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Biomedical subjects

S Sander

Publications and source records attributed to S Sander.

At least 37 records · Page 2Linked to original sources

Role of the native kidney in experimental post-transplantation hypertension.

In experimental renal transplantation studies using several animal models of primary hypertension, including stroke-prone spontaneously hypertensive rats (SHRSP) and their normotensive Wistar-Kyoto controls (WKY), single transplanted kidneys from genetically hypertensive but not normotensive donors elicited post-transplantation hypertension in bilaterally nephrectomized genetically normotensive recipients. The underlying mechanisms are presently unclear. The present study was designed to investigate the effects of a remaining native kidney on post-transplantation blood pressure, plasma renin activity and plasma angiotensin II concentration in (WKYxSHRSP) F1 hybrid recipients of a WKY or SHRSP kidney. The presence of a native kidney markedly reduced, but did not prevent, post-transplantation hypertension in recipients of an SHRSP kidney. WKY kidney grafts did not significantly alter blood pressure in bilaterally or unilaterally nephrectomized recipients. Plasma renin activity was lower in bilaterally than in unilaterally nephrectomized recipients, regardless of the source of the graft. The plasma angiotensin II concentration was similar in all groups. Renal graft function as assessed by 99mtechnetium-mercaptoacetyltriglycine scintigraphy was well preserved. These data suggest that post-transplantation hypertension in recipients of an SHRSP kidney may be partly due to the failure of the graft to eliminate a hypertensinogenic substance or to produce a blood pressure lowering agent.

Angiotensin II

Analysis of 21 Stargardt's disease families confirms a major locus on chromosome 1p with evidence for non-allelic heterogeneity in a minority of cases.

BACKGROUND: Autosomal recessive Stargardt's disease is a macular degeneration characterised by a juvenile onset and a rapidly progressive course resulting in an atrophic macular area typically surrounded by yellowish retinal flecks. METHOD: The disease locus has previously been assigned to markers from chromosome 1p21-p13 by genetic linkage analysis in eight multiplex Stargardt's disease families. RESULTS: In an extended analysis, the assignment to chromosome 1p was confirmed in the majority of the 21 families with Stargardt's disease who were studied. In addition, a series of recombinant chromosomes further narrowed the Stargardt's disease region to an approximately 3 cM interval between markers at D1S424 and D1S497. CONCLUSION: Multipoint linkage analysis most probably excludes this locus in three of these families suggesting non-allelic heterogeneity with at least one additional minor Stargardt's disease locus.

Chromosomes, Human, Pair 1

X-linked juvenile retinoschisis (RS) maps between DXS987 and DXS443.

X-linked juvenile retinoschisis (RS) has previously been localized to a 7-8 cM interval between markers at (DXS43, DXS207) and (DXS274, DXS41). Our analysis of more than 300 meioses in two multigeneration RS families identified eight recombinant RS chromosomes and narrowed the RS locus to an interval between DXS987 and DXS443. Our data suggest the following order of loci: Xpter-DXS207-DXS987-([DXS418-DXS999], RS)-DXS443-DXS365-DXS274-Xcen.

Base Sequence

Stimulation of DNA synthesis by endothelin-1 in primary cultures of human dental pulp.

Endothelin (ET), besides being a powerful vasoactive agent, acts as a mitogen in some cell types. ET-like immunoreactivity has been recently detected by immunocytochemistry in the vascular endothelium of human tooth germ and dental pulp, thus providing evidence for local ET production in these tissues. The effects of ET-1 on DNA synthesis in primary cultures of human dental pulp were now investigated. DNA synthesis was evaluated by flow cytometric assay and by 5-bromo,2'deoxyuridine incorporation as detected by immunocytochemistry. Cultured cells were morphologically similar to dental pulp cells and displayed vimentin immunoreactivity. Incubation of cultures with ET-1 resulted in a dose-dependent increase in the number of S-phase-traversing cells over control (unstimulated) cultures. Control skin fibroblasts were also responsive to ET. This finding raises the possibility that the multifunctional peptide ET-1 might subserve growth-promoting activity in the human tooth. It is tentatively suggested that such as an activity might be important during tooth development and in pulp inflammation and healing.

Adolescent

High-resolution meiotic and physical mapping of the best vitelliform macular dystrophy (VMD2) locus to pericentromeric chromosome 11.

Best vitelliform macular dystrophy (VMD2) has previously been linked to several microsatellite markers from chromosome 11. Subsequently, additional genetic studies have refined the Best disease region to a 3.7-cM interval flanked by markers at D11S903 and PYGM. To further narrow the interval containing the Best disease gene and to obtain an estimate of the physical size of the minimal candidate region, we used a combination of high-resolution PCR hybrid mapping and analysis of recombinant Best disease chromosomes. We identified six markers from within the D11S903-PYGM interval that show no recombination with the defective gene in three multigeneration Best disease pedigrees. Our hybrid panel localizes these markers on either side of the centromere on chromosome 11. The closest markers flanking the disease gene are at D11S986 in band p12-11.22 on the short arm and at D11S480 in band q13.2-13.3 on the proximal long arm. This study demonstrates that the physical size of the Best disease region is exceedingly larger than previously estimated from the genetic data, because of the proximity of the defective gene to the centromere of chromosome 11.

Base Sequence

Survival after transurethral and transvesical surgery in localized cancer of the prostate, Norway 1957-1981.

BACKGROUND: During the period 1957-1981, there has been a gradual change in the choice of surgical methods for patients with prostate cancer in Norway, from transvesical surgery to transurethral resections (TUR-P). Radical prostatectomy was practically nonexistent in the early years of this time period. Sixty-five percent (17,696 patients) of all patients with prostate cancer reported to the Cancer Registry had no metastases at the time of diagnosis. Of these, 5414 patients underwent TUR-P, whereas 6160 patients underwent transvesical operations as primary surgery. Interest was raised in analyzing survival after primary surgery. METHODS AND RESULTS: Five-year relative survival rates were calculated for the groups of patients undergoing each type of surgery; the rates increased steadily for both groups during the later years of the 1957-1981 period. However, survival consistently was better for patients who had transvesical surgery. The difference in 5-year relative survival rates was 10-15%. The same pattern was seen long-term survival (more than 10 years). In addition, survival rates for patients with similar grade of tumor differentiation were better for patients undergoing transvesical surgery. A multivariate analysis of survival that related age, surgical methods, grades of tumor differentiation, and diagnostic periods showed that survival was influenced most by differentiation, followed by surgery. Age was not an important factor in this analysis. CONCLUSION: The results underline the importance of additional research regarding the precise classification of prostatic cancer at the time of diagnosis so that clinicians can better choose the proper method of surgery.

Age Factors

[Single transurethral microwave therapy of benign prostatic hyperplasia].

We have used transurethral microwave thermotherapy in the treatment of benign prostatic hyperplasia since October 1991. Irreversible cell damage occurs when the microwaves heat the periurethral prostatic tissue. The urethra is simultaneously cooled, and is not destroyed during treatment. The patients are not hospitalized. Transurethral microwave thermotherapy is performed under local anaesthesia, no other form of analgesia has been found necessary. We have included patients with symptomatic prostatic obstruction who would otherwise have received operative or pharmacologic treatment. Patients with high residual urine, large middle lobe, urethral stricture, prostatic cancer, decreased renal function, urinary infection or metal implants were excluded. We observed a marked improvement in the Madsen symptom score after transurethral microwave thermotherapy. The score decreased from 12 before treatment to five after six weeks and 4.6 after six months (p < 0.0001). Flow increased from 8.9 to 9.7 ml/s. There was a significant reduction in the residual urine from 102 ml preoperatively to 69 ml after six months (p < 0.001). The volume of the prostate was only slightly reduced after transurethral microwave thermotherapy. Postoperative edema caused urinary retention in 13% of the patients. Two patients required transurethral resection of the prostata.

Aged

[Endocrine treatment of prostatic cancer. A renaissance for parenteral estrogen].

The standard treatment for advanced cases of cancer of the prostate is castration. Oestrogens, administered per os may have serious side effects, in particular thrombosis and cardiovascular complications. If the oestrogens are administered parenterally, changes in liver function can be avoided and risk of side effects markedly reduced. 38 patients have been treated at Huddinge Hospital in Stockholm, and 14 patients at Aker Hospital in Oslo, with polyoestradiol phosphate (Estradurin) 240 mg injected intramuscularly every 4th week (initial dose 320 mg). We can sum up our own experience as follows: Plasma testosterone is reduced to castration level after 2-3 weeks. Liver function, evaluated by the sexual hormone binding globulin level in plasma, remains unchanged. Morbidity and mortality from cancer are the same as may be achieved by surgical orchidectomy. The only side effect of significance is gynaecomastia. Follow-up of the patients does not indicate any increased risk of thrombosis or cardiovascular disease. The treatment is fairly cheap compared with other alternative methods of endocrine treatment.

Estradiol

Neoadjuvant chemotherapy in bladder cancer: a randomized study. Nordic Cystectomy Trial I.

An analysis by the Nordic Cooperative Bladder Cancer Study Group concerned the possible benefit of neoadjuvant chemotherapy--given before scheduled low-dose irradiation and cystectomy. In the trial, started in 1985, 311 patients with locally advanced bladder cancer, T1 grade 3, T2-T4a NXMO, were randomly allocated to a 'chemotherapy' or a 'no chemotherapy' group. Chemotherapy consisted of two cycles comprising cisplatin 70 mg/m2 and doxorubicin 30 mg/m2, with a 3-week interval between cycles 1 and 2. All patients were locally irradiated with 4 Gy daily for 5 consecutive days. The follow-up included 266 cystectomized patients. In May 1992 the mean observation time was 18 months for all patients and 47 months for those still alive. The results suggest that a significant downstaging in the group randomized to chemotherapy was found only in T1, grade 3 tumours (56 patients, p = 0.002). The overall survival rate in all 311 patients was significantly higher in the chemotherapy group (p = 0.03) and likewise among the 253 patients with T2-T4a tumour (p = 0.018). For the 210 patients who underwent cystectomy for T2-T4a tumour, there was a trend towards longer survival when chemotherapy was given (p = 0.057). Patients with initially muscle-invasive tumour who responded to neoadjuvant treatment survived longer than non responders (p = 0.0005). The results suggest that neoadjuvant chemotherapy improve the outcome of radical surgery for muscle-invasive bladder cancer, though the effect on long-term survival is inconclusive. Further studies on the effect of neoadjuvant chemotherapy is initiated.

Antineoplastic Combined Chemotherapy Protocols

Localized prostate carcinoma treated with TUR and neodymium-YAG laser irradiation.

Neodymium-YAG laser irradiation subsequent to extended transurethral resection has been practised in our department since 1981 as an alternative treatment for patients with localized prostate carcinoma. The treatment is performed endoscopically in two separate steps. The procedure is simple and complications are few. One hundred and twenty-four patients have been treated and followed up for more than 6 months. One hundred and ten patients are evaluated as disease free survivors and the overall actuarial disease free survival rate is 88% at 4-9 years of follow-up. The initial promising results persist and the results from other clinics confirm the method to be a fair alternative or patients with localized prostate carcinoma.

Humans

Neodymium-YAG laser irradiation of stage T2 muscle-invasive bladder cancer. Long-term results.

The study group consisted of 15 patients with solitary stage T2 bladder tumours treated with transurethral resection (TUR) and subsequent neodymium-YAG laser irradiation. Ten patients are alive without evidence of cancer 56 to 78 months (mean 67) after treatment; 1 died of cardiovascular disease 2 years after treatment and autopsy revealed no cancer. In 4 patients the treatment failed and cystectomy or external beam radiation was carried out. The long-term results indicate the combination of TUR and laser irradiation to be beneficial in the management of T2 tumours in selected cases.

Aged

A randomized study on hormone-resistant prostatic cancer: estramustine phosphate versus low dose epirubicin with or without medroxyprogesterone acetate. A Norwegian multicenter study.

A prospective randomized study has been carried out in order to compare three different treatment modalities for symptomatic metastatic hormone-resistant prostatic cancer. A total of 79 patients were included. One group was treated with estramustine phosphate, another with Epirubicin plus Medroxyprogesterone acetate (MPA), while the third arm consisted of Epirubicin plus placebo. Best palliation was obtained by the combination of Epirubicin and MPA. This combination also seemed to be associated with the longest response duration.

Administration, Oral

Kinetic analysis and simulation of glucose transport in plasma membrane vesicles of glucose-repressed and derepressed Saccharomyces cerevisiae cells.

In this study experimental data on the kinetic parameters investigated by other authors 1-5, 11 together with own data on plasma membrane vesicles, have been subjected to a computer simulation based on the equations describing facilitated diffusion. The simulation led to an ideal fit describing the above data. From this it can be concluded that glucose is transported by facilitated diffusion, and not by active transport as was postulated by Van Steveninck 14,15. The simulation method also demonstrates that the fast sampling technique used by these authors 1-5, 11 underestimated the fluxes. Thus, the parameters given do not contribute to the understand of glucose transport under different metabolic conditions. The K value of plasma membrane vesicles prepared from glucose-repressed cells is around 7 mM. Derepression, particularly by galactose, causes a highly significant increase in affinity as shown by a decrease in the K value to 2 mM. The highest affinity was measured in a triple kinaseless mutant grown on glycerol with a K value of 1 mM. It seems, therefore, that the kinetic parameters derived from initial uptake rates of glucose in intact cells 1-5, 11 using single flux analysis, such as Eadie-Hofstee- or Lineweaver-Burk-plots, are in error.

Biological Transport

[Intravesical BCG vaccine in bladder cancer].

We present a preliminary report on intravesical BCG instillation in four patients. The indications are prevention of new superficial tumors and treatment of carsinoma in situ. 120 mg Connaught BCG-vaccine in 50 cc saline is instillated weekly for a total of six treatments. Follow-up was performed every three months and included cystoscopy and urine cytology. The prophylactic effect is encouraging, even in patients who have previously not responded to intravesical chemotherapy. There were no serious complications and the common side effects of fever and dysuria did not delay or interrupt treatment.

Administration, Intravesical