

At least 253 records · Page 14Linked to original sources

The efficacy of preoperative systemic chemotherapy in the local control of muscle-invasive transitional cell carcinoma of the urinary bladder.

Transitional cell carcinoma of the urinary bladder has a poor prognosis, once the muscle layers of the bladder wall have been invaded, irrespective of whether operative or radiation therapy is chosen for local treatment. The main reason for this is probably the existence of disseminated micrometastases at the time of primary treatment. Thus, a combination of systemic and local treatment would seem logical. The present study reports the response to chemotherapy in 30 patients with muscle-invasive urinary bladder tumours and the findings at subsequent cystectomy. The chemotherapy comprised cisplatin, methotrexate and leucovorin rescue and was tolerated without any alarming side-effects or increase in perioperative morbidity or mortality. The complete response rate was 43% (13/30) and, in 27% (8/30), there was a partial response with conversion into a more superficial tumour stage. The total, beneficial response rate was thus 70%.

Adult↗

Combined systemic chemotherapy and irradiation of muscle-invasive transitional cell carcinoma of the urinary bladder.

A phase II study is presented, which encompasses the period June 1987 until July 1993, and includes 53 patients with muscle-invasive bladder cancer T2-4b who, due to age and/or poor health (37 cases) or primarily extensive lesions (18 cases), were considered inoperable and for whom treatment with neoadjuvant chemotherapy (cisplatin/methotrexate/leucovorin rescue) and radical irradiation was planned. The total number of intended chemotherapy courses could be delivered without undue toxicity to 46 patients (83%) and 44 subsequently underwent radiotherapy: this modality was, by and large, well tolerated. The primary transurethral resection and chemotherapy produced an objective response in 62% of the 53 patients and in 75% of the 44 evaluable patients. The combined programme produced an objective response in 83% of the 37 evaluable patients, 71% in the 44 patients who completed the combined programme and in 59% of the total group of 53 patients. The follow-up ranged from 3 to 62 months. Radiotherapy increased the total objective response rate, proving effective in approximately 50% of patients who did not respond to chemotherapy. The results of this study are regarded as promising and pave the way for a phase III trial.

Aged↗

[How the X-rays reached Dalarna and the hospital in Falun. Regarding the spread of X-ray technology to the provinces at the turn of the Century].

When Röntgen had discovered the X-ray, in the end of 1895, the practical application was obvious. Technology and equipment was relatively simple. The technology was brought to Sweden and Stockholm already in the spring of 1896 by the initiative of Dr Theodor Stenbäck. By the arrangement of Dr Per Söderbaum an X-ray apparatus was introduced at the hospital in Falun in 1899. This study discusses the individual initiative, how an idea arises, and describes the different decisions, the delivery of the apparatus, installation and early use--until it disappears from the inventory in 1912.

History, 19th Century↗

Imaging in the diagnosis and assessment of prognosis in localized prostate cancer. Consensus Conference on Diagnosis and Prognostic Parameters in Localized Prostate Cancer. Stockholm, Sweden, May 12-13, 1993.

As part of a WHO consensus conference on diagnosis and prognostic parameters in localized prostate cancer, a working group of experts discussed the role of various modern imaging techniques. Special attention was focused on transrectal ultrasound (TRUS) in combination with biopsies, magnetic resonance imaging (MRI) using endorectal coil and recent advances in these techniques. Some experimental techniques, especially hormone receptor scintigraphy and positron emission tomography were also discussed and new results were presented. We concluded that MRI seems to be superior to other imaging techniques in the preoperative assessment of local tumor stage. TRUS defends its place in the diagnostic armament; it is easily combined with multiple biopsies, the results of which are important in the assessment of the biological aggressiveness of prostate cancer. The present development in the field of nuclear medicine may result in techniques for in vivo characterization of tumors and will most certainly have important implications for diagnosis of prostate cancer in the future.

Animals↗

The crocodilian heart and central hemodynamics.

The crocodilian heart is completely divided into two atria and two ventricles, resembling the arrangement in birds and mammals. However, in addition to the systemic aorta (right aorta, RAo) which emerges from the left ventricle, there is a second aorta (left aorta, LAo) that leaves the right ventricle beside the common pulmonary artery. The two aortae communicate immediately outside the valves through a small aperture, the foramen of Panizza. During diastole, the blood pressures in the RAo and LAo equalize through the foramen, and the pressure in the LAo therefore remains higher (under most circumstances) than that generated by the right ventricle preventing the LAo valve from opening. Blood flow in the LAo is biphasic, with a reversal of blood flow in systole due to the closure of the foramen of Panizza by the medial cusp of the RAo valve. Under these circumstances net LAo flow is low, and due solely to flow through the foramen. When peak systolic right ventricular pressure rises above that in the LAo, the valve will open, producing a (partial) pulmonary bypass (right-to-left shunt). This may occur during pulmonary vasoconstriction, or when the systemic (and hence the LAo) blood pressure decreases.

Alligators and Crocodiles↗

Effect on sports drug tests of ingesting meat from steroid (methenolone)-treated livestock.

Anabolic-androgenic steroids are widely misused in human sports and are also used as growth promoters in livestock. Athletes who consume meat containing such hormone residues may risk failing a sports drug test. Prompted by an athlete's defense case, we questioned whether the consumption of small livestock given doses of anabolic steroid, orally or intramuscularly, could generate positive results in samples tested by our analytical procedures. We analyzed urine from eight men who consumed chickens that had been either fed with methenolone acetate (1 mg/day) from day 0 to 21 or injected with methenolone heptanoate depot (1 mg/intramuscular injection) on days 0, 7, and 14 and slaughtered on day 22. No methenolone or characteristic major metabolite was detected in samples from subjects who ate meat from the orally dosed chickens. However, 50% of the samples collected 24 h after consumption of the intramuscularly dosed chickens were confirmed positive. Hence, eating meat containing small amounts of injected hormone may constitute a serious liability to the athlete.

Administration, Oral↗

Lack of the latent transforming growth factor beta binding protein in malignant, but not benign prostatic tissue.

Transforming growth factor beta (TGF-beta) is a family of proteins which act as a potent growth inhibitor for most cell types including epithelial cells. TGF-beta is synthesized as latent high molecular weight complexes, composed of TGF-beta, the NH2-terminal part of the TGF-beta precursor and the third molecule, the latent TGF-beta binding protein (LTBP). We here ascertain that TGF-beta is expressed in human prostatic cancer tissue as well as in cystectomized prostatic tissue and in materials from transurethral resections with benign prostatic hyperplasia, analyzed by immunohistochemistry. TGF-beta is observed in both epithelial cells and stromal cells. No significant correlation was obtained between TGF-beta expression in tumor cells and their degree of differentiation. However, analysis by immunohistochemistry using antibodies against LTBP revealed that specimens from histopathologically verified human prostatic cancer are mostly negative for this molecule, although it is expressed in cystectomized prostatic and benign prostatic hyperplasia tissues. These results indicate that in cystectomized prostatic and benign prostatic hyperplasia tissues, TGF-beta may be produced in a complex associated with LTBP; whereas in prostatic carcinoma, TGF-beta is produced without associating with LTBP. The biological significance of the production of TGF-beta in relation to LTBP and the possible association with prognosis are discussed.

Amino Acid Sequence↗

Sonographic dating of pregnancies conceived after contraceptive pill therapy.

A total of 358 women succeeded in conceiving in the first cycle after stopping oral contraception. The estimated day of delivery was calculated from both an ultrasonographically measured fetal biparietal diameter, in the second trimester, and from the date of the withdrawal bleed. According to the biparietal diameter measurement, the estimated day of delivery was postponed more than 1 week in 138 cases (38.5%). For 304 women who delivered after the spontaneous onset of labor, the biparietal diameter estimate gave the best prediction of the day of delivery in 175 cases (57.6%), the date of the withdrawal bleed gave the best estimate in 91 (29.9%) (p < 0.001) and they were equally good in 38 (12.5%). The estimated day of delivery using a biparietal diameter measurement was within +/- 14 days of the day of delivery for 267 of these 304 women (87.8%). The corresponding figure for the withdrawal bleed date was 218 (71.7%) (p </= 0.001). According to the withdrawal bleed date estimate, 68 women (22.4%) delivered beyond the estimated 42 weeks, compared to only 2.6% according to the biparietal diameter estimate. The median length of a pregnancy from the first day of the withdrawal bleed was 286 days and from the biparietal diameter was 281 days.

Journal Article↗

Behavior of cervical intraepithelial neoplasia (CIN) associated with various human papillomavirus (HPV) types.

201 cervical punch biopsies which showed CIN lesions and were obtained between 1967 to 1977 from Falu Hospital patients, with long-term follow-up data were examined histologically and by DNA typing for human papillomavirus (HPV). We used in situ hybridization for HPV types 6, 11, 16, 18, 31 and 33 and related our findings to the behaviour of the lesion (103 regressed spontaneously and 98 progressed, some of them to invasive cervical carcinoma). There was evidence of HPV infection in 75.6% (152/201) of these lesions on histological examination, and in 53.2% (107/201) on in situ DNA hybridization. Lesions positive for HPV by both methods occurred in the younger age group (Pearson's correlation coefficient, P = 0.008). HPV 16 was found in 51/152 (33.6%) of the HPV lesions, HPV in 12.5%, and HPV 33 in 8.5% HPV 16 was highly significantly (P = 0.0001), and HPV 18 and HPV 33 were significantly (P = 0.008 and P = 0.007, respectively) associated with increasing grades of CIN. Progression to invasive carcinoma was directly (and regression inversely) correlated with the severity of CIN in the first biopsy (P = 0.005). Almost 74% (17/23) of the HPV-CIN III lesions progressed, while only 25% of the HPV-NCIN lesions (6/24) did so. The progression rate was 84.6% for HPV 33 lesions and 52.9% for HPV 16. On the other hand, progression was less common with HPV 6 (25%), and HPV 31 (30.0%). Histological grade and HPV type appear to be of value as prognostic indices.

Adolescent↗

Long-interval treatment regimen with a desogestrel-containing oral contraceptive.

A randomized multicenter study was performed in order to investigate the acceptance of a low-dose OC (30 micrograms of ethinyloestradiol and 150 micrograms of desogestrel), using a 9 weeks on and 1 week off schedule (prolonged regimen, n = 198), compared to a traditional 3 weeks on, 1 week off schedule (standard regimen, n = 96). Haemoglobin and blood pressure remained the same in both groups during the study. No significant differences were found in body weight changes between the two groups. There was significantly more breakthrough bleeding and spotting in the group with prolonged regimen than in the group with standard regimen, but both breakthrough bleeding and spotting decreased during the trial. Irregular bleeding was significantly less in women who were already using OC, compared to "new starters." No serious side effects occurred. Significantly more women stopped the trial because of bleeding problems in the group with prolonged regimen, while there were significantly more women who stopped the trial because of headache in the group with standard regimen. After completing 12 months, or after premature withdrawal from the study, each women completed a questionnaire. Sixty-three per cent of the women preferred the studied alternative and twenty-six per cent preferred the traditional OC.

Adolescent↗

Respiratory and cardiovascular responses to hypoxia in the Australian lungfish.

Simultaneous measurements of pulmonary blood flow (qPA), coeliacomesenteric blood flow (qCoA), dorsal aortic blood pressure (PDA), heart rate (fH) and branchial ventilation frequency (fv) were made in the Australian lungfish, Neoceratodus forsteri, during air breathing and aquatic hypoxia. The cholinergic and adrenergic influences on the cardiovascular system were investigated during normoxia using pharmacological agents, and the presence of catecholamines and serotonin in different tissues was investigated using histochemistry. Air breathing rarely occurred during normoxia but when it did, it was always associated with increased pulmonary blood flow. The pulmonary vasculature is influenced by both a cholinergic and adrenergic tonus whereas the coeliacomesenteric vasculature is influenced by a beta-adrenergic vasodilator mechanism. No adrenergic nerve fibers could be demonstrated in Neoceratodus but catecholamine-containing endothelial cells were found in the atrium of the heart. In addition, serotonin-immunoreactive cells were demonstrated in the pulmonary epithelium. The most prominent response to aquatic hypoxia was an increase in gill breathing frequency followed by an increased number of air breaths together with increased pulmonary blood flow. It is clear from the present investigation that Neoceratodus is able to match cardiovascular performance to meet the changes in respiration during hypoxia.

Animals↗

Protein-protein interactions between the DNA-binding domains of nuclear receptors: influence on DNA-binding.

The glucocorticoid and thyroid hormone receptors have the capacity to bind as dimers to palindromic DNA-binding sites. Protein-protein interactions between the DNA-binding domains of glucocorticoid receptor dimers restrict the DNA-binding to elements where the half-sites are separated by three base pairs, whereas DNA-binding by the thyroid hormone receptor does not appear to require a strict half-site spacing. We have previously shown that a five amino-acid segment close the the C-terminal zinc-binding site (D-box) was involved in dimerization of the glucocorticoid receptor (GR) DNA-binding domain (Dahlman-Wright et al., 1991, J. Biol. Chem., 266, 3107-3112). Here we provide functional evidence, using mutated thyroid hormone receptor DNA-binding domains, that this five amino acid segment (D-box) of the GR interacts with the equivalent segment on the second DNA-binding domain in the dimer. In contrast, the thyroid hormone receptor DNA-binding domain binds to palindromic thyroid hormone response elements in a weakly co-operative manner, independent of the D-box.

Amino Acid Sequence↗

Flow disturbances in early femoral atherosclerosis--an in vivo study with digitized cineangiography.

Disturbances in arterial flow are believed to influence the localization and development of atherosclerotic plaques. The femoral arteries of 26 patients were studied with cineangiography, after which the films were digitized and analyzed with an image analysis computer. The image sequence was converted to a set of time-intensity curves, from which time parameters were calculated, representing the arrival time of the contrast medium at each pixel. In the resulting parametric images, zones of delayed contrast filling (ZDF) were identified by an adaptive thresholding, which identifies lighter regions within the vessel, excluding the smallest ones. The ZDF, which have been shown, in a model study, to correspond to disturbed flow, were more frequent in the inner curvature than in the outer curvature of the curved vessels. Accordingly, they were more frequent along the lateral wall than along the medial wall of the artery. Several ZDF were also found in the vicinity of bifurcations. Most of the findings tally closely with fluid mechanical theory. In future studies, flow disturbances are to be correlated with the progression of atherosclerotic lesions.

Adult↗

Localization of DNase I hypersensitive sites in the human oestrogen receptor gene correlates with the transcriptional activity of two differentially used promoters.

The human oestrogen receptor (hER) gene has recently been shown to be transcribed from two different promoters. In order to study the hER gene promoter region we initially isolated and sequenced 3.3 kb of the 5' region of the hER gene. DNase I hypersensitivity experiments with nuclei from the ER-expressing cell line MCF-7 mapped three different hypersensitive sites, located in the vicinity of the two hER promoters previously identified. However, in another ER-positive cell line, ZR-75-1, DNase I hypersensitivity was observed only in the region of the downstream promoter, suggesting differences between the two cell lines in promoter usage. Polymerase chain reaction-mediated detection of mRNAs transcribed from the two different promoters demonstrated transcripts from the downstream promoter in both the cell lines studied. However, mRNAs transcribed from the upstream promoter could only be detected in MCF-7 cells. Thus, the pattern of DNase I hypersensitivity correlates with the transcriptional activity of the two promoters in the hER gene. Based on these data, we suggest that differential promoter usage might be a novel level of regulation of the hER gene.

Base Sequence↗

Comparison of ultrasonic measurement of biparietal diameter and last menstrual period as a predictor of day of delivery in women with regular 28 day-cycles.

Within a randomised trial, 1713 women with regular 28-day cycles were studied to evaluate whether the day of delivery is predicted best from the last menstrual period (LMP) or ultrasonic measurement of the fetal biparietal diameter (BPD). Among 727 women, with a spontaneous onset of labor, where the estimated day of delivery (EDD) was derived from BPD, 91.8% delivered within +/- 14 days and 61.8% delivered within +/- seven days of EDD. Corresponding figures for 741 women where EDD was derived from LMP were 91.6% and 61.1%, respectively. Comparison of EDDs calculated from BPD and LMP in the same woman showed that BPD postponed EDD more than seven days in 18.0% and advanced EDD more than seven days in 1.8%. When the difference in EDD between the two methods was more than seven days the BPD estimate was a better predictor of day of delivery.

Anthropometry↗

Intractable singultus: a diagnostic and therapeutic challenge.

Hiccup or singultus is a repeated involuntary, spasmodic contraction of the diaphragm accompanied by a sudden closure of the glottis mediated by sensory branches of the phrenic and vagus nerves as well as dorsal sympathetic afferents. The principle efferent limb and diaphragmatic spasms are mediated by motor fibers of the phrenic nerve. Hiccup has been classified as a respiratory reflex and the central connection probably consists an interaction among the brainstem respiratory centers, phrenic nerve nuclei, medullary reticular formation and the hypothalamus. Chronic intractable hiccup may be due to brainstem seizures, and baclofen may be the long-awaited remedy for intractable hiccup as demonstrated in three illustrative cases.

Afferent Pathways↗