Matti Taavitsainen

Gene expression profiling of malignant mesothelioma cell lines: cDNA array study

To reveal genes relevant for malignant mesothelioma (MM), we carried out cDNA array experiments on 4 MM cell lines and 2 primary mesothelial cell cultures established from pleural fluid of non‐cancer patients. Human cancer gene filters including 588 genes were used for the cDNA array experiments. Our study revealed 26 over‐expressed genes that play a role in the regulation of cell fate, cell cycle, cell growth and DNA damage repair and 13 under‐expressed genes encoding growth factors, receptors and proteins involved in cell adhesion, motility and invasion to be common to 3 or 4 MM cell lines. We confirmed the cDNA array results using RT‐PCR for 5 of the over‐expressed genes and for 3 of the under‐expressed genes. Our study presents gene expression profiles in MM cell lines and shows the involvement of several genes, such as those encoding JAGGED1, ser/thr protein kinase NIK, Ku80 and cyclin D2, novel in MM.

Measurement of Testicular Volume: Comparison of 3 Different Methods

PURPOSE We compared 3 commonly used clinical methods to measure testicular volume. MATERIALS AND METHODS The volumes of 151 testes in 76 adults treated for cryptorchidism during childhood were measured with an ordinary ruler, an orchidometer and ultrasonography. RESULTS Mean testicular volume was 15 +/- 8 ml. (standard elevation) measured with a ruler, 16 +/- 7 ml. with an orchidometer and 17 +/- 8 ml. with ultrasonography. The correlation among methods was significant. CONCLUSIONS To measure testicular size use of an ordinary ruler is recommended for clinical purposes because of its simplicity, availability and low cost.

Technetium-99m hexamethyl propylene amine oxine leucocytes in the assessment of disease activity in inflammatory bowel disease

The inflammatory activity in 108 bowel segments of 40 patients with suspected or known inflammatory bowel disease was assessed macroscopically by endoscopy, histology and technetium-99m hexamethyl propylene amine oxine (99mTc-HMPAO) leucocytes using a numerical grading system (scores 0–3). A 4-h series of scintigrams showed a significant correlation with both histological and macroscopical assessment of disease activity (rho = 0.850, P<0.001 and rho = 0.773, P<0.001, respectively). Sensitivity, specificity and accuracy of scintigraphy in detecting active inflammatory segments were 85%, 92% and 89%, respectively. A normal scintigram did not completely exclude mild inflammatory activity, especially in the rectosigmoid area. 99mTc-HMPAO leucocytes offer an accurate and non-invasive alternative for the assessment of disease activity in ulcerative colitis and Crohns disease.

Fatal liver necrosis following percutaneous ethanol injection for hepatocellular carcinoma

A 76-year-old man underwent an injection of 5 ml of ethanol for the treatment of a hepatocellular carcinoma 3 cm in diameter. Shortly after the procedure, he had an attack of abdominal pain. His condition soon deteriorated and he died 5 days later. Massive hepatic necroses distant from the injection site and a myocardial infarction were found at autopsy. To our knowledge, this is the first fatality associated with percutaneous ethanol injection therapy.

Prolonged low-back pain in young athletes: a prospective case series study of findings and prognosis.

Abstract We investigated the prognosis of low-back pain and the association of clinical symptoms and anatomic findings among young athletes. Consecutive patients, aged between 12 and 18 years, who had low-back pain that had interfered with their training for at least 4 weeks were included in the case series. All the patients participated in a standardized interview and clinical examination, and plain radiographs and magnetic resonance images were also obtained. Most patients also participated in technetium bone scan examination. In 15 out of 19 subjects there were anatomic abnormalities that corresponded with the location and type of clinical symptoms. Twelve subjects had changes in the disk-vertebral end plate complex and eight had a positive bone scan indicative of posterior vertebral arch stress reaction. Six out of eight boys and two out of 11 girls had stress reaction (P = 0.043). Restriction of painful activities was recommended to all subjects, restriction of activities and the use of a dynamic low-back brace for the first 3 months was recommended to patients with posterior vertebral arch stress reaction. The self-reported intensity of low-back pain (scale 0–100) among all the patients was 69 ± 16 (mean ± SD) at baseline and 18 ± 21 at the 1-year follow-up (P < 0.0001). In conclusion, the reasons for prolonged back pain among young athletes are usually established by imaging studies. A knowledge of anatomic abnormalities may help in tailoring training programmes and avoiding the progression of changes during growth. Simple restriction of painful activities usually leads to good recovery.

Cytogenetic response to asbestos fibers in cultured human primary mesothelial cells from 10 different donors

The ability of amosite asbestos fibers to induce chromosomal aberrations in human primary mesothelial cells obtained from pleural effusions of 10 noncancerous patients was investigated. The glutathione S-transferase M1 (GSTM1) genotypes of the patients were determined, since the GSTM1 null genotype has been associated with increased susceptibility to lung cancer and chemically induced cytogenetic damage. Four of the patients represented the GSTM1 null genotype, and six the GSTM1 positive genotype. Successful chromosome aberration analyses were obtained from six cases, three of them with the GSTM1 null genotype. The level of aberrant cells in unexposed cultures ranged from 2.0% to 7.5%. Statistically significant increases (2.3-3.0-fold compared to controls) in the number of aberrant cells were observed in two cases only: in one case treated with 1 microgram/cm2 of amosite, and in another treated with 2 micrograms/cm2 of amosite. Cell cultures from four individuals showed minor or no increases in the numbers of aberrant cells in the doses tested (1 and 2 micrograms/cm2). Chromosome breaks were the major type of aberration. The amosite exposed cells with significantly increased aberrations were from patients with GSTM1 positive genotypes. Two cases that showed no cytogenetic response to asbestos fibers were of the GSTM1 null genotype. Thus, our results suggest that the lack of the GSTM1 gene does not render human mesothelial cells more susceptible to chromosomal damage induced by asbestos. GSTM1 null cells appeared, however, to be more sensitive to the growth inhibitory effects of asbestos than did GSTM1 positive cells. Variation in the cytogenetic response of human primary mesothelial cells to asbestos fibers was observed to exist, but the fibers do not appear to be potent inducers of structural chromosomal aberrations in these cells. It remains to be established whether individual sensitivity to asbestos fibers, due to specific genetic traits, exists.

Painful Ankle Region in Rheumatoid Arthritis: Analysis of Soft-Tissue Changes with Ultrasonography and MR Imaging

Purpose: To establish the diagnostic usefulness of ultrasonography (US) and MR imaging in patients with rheumatoid arthritis (RA) suffering from prolonged pain in the ankle region, where plain radiography did not demonstrate any changes. Material and Methods: Seventeen patients were studied with 0.1 T MR imaging and with high-frequency US. Talocrural and subtalar joints (including talonavicular joints), and medial, lateral, and extensor tendons and their synovial sheaths were examined by MR and US. Results: Abnormal findings were found by MR imaging and US in altogether 76% of the patients, by MR alone in 53%, and by US alone in 59%. In 41% of the patients, lesions were demonstrated only by one method. Talocrural and subtalar joints were the most often affected sites (41% each), followed by the peroneus tendon (23%). In the joints, the abnormal findings were interpreted as synovitis; in the tendon areas, mostly as tenosynovitis. MR and US were highly significantly concordant (p<0.0001), but correlation with clinical features was poor. Conclusion: In patients with pain in the ankle region, US and MR imaging can contribute to the diagnosis and localization of the abnormality when the plain radiography is normal. Easily available and inexpensive US can be recommended as the first imaging method after plain radiography. Some divergence seems to exist between US and MR, and in complicated cases both methods are recommended.

In vitro sensitivity of normal human mesothelial and malignant mesothelioma cell lines to four new chemotherapeutic agents.

In this study, we used four human mesothelioma cell lines (M14K, M24K, M25K and M38K), one transformed human mesothelial cell line (MeT-5A) and one primary mesothelial culture (UPL) to test for in vitro sensitivity to docetaxel, paclitaxel, SN-38 [an active metabolite of irinotecan (CPT-11)] and gemcitabine, as single agents. Subconfluent cell cultures were treated with 2×10−9, 5×10−9, 10−8, 2×10−8 and 5×10−8 M concentrations of each drug for 48 h. The sensitivity was measured in terms of cell viability using the Trypan blue exclusion method. All four drugs were potent inhibitors of mesothelioma cell growth, but cell lines from different patients diverged in their sensitivity to the individual agents. In most cases docetaxel, paclitaxel and SN-38 were more potent killers of mesothelioma cells than gemcitabine. The induction of DNA damage was investigated using the Comet assay; cells from two cell lines (M14K and M25K) were treated with subtoxic 10−8 M concentrations of each drug for 4, 24 and 48 h. Each of the agents caused a slight increase in DNA single-strand breaks at a concentration of 10−8 M.

Toxicity of Ethanol in Low Concentrations Experimental Evaluation in Cell Culture

Purpose: To define the threshold ethanol concentration that is toxic to cultured cells. Methods: Three malignant cell lines and freshly isolated normal rat hepatocytes were exposed to 0–50% (vol.) ethanol (concentrations used were 0, 5, 10, 15, 20, 25, 30, 40 and 50%) on tissue culture plates for 0.25–60 min (exposure times used were 0.25, 5, 10, 20, 30, 40, 50 and 60 min). Cytotoxicity was estimated by trypan blue exclusion test and from 3H-thymidine incorporation. Results: All cells were killed by a 15-s exposure to 30–40% ethanol while a concentration as low as 15–20% gave a total response after 5–10-min exposures. After a one-hour exposure of F9 carcinoma cells and hepatocytes, a total or nearly total response was achieved with 10% ethanol. The cytotoxic effect was thus dependent both on the exposure time and on the concentration of ethanol. There were no significant differences in ethanol tolerance among the cell types. Conclusion: Ethanol seemed to kill cells in the cell culture effectively in much lower concentrations than those currently used in tumour ablation.

Ultrasonically Guided Fine-Needle Aspiration Biopsy in Focal Pancreatic Lesions

Ultrasonically guided fine-needle aspiration biopsy was performed in 100 patients with a focal pancreatic lesion. The lesion was a well-defined solid mass of 1 to 4 cm in 37 cases, a well-defined solid mass of 4.5 to 10 cm in 28 cases, an intrapancreatic cystic lesion in 23 cases, and an ill-defined prominent area in 12 cases. The samples were taken with a one-hand instrument and 0.7 to 0.9 mm disposable needles without a puncture adaptor. The material was sufficient for cytologic analysis in 98 cases. Malignant cells were obtained in 44 of the 49 cases with pancreatic carcinoma and lymphoma cells in one case with lymphomatous infiltration. Four of the six cases of cystadenoma could be identified cytologically. In solid inflammatory lesions, the nature of the lesion was seen in 12 of the 17 cases. There were no false positive reports of malignancy. The solid prominent areas of normal pancreatic tissue yielded normal cytologic samples. Aspirates of cystic lesions in the pancreas revealed one malignant case, and infected lesions could be differentiated from ***non-infected in the rest. There was one complication in a patient with an obstructed and dilated common bile duct. The aspiration procedure caused severe pain and the operation was performed earlier than scheduled. Diagnostic material is obtained in the majority of ultrasound guided aspiration biopsies of the pancreas. In malignancy, false negative results occur in about 10 per cent of cases.