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Biomedical subjects

A Jakobsen

Publications and source records attributed to A Jakobsen.

At least 55 records · Page 3Linked to original sources

A Scandinavian two-center study of BMA 031 in steroid-resistant rejection of renal grafts.

BMA 031 (Behring Monoclonal Antibody) was given to 25 renal graft recipients with biopsy-proven steroid-resistant rejections. A dose of 50 mg of BMA 031 was given i.v. on 7 consecutive days concomitantly with a standard triple-drug regimen. No premedication was administered before the first BMA 031 dose. After the first dose, 7 patients experienced moderate fever (< 39 degrees C), 5 patients had high fever (> 39 degrees C), 4 patients had nausea/vomiting, 3 diarrhea, 1 headache, and 1 hypertension. These reactions were seen only after the first dose except for 1 patient who developed urticaria on days 3-4. All the rejection episodes were reversed or partially reversed. Twenty-one patients experienced re-rejections 3-46 days after the last BMA 031 dose, and were treated with methylprednisolone and/or rabbit antihuman thymocyte globulin. Seven patients lost their grafts within 1 year (28%), including 2 patients who died of infection with a functioning graft. BMA 031 seems to be a safe drug with only few mild side effects, and it effectively reverses steroid-resistant rejections. Re-rejections were frequent, but mostly reversible.

Adolescent↗

Quality of life in Norwegian kidney donors.

The Norwegian kidney transplant programme is based on more extensive use of living donors than in other countries. Re-examination of the physical health of kidney donors has in the majority of studies revealed no long-term medical risk. The quality of life after donation has only been described in very few studies, and with a small number of donors. This report concerns a cross-sectional study of 494 donors with a mean observation time from donation of 6.7 years. A standardized questionnaire containing 19 items related to quality of life was used. The donors were compared to the general adult population in a county in mid-Norway. Out of the 19 quality of life items, the donors scored significantly better in 13. Donors who had experienced that the corresponding recipient had died have been tested separately. The results in this subgroup were equal to the population, but inferior compared to the rest of the donors. We conclude that the quality of life of Norwegian kidney donors is better than the general population. We will continue our policy of an extensive use of living kidney donors.

Adult↗

[Central venous dialysis catheter. Silicone rubber dialysis catheter used for permanent vascular access].

51 dual lumen jugularis dialysis catheters (Permcath, Quinton) were placed by surgical technique in 34 patients and by percutaneous technique in eight patients. Mean catheter life-time was 4.1 months. Seven catheters were removed due to complications (infection three catheters, clotting four catheters). Minor flow problems occurred in 8.8% of all procedures. Seven occluded catheters were successfully reopened by use of locally applied streptokinase. A strict aseptic technique is essential to avoid infection. Permcath is an acceptable vascular access device for patients in whom it is impossible to create an arterio-venous fistula.

Adolescent↗

DNA level and stereologic estimates of nuclear volume in squamous cell carcinomas of the uterine cervix. A comparative study with analysis of prognostic impact.

Grading of malignancy in squamous cell carcinomas of the uterine cervix is based on qualitative, morphologic examination and suffers from poor reproducibility. Using modern stereology, unbiased estimates of the three-dimensional, volume-weighted mean nuclear volume (nuclear vv), were obtained in pretreatment biopsies from 51 patients treated for cervical cancer in clinical Stages I through III (mean age of 56 years, follow-up period greater than 5 years). In addition, conventional, two-dimensional morphometric estimates of nuclear and mitotic features were obtained. DNA indices (DI) were estimated by flow cytometry. Finally, the semiquantitative malignancy grade score value (MGS) was determined according to previously published methods. Estimates of nuclear vv were on average increased in euploid lesions (2P = 0.01), but the overall relationship between nuclear vv and DI was poor. Different clinical stages of disease did not differ with regard to nuclear vv (2P = 0.99) and DI (2P = 0.56). No relationship was disclosed between MGS and nuclear vv (2P = 0.85). Single-factor analysis showed prognostic impact of clinical stage of disease (2P = 0.0001) and DI (2P = 0.04), whereas estimates of nuclear vv were only of marginal prognostic significance (2P = 0.07). However, Cox multivariate regression analysis showed independent prognostic value of patient age and nuclear vv along with clinical stage and DI. All other investigated variables were rejected from the model. A prognostic index with highly distinguishing capacity between prognostically poor and favorable cases was constructed (2P = 1.9 x 10(-7)). It is concluded that realistic estimates of nuclear volume are independent of nuclear DNA content and are of prognostic value for objective malignancy grading in patients with squamous cell carcinoma of the uterine cervix.

Adult↗

Renal handling of carboplatin.

The mechanism for renal handling of carboplatin was studied in 17 ovarian cancer patients treated with a combination of carboplatin and cyclophosphamide. Carboplatin and [51Cr]-ethylenediaminetetraacetic acid (EDTA) renal clearances were measured simultaneously during short intervals of from 45 to 120 min. A total of 131 clearance intervals were analyzed during 35 chemotherapy courses. The carboplatin/[51Cr]-EDTA clearance ratio (R) served as an indicator of the net tubular reabsorption (R less than 1) or secretion (R greater than 1). The R value was calculated for each sampling interval. No significant difference was found between interpatient and intertreatment variation. The intertreatment variation as tested against the variation in the short intervals by an F-test was highly significant. We calculated the average R value for each treatment and consequently based our results on a total of 35 observations. The mean R value was 0.77 (t-test for R = 1; P less than 0.001). We conclude that the renal elimination of carboplatin takes place by glomerular filtration followed by tubular reabsorption.

Adult↗

Chemotherapy in perineal leiomyosarcoma.

A case report of a woman with perineal leiomyosarcoma who was cured by combination chemotherapy is presented, and the literature on chemotherapy of soft tissue is reviewed.

Antineoplastic Combined Chemotherapy Protocols↗

Carcinoma of the cervical stump.

Treatment, prognosis, and complication rate were retrospectively studied in 46 patients with cervical stump cancer. There were no differences in clinical stage distribution and histopathological findings between these patients and patients with cervical cancer of the intact uterus. However, 43 patients were treated by radiation therapy and only 3 patients had a cervical amputation. The 5-year survival rate was 62%, which is comparable to that of cervical cancers. Late complications were found in 22 patients: 3 (7%) had symptoms of severe radiation reactions of the bladder (necrosis or vesicovaginal fistels), 14 (31%) had severe radiation reactions in the rectum and the sigmoid (severe proctitis, stenosis, or rectovaginal fistels) and 7 (18%) had large vault necrosis. It is concluded that the frequency of cervical stump cancer is low, but cancer in the cervical stump is difficult to treat and the rate of severe late complications is so high that it should be considered when one is deciding between supravaginal and total hysterectomy. Moreover, screening for cervical cancer should be performed regularly after supravaginal hysterectomy.

Adult↗

Bleomycin/cis-platin as neoadjuvant chemotherapy before radical radiotherapy in localized, inoperable carcinoma of the esophagus. A prospective randomized multicentre study: the second Scandinavian trial in esophageal cancer.

Survival and swallowing function were studied in a randomized trial of 97 patients with inoperable, localized esophageal carcinoma. Radical radiotherapy was given to 51 patients, while 46 patients had two courses of bleomycin/cisplatin before radiotherapy. The survival was 29% after one year, and 6% after 3 years in the radiotherapy group. The survival in the combined treatment group was 18 and 0%, respectively; p = 0.1895. The number of patients who could swallow any food increased from 6% before treatment to 38% after 3 months in the radiotherapy group, and from 0% to 23% in the combined group. No benefit was found by combining bleomycin/cisplatin with radiotherapy.

Aged↗

Fibro-muscular renal artery disease treated by extracorporeal vascular reconstruction and renal autotransplantation: short- and long-term results.

Over a 16-year period (1973-1989), 63 renal autotransplants were performed in 59 patients for fibro-muscular dysplasia (FMD) with renal artery stenoses (42 kidneys) or aneurysms (21 kidneys). About two-thirds of the autotransplants were performed before percutaneous transluminal angioplasty (PTA) was established for clinical use. However, vascular disease at a site or type not suitable for PTA was present in 57 (90%) of the kidneys. Hypertension was the leading symptom in 56 patients, including four in whom renal autotransplantation was performed as an emergency for acute renal artery occlusion or malignant hypertension. Blood pressure returned to normal or improved in 51 (91%) and remained unchanged in five patients (9%) following autotransplantation. Three patients with renal artery aneurysm in whom haematuria and loin pain were the indications for treatment, became asymptomatic following surgical intervention. Bilateral renal autotransplantation was performed synchronously in one and sequentially in three patients. There were no operative deaths, but two kidneys were lost postoperatively in two 2-year-old children owing to renal vascular thrombosis. In the follow-up period (mean 4.3 years), one additional kidney was lost at 3 months owing to progressive FMD. Blood pressure and renal function remained stable in all other patients. Based on the excellent results achieved in this series, it is concluded that extracorporeal vascular repair and renal autotransplantation is a safe procedure for the patient as well as the kidney affected by FMD. The procedure is advocated as an alternative to in situ reconstruction in patients with renal artery disease not accessible to PTA, such as aneurysms and complex branch renal artery stenoses.

Adolescent↗

Dose-toxicity relationship of carboplatin in combination with cyclophosphamide in ovarian cancer patients.

A study was undertaken to examine the relationships between carboplatin's pharmacokinetic parameters and the myelotoxicity associated with its administration in combination with cyclophosphamide. An additional aim of the study was to test the applicability of the method proposed by Calvert et al. for calculation of the carboplatin dose to be used in the combination regimen. A total of 24 previously untreated ovarian cancer patients were given a combination of 250-500 mg/m2 carboplatin and 500 mg/m2 cyclophosphamide every 4 weeks for 4 months. The pharmacokinetics of carboplatin and the associated myelotoxicity were investigated in 64 courses. The results showed a significant correlation (r = 0.89) between the AUC calculated for carboplatin and that predicted according to Calvert's formula [carboplatin dose in milligrams = AUC (glomerular filtration rate +25)]. We conclude that the model is a useful guide in the calculation of the carboplatin dose to be given in combination with cyclophosphamide, and it enables a more precise prediction of the carboplatin exposure than does the conventional calculation, which is based on milligrams of drug per square meter of body surface. The AUC for carboplatin was a reliable predictor of the myelotoxicity as measured by the relative decrease in thrombocyte count. However, the relationship between AUC and myelotoxicity changed during the treatment because of increasing bone marrow toxicity. Despite this finding, dose calculation based on carboplatin's AUC appears to provide an improvement in the clinical use of the drug, and the method also seems to be fully applicable in combination chemotherapy with cyclophosphamide.

Antineoplastic Combined Chemotherapy Protocols↗

Stereological estimates of nuclear volume in squamous cell carcinoma of the uterine cervix and its precursors.

Using modern stereology, this study was carried out to obtain base-line data concerning three-dimensional, mean nuclear size in precancerous and invasive lesions of the uterine cervix. Unbiased estimates of the volume-weighted mean nuclear volume (nuclear vv) were obtained by point-sampling of nuclear intercepts in 51 pre-treatment biopsies from patients with invasive squamous cell carcinomas (SCC). Vertical sections from 27 specimens with cervical intraepithelial neoplasia (CIN) grades I through III were also investigated, along with 10 CIN III associated with microinvasion (CIN III + M). On average, nuclear vv was larger in SCC than in CIN III and CIN III + M together (2 P = 8.9 . 10(-5). A conspicuous overlap of nuclear vv existed between all investigated lesional groups. The reproducibility of estimates of nuclear vv in biopsies with SCC was acceptable (r = 0.85 and r = 0.84 in intra- and inter-observer studies, respectively). The efficiency of the sampling scheme was high, with more than 60% and more than 80% of the total observed variance contributed by differences between individual lesions with CIN and SCC, respectively. Estimates of nuclear vv based on sampling within the whole epithelial thickness and on sampling in the lower one-third in CIN I and the lower two-thirds in CIN II lesions were of the same magnitude. Approximate estimates of the absolute variation of nuclear vv were directly proportional to individual estimates of nuclear vv, whereas the relative variation of nuclear vv tended to decrease with increasing mean nuclear volume. Based on the rather small number of cases investigated, estimates of nuclear vv are unable to distinguish between different grades of CIN. However, the estimation of nuclear vv is well-suited for the purposes of objective grading of malignancy in SCC.

Carcinoma, Squamous Cell↗

Treatment of extensive small cell lung cancer with carboplatin and teniposide.

The combination of carboplatin and teniposide has been evaluated in a phase II trial including 47 previously untreated patients with extensive small cell lung cancer. Treatment was given at monthly intervals at a dose of 200 mg/m2 of carboplatin intravenously on day 1 and teniposide at a daily dose of 60 mg/m2 intravenously on days 1-5. Treatment response was complete in 4 (8.9%) and partial in 19 (42.2%) of 45 evaluable patients. The overall response rate was 51.1% (95% confidence interval 36%-66%). The median duration of response was 7.1 months (range 2.1-14.8) and the median survival was 6.7 months (0.3-22.2). Myelosuppression was the most prominent side-effect. Leukopenia (WHO grade 3-4) developed in 17 (37.8%) and thrombocytopenia (grade 3-4) in 5 (11.1%) of 45 patients evaluable for toxicity. 2 treatment-related deaths were registered. The present study shows that the combination of carboplatin and teniposide produces an acceptable response rate, but response duration and survival time are short.

Adult↗

DNA level, tumor thickness, and stereological estimates of nuclear volume in stage I cutaneous malignant melanomas. A comparative study with analysis of prognostic impact.

The mutual relation and prognostic value of three quantitative variables were investigated in a retrospective series of 56 stage I cutaneous malignant melanomas. Unbiased stereological estimates of nuclear volume, nuclear nu v were obtained along with measurements of melanoma thickness. The DNA index (DI) was determined by flow cytometry in adjacent sections from the same paraffin-embedded specimens. The correlation between tumor thickness and nuclear nu v was only moderate (r = .60). Euploid lesions had a smaller nuclear nu v than aneuploid tumors (2p = .01), but with considerable overlap. No significant association between tumor thickness and DI could be demonstrated. Single-factor analysis showed prognostic value of nuclear nu v and tumor thickness (2p = .0007 and 2p = .03, respectively), whereas DI was without prognostic impact (2p = .54). When analyzing the three parameters in a Cox model, nuclear nu v was the only independent, prognostically significant variable. Physical, three-dimensional nuclear volume is not solely a reflection of nuclear DNA content, and may represent a valuable, quantitative prognostic indicator in cutaneous malignant melanomas.

Adult↗

Treatment of advanced bladder cancer category T2 T3 and T4a. A randomized multicenter study of preoperative irradiation and cystectomy versus radical irradiation and early salvage cystectomy for residual tumor. DAVECA protocol 8201. Danish Vesical Cancer Group.

From 1983 to 1986 183 patients with transitiocellular carcinoma of the urinary bladder, category T2-T4a, entered a randomized study. The patients were allocated to receive either preoperative irradiation (40 Gy) followed by cystectomy or radical irradiation (60 Gy) followed by salvage cystectomy in cases of residual tumor. The two randomization groups were comparable in regard to sex, age, T-categories, tumor size, histological grade and concomitant dysplasia. The two randomization groups included 88 and 95 patients respectively. The treatment plan was followed by 66 patients (75%) in the planned cystectomy group and by 88 (92%) in the radical radiotherapy group of which 27 (28%) were treated with salvage cystectomy. The results showed a trend to a higher survival rate following the combined treatment with preoperative irradiation and cystectomy compared to radical irradiation followed by salvage cystectomy in case of residual tumor, but a statistical significant difference could not be demonstrated. The lack of difference also applied according to the actually given treatment. There was no difference in surgical complications between planned and salvage cystectomy and there were no postoperative deaths among the cystectomized patients. The type of late complications was different in the two treatment groups, but there were no major differences in the number of complications except for the fact that all male patients experienced erective impotence after cystectomy. The T-category, response to radiotherapy and frequency of lymph node metastases were found to be of prognostic importance.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Transitional Cell↗

[Kidney transplantation in Norway].

Twenty years ago, in 1969, a national kidney transplant program was established, based on uniform indications and preparations for transplantation. Since 1983, all transplants have been performed at one centre. We describe the organization, development, treatment policies and results of the program. The national transplant rate of 42 patients per million population per year (p.m.p.) keeps up with the demand. In contradiction to the international experience of rapidly expanding waiting lists and dialysis populations, a balance has been achieved in Norway, with a high transplant rate, a restricted and stable waiting list (mean 23 p.m.p.), waiting time (mean 5 months) and dialysis population. Approx. 80 per cent of all patients requiring long term renal replacement therapy actually receive a transplant, as against approx. 50% in Western Europe. Seventy-five to 100 per cent of the transplants function for more than a year, and 55-80 per cent for more than five years, depending on the donor and HLA compatibility. Other significant risk factors are age and HLA sensitization. Since 1983, 46 diabetics with renal failure have been treated by combined renal and pancreatic transplantation.

Humans↗