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Biomedical subjects

E Jonsson

Publications and source records attributed to E Jonsson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Health technology assessment in Sweden.

Sweden has a welfare system that is based on the fundamental principle that all citizens are entitled to good health and medical care, regardless of where they live or what their economic circumstances are. Health and medical care are considered to be public sector responsibilities. However, there is growing interest in establishing more private alternatives to public care. An important characteristic of the Swedish healthcare system is its decentralization, with a major role for county councils. County councils are now merging into larger administrative units (region). The whole Swedish system is in the process of reform, mainly because of perceptions that it was too rigid and had insufficient patient orientation. An important factor in the reforms is that power in the system will be even more decentralized and will have greater public input. This change is seen as calling for increased central follow-up and evaluation of matters such as social, ethical, and economic aspects. Although the state has decentralized control, it still attempts to control the general direction of the system through regulation, subsidy, recommendations, and guidelines. An important actor in the system is the Swedish Council on Technology Assessment in Health Care (SBU). SBU began in 1987 with assessments of health technologies, but its success has recently led policy makers to extend its coverage to dental care. Health technology assessment is increasingly visible to policy makers, who find it useful in decision making.

Delivery of Health Care↗
PubMed2000

Rectal carcinoma: double-contrast MR imaging for preoperative staging.

PURPOSE: To evaluate and compare the imaging findings and staging of rectal carcinoma by using conventional magnetic resonance (MR) imaging, MR imaging with an enema of superparamagnetic ferristene-based contrast material, and MR imaging with an enema of ferristene solution plus intravenous injection of gadodiamide. MATERIALS AND METHODS: Twenty-nine patients (17 women, 12 men; age range, 39-91 years) referred with a diagnosis of rectal carcinoma were examined. Analysis of the rectal wall and staging of the tumor were performed. In all patients, the MR imaging findings were correlated with the histopathologic findings. RESULTS: The contrast material enema caused distention of the rectum and an intraluminal signal void, whereas the gadodiamide injection caused enhancement of the mucosa on T1-weighted images. This enhancement enabled evaluation of the normal rectal wall and differentiation of the mucosa, tunica muscularis, and perirectal space, which was not possible on the nonenhanced images. Double-contrast (ferristene solution plus gadodiamide) MR imaging was superior to imaging with only ferristene-based contrast material and had a sensitivity of 100%, specificity of 70%, and accuracy of 90% in distinguishing tumor stages worse than Dukes A. CONCLUSION: Double contrast material-enhanced MR imaging enables accurate rectal carcinoma staging, which is not possible at nonenhanced imaging.

Adult↗
PubMed1999

CHS 828, a novel pyridyl cyanoguanidine with potent antitumor activity in vitro and in vivo.

A new class of recently discovered antineoplastic agents, the pyridyl cyanoguanidines, exert a potent antitumor activity in rodents after oral administration. Optimization in vitro and in vivo has resulted in the selection of the lead candidate CHS 828 (N-(6-chlorophenoxyhexyl)-N'cyano-N"-4-pyridylguanidine). CHS 828 was found to exert potent cytotoxic effects in human breast and lung cancer cell lines, with lesser effects on normal fibroblasts and endothelial cells. In a study using a panel of cell lines with different resistance patterns, the effects of CHS 828 showed a low correlation with the activity patterns of known anticancer agents, and no sensitivity to known mechanisms of multidrug resistance was observed. In nude mice bearing human tumor xenografts, CHS 828, at doses from 20 to 50 mg/kg/day p.o., inhibited the growth of MCF-7 breast cancer tumors and caused regression of NYH small cell lung cancer tumors. Oral administration of CHS 828 once weekly improved efficacy without increasing toxicity. CHS 828 was found to compare favorably with established chemotherapeutic agents such as cyclophosphamide, etoposide, methotrexate, and paclitaxel. In mice with NYH tumors, long-term survival (>6 months) was observed after treatment with CHS 828 was stopped. In conclusion, CHS 828 is an effective new antitumor agent, with a potentially new mechanism of action. CHS 828 is presently being tested in Phase I clinical trials in collaboration with the European Organization for Research and Treatment of Cancer.

Animals↗
PubMed1999

Relationship between diagnosis-specific activity of cytotoxic drugs in fresh human tumour cells ex vivo and in the clinic.

The aim of this investigation was to evaluate the relationship between the disease-specific activity of cytotoxic drugs in the clinic and in fresh human tumour cells from patients, as detected by a non-clonogenic cytotoxicity assay. The activity of 18 different cytotoxic drugs in fresh human tumour cells ex vivo was analysed in up to 15 samples from each of 13 different diagnoses using the fluorometric microculture cytotoxicity assay (FMCA). For each drug and diagnosis, relative activity indices (RAIs) were calculated, defined as the fraction of samples within the diagnosis having a survival index (SI) less than the median SI for the drug in all tested samples. Clinical response rates for the drug in the same diagnoses were collected from published phase II trials and were compared with the RAIs using Spearman's rank correlation (Rho) and Pearson's correlation coefficient (R). Correlation coefficients could be calculated for 12 drugs. The coefficients varied between 0.02 and 0.92 (Rho) and between 0.07 and 0.91 (R), but for most drugs the correlation between RAI and clinical response rates was good, with Rho > 0.6 and R > 0.7. Weak correlations were observed for cyclophosphamide and vincristine (Rho = 0.32 and 0.16, respectively), which might be due to old clinical data, and for paclitaxel (Rho = 0.02), which perhaps could be explained by in vitro activity of the solvent, Cremophor EL. The 18 drugs were also categorised according to their suggested clinical use in solid or haematological tumours, and were then compared regarding the activity in solid compared with haematological tumours ex vivo, expressed as the ratio between the number of responders among solid and haematological tumours (S/H ratio). The mean ex vivo S/H ratios in the group of drugs registered for use in haematological tumours was only 0.09 and was significantly different (P = 0.05) from the mean S/H ratios for the drugs used in both haematological and solid tumours (0.31) and in solid tumours only (0.47). Furthermore, the FMCA could identify the 50% most and least sensitive diagnoses with respect to clinical phase II activity with 74% (78/106) correct classifications. The results indicate that the relative activity of cytotoxic drugs in different diagnoses may be detected by the FMCA. Thus, 'phase II trials ex vivo' using non-clonogenic cytotoxicity assays might be used to make clinical trials more effective by targeting trials to diagnoses in which a new agent is most likely to be active.

Antineoplastic Agents↗
PubMed1999

Sick leave and disability pension before and after treatment for obesity: a report from the Swedish Obese Subjects (SOS) study.

OBJECTIVES: To analyse sick leave and disability pension among surgically and conventionally treated obese patients. DESIGN: A prospective study over five years. Differences in sick leave and disability pension were analysed using multiple and logistic regressions. Possible confounding factors were analysed and controlled for. SETTING: Nine counties in Sweden. SUBJECTS: 369 surgically treated patients and 371 matched obese controls, included in the Swedish Obese Subjects (SOS) study. At baseline, mean body mass index (BMI) was 42 kg/m2 in surgical patients and 41 kg/m2 in controls. After four years of treatment, weight reduction was 20% among surgical patients while the control patients kept their initial weight. INTERVENTION: Gastric bariatric surgery. MEASUREMENTS: Days of sick leave plus disability pension, and days of disability pension. RESULTS: In the year prior to treatment, adjusted average number of days of sickness due to sick leave plus disability pension was similar in surgical patients and controls. Compared with controls, the surgical group had 35% more days of sickness during the first year after initiation of treatment, but 10-14% fewer days during years 2-3. During year four, days of sickness tended to be lower in the surgical group (P = 0.07). In the sub-group, aged above the median, surgical patients had 14-18% fewer days of sickness than controls, during years 2-3 after initiation of treatment This difference did not occur in the group below median age. CONCLUSION: Surgical treatment of obesity results in a reduction of sick leave and disability pension, compared to controls, particularly in subjects aged 47-60 y.

Adult↗
PubMed1999

A prospective randomised study (named SVEA) of three methods of delayed breast reconstruction. Study design, patients' preoperative problems and expectations.

A randomised study named SVEA to compare three methods for delayed breast reconstruction was initiated in 1994. The methods were: the lateral thoracodorsal flap, the latissimus dorsi flap, and the pedicled transverse rectus abdominis muscle flap. In the present paper we describe the study design, primary endpoints, and inclusion and exclusion criteria. Results from preoperative questionnaires about problems after mastectomy and expectations of the reconstruction are presented. The preoperative questionnaires, completed before randomisation, included a health related quality of life questionnaire, the SF-36, and a questionnaire concerning the impact of breast loss and expectations of the reconstruction. A total of 87 patients have been randomised in SVEA and 30 patients have been followed up outside the randomised study, comprising a reference group. The results from preoperative questionnaires, completed by 106 of the total 117 women, showed that they encountered many problems after mastectomy, primarily about feeling mutilated and being bothered socially. They held high expectations on the breast reconstruction in these areas. The women in the present study did not differ from Swedish women in general regarding health related quality of life, with two exceptions: the study sample scored lower on physical functioning and mental health.

Attitude to Health↗
PubMed1999

Heterologous expression and kinetic characterization of human cytochromes P-450: validation of a pharmaceutical tool for drug metabolism research.

Drug metabolism studies in the early phases of drug discovery and development will improve the selection of new chemical entities that will be successful in clinical trials. To meet the expanding demands for these studies on the numerous chemicals generated through combinatorial chemistry, we have heterologously expressed nine human drug-metabolizing cytochromes P-450 (CYPs) in Saccharomyces cerevisiae. The enzymes were characterized using known marker substrates CYP1A1/1A2 (ethoxyresorufin), 2C8 (paclitaxel), 2C9 (diclofenac), 2C19 (S-mephenytoin), 2D6 (bufuralol), 2E1 (chlorzoxazone), and 3A4/3A5 (testosterone). All of the CYPs showed the expected substrate specificity except for chlorzoxazone hydroxylation, which, in addition to CYP2E1 and 1A2, was also catalyzed by CYP1A1 with a high turnover. The apparent Michaelis-Menten parameters obtained for each CYP were within the ranges of those reported in the literature using human liver microsomes and/or recombinant CYPs. The K(m) for CYP2E1-catalyzed chlorzoxazone hydroxylation was, however, much higher (177 microM) than that obtained using liver microsomes (40 microM). CYP-selective inhibitors, alpha-naphthoflavone (CYP1A1/1A2), quercetin (2C8), sulfaphenazole (2C9), quinidine (2D6), and ketoconazole (3A4/3A5) showed significant isoform-selective inhibitory effects. We have shown that ticlopidine is a potent inhibitor of CYP2C19 (IC(50) = 4. 5 microM) and CYP2D6 (IC(50) = 3.5 microM) activities. We have therefore successfully set-up and validated an "in-house" heterologous system for the production of human recombinant CYPs for use in metabolism research.

Cytochrome P-450 Enzyme Inhibitors↗
PubMed1998

Synergistic interactions of combinations of topotecan with standard drugs in primary cultures of human tumor cells from patients.

OBJECTIVE: Combination therapies are important in the treatment of many tumor types. This study was undertaken to find candidates for combination therapy with the novel topoisomerase I inhibitor topotecan. METHODS: The cytotoxic effect of topotecan alone and in combination with five standard cytotoxic drugs was studied in 27 primary cultures of human tumor cells from patients with various diagnoses using the fluorometric microculture cytotoxicity assay (FMCA). The combinations were analysed according to the multiplicative concept of drug interaction. RESULTS: The additive model was shown to be a better descriptor than the effect of the most effective agent (Dmax) for all drug combinations tested. Topotecan in combination with cisplatin (CisP) was the drug combination showing synergy in the highest percentage of samples (54%), followed by topotecan in combination with doxorubicin (Dox: 39%), etoposide (P16; 23%), paclitaxel in the formulation Taxol (22%) and cytarabine (AraC; 12%). The high percentage of synergistic interactions was especially pronounced in solid tumors. In 28% of the samples tested, drug sensitivity testing of only single drugs failed to predict response to the drugs in combination. CONCLUSION: Cisplatin and doxorubicin showed promising effects in combination with topotecan, and clinical trials with these combinations seem warranted. The results also indicate the value of testing drug combinations in in vitro drug sensitivity testing.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

International collaboration in health technology assessment: a study of technologies used in management of osteoporosis.

A collaborative study was undertaken by members of the International Network of Agencies for Health Technology Assessment (INAHTA). The evidence of the effectiveness of bone density measurement and selected treatments in preventing fractures in later life was reviewed. There was fair evidence that bone density measurement can predict risk of fractures and that hormone replacement therapy and intranasal salmon calcitonin preserve bone mass and decrease the risk of fractures. However, it was estimated that only 1-7% of hip fractures would be prevented if these technologies were used in a screening program for menopausal women. Results of the assessment were endorsed by 13 INAHTA members, disseminated widely and provided input to policy and further work in this area. The project demonstrated the feasibility of international collaborative health technology assessment.

Bone Density↗
PubMed1997

BRCA2 mutation in Icelandic prostate cancer patients.

Molecular genetic analysis of prostate cancer has gained considerable attention in recent years. The hope is to find genetic markers that can help to determine which patients are likely to develop a progressive or lethal disease and would therefore benefit from early treatment. The BRCA2 gene on chromosome 13 has been associated with familial male and female breast cancer. A founder mutation in this gene has been detected in the Icelandic population. This is a 5-bp deletion that leads to an early termination and truncated protein. Clustering of prostate cancers in some of the Icelandic BRCA2 families implies that mutation carriers are at increased risk of developing cancer of the prostate. The aim of the study was to investigate this mutation in Icelandic prostate cancer patients related to BRCA2 positive breast cancer probands and to estimate the prevalence of this mutation in unselected prostate cancer patients. To examine the potential role of this mutation in prostate cancer we analyzed prostate cancer cases from 16 BRCA2 families and all available samples from individuals diagnosed with prostate cancer in Iceland over a period of 1 year. The risk ratio of prostate cancer was 4.6 (1.9-8.8) in first-degree relatives and 2.5 (1.2-4.6) in second-degree relatives of the 16 BRCA2 positive breast cancer probands. Of 26 prostate cancer cases found in these families 12 were analyzed, and 8 of these (66.7%) had the BRCA2 mutation. All of these patients developed an advanced disease, and all have died of prostate cancer (median survival 22.5 months). Among unselected cases 3.1% (2/65) had the mutation and developed an advanced disease as well. This specific mutation in the BRCA2 gene is found in a subset of Icelandic prostate cancer cases and appears to be a marker for poor prognosis.

Aged↗
PubMed1997

Recommendations for the application of bone density measurement. What can you believe?

This study examined the conclusions of published reports that review the literature and make recommendations about appropriate applications of bone density measurement. It is based on a survey of 22 organizations producing such reports between 1986 and Spring 1995. Overall, the application of bone density measurement for the diagnosis of osteoporosis was supported by 65% of reports, by 44% for the monitoring and follow-up of patients with previously diagnosed disease, and by 59% for monitoring and follow-up of patients receiving treatment that may affect their bone density. A smaller proportion of reports from government and public organizations compared with other types of organizations and a smaller proportion of reports using more rigorous methods supported the applications for bone density measurement identified in the survey. A larger proportion of the reports published after 1990 compared with those published between 1986 and 1990 support the applications of bone density measurement, with the exception of population screening. The results of this survey suggest that there is considerable disagreement about the potential applications of bone density measurement. Publicly funded organisations and those using more rigorous methods tended to be more conservative in their conclusions.

Bone Density↗
PubMed1997

Cytotoxic activity of topotecan in human tumour cell lines and primary cultures of human tumour cells from patients.

The cytotoxic activity and cross-resistance pattern of the novel topoisomerase I inhibitor topotecan (Topo) were investigated in ten cell lines, representing different mechanisms of cytotoxic drug resistance, and in 218 fresh human tumour samples using the fluorometric microculture cytotoxicity assay (FMCA). Resistance to Topo in the cell lines was associated with expression of the multidrug resistance-associated protein (MRP), whereas the cell lines with P-glycoprotein (P-gp), topoisomerase II and glutathione-associated resistance did not show decreased sensitivity to the drug. Topo was more active in haematological than in solid tumour samples, but substantial activity was observed in carcinomas of the ovary and breast, sarcoma and childhood solid tumours. Cross-resistance to standard drugs representing different mechanisms of action was generally low in patient cells. The effect of Topo was better after longer exposure, but this time-dependent effect was largely abolished when adjustment for in vitro exposure was made. Topo showed activity both in proliferative and non-proliferative cell systems. The results indicate that Topo is insensitive to major mechanisms of resistance except for MRP. Proliferation does not seem to be necessary for the effect of Topo, and no superiority for protracted dosing schedules was observed. The results also suggest that, for example, leukaemias, lymphomas, sarcomas and childhood solid tumours may be suitable targets for future phase II trials.

Camptothecin↗
PubMed1996

Neglected aspects of false positive findings of mammography in breast cancer screening: analysis of false positive cases from the Stockholm trial.

OBJECTIVES: To examine the implications of false positive results of mammography in terms of the time lag from screening and complete mammography to the point when women with false positive results are declared free of cancer; the extra examinations, biopsies, and check ups required; and the cost of these extra procedures. DESIGN: Review of women with false positive results from the Stockholm mammography screening trial. SETTING: Department of Oncology, South Hospital, Stockholm. SUBJECTS: 352 and 150 women with false positive results of mammography from the first and second screening rounds of the Stockholm trial. MAIN OUTCOME MEASURES: Extra examinations and investigations required and the cost of these procedures. RESULTS: The 352 women from the first screening round made 1112 visits to the physician and had 397 fine needle aspiration biopsies, 187 mammograms, and 90 surgical biopsies before being declared free of cancer. After six months 64% of the women (219/342) were declared cancer free. The 150 women in the second round made 427 visits to the physician and had 145 fine needle aspiration biopsies, 70 mammograms, and 28 surgical biopsies, and after six months 73% (107/147) were declared cancer free. The follow up costs of the false positive screening results were Kr2.54m (250,000 pounds) in the first round and Kr0.85m (84,000 pounds) in the second round. Women under 50 accounted for about 41% of these costs. CONCLUSIONS: The examinations and investigation carried out after false positive mammography --especially in women under 50--and the cost of these procedures are a neglected but substantial problem.

Adult↗
PubMed1996

Health policy on bone density measurement technology in Sweden and Australia.

The possible adverse consequences of osteoporosis, particularly hip fractures, are a considerable health concern that is particularly relevant for elderly women. Bone density measurement is a method to assess bone mineral that has grown rapidly in recent years in both Sweden and Australia. The types of technologies adopted, their location and their level of use reflect the characteristics of the different health care systems, health technology assessments and policies adopted by health authorities. The health policy issues related to use of these technologies are complex and include consideration of who should be examined and treated, potential risks and benefits, machine performance, patient compliance and evidence of benefit.

Absorptiometry, Photon↗
PubMed1996

Tolerance and efficacy of Omniscan (gadodiamide injection) in MR imaging of the central nervous system.

PURPOSE: This Swedish multicenter trial was performed on patients with known or suspected lesions of the CNS for which an MR examination using a contrast medium was indicated. A total of 8 MR centers participated in the study to establish the safety and efficacy of Omniscan (gadodiamide injection) in clinical routine using a standard dose of 0.1 mmol Gd/kg b.w. MATERIAL AND METHODS: Seven hundred adult patients who had been referred for MR investigation of suspected CNS lesions were included in the study. Since most patients were examined on an outpatient basis, it was decided to use an explicit questionnaire regarding adverse events that developed within 24 h after examination. The efficacy evaluation involved comparisons of detectability, delineation, and number of lesions before and after injection of Omniscan. RESULTS: No serious or unexpected adverse event was found. There were a total of 70 (10.2%) patients with adverse events, excluding those judged not to be contrast media-related. However, only 15 patients (2.2%) had adverse events that possibly or probably were related to the contrast medium. Usually, the symptoms were headache, dizziness, abnormal taste, and nausea. Two patients complained of itching, but only one developed urticaria. The efficacy was similar to that of other currently used Gd-based MR agents. Lesions were more often seen on T2-weighted images, but the contrast medium improved lesion delineation, contributing to higher certainty in diagnosis, and provided more confidence in excluding suspected abnormality. CONCLUSION: Omniscan was found to be a safe and clinically valuable contrast medium for MR imaging of the CNS.

Adolescent↗
PubMed1996

MR imaging in recurrent pain after back surgery. A comparative study using standard and high doses of gadolinium contrast agents.

PURPOSE: To compare the diagnostic results following injection of (a) a high dose (0.3 mmol/kg b.w.) of gadodiamide injection and (b) the standard dose (0.1 mmol/kg b.w.) of Gd-DTPA, in patients with recurrent symptoms after surgery for lumbar disc herniation. MATERIAL AND METHODS: Twenty patients with recurrent or sustained symptoms after surgery for lumbar disc herniations were examined. MR imaging (0.3 T) was first performed before and after Gd-DTPA at 0.1 mmol/kg b.w., and then within one month (17 patients) or within 3 months (3 patients) before and after gadodiamide injection at 0.3 mmol/kg b.w. The examinations were first evaluated by 2 neuroradiologists blinded to dose but not to patient as the images were presented in pairs. Six months later the same investigators evaluated the examinations again, this time blinded to both dose and patient. RESULTS: At the evaluation in pairs (with the investigators blinded to dose only) the high-dose examinations were considered the most informative (p=0.05). However, at the later evaluation (with the investigators blinded both to dose and patient) no significant difference between high and standard dose was found regarding diagnosis or diagnostic certainty. CONCLUSION: In this study the high-dose contrast enhancement of MR imaging at 0.3 T did not increase the diagnostic information for differentiating between scar and recurrent hernia. The high-dose images were considered more informative when evaluated in pairs, but gave no additional or different information when evaluated separately. The study also indicated that comparisons in pairs should be interpreted with caution.

Adult↗