Declining socioeconomic differences in the use of menopausal and postmenopausal hormone therapy in Finland

Objective: Sales figures for the use of menopausal and postmenopausal hormone therapy in Finland show a rapid increase during the 1980s continued into the first half of the 1990s. Hormone therapy use became very common in Finland compared to many other Western countries. The aim of our study was to investigate the sociodemographic distribution of hormone therapy among Finnish women aged 45–64 years. Methods: The study is based on population-based surveys conducted in 1989 and 1996 (response rates 87% and 78%). Results: Between 1989 and 1996 the current use of hormone therapy increased from 22% to 27%; in 1989 it was most common in the age group 50–54 years, but in 1996 among 55–59-year-olds. In 1989 it was significantly more common among women with longer education than other women in every age group, but in 1996 this difference was significant only in those 55 years and older. In 1989 the use was more common in the capital area than elsewhere and this difference decreased but remained significant in 1996. Conclusion: Our results suggest that hormone therapy has become a routine treatment during the menopause in all educational groups and throughout the country. The lack of socioeconomic differences indicates that among women under 55 year of age the saturation point in short-term hormone use was reached in 1996. However, the persistence of socioeconomic differences among older women suggests that the use of long-term postmenopausal hormone therapy will continue to increase for some time.     

Population-based mammography screening results in substantial savings in treatment costs for fatal breast cancer

SummaryAims The aim was to assess the effect of population-based mammography screening on treatment costs for fatal breast cancer in Turku, Finland.Materials and methods The study included 556 women with invasive breast cancer, diagnosed at the age of 40–74 years in 1987–1993: 427 in the screened group (screen-detected or interval cancer) and 129 in the unscreened group (not yet invited or refused screening). Both groups were followed up for 8 years from diagnosis.Results In the unscreened group, 32 (25%) patients died of breast cancer versus 49 (12%) in the screened group (p < 0.001). The non-discounted mean treatment costs were 2.8-fold for those dying of breast cancer compared to survivors: €26,222 versus €9,434; the difference between means was €16,788 (95% CI 14,915–18,660) (p<0.001). The mean costs for fatal cases were high, irrespective of the way cancer was detected: €23,800 in the unscreened group versus €27,803 in the screened group; the difference between means was €−4,003 (−10,810 to 2802) (p=0.245). In the unscreened group, patients with fatal breast cancer accounted for 41% (€0.76/1.87 million) of the total treatment costs versus 29% (€1.36/4.76 million) in the screened group. It was estimated that about one third of costs for fatal breast cancer were avoided through mammography screening, accounting for 72–81% of the estimated total treatment cost savings achieved by screening. About 31–35% of the screening costs for 1987 to 1993 were offset by savings in treatment costs.Conclusions Treatment costs for fatal breast cancer are high. Mammography screening results in substantial treatment cost savings, in which reduction of fatal disease is the key element.     

Official marital status, cohabiting, and self-rated health-time trends in Finland, 1978-2001

BACKGROUND: Married persons are healthier and live longer than single, divorced, and widowed persons. Time trends in self-rated health (SRH) by marital status and cohabitation have remained largely unstudied. We aim to assess the levels and trends of SRH by official marital status and cohabitation, and to study the causes of these differences. METHODS: Two nationally representative cross-sectional surveys were conducted 20 years apart in Finland. Data on self-reported marital status, SRH, education, smoking, and long-standing illness were collected from Finns aged 30-64 years in 1978-80 (Mini-Finland Health Survey, N = 6102, response rate 96%) and 2000-01 (Health 2000 Survey, N = 5871, response rate 92%). RESULTS: SRH has improved in the last 20 years, but differences between marital status groups have not reduced. In 2000-01, non-married persons reported worse SRH than married persons. Among men, single [cumulative odds ratio (COR) = 1.55; 95% confidence interval (95% CI) 1.22-1.99] and divorced (COR = 1.55; 95% CI 1.17-2.05) persons showed the poorest SRH, while among women widows (1.53; 95% CI 1.04-2.26) were the most disadvantaged group. The SRH of cohabiting persons did not significantly differ from that of married persons. Differences in educational structure, smoking, and the prevalence of long-term illness explain part of the marital status differences in SRH among men, but less so among women. Among both single men and women as well as among widowed women, SRH had improved slightly less than in the other groups. CONCLUSION: The challenges on public health posed by growing numbers of currently not married people are likely to increase.     

Treatment of squamous cell carcinoma of the oral cavity, oropharynx and hypopharynx--an analysis of 174 patients in south western Finland

The purpose of this study was to determine the efficacy and feasibility of full-dose preoperative radiation therapy (RT) in head and neck cancer presenting in the oral cavity, oro- and hypopharynx, within a single university hospital district. During a seven-year period, 1989 to 1995, 174 patients with squamous cell carcinoma (SCC) of the oral cavity (OC, 70% of all patients), oropharynx (OP, 15%) and hypopharynx (HP, 15%) were referred to Turku University Central Hospital. All patients were seen by a tumor board consisting of an ENT (ear-nose-throat) head and neck surgeon, a radiation oncologist and a dentist. Potentially curative treatment was given to 142 patients. Of these, 88 (62%) had preoperative RT, 6 (4%) postoperative RT, 34 (24%) definitive RT and 14 patients (10%) were treated with surgery only. The radiation dose was ≥50 Gy, averagely 64 Gy. The major endpoints of the study were local control, overall survival and major complications of the combined treatment. The 5-year relative survival rate (RSR) was 40% for all, and 43% for patients treated with curative intent. For these, the local control at 5 years was 60%; the disease-specific 5-year survival rate was 65% for the patients with lingual SCC, 45% for those with other oral tumor localizations, 64% for the oropharynx patients and 47% for those with tumor in their hypopharynx, while it was 55% for all patients. The preoperative radiotherapy was fairly well tolerated. Ten (7%) of the patients treated with curative intent suffered major complications, and four patients had evidence of osteoradionecrosis. With the exception of patients with early SCC the outcome remains rather poor in this group of cancer patients who often have marked co-morbidity. In our opinion, preoperative radiotherapy to a dose of 62-64 Gy can safely be given, and remains a feasible means to treat patients with oral, oropharyngeal or hypopharyngeal cancer.     

Amino acid uptake in the skeletal muscle measured using [11C]methylaminoisobutyrate (MEAIB) and PET

An amino acid analogue, [(11)C]MeAIB, recently introduced for oncological positron emission tomography (PET) studies, is a highly selective substrate for insulin-sensitive amino acid transport system A. The aim of this study was to study the uptake kinetics of [(11)C]MeAIB in skeletal muscle in the fasting state and during insulin stimulation. Two dynamic PET studies were carried out in 11 healthy subjects, once in the fasting state and once during euglycaemic hyperinsulinaemia (serum insulin 67+/-12 mU l(-1)). Graphical analysis was used to calculate the fractional [(11)C]MeAIB uptake rate ( K(i)). Amino acid uptake was estimated by multiplying K(i) by the serum amino acid concentration. After tracer injection, rapid uptake in muscle tissue was detected both in the fasting state and during insulin stimulation and femoral muscles were clearly visualised in both studies. In the graphical analysis, the volume of distribution of [(11)C]MeAIB plotted against normalised plasma time yielded a linear curve (the slope of which = K(i)). The fractional [(11)C]MeAIB uptake rate ( K(i)) in the femoral muscle regions increased from 0.0070+/-0.0018 min(-1) (mean+/-SD) in the fasting state to 0.0079+/-0.0020 min(-1) ( P<0.05) during insulin stimulation. When compared with the fasting state, serum total amino acid concentration decreased from 2.49+/-0.22 to 2.16+/-0.18 mmol l(-1) ( P<0.0001) and the serum concentration of six amino acids typically using system A for their transport decreased from 0.72+/-0.1 to 0.63+/-0.07 mmol l(-1) ( P=0.0001) during hyperinsulinaemia. The calculated skeletal muscle total amino acid uptake and the uptake of the six amino acids typically using system A were similar in the fasting state and during insulin clamp (17.1+/-3.2 vs 17.7+/-3.7 micro mol kg(-1) min(-1), NS, and 5.0+/-1.3 vs 5.0+/-1.4 micro mol kg(-1) min(-1), NS, respectively). The uptake rates correlated with perfusion both in the fasting state and during hyperinsulinaemia ( P<0.05). [(11)C]MeAIB PET appears to be a feasible method for measurement of amino acid uptake in human skeletal muscle. As a tracer that is not metabolised in the tissues, [(11)C]MeAIB provides simple modelling and robust data analysis and thus provides a means to investigate amino acid uptake into muscle tissue in various disease conditions known to affect protein metabolism.     

Quantitation of erbB2 positivity for evaluation of high-risk patients

BACKGROUND. Because trastuzumab therapy is expected to be effective in a large fraction of erbB2 (HER-2/neu) overexpressing breast cancers, it is important to find the optimal method for evaluation of erbB2 positivity, and the patient group at greatest risk of dying without this therapy. AIM. We evaluated erbB2 immunopositivity in breast cancer with the aim of finding a high-risk group for primary trastuzumab therapy. METHODS. Three hundred and seventeen samples were evaluated with an immunostaining index. Optimal cut point was systematically tested, and the effect of bcl-2 status on survival in the high-risk group was studied. RESULTS. Among N+ patients the index value 1.5 reflected the biggest difference in survival. There was a significant correlation between erbB2 positivity and bcl-2 negativity. ErbB2 was a prognosticator among postmenopausal, N+, and postmenopausal N+ patients. In multivariate analysis, erbB2 was the best prognosticator among postmenopausal N+ patients. Six out of seven N+ patients with erbB2 index 1.5 or above died including all postmenopausal patients. Bcl-2 positivity was associated with longer survival in the erbB2 positive patient group. CONCLUSIONS. The most obvious patients for primary trastuzumab therapy in breast cancer are N+ patients with high erbB2 immunostaining index (> 1.5) and bcl-2 negative immunostaining. In our material 2% of all breast cancer patients fell in this category. This patient group should be selected for testing trastuzumab in the primary treatment.     

The effect of breakfast cereal on diet and serum cholesterol: a randomized trial in North Karelia, Finland.

OBJECTIVE: To test the hypothesis that a high carbohydrate breakfast with breakfast cereal leads to a meaningful reduction in dietary energy intake from fat, especially from saturated fat, and thus lower serum cholesterol levels. DESIGN: An open randomized controlled cross-over trial. The subjects were randomized into intervention breakfast cereal or usual breakfast (control) groups. SETTING: Free-living subjects aged 29-71 y in Eastern Finland SUBJECTS: 224 enrolled, 209 completed the study. The subjects were recruited from a survey of a random population sample and from other sources, and their serum cholesterol was not lower than 5.0 mmol/l. Recruited persons did not have any chronic disease or very low saturated fat intake. INTERVENTION: The cereal group consumed 80 g (men) or 60 g (women) cereal at breakfast and the control group continued their usual dietary habits for six weeks. After a wash out of six weeks, a cross-over with another six week trial period took place. Measurements (including serum samples and a 3 d food record) took place before and after the two trial periods. RESULTS: The intervention period led to 2.5 en% (energy percent units) reduction in saturated fatty acids intake. The reduction in total fat intake was 5.5 en%. This was compensated for by increased intake of carbohydrates. The reduction in saturated fatty acids intake led to modest (but in group 1 significant) 0.15 mmol/l (2.5%) reduction in total serum cholesterol level. CONCLUSIONS: The trial showed that regular cereal breakfast can lead to reduced intake of total and saturated fatty acids of the daily diet and consequently to reduction in serum cholesterol level.     

ADAM12 alleviates the skeletal muscle pathology in mdx dystrophic mice

Muscular dystrophy is characterized by muscle degeneration and insufficient regeneration and replacement of muscle fibers by connective tissue. New therapeutic strategies directed toward various forms of muscular dystrophy are needed to preserve muscle mass and promote regeneration. In this study we examined the role of the transmembrane ADAM12, a disintegrin and metalloprotease, which is normally associated with development and regeneration of skeletal muscle. We demonstrate that ADAM12 overexpression in the dystrophin-deficient mdx mice alleviated the muscle pathology in these animals, as evidenced by less muscle cell necrosis and inflammation, lower levels of serum creatine kinase, and less uptake of Evans Blue dye into muscle fibers. These studies demonstrate that ADAM12 directly or indirectly contributes to muscle cell regeneration, stability, and survival.     

Effects of training and anabolic steroids on collagen synthesis in dog heart

Summary The effects of endurance training and anabolic steroid (Methandienone 1.5 mg · kg^–1 p. o. daily) and their combination on regional collagen biosynthesis and concentration in the hearts of male beagle dogs were studied by measuring prolyl 4-hydroxylase (PH) activity and hydroxyproline (HYP) concentration. The PH (P<0.05) and HYP (P<0.05) were both greater in the subendocardinal layer than in the subepicardium (EPI) of the left ventricular wall in controls, whereas opposite gradients (P<0.05) were observed in the right ventricle. Endurance exercise caused an increase of PH activity in EPI of the left ventricular wall (P<0.01). The HYP concentration increased in both layers of the right ventricle in the exercise plus steroid group (P<0.05). The results suggest that transmural differences exist in the rate of collagen synthesis and concentration in canine cardiac ventricles and that endurance exercise may accelerate collagen synthesis in EPI of the left ventricle and the combination of exercise and anabolic steroid causes an increase in collagen concentration in the right ventricular wall.     

Overexpression and nuclear translocation of hypoxia-inducible factor prolyl hydroxylase PHD2 in head and neck squamous cell carcinoma is associated with tumor aggressiveness.

PURPOSE: Hypoxia in tumors is associated with poor prognosis and resistance to treatment. The outcome of hypoxia is largely regulated by the hypoxia-inducible factors (HIF-1alpha and HIF-2alpha). HIFs in turn are negatively regulated by a family of prolyl hydroxylases (PHD1-3). The PHD2 isoform is the main down-regulator of HIFs in normoxia and mild hypoxia. This study was designed to analyze the correlation of the expression and subcellular localization of PHD2 with the pathologic features of human carcinomas and HIF-1alpha expression. EXPERIMENTAL DESIGN: The expression of PHD2 was studied from paraffin-embedded normal tissue (n = 21) and head and neck squamous cell carcinoma (HNSCC; n = 44) by immunohistochemistry. Further studies included PHD2 mRNA detection and HIF-1alpha immunohistochemistry from HNSCC specimens as well as PHD2 immunocytochemistry from HNSCC-derived cell lines. RESULTS: In noncancerous tissue, PHD2 is robustly expressed by endothelial cells. In epithelium, the basal proliferating layer also shows strong expression, whereas the more differentiated epithelium shows little or no PHD2 expression. In HNSCC, PHD2 shows strongly elevated expression both at the mRNA and protein level. Moreover, PHD2 expression increases in less differentiated phenotypes and partially relocalizes from the cytoplasm into the nucleus. Endogenously high nuclear PHD2 is seen in a subset of HNSCC-derived cell lines. Finally, although most of the tumor regions with high PHD2 expression show down-regulated HIF-1alpha, regions with simultaneous HIF-1alpha and PHD2 expression could be detected. CONCLUSIONS: Our results show that increased levels and nuclear translocation of the cellular oxygen sensor, PHD2, are associated with less differentiated and strongly proliferating tumors. Furthermore, they imply that even the elevated PHD2 levels are not sufficient to down-regulate HIF-1alpha in some tumors.