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Biomedical subjects

A Jacobsen

Publications and source records attributed to A Jacobsen.

At least 19 recordsLinked to original sources
PubMed1998

Long-term results from a phase II study of single agent paclitaxel (Taxol) in previously platinum treated patients with advanced ovarian cancer: the Nordic experience.

BACKGROUND: Owing to the wide spread perception of a possible benefit from paclitaxel in the second-line situation the Nordic Gynecologic Oncology Group (NGOG) conducted two prospective phase II studies of paclitaxel single agent treatment (175 mg/m2, three-hour i.v. infusion with standard pre-medication every third week) in patients with relapsing or progressing epithelial ovarian cancer following platinum. PATIENTS AND METHODS: Between 1992-1994 138 patients in total were enrolled of whom 136 received paclitaxel and were included in the toxicity and survival analysis, while 112 were evaluable for response. RESULTS: The overall response rate (CR + PR) was 28% with 16 patients achieving a CR (14%). The estimated median (range) time to progression was 4.1 (0.7-60.7) months. The projected four-year overall survival was 7%, with a median (range) of 9.6 (0.3-60.7) months. A multivariate logistic regression analysis showed that platinum resistance, and WHO performance status at baseline, independently correlated with survival at all three time points (median survival time 9.6, 18, and 24 months). Patients with platinum sensitive tumors and WHO performance status 0 had a median survival of 25.6 months compared to 7.0 months for the rest of the patients (P < or = 0.0001). No serious toxicity was registered. CONCLUSION: Paclitaxel could safely be administered in an outpatient setting using this schedule. Patients with platinum sensitive tumors and a good performance status were most likely to survive. However, these patients are also most likely to respond to re-treatment with a platinum compound. With reference to the reasonably good tumor control and limited toxicity observed in this study, we conclude that paclitaxel single agent therapy is a viable option in the salvage situation, which in some patients can give long-lasting responses. However, although responses can be induced in a significant number of patients, the survival figures remain poor.

Adult↗
PubMed1996

A phase 2 study with epirubicin as second-line treatment of patients with advanced epithelial ovarian cancer.

Thirty-six patients with advanced epithelial ovarian cancer received epirubicin as second-line therapy after primary treatment with carboplatin and cyclophosphamide. Thirty-four patients were evaluatable for response, 36 for toxicity. There were 9 responses (response rate 26.4%, 95% CI = 12.9-44.4), 2 complete and 7 partial. Median duration of response was 149 days (range 42-183); 4 patients with partial remission are still on study. Toxicity consisted of fatal cardiac failure and paravenous injection (1 patient), fatal leukopenia and sepsis (1 patient), and severe loss of appetite, nausea and vomiting, fatigue, and general malaise in 3 patients. Platelet nadir grade 4 (WHO) was observed in 2 patients while leukocyte nadir grade 4 was seen in 3 patients. The present study showed a high response rate from standard-dose epirubicin. Toxicity was acceptable in most patients, but 2 patients died from treatment complications which gives a treatment-related mortality rate of 6%. Response was primarily seen in patients with minor tumor load and in good general condition.

Adult↗
PubMed1995

Suppression of ventricular arrhythmias during ischemia-reperfusion by agents inhibiting Ins(1,4,5)P3 release.

BACKGROUND: Reperfusion following myocardial ischemia causes a rapid and transient release of inositol (1,4,5)triphosphate [Ins(1,4,5)P3]. The aim of this study was to test whether this increased Ins(1,4,5)P3 release was important for the development of ventricular arrhythmias and whether agents that inhibit this signal transduction pathway, such as aminoglycoside antibiotics, suppress arrhythmias. METHODS AND RESULTS: In perfused rat hearts, ventricular tachycardia (VT), ventricular fibrillation (VF), and accumulation of Ins(1,4,5)P3 were measured during early reperfusion. A number of different compounds, including neomycin, gentamicin, streptomycin, spermine, reserpine, and prazosin, were effective in inhibiting the reperfusion-induced Ins(1,4,5)P3 release and the onset of VT and VF in parallel. A strong correlation existed between Ins(1,4,5)P3 content, measured at 2 minutes of reperfusion, and the incidence of reperfusion VT and VF. In addition, intravenous gentamicin suppressed the onset of arrhythmias under ischemic and reperfusion conditions in vivo. CONCLUSIONS: Our results are consistent with the view that Ins(1,4,5)P3 release plays a pivotal role in mediating arrhythmias during early reperfusion. Agents inhibiting Ins(1,4,5)P3 release are antiarrhythmic and may have potential use clinically.

Alkaloids↗
PubMed1993

Structure, expression, and phylogenetic relationships of a family of ypt genes encoding small G-proteins in the green alga Volvox carteri.

In addition to the previously described gene yptV1 encoding a small G-protein we have now identified and sequenced four more ras-related ypt genes (yptV2-yptV5) from the green alga Volvox carteri. The four new genes encode polypeptides consisting of 203 to 217 amino-acid residues that contain the typical sequence elements (GTP-binding domains, effector domain) of the ypt/rab subgroup of the Ras superfamily. Comparison of the derived amino-acid sequences from the V. carteri ypt gene products and their Ypt homologs from other species revealed similarity values ranging from 60% to 85%, whereas intraspecies similarities were found to approach only 55%. The coding sequences are interrupted by 5-7 introns of variable size (70-1000 nucleotides) occupying different positions in the genes. Reverse-transcribed samples of stage-specific RNAs were PCR-amplified with primers specific to yptV1, yptV3, yptV4, and yptV5 to determine if yptV transcription might be restricted to either cell type or to a specific stage of the life cycle. These experiments demonstrated that each of these genes is expressed throughout the entire Volvox life cycle and in both the somatic and the reproductive cells of the alga. The transcription start sites of yptV1 and yptV5 were mapped by primer extension. Expression of recombinant yptV cDNA in E. coli yielded recombinant proteins that bound GTP specifically, demonstrating a property which is typical for small G-proteins. The derived YptV polypeptide sequences were used to group them into four distinct classes of Ras-like proteins. These are the first proteins of the Ras superfamily to be identified in a green alga. We discuss the possible role of the YptV-proteins in the intracellular vesicle transport of Volvox.

Amino Acid Sequence↗
PubMed1992

Adjuvant radiotherapy and risk of contralateral breast cancer.

BACKGROUND: The risk of contralateral breast cancer is increased twofold to fivefold for breast cancer patients. A registry-based cohort study in Denmark suggested that radiation treatment of the first breast cancer might increase the risk for contralateral breast cancer among 10-year survivors. PURPOSE: Our goal was to assess the role of radiation in the development of contralateral breast cancer. METHODS: A nested case-control study was conducted in a cohort of 56,540 women in Denmark diagnosed with invasive breast cancer from 1943 through 1978. Case patients were 529 women who developed contralateral breast cancer 8 or more years after first diagnosis. Controls were women with breast cancer who did not develop contralateral breast cancer. One control was matched to each case patient on the basis of age, calendar year of initial breast cancer diagnosis, and survival time. Radiation dose to the contralateral breast was estimated for each patient on the basis of radiation measurements and abstracted treatment information. The anatomical position of each breast cancer was also abstracted from medical records. RESULTS: Radiotherapy had been administered to 82.4% of case patients and controls, and the mean radiation dose to the contralateral breast was estimated to be 2.51 Gy. Radiotherapy did not increase the overall risk of contralateral breast cancer (relative risk = 1.04; 95% confidence interval = 0.74-1.46), and there was no evidence that risk varied with radiation dose, time since exposure, or age at exposure. The second tumors in case patients were evenly distributed in the medial, lateral, and central portions of the breast, a finding that argues against a causal role of radiotherapy in tumorigenesis. CONCLUSIONS: The majority of women in our series were perimenopausal or postmenopausal (53% total versus 38% premenopausal and 9% of unknown status) and received radiotherapy at an age when the breast tissue appears least susceptible to the carcinogenic effects of radiation. Based on a dose of 2.51 Gy and estimates of radiation risk from other studies, a relative risk of only 1.18 would have been expected for a population of women exposed at an average age of 51 years. Thus, our data provide additional evidence that there is little if any risk of radiation-induced breast cancer associated with exposure of breast tissue to low-dose radiation (e.g., from mammographic x rays or adjuvant radiotherapy) in later life.

Adult↗
PubMed1990

Histopathological features in stage I non-seminomatous testicular germ cell tumours correlated to relapse. Danish Testicular Cancer Study Group.

156 patients with stage I non-seminomatous testicular germ cell tumour entered a countrywide randomized study comparing the effect of postoperative irradiation of retroperitoneal lymph nodes with surveillance only. A total of 150 patients were included in this investigation of factors associated with increased risk of relapse. Thirty-four patients (23 per cent) had a relapse, i.e. 11/67 (16 per cent) in the former and 23/83 (28 per cent) in the latter group. Histopathological studies of the orchidectomy specimens were performed in order to identify features associated with relapse. Pure embryonal carcinoma and vascular involvement were significantly associated with increased risk of relapse. Thus, the relapse rate in the observation group in patients with pure embryonal carcinomas was 50 per cent (5/10) and 36 per cent (19/53) in all patients with tumours with vascular involvement.

Choriocarcinoma↗
PubMed1989

[Psychological follow-up study of families of children with acute lymphoblastic leukemia].

The qualities of the multi-disciplinary social, psychological, medical and nursing contributions for children diagnosed consecutively as having acute lymphoblastic leukaemia and their families were investigated. The parents of a total of 39 children, 31 fathers and 36 mothers, participated in a semi-structured interview with the psychologist attached to the department concerning the extent to which the psycho-social requirements of the family had been met by offers from the hospital. The interview concerning the diagnosis took place equally frequently in local hospitals and in Rigshospitalet. In both of these locations only half of the parent couples were satisfied with the course of the conversation. In the course of the disease, the mothers and the fathers experienced three situations differently: the situation at work, the parents' married life and the responsibility for treatment of the child. The family dynamic situation was altered in all of the families. Parents developed a closer relationship to the sick child while the relationship to the siblings equally frequently improved or deteriorated. At the conclusion of treatment, 2/3 felt that a form of security disappeared even though they were pleased to have got so far. In cases with relapse, another crisis developed and was just as difficult as the first, regardless of whether attempts had been made to prepare the families for this possibility. This investigation has pointed out a series of circumstances which the therapeutic system should be familiar with and which they can be prepared for.

Adolescent↗
PubMed1986

Treatment of xerostomia in patients with primary Sjögren's syndrome with sulfarlem.

Stimulated by a recent report on the favorable effect of Anetholtritione (Sulfarlem S 25) on symptoms and salivary flow rate in patients with Sjögren's Syndrome (SS), we examined the effect of Sulfarlem in an open study on 16 patients characterized by severe xerostomia. Fourteen had primary SS and two xerostomia only. The patients were examined by whole resting saliva secretion rate measurement (SR) once a week during the study period of 7 weeks. At the same time the patients assessed their symptoms of xerostomia on a 1-10 visual analogue scale. Following the third examination (2 weeks), Sulfarlem was given p.o. 25 mg X 3 daily for 3 weeks, after which the patients were examined for another 2 weeks. The average SR before treatment was 0.07 ml/15 min. Two patients had increased secretion rates, but only one of these described improvement in symptoms. Two had improvement in symptoms and 12 had no positive subjective or objective effect from treatment. Side effects were abdominal discomfort and flatulence, seen in 7 patients (44%). One of these patients in addition had diarrhea and nausea. The side effects were persistent during treatment only. The medication was terminated following one week of treatment in two patients. It is concluded that Sulfarlem in a daily dose of 75 mg have no marked effect on salivation in patients with primary SS and severe xerostomia. Gastrointestinal side effects may occur.

Anethole Trithione↗
PubMed1984

Perception of lightness and illumination in a world of one reflectance.

Observers looked into a miniature room in which everything was painted matte white, or--in another room--matte black. They made both reflectance and illumination judgments for eight test spots. The test spots (which varied in luminance) were perceived as approximately equal in reflectance--not different, as conventional contrast theories would seem to require. The illumination matches made to the same points, however, closely paralleled the pattern of actual illumination levels, and this result is discussed as evidence that edges are classified as changes in either reflectance or illumination. The white room was correctly perceived as white, and the black room was perceived as middle gray; similar results were obtained even when the luminances in the black room were higher (owing to higher illumination) than the corresponding luminances in the white room. An explanation in terms of differences in gradient patterns is presented and supported with luminance profiles.

Discrimination, Psychological↗
PubMed1983

Ethanol metabolism in heavy drinkers after massive and moderate alcohol intake.

Some alcoholics have a regular daily alcohol consumption of more than 100 g. In preliminary observations we had the impression that the claimed alcohol intake in such 'heavy drinkers' was higher than could be accounted for by the ethanol elimination rate as measured routinely at 10 mmol/l (0.5 g/l). We therefore measured the ethanol elimination rate at very high blood ethanol concentrations of 40-80 mmol/l (2-4 g/l) found in eight alcoholics following heavy alcohol intake by measuring the falling blood ethanol concentrations until being less than 1 mmol/l. The elimination rate, on average 83 mumol/min per 1 blood, was about 49% higher than the elimination rate measured at 10 mmol/l in the same subject, being on average 58 mumol/min per 1/blood (paired t-test, P less than 0.05). The elimination rate following the high initial ethanol concentrations remained high until the concentration was below 5 mmol/l. Calculations of elimination rates are based on a number of assumptions concerning the physiologic and metabolic conditions. We examined specifically if the concentration-time curves could be adequately described by assuming metabolism according to a Michaelis-Menten pathway with a low Km value (simulating alcoholdehydrogenase with Km 0.2 mmol/l) or by assuming metabolism by two pathways with an alternative high-Km pathway with Km about 10 mmol/l. It was not necessary, in the statistical analysis, to include an alternative high-Km pathway. On the other hand, the data does give room for up to 50% elimination via such alternative pathways. The elimination rate at the high concentrations corresponded roughly to the claimed daily alcohol intake; furthermore the measured elimination rate at the lower concentrations were similar to values in non-alcoholics.

Alcohol Drinking↗