An explorative study on the clinical utility of baseline and serial serum tumour marker measurements in advanced upper gastrointestinal cancer.

The value of early tumour marker changes during palliative chemotherapy in patients with upper gastrointestinal adenocarcinoma (UGIA) is unclear. Seventy-three patients with advanced UGIA were randomised to receive 45 mg/m2 docetaxel or 180 mg/m2 irinotecan with 5-FU/leucovorin. After every 2nd course the patients were crossed over to the other regimen. Serum was sampled before start of chemotherapy and every 2nd week during 8 weeks for CEA, TPA, TPS, CA72-4, CA19-9 and CA242 measurements. Eighteen patients (25%) had partial response (PR) and 21 patients had stable disease for at least 4 months (SD4). All baseline marker levels, except CA72-4, correlated with time to progression and survival. Patients with normal levels, except CA72-4, also had more clinical responses (PR+SD4) than patients with elevated values. Tumour marker changes early during treatment provided modest predictive information for tumour response and survival. A model combining baseline level, the change and the interaction between them gave the best prediction of outcome, however, insignificantly better than baseline level for all markers except CA242. Baseline tumour marker levels provide prognostic information for patients with UGIA on palliative chemotherapy. Early changes generally failed to provide accurate information for tumour response and survival.

A high activity index of stearoyl-CoA desaturase is associated with increased risk of fracture in men.

UNLABELLED: The activity index of stearoyl-CoA desaturase (SCD), a key enzyme in lipogenesis, was associated with increased risk of fracture in a longitudinal population-based cohort of men. This indicates that elevated levels of endogenous lipogenesis increase the risk of fracture and suggest a role for saturated fat in the pathogenesis of osteoporosis. INTRODUCTION: Osteoblasts and marrow adipocytes are derived from a common mesenchymal progenitor, and experimental studies have indicated that increased adipogenesis can occur at the expense of osteoblasts, leading to bone loss. Stearoyl-CoA desaturase (SCD) converts saturated to monounsaturated fatty acids and is a key enzyme in lipogenesis. METHODS: Analysis was performed in a population-based, longitudinal cohort study of men (n = 2009). A product-to-precursor index (palmitoleic acid/palmitic acid) was used to estimate SCD activity in fasting serum analyzed in samples obtained at enrollment at age 50 years. Fractures were documented in 422 men during 35 years of follow-up. Cox regression analysis was used to determine the risk of fracture according to SCD activity index. RESULTS: The risk of fracture was highest among men with the highest levels of SCD activity index. Multivariable analysis of the risk of fracture in the highest quintile as compared to the lowest one showed that the rate ratio was 1.71 (95% CI 1.26-2.33) for any fracture, with an estimated population attributable risk of 15%. The risk was further increased within the highest quintile. CONCLUSIONS: Our results indicate that elevated levels of endogenous lipogenesis increase the risk of fracture and suggest a role for saturated fat in the pathogenesis of osteoporosis.

Incidence and geographical distribution of sudden infant death syndrome in relation to content of nitrate in drinking water and groundwater levels.

BACKGROUND: Previous studies indicate that the enteral bacterial urease is inhibited in victims of sudden infant death syndrome (SIDS). One possible inhibitor of this bacterial activity is nitrate. If ambient pollution by nitrate is involved in the etiology of SIDS only a fraction of the nitrate concentration not infrequently found in drinking water would be enough for this inhibition. METHODS: Occurrence of SIDS (n = 636) in Sweden during the period 1990 through 1996 were analysed regarding geographical and seasonal distribution in relation to the nitrate concentration in drinking water and changes in the groundwater level. RESULTS: Both the birth rate and the incidence of SIDS decreased during the study period. One quarter of the municipalities constituting 11% of the population had no cases, the maximum incidence being 6.5 per 1000 live births. Seasonality: The northernmost parts of the country had its highest incidence when the rest of the country had its lowest incidence, and the occurrence of individual deaths was associated with the recharge of groundwater which increases its nitrate content. The local incidence of SIDS was correlated (rs = 0.34-0.87) to maximally recorded concentrations of nitrate in drinking water. CONCLUSIONS: The seasonal distribution of SIDS was widely different from the south to the north of the country and seems to be associated with differences in the groundwater level changes subsequent to precipitation, frost penetration, and melting of snow. Use of drinking water with high peak concentrations or great variations in nitrate concentration was correlated to the incidence of SIDS.

PCB and chlorinated pesticide concentrations in swine and bovine adipose tissue in Sweden 1991-1997: spatial and temporal trends.

Results from the Swedish control programme regarding organochlorines in food were used to determine time trends of organochlorine concentrations in adipose tissues from swine (4-8 months old) and bovines (non-dairy, 12-36 months) slaughtered between 1991 and 1997. Moreover, possible regional differences in concentrations were studied, as well as differences in concentrations depending on sex and age of the slaughtered animals. Multiple linear regression indicated that the concentrations of PCB, p,p'-DDE, HCB and alpha-HCH decreased by 4-17% per year, suggesting that the decline in organochlorine concentrations in the Swedish environment and biota reported during the 1970s-1990s also has occurred in meat-producing animals during the 1990s. The concentrations of PCB, DDE and HCB in bovines and PCB and DDE in swine were 1.4-3.8-fold higher in the southern parts of Sweden than in the northern parts of the country, indicating a regional difference in exposure of the animals. The organochlorine concentrations were higher in bovines than in swine, and declined faster in swine than in bovines. Moreover, the concentrations of CB 153 and p,p'-DDE were similar in bovines, but in swine the average concentrations of the two compounds differed two-fold. Apart from possible species differences in metabolism of organochlorines, this may be due to differences in the age at slaughter between swine and bovines, and differences in husbandry of the animals. In the latter case, swine are generally kept inside during their whole life span, whereas bovines are kept outside grazing during the summer period. Finally, a sex-dependent difference in concentrations was indicated in swine, but not in bovines. Our study shows that a lot of information can be 'extracted' from control program results.