Dna adducts, mutations, and cancer 2000

The main achievements in the DNA adduct field in the 1990s have been technical innovations of methods for specific adducts reaching sensitivities required for low levels encountered in humans. Over 20 specific adducts or closely related groups of adducts have been determined in humans. The sources of the DNA-binding agents are endogenous and exogenous or both. In some of these studies adduct levels have been correlated to metabolic or DNA repair genotypes. An example of DNA adduct studies in human target tissue is taken on UV photoproducts in skin in situ. Adduct-induced mutations, specific mutation spectra, and their relationship to cancer are discussed. The quantitative adduct techniques will enable comparisons of endogenous and exogenous adduct levels and will give important clues to the etiology of human cancer. Furthermore, adducts will provide an intermediary tool for genotyping studies, both for metabolic enzyme and for DNA repair system genotypes. As the common polymorphisms are likely to cause at most moderate increases in the risk of cancer, the intermediary adduct endpoint is a necessary proof of causal relationships. The present and future biomonitoring studies will cover many endpoints to link the mechanistic steps from DNA adducts to cancer via mutations and modulating host susceptibility factors.     

Quinapril and blood lipids.

To assess the effects of angiotensin-converting enzyme inhibition with quinapril on blood lipid profile, serum total cholesterol and triglycerides, together with high-density and low-density lipoprotein cholesterol were analysed in 23 hypertensive patients receiving either placebo (7 patients) or quinapril hydrochloride (16 patients). After 12 weeks of therapy there were no significant changes in blood lipids in either group. No unfavourable changes in blood lipid profile were observed even after 1 year of therapy with quinapril hydrochloride in 13 patients.     

Use of the modulation transfer function in comparing the visual outcome units of gamma camera

Modulation transfer function (MTF) was used in comparing the visual outcome units of gamma camera. Polaroid camera system and Micro Dot imager were studied using Polaroid film type 105 positive/negative and Kodak SO-179 X-ray film. It was proved that resolution in the Micro Dot imager is better than in the Polaroid camera system used, especially near the surface of the measuring object.     

CLEVER-1 mediates lymphocyte transmigration through vascular and lymphatic endothelium

Common lymphatic endothelial and vascular endothelial receptor-1 (CLEVER-1; also known as stabilin-1 or FEEL-1) is a large multifunctional glycoprotein implicated in scavenging, angiogenesis, and cell adhesion. Here we studied the function of human CLEVER-1 in leukocyte trafficking. Lymphatic vessels expressed CLEVER-1 constitutively in skin in vivo, whereas on vascular endothelium it appeared only upon inflammation. On isolated vascular endothelial cells, CLEVER-1 supported rolling and transmigration of peripheral blood mononuclear cells (PBMCs) under physiologically relevant laminar shear stress. Intriguingly, CLEVER-1 also mediated transmigration of leukocytes through cultured lymphatic endothelium under static conditions. Thus, synthesis of CLEVER-1 is differentially regulated on the 2 anatomically distinct vascular beds, and CLEVER-1 mediates the transmigration step of the leukocyte traffic in both of them. Notably, CLEVER-1 is the first adhesion molecule shown to be involved in the PBMC transmigration through the lymphatic arm of the immune system.     

Correspondence between three olfactory tests and suprathreshold odor intensity ratings

OBJECTIVES: The capability of three olfactory tests (European Test of Olfactory Capabilities, Sniffin' Sticks and Cross-Cultural Smell Identification Test) to similarly classify subjects as normosmics, hyposmics and anosmics as well as the relation between test performance and suprathreshold ortho- and retronasal odor intensity ratings were examined. MATERIAL AND METHODS: A total of 48 subjects (age range 15-84 years; mean age 49.5 years) completed the 3 olfactory tests, rated aqueous solutions of vanilla (0-0.31%) and lemon aroma (0-0.17%) for odor and flavor intensity and filled in a background questionnaire. Ten subjects had case histories indicating anosmia, with the remainder having subjectively normal olfaction. RESULTS: The test results were highly correlated and differentiated anosmic, hyposmic and normosmic subjects. At an individual level, some discrepancy was seen in the olfactory diagnoses given by the three tests. In principal component analysis, olfactory measurements were loaded on three components: (i) odor detection, discrimination and identification; (ii) suprathreshold intensity ratings; and (iii) threshold for n-butanol. Advanced age was related to impaired olfactory performance. CONCLUSIONS: Although the three olfactory tests diagnosed the individuals slightly differently, all were considered to be valid for clinical evaluation of olfactory capabilities. The tests separated anosmics and normosmics highly significantly, and permitted an assessment of hyposmia. The suprathreshold odor intensity ratings reflected a different dimension of olfaction than the three olfactory tests.     

Occurrence of comminution (type IIA) in type II odontoid process fractures: a multi-slice CT study

The classification of odontoid process fractures introduced by Anderson and D'Alonzo in 1974 has gained wide acceptance among researchers and clinicians. In type II fractures the injury is located in the base of the odontoid process. In 1988 Hadley et al. introduced a comminuted subtype of this fracture, type IIA. Since then several authors have recommended a more aggressive surgical approach in treatment of this subtype. However, only a few cases of comminuted type II fractures have been reported. The objective of this study is to assess the occurrence of comminution in type II fractures. Twenty-six type II fractures imaged by multislice CT were reviewed. Subtle comminution of the fracture was observed in 12 of the cases. We conclude that, when imaged by multislice CT, subtle comminution in type II odontoid fractures is seen more commonly than previously reported in the literature.     

Platelet-derived growth factor receptor inhibition reduces allograft arteriosclerosis of heart and aorta in cholesterol-fed rabbits

BACKGROUND: Crosstalk between pro-inflammatory cytokines and platelet-derived growth factor (PDGF) regulates smooth-muscle-cell proliferation in cardiac-allograft arteriosclerosis. In this study, we tested the effect of STI 571, a novel orally active protein tyrosine kinase (PTK) inhibitor selective for PDGF receptor (PDGF-R) on transplant and accelerated arteriosclerosis in hypercholesterolemic rabbits. METHODS: Cardiac allografts were transplanted heterotopically from Dutch Belted to New Zealand White rabbits. A 0.5% cholesterol diet was begun 4 days before transplantation. Recipients received STI 571 5 mg/kg per day or vehicle intraperitoneally throughout the study period of 6 weeks. Cyclosporine A was given as background immunosuppression. RESULTS: In cardiac allografts of vehicle-treated rabbits, 76.2+/-2.1% of medium-sized arteries were affected by intimal thickening, and the percentage of arterial occlusion was 45.0+/-5.0%. Treatment with STI 571 reduced the incidence of affected medium-sized arteries to 41.2+/-8.1% (P <0.05) and the arterial occlusion to 27.6+/-5.0% ( P<0.05). In addition, we observed that STI 571 treatment reduced intimal lesion formation in proximal ascending aorta of transplanted hearts from 72.3+/-19.9 to 12.7+/-1.9 microm ( P<0.05). Our results also show that STI 571 significantly inhibited accelerated arteriosclerosis in medium-sized arteries of recipients' own hearts. CONCLUSIONS: The results of the present study suggest that PDGF-R activation may regulate the development of transplant and accelerated arteriosclerosis in hypercholesterolemic rabbits. Thus, PTK inhibitors may provide new strategies for prevention of these fibroproliferative vascular disorders.     

Nuss Procedure for Pectus Excavatum – An early Experience

The technique of minimally invasive repair of pectus excavatum is a new operation that allows for repair of this deformity without any cartilage resection or sternal osteotomy. The procedure has revolutionized the management of pectus excavatum. Six cases of pectus excavatum were referred to our centre for surgical correction. However, based on Haller''s CT index 2 merited surgery. Our results suggest that the minimally invasive repair of pectus excavatum is an exciting operation with minimal morbidity and excellent results. The innovative incorporation of thoracoscopic techniques and small but important modifications to the techniques will make this operation very effective and safe.Key Words: Minimally invasive surgery, Pectus excavatum     

Intracoronary Radiation

With in-stent restenosis remaining major limitation of coronary stenting and adjunctive pharmacologic therapy and re-stenting having failed to reduce the rates of in-stent restenosis, a new treatment alternative is warranted. Vascular brachytherapy – the intracoronary delivery of radiation has been proposed as one such therapy. Thus far it is an important break-through in combating re-stenosis. Todate, 5 years of clinical data has been generated and further studies are underway to perfect the technology.Key Words: Coronary artery, Ionising radiation, Re-stenosis     

Incidence of cancer among the participants of the Finnish Asbestos Screening Campaign

OBJECTIVES: Cancer risk has been estimated for asbestos production workers or other heavily exposed asbestos workers in numerous studies. The bulk of the asbestos epidemic results come, however, from past intermittent exposures during asbestos product use. This study concentrated on estimating the risk of cancer in such a population. METHODS: Altogether 23285 men and 930 women invited to a nationwide screening campaign for benign asbestos-related diseases in 1990-1992 were followed for cancer through the Finnish Cancer Register up to 1998. Standardized incidence ratios (SIR) were calculated in comparison with the total Finnish population. RESULTS: Altogether 1392 cases of cancer were found among the men. The risk was slightly, but significantly elevated for lung cancer [SIR 1.14, 95% confidence interval (95% CI) 1.01-1.26), mesothelioma (SIR 2.77, 95% CI 1.66-4.31), and prostate cancer (SIR 1.21, 95% CI 1.09-1.34). The risk of lung cancer was slightly higher among the invited nonparticipants (SIR 1.48, 95% CI 1.20-1.79) than among the participants (SIR 1.02, 95% CI 0.88-1.17). About 98% of the lung cancers occurred in current or ex-smokers. CONCLUSIONS: In a population of long-term construction workers, the risk of lung cancer and mesothelioma was increased, but considerably lower than among insulators, asbestos sprayers, or patients with asbestosis. As it was not possible to follow most of the invited nonparticipants in the original screening study, selection bias by smoking or other life-style factors possibly correlated to the individual's decision to participate in the health screening cannot be excluded.