Urban Nylen

Improvements in patient satisfaction at an outpatient clinic for patients with breast cancer

The present study prospectively investigated changes in patient satisfaction at an outpatient clinic for patients with breast cancer. Consecutive patients were asked to anonymously complete a questionnaire after their medical examination. The questionnaire consisted of 12 multiple-choice items concerning waiting time, interpersonal skills of physician and nurse, continuity of care, length of medical visit, communication and expectations. Finally, patients were asked for suggestions for improvements at the clinic in an open-ended question. The first measurement was conducted in 2000/2001 and the last in 2004, and between the two points of assessments efforts to develop care were introduced. Statistically significant improvements were found in eight of the 12 items: waiting time, length of medical visit, information, expectations and continuity of care. In conclusion, the questionnaire captured positive changes in patient satisfaction between the two measurements. Further changes for the better were still requested concerning continuity of care despite reported improvement.

Gene Amplification Detected in Carcinoma Cells from Human Urinary Bladder Washings by the Polymerase Chain Reaction Method

Background. Urinary bladder carcinoma often is diagnosed from malignant cells in bladder washings obtained at cystoscopic examination. In some cases, there are difficulties distinguishing between cytologic Grades 1 and 2. Detection of genetic alterations in combination with morphologic analysis may facilitate the diagnosis.

Detection and temporal appearance of multiple copies of c-erb-B2 genes in advanced mammary carcinoma using fine needle biopsies and the polymerase chain reaction

Aspiration of tumor cells by the fine-needle biopsy method yields only a small number of cells, which hampers conventional molecular analysis for the presence of multiple copies of oncogenes. We have therefore adopted the polymerase chain reaction (PCR) method to study semi-quantitatively the level of the c-erb-B2 gene in human breast tumor samples. Of 39 patients with mammary carcinoma, 7 (19%) contained multiple copies of c-erb-B2 genes, whereas only two samples failed to give informative data. Next the temporal appearance of multiple gene copies was examined in 20 patients with clinical stage IV disease. Tumor samples were obtained every second to third month from the same tumor lesion of each patient. None of the initial samples from each patient contained multiple copies of c-erb-B2. Of 16 patients that showed progressive clinical disease, 5 developed multiple gene copies, showing that the event occurs in clinical stage IV disease.

Standardized Precision Radiotherapy in Choroidal Metastases

Metastases in the choroid of the eye are frequent in patients with disseminated malignancy. We here report the results using the precision radiotherapy technique described by Schipper et al. to treat 14 of 17 consecutive patients (21 eyes) with symptoms from such metastases. A beam defining collimator was used and a lateral field was given with the treated eye individually fixed. Varying fractionations and doses were used. The biologically effective dose for early effects (BED3) was 47 to 90 Gy and for late effects (BED10) 28 to 59 Gy. In 14 eyes (82%) the metastases regressed completely. The visual acuity was stabilized or improved in all patients and none needed local surgery. Three patients developed signs of radiation retinopathy, but only in one case the visual function was compromised. With this standardized technique no individualized dose planning was needed, the risk of radiation cataract was minimized and a dry eye avoided.

Effects of 5-fluorouracil on cell cycle arrest and toxicity induced by X-irradiation in normal mammalian cells

From clinical studies in cancer patients and experimental in vitro studies, there is evidence of an increased cytotoxic effect, and even synergy, when irradiation is combined with 5‐fluorouracil (5‐FU). The mechanism for this is unclear.

Bleomycin-induced DNA lesions are dependent on nucleosome repeat length

Treatment of cells or nuclei with bleomycin induces DNA lesions. We detect the presence of lesions as the release of fragments from bulk DNA when cells (or nuclei) are lysed in dilute alkali. To further characterize the lesions we have altered experimentally the average nucleosome repeat length and probed the lysate with nuclease S1 in order to remove single-stranded DNA. In salt-incubated nuclei with short average nucleosome repeat length (140-145 base pairs) (and also with long nucleosome-free stretches of DNA) one can induced fewer DNA lesions in the nucleosome-containing DNA as compared to nuclei with 190-195 base pairs average nucleosome repeat length. Hence the ability of bleomycin to induce DNA lesions is dependent on nucleosome repeat length.

Cisplatin-Induced Inhibition of p34cdc2 is Abolished by 5-Fluorouracil

Clinical (Dimery and Hong, J Nat Cancer Inst 1993; 85: 95- 111) and experimental studies (Scanlon et al., Proc Natl Acad Sci USA 1986; 83: 8923-5; Lewin et al., In Vivo 1990; 4: 277-82) have indicated an increased cytotoxic effect, when cisplatin (CDDP) is combined with 5-fluorouracil (5-FU). Addition of 5-FU abolishes the G2-arrest induced by CDDP (Lewin et al., In Vivo 1990; 4: 277-82; Nylén et al., Acta Oncol 1996; 35: 229 35). The mechanism for the synergy is unclear. Activation of p34cdc2 is necessary for progression from G2 to mitosis (Lewin et al., Anti-Cancer Drugs 1995; 6: 465-70). The aim was to study p34cdc2, cdc25C and weel after treatment of mammalian tumour cells in vivo with CDDP as single agent or in combination with 5-FU. CDDP prevented activation of p34cdc2 by keeping cdc25C inactive and weel active. Addition of 5-FU to CDDP decreased the expression of weel and promoted cdc25C-activation. p34cdc2 was dephosphorylated by cdc25C and activated. Alterations in activity of cdc25C and weel after drug combination were due to changes in the protein amount, rather than to changes in the phosphorylation degree.

Amplification of oncogenes in mammary carcinoma shown by fine-needle biopsy.

A procedure that measures the amplification of oncogenes in human cancer cells is described. The cells were obtained by fine‐needle biopsy to allow repeated sampling from individual metastases. A drawback was the low number of cells obtained, but this could be overcome by using a slot–blot hybridization technique to measure gene amplification. Two patients with mammary cancer (primary tumors or metastases), analyzed for the levels of amplification of the oncogene erb‐B2, are described in detail. This technique is suitable for analyzing alterations occurring during cancer progression and for identifying subgroups of mammary cancer with different characteristics.

Absence of Misincorporation of Pyrimidines in DNA After Treatment with a Combination of Cisplatin (CIS-Diammine-Dichloro-Platinum) and 5-Fluorouracil of Mouse Sarcoma Cells

The effects on incorporation into DNA of the deoxyribonucleotides dCTP and dTTP and the DNA synthesis rate after treatment with cisplatin (CDDP), 5-fluorouracil (5-FU) or a combination of CDDP and 5-FU were studied in ascites sarcoma (Bp8) growing in mice. Single administration of CDDP gave an early (1 h) transient increase in the DNA-synthesis followed by a decrease. 5-FU as single agent did increase the rate of DNA synthesis after 6 h with a maximum at 10 h. The combination of CDDP and 5-FU markedly increased the rate of DNA synthesis up to 6 h as compared to single drug treatment. Although the dCTP pool increased after combined treatment, while the dTTP pool was unchanged, no alterations in the proportions of dTTP and dCTP incorporated into DNA could be detected. Hence, misincorporation of pyrimidines is not the mechanism for the synergistic effect of the combination of CDDP and 5-FU.

Appearance of a late stage during mammalian DNA replication when cells resume formation of 10 kb DNA replication intermediates.

After the joining of human large DNA replication intermediates and before the appearance of mature chromatin DNA, there exists a distinct stage — ‘the post‐elongation stage’. This stage reappears during recovery of DNA synthesis simultaneously with the reappearance of a large DNA replication intermediate, 10 kb DNA.