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Biomedical subjects

N Raabe

Publications and source records attributed to N Raabe.

At least 19 recordsLinked to original sources

Immunotherapy with allotumour mRNA-transfected dendritic cells in androgen-resistant prostate cancer patients.

Here, we present results from a clinical trial employing a new vaccination method using dendritic cells (DCs) transfected with mRNA from allogeneic prostate cancer cell lines (DU145, LNCaP and PC-3). In all, 20 patients were enrolled and 19 have completed vaccination. Each patient received at least four weekly injections with 2 x 10(7) transfected DCs either intranodally or intradermally. Safety and feasibility of vaccination were determined. Immune responses were measured as delayed-type hypersensitivity and by in vitro immunoassays including ELISPOT and T-cell proliferation in pre- and postvaccination peripheral blood samples. Serum prostate-specific antigen (PSA) levels and bone scans were monitored. No toxicity or serious adverse events related to vaccinations were observed. A total of 12 patients developed a specific immune response to tumour mRNA-transfected DCs. In total, 13 patients showed a decrease in log slope PSA. This effect was strengthened by booster vaccinations. Clinical outcome was significantly related to immune responses (n = 19, P = 0.002, r = 0.68). Vaccination with mRNA-transfected DCs is safe and results in cellular immune responses specific for antigens encoded by mRNA derived from the prostate cancer cell lines. The observation that in some patients vaccination affected the PSA level suggests that this approach may become useful as a treatment modality for prostate cancer patients.

Aged↗

Consequences of local recurrence of soft tissue sarcoma: 205 patients from the Scandinavian Sarcoma Group Register.

From the Scandinavian Sarcoma Group Register, information on 1,224 surgically-treated patients with soft tissue sarcoma (STS) of the extremity or trunk wall, diagnosed between 1987 and 1995, was collected. 205 patients, one third of whom were referred to a center with a local recurrence, had a total of 284 local recurrences. This analysis describes the treatment for these local recurrences, complications and risk of further recurrences. 169 patients were surgically treated for their first local recurrence. An intralesional or marginal margin was achieved in 110 of these patients, 59 of whom were also given radiotherapy. 54 of the 169 patients had a second local recurrence. The second local recurrence rate was 0.50 if the first local recurrence had been treated with only surgery with a marginal margin, compared to 0.28 if treated with surgery with a marginal margin and radiotherapy or with a wide margin (p = 0.0008). In extremity STS, the crude amputation rate for local recurrences was 0.22 (31 of 142)-i.e., higher than for primary tumors 0.09 (96 of 1065) (p < 0.0001). A high local recurrence rate after treatment outside of sarcoma centers has earlier been shown. We conclude that the consequences of local recurrence in terms of morbidity and costs justifies referral of STS patients for multidisciplinary evaluation and multimodality treatment.

Adult↗

Influence of droloxifene on metastatic breast cancer as first-line endocrine treatment.

The effect of droloxifene (3-hydroxytamoxifen) given as first-line endocrine treatment was evaluated in 39 postmenopausal women with advanced receptor-positive or receptor-unknown breast cancer. The patients had not received any previous anticancer therapy apart from adjuvant treatment. The overall response rate (CR + PR) was 51% (8% CR, 43% PR), 95% confidence interval+/-15.7%. Median time to progression (all patients) was 8 months, the median time to response 2 months, while the median duration of response was 10 months. The drug was well tolerated with no major side effects recorded; 16% of the patients experienced hot flushes. The response to droloxifene recorded in the present study is in accordance with the response rates to tamoxifen as first-line treatment in identical groups of patients.

Aged↗

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↗

Ifosfamide and continuous infusion etoposide in advanced adult soft tissue sarcoma. A Scandinavian Sarcoma Group Phase II Study.

The purpose of this study was to evaluate tumour response and toxicity to ifosfamide and continuous infusion etoposide in metastatic or locally advanced soft tissue sarcoma, with dose escalations under G-CSF (granulocyte colony-stimulating factor) support. Of 92 eligible patients (median age 51 years), 85% had tumours of high-grade malignancy and 82% had metastatic disease. Chemotherapy, the baseline dose, consisted of etoposide 600 mg/m2 as a 72 h infusion and ifosfamide 1500 mg/ m2/day for 3 days, followed by G-CSF support (VIG regimen). Stepwise 10% dose escalations were performed depending on haematological toxicity. For patients considered operable after induction chemotherapy, surgical resection of all identifiable residual tumour was attempted. Complete and partial response rates were 11% and 31%, for an overall response rate of 42% (95% CI 31-52%). Forty-eight per cent of courses were dose escalated by a median of 20%. Complete responders had significantly higher, and patients with progressive disease had significantly lower, dose levels than other patients. None of 20 patients with liver metastases responded despite high dose levels. Compared to a preceding pilot study, the addition of G-CSF led to significantly higher dose levels, improved schedule adherence and less haematological toxicity, but no apparent increase in response rate. In view of the modest dose of ifosfamide applied in this study, it is possible that the prolonged infusion of etoposide made a significant contribution to the regimen's antitumour activity, although this can only be determined definitively in a randomised study.

Adolescent↗

Influence of treatment with the anti-oestrogen 3-hydroxytamoxifen (droloxifene) on plasma sex hormone levels in postmenopausal patients with breast cancer.

Plasma levels of oestradiol (Oe2), oestrone (Oe1) oestrone sulphate (Oe1S), androstenedione, testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), sex hormone-binding globulin (SHBG) and the gonadotrophins (FSH and LH) were determined in 20 postmenopausal women with breast cancer treated with the anti-oestrogen droloxifene (3-hydroxytamoxifen). Plasma oestrogens were measured before and after 3, 6 and 12 months of therapy. The other hormones were measured before and after 6 months of therapy. Droloxifene treatment had no significant influence on plasma levels of Oe2. Plasma levels of Oe1 and Oe1S increased during treatment (mean increase of 11.9-15.9% and 24.5-69.4% respectively after different time-intervals on treatment). The Oe1S/Oe1 and Oe1S/Oe2 ratios increased by mean values of 13.8-45.2% and 25.9-52.4% respectively. Plasma SHBG increased significantly by a mean value of 73.9%, while FSH and LH fell non-significantly by 19.7% and 20.4% respectively. Plasma levels of testosterone, androstenedione, DHEA and DHEAS all increased during treatment, but none of these alterations were of statistical significance. While the influence of droloxifene on plasma SHBG resembled that which is seen during treatment with tamoxifen, its influence on plasma oestrogens and the gonadotrophins seems to be different. Possible explanations of such differences and the clinical implications of alterations in plasma hormones during treatment with droloxifene are discussed.

Aged↗

Transitional cell carcinoma of the renal pelvis and its expression of p53 protein, c-erbB-2 protein, neuron-specific enolase, Phe 5, chromogranin, laminin and collagen type IV.

Expression of p53 protein, c-erbB-2 protein, neuron-specific enolase (NSE), Phe 5, chromogranin, laminin and collagen type IV was studied by immunohistochemistry in formalin-fixed and paraffin-embedded specimens from 20 patients with renal pelvic carcinoma. Positive membrane-bound c-erbB-2 staining was not found in any case. Two tumors stained for p53 protein. Focal immunoreactivity for laminin was present in 55% and for collagen type IV in 80%. 25% of the cases were NSE positive. None of the tumors stained for Phe 5 or chromogranin. The results were compared with the clinical outcome and the immunohistological findings of p53 protein and c-erbB-2 protein in 13 cases of bladder carcinoma in the same patient group. Four of the thirteen bladder cancer specimens, but only 2 of the 20 renal pelvic cancer specimens, expressed p53 protein. As for renal pelvic carcinoma, c-erbB-2 protein was not expressed in bladder carcinoma. We conclude that p53 gene abnormalities may be of importance in the development of carcinoma in the renal pelvis and urinary bladder, but c-erbB-2 protein expression does not play a major role.

Adult↗

Droloxifene--a new anti-estrogen. A phase II study in advanced breast cancer.

Twenty-six patients with advanced breast cancer were treated with a new anti-estrogen, Droloxifene (3-hydroxy-tamoxifen). They had all used tamoxifen either in the adjuvant or the advanced situation. The dose schedule was 100 mg orally daily. Partial remissions were observed in 4 (15%) of the patients, and in another 5 patients stable disease (greater than 24 weeks of duration) was observed. Three of the responders were resistant to tamoxifen. Fourteen of the 26 patients had no side-effect. In 2 patients therapy had to be stopped due to fatigue. Droloxifene seems to be an interesting new anti-estrogen which should be further exploited.

Adult↗

Recombinant interferon-alpha with or without vinblastine in metastatic renal carcinoma. Results of a randomised phase II study.

In a randomised phase II study, 5 of 24 patients with metastatic renal carcinoma responded to treatment with interferon (IFN) (Roferon A, Roche, Basle, Switzerland) (18 x 10(6) u i.m. 3 times/week). The combination of IFN with vinblastine (0.1 mg/kg every third week) yielded a response rate of 16% (4 of 25 patients). Three patients continue to show a response (2 complete, 1 partial) more than 20 months after cessation of treatment. Flu-like symptoms represented the major side effect and often led to modification or discontinuation of treatment. It was concluded that IFN is the treatment of choice in patients with metastatic renal carcinoma who are candidates for medical treatment. The significance of additional vinblastine is uncertain.

Antineoplastic Combined Chemotherapy Protocols↗

Carcinoma in situ of the vulva. Long term prognosis.

Seventy-four patients with carcinoma in situ (CIS) of the vulva were followed over a 10-year period. The mean age was 52.8 years (range 21 to 90 years). Pruritus was the most common symptom. Forty per cent of the women were asymptomatic. Twenty-three per cent had a history of carcinoma in situ of the uterine cervix. Single lesions of CIS were found in the perineal area in 22 per cent, in the labia major and minor in 23 per cent, and in the clitoris in 7 per cent. Forty-two per cent of the patients had CIS in two or more of those areas. Seven of 74 patients (10%) had previously been irradiated for pelvic malignant tumours. Three women developed invasive squamous cell carcinoma of the vulva, two of them were previously irradiated. All 74 patients were treated surgically in different ways. Out of 38 women with histologically free margins of surgery, 6 had recurrence of dysplasia or CIS.

Adult↗

Per- and postoperative changes in coagulation and fibrinolytic variables during abdominal hysterectomy under epidural or general anaesthesia.

Blood coagulation and fibrinolysis were studied in 20 premenopausal women undergoing abdominal hysterectomy under general anaesthesia (GA) or high epidural analgesia (EDA). As expected, the adrenocortical stress response was suppressed in the EDA group. The Factor VIII complex (F VIII:C, F VIII R:Ag = von Willebrand factor), known to be related to adrenocortical activity and/or vessel wall reactivity, was found to increase less in the EDA group. With regard to all the other variables analysed there were no significant differences between the groups. With both anaesthetic procedures activation of coagulation could be demonstrated by a decrease in prekallikrein, F X and antithrombin as well as by an increase in fibrinopeptide A levels. A decrease in plasminogen and alpha 2-antiplasmin suggested activation of the fibrinolytic system and a decrease in prekallikrein and kallikrein inhibition activity (C-1-esterase inhibitor) an activation of the kallikrein system. In this study only the differences in F VIII complex could explain the previously reported higher thromboembolic frequency after GA as compared to EDA.

Adult↗

Neonatal depression after obstetrical analgesia with pethidine. The role of the injection-delivery time interval and of the plasma concentrations of pethidine and norpethidine.

Pethidine (100 mg) was administered i.m. to women in labor at different times before delivery. The interval before respiration in the newborn became sustained was shorter if pethidine was given less than one hour before delivery. The respiratory rate of the newborn increased after naloxone injection in 40 per cent of the cases, mostly when intrauterine exposure to pethidine exceeded one hour. The plasma concentrations of pethidine and norpethidine were measured in mother and newborn. The concentrations in the umbilical vein and artery indicted a continuous net transfer of pethidine from mother to fetus for approximately two hours. This correlated with the clinical finding of maximal neonatal depression 2-3 hours after maternal injection. The concentrations of norpethidine increased with a longer time interval between injection and delivery, but were probably too low to have any effect on the newborn. Neonatal depression seems to be related to the amount of unmetabolized pethidine that has been transferred from mother to fetus but not to norpethidine as had been suspected earlier.

Anesthesia, Obstetrical↗

Performance, mood, and clinical symptoms in men exposed to prolonged, severe physical work and sleep deprivation.

There were 44 young men who participated in strenuous combat courses of 4 d (course I) or 5 d (course II), almost without sleep. They were tested and examined clinically each morning. Groups 1 and 2 had no organized sleep, whereas groups 3 and 4 got 3 and 6 h, respectively, in the middle of each course. Substantial impairment was observed in all tests, as well as clinical symptoms toward the end of the courses for groups 1 and 2. In the vigilance test, the reaction time task, the code test, and the profile of mood-state, significant impairment was observed even after 24 h. Complaints of symptoms came first. Disturbance of senses and behaviour appeared later. Group 4 had significantly better results than groups 1 and 2 in clinical symptoms and all tests, except the positive score in mood-state. Group 3 occupied an intermediate position. Corresponding results were obtained in the two separate courses. In the morning following the course, recovery after 4 h of sleep was less extensive for courses II than course I participants.

Achievement↗

General anaesthesia or lumbar epidural block for caesarean section? Effects on the foetal heart rate.

Caesarean section was performed in 10 patients under general anaesthesia and in 10 other patients under epidural block. The foetal heart rate was monitored continuously during anaesthesia and operation with a scalp electrode and a cardiotocograph. There was no major difference between the two anaesthetic techniques in their effect on the foetal heart rate. The most common finding was a reduction of the beat-to-beat variation. The operative time was longer in the epidural group than in the general anaesthesia group, due to a higher frequency of Pfannenstiel incisions and repeat caesarean sections in the epidural group. Clinically, all newborns seemed to be unaffected, with normal Apgar scores. Epidural block seems to be a good alternative to general anaesthesia for caesarean section, particularly when a long operative time is expected.

Anesthesia, Epidural↗