Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m²: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.     

Lung cell reactions in guinea pigs after inhalation of asbestos (amosite)

To study the long-term effect of inhaled asbestos, guinea-pigs were exposed to airborne amosite at a concentration of 49 mg/m3, 2 h/day for 3 or 6 weeks and examined up to 2 years after exposure. Macrophages in lung lavage fluid (LLF) were increased at 16, 24 and 93 weeks and lymphocytes at 24 weeks. Examination of lung wall cells (LWC) 2 years after exposure compared to cells obtained by LLF showed higher proportions of LWC lymphocytes and neutrophils. Percoll gradient centrifugation of these cells showed a higher proportion of high density macrophages in LLF from the amosite-exposed animal and an increased number of low density lymphocytes in the LW. Cathepsin D was increased in LLF at 8 and 24 weeks and in alveolar macrophages 24 weeks and 2 years after exposure. Fibroblast cultures exposed to LLF did not show any statistical significant changes in their collagen synthesis. Histology 93 weeks after exposure showed macrophage and mediastinal lymph node accumulation of asbestos, as well as collagen in alveolar walls. Granulomas were found in the vicinity of blood vessels and in connection with the bronchioles. The data suggest that amosite at low doses ultimately causes fibrosis with a reaction pattern different from that seen in silicosis. The inflammation and fibrosis seems to develop only within the interstitium.     

Healing-in of root analogue titanium implants placed in extraction sockets. An experimental study in the beagle dog.

The aim of these animal experiments was to characterize and evaluate the healing-in of root analogue titanium implants fitting with high precision to the alveolar wall. Four beagle dogs were used in the study. The roots of the 3rd and 4th mandibular premolars in both quadrants of 3 dogs and in 1 quadrant of 1 dog (dog 4) were extracted after hemisection. Each root was machine-copied to 1 titanium analogue. In dog 4, however, 2 titanium analogues were fabricated from each of the 4 extracted roots. This enabled insertion of analogues also into the contralateral sockets obtained by extraction of the corresponding roots immediately before implant installation, which was undertaken 2 weeks after the first extractions. Thus, in all, 32 analogues were implanted in their respective (or contralateral) sockets following ridge incision and elevation of mucoperiosteal flaps. The analogues were carefully covered by the repositioned flaps. In dog 4, 2 analogues from the immediate sockets and 2 from the 2-week sockets were surgically exposed and supplied with titanium crowns after a healing period of 2 months. The healing after implantation was evaluated by clinical, radiographic and histological measures after 2, 12 or 36 months. Two analogues (6%) were lost due to early (during the 1st week) exposure to the oral cavity. Another 2 analogues (6%) were, although not exposed, encapsulated by soft tissue and were easily removed with a surgical forceps. Twenty-eight analogues (88%) were healed-in by contact between bone and implant (osseointegration).(ABSTRACT TRUNCATED AT 250 WORDS)     

Ultrasensitive analysis of the intestinal absorption and compartmentalization of aluminium in uraemic rats: a 26Al tracer study employing accelerator mass spectrometry

BACKGROUND: Developments in accelerator mass spectrometry (AMS) now permit the determination of femtogram amounts of 26Al in blood and in various tissues with good precision and free of external contamination. METHODS: In the present study we used trace quantities of 26Al to investigate the intestinal absorption and compartmentalization of aluminium in rats with renal failure (Nx, 5/6 nephrectomy) and in pair- fed controls (C). Single oral doses of 20 ng 26Al were administered to six animals in each group and, subsequently, 24-h post-load 26Al was analysed in serum, urine, bone, liver, and spleen by means of AMS. RESULTS: Serum concentrations of 26Al were significantly lower in uraemic rats compared to controls, whereas urinary excretion was comparable (Nx, 7.11 +/- 5.78 pg/day vs C, 9.46 +/- 6.10 pg/day), suggesting a higher fraction of ultrafiltrable serum 26Al in uraemia. The target tissues of cellular transferrin-mediated 26Al uptake, liver and spleen, tended to show a larger degree of aluminium accumulation in controls (0.26 +/- 0.31 pg/g vs Nx, 0.14 +/- 0.10 pg/g and 0.37 +/- 0.27 pg/g vs Nx, 0.25 +/- 0.27 pg/g respectively). In contrast, in bone, a site of extracellular aluminium deposition, 26Al concentrations were more elevated in uraemia (1.22 +/- 0.59 pg/g vs C: 0.68 +/- 0.30 pg/g). Estimated total 26Al accumulation in all measured target tissues was significantly higher in uraemic rats (28.15 +/- 9.90 pg vs C: 17.03 +/- 7.03 pg) and total recovery of 26Al from tissue and urine was 26.58 +/- 6.74 pg in controls and 35.75 +/- 7.03 pg in uraemic animals, suggesting a fractional absorption of 0.133% and 0.175% respectively. CONCLUSIONS: Our data suggest that fractional absorption from a dietary level dose of 26Al is about 0.13%. Compartmentalization occurs in transferrin-dependent target tissues such as liver and spleen; however, in quantitative terms extracellular deposition in bone is more important. Uraemia has a significant effect on the intestinal absorption and compartmentalization of aluminium. It enhances fractional absorption and increases subsequent extracellular deposition of aluminium in bone. However, at the same time uraemia does not increase transferrin-dependent cellular accumulation of aluminium in liver and spleen.      

The epidemiologist facing assessment of low risk]

Epidemiological studies on low risks involve a number of major methodological difficulties. This review defines the concept of low risk and emphasises the need to control all large, possibly disease-related risk factors, before low risk factors can be evaluated. This procedure is also essential in identifying confounding factors. There is a special need to evaluate statistical power in studies on low risk factors, and the representativeness of both cases and controls should be carefully verified, particularly in case-control studies. The need to control the researcher's wish bias and the main requirements for meta-analysis are also presented.     

Mortality and cancer incidence among secondary lead smelter workers.

OBJECTIVES--To examine the mortality pattern and the cancer incidence in a cohort of long term smelter workers exposed to lead. METHODS--The cohort consists of 664 male lead battery workers, employed for at least three months in 1942-87. From 1969 the values of all blood lead samples repeatedly obtained from these workers every two to three months, have been collected in a database. The expected mortality and morbidity 1969-89 was estimated from the county rates, specified for cause, sex, five-year age groups, and calendar year. Individual exposure matrices have been calculated and used for dose-response analyses. RESULTS--The total cohort showed an increased overall mortality (standardised mortality ratio (SMR) 1.44; 95% confidence interval (95% CI) 1.16-1.79), an increased mortality from ischaemic heart diseases (SMR 1.72; 95% CI 1.20-2.42) and all malignant neoplasms (SMR 1.65; 95% CI 1.09-2.44). These risk estimates were unaffected or slightly decreased when applying a latency period of 15 years, and no dose-response pattern was shown. The non-significantly raised cancer incidence in the gastrointestinal tract (11 malignancies) in the total cohort, increased to a barely significant level in the quartile with the highest cumulative lead exposure (standardised incidence ratio (SIR) 2.34, 95% CI 1.07-4.45). No clear dose response pattern was evident when further subdividing the data into those first employed up to 1969 v those first employed after 1969 when the blood lead monitoring programme started. The risk estimate for malignancies in the gastrointestinal tract was not related to latency time. The cancer incidence was not increased at other sites. CONCLUSIONS--A slightly increased incidence of gastrointestinal cancers was found in workers exposed to lead and employed before 1970. The lead cohort also showed an increased mortality from ischaemic heart diseases. These risk estimates did not show a dose-response pattern and were not associated with latency time. The results must also be interpreted with caution because of limited numbers, and lack of dietary and smoking data.     

Acute pulmonary toxicity of inhaledβ-1,3-glucan and endotoxin

The number of inflammatory cells was studied in lung walls and airways after inhalation of endotoxin or -1,3-glucan. In the water unsoluble form, -1,3-glucan caused a delayed response in terms of a decrease in macrophages and lymphocytes in the lung wall, 1 to 7 days after exposure but no invasion of neutrophils into the airways. When solubilized in 0.02 N NaOH, the cell response was the same as that observed after exposure to endotoxin.     

Healthy subjects express differences in clinical responses to inhaled lipopolysaccharide that are related with inflammation and with atopy

BACKGROUND: Endotoxin and its purified derivative LPS are important contaminants of both domestic and occupational environments that have been related to airway diseases. A body of data suggests that there is considerable interindividual variability in LPS sensitivity. OBJECTIVE: The aim of the study was to relate the individual clinical responses to inhaled LPS with the inflammatory process and the atopic status. METHODS: Fifteen healthy subjects were challenged each week by inhalation with saline solution or LPS (0.5, 5, or 50 microg). The systemic response was defined by the increase in body temperature, blood neutrophilia, acute-phase proteins (C-reactive protein and LPS-binding protein [LBP]), and E-selectin. The LPS-induced airway response was defined as the increase in airway responsiveness and related to the cell count and concentration of TNF-alpha, myeloperoxidase, and eosinophil cationic protein in induced sputum. The atopic status was defined as an increase in IgE or a positive skin prick test result. RESULTS: Subjects (n = 7) with a significant increase in body temperature had a larger increase in the systemic inflammatory response (blood neutrophilia; P <.01) and in blood concentrations of C-reactive protein (P <.02) and LBP (P <.01). Subjects with a significant increase in airway responsiveness (n = 8) had an increase in the sputum concentration of eosinophil cationic protein (P <.01). The amplitude of the systemic response (increase in body temperature [P <.001], blood neutrophilia [P <.02], and rise in LBP [P <.05] and decrease in FEV(1) [P <.01]) were inversely associated with the atopic status, suggesting a link between atopy and LPS responsiveness. CONCLUSIONS: The clinical response to LPS occurs systemically or locally and is associated with inflammation. The atopic status was inversely related to the systemic inflammation.     

Modulation of pulmonary inflammation after endotoxin inhalation with a platelet-activating factor antagonist (48740 RP)

An acute pulmonary response was induced in guinea pigs and hamsters by inhalation of bacterial endotoxin in the form of a purified lipopolysaccharide (LPS). Pretreatment with the platelet-activating factor (PAF) antagonist, 48740 RP, inhibited damage to endothelial cells, decreased vascular permeability and the number of neutrophils in the airways 24 h after exposure to LPS. The increase in the number of platelets in the airways caused by endotoxin was not affected. The results suggest that PAF modulates early inflammation after endotoxin inhalation.     

Byssinosis in carpet weavers exposed to wool contaminated with endotoxin

All the 303 full time day workers in a carpet weaving factory were submitted to a physical examination, chest radiography, and vitalograph test, and answered a respiratory questionnaire. Fifty four healthy non-exposed subjects served as controls. Dust concentrations and concentrations of bacterial endotoxin were measured. Of the 303 workers, 259 (85.5%) had airway symptoms and 62 (20.5%) had maximum mid-expiratory flow (MMF) values of less than 60% compared with 9.2% of the controls. The symptoms in 68 workers (22%) were compatible with byssinosis and 36 of these workers underwent vitalography before starting work and after four hours work on Mondays when significant reductions of their FEV1 and MMF were found. Twenty one of these 36 workers were tested on Tuesday and no differences in these measurements were found between measurements before work started and four hours later. The airborne dust concentrations in the factory were high and bacterial endotoxin was found. These findings suggest that a large number of workers in this carpet weaving factory suffer from a disease indistinguishable from byssinosis even though wool is used almost exclusively, the only cotton being the warp. The finding of endotoxin together with the absence of cotton confirms the theory that "byssinosis" is due to bacterial endotoxin rather than to cotton per se.