To assess the associations between both uric acid levels and hyperuricaemia, with ischaemic heart disease and blood pressure, and to explore the potentially confounding role of body mass index.
Mendelian randomisation analysis, using variation at specific genes (SLC2A9 (rs7442295) as an instrument for uric acid; and FTO (rs9939609), MC4R (rs17782313), and TMEM18 (rs6548238) for body mass index).
Two large, prospective cohort studies in Denmark.
We measured levels of uric acid and related covariables in 58,072 participants from the Copenhagen General Population Study and 10,602 from the Copenhagen City Heart Study, comprising 4890 and 2282 cases of ischaemic heart disease, respectively.
Blood pressure and prospectively assessed ischaemic heart disease.
Estimates confirmed known observational associations between plasma uric acid and hyperuricaemia with risk of ischaemic heart disease and diastolic and systolic blood pressure. However, when using genotypic instruments for uric acid and hyperuricaemia, we saw no evidence for causal associations between uric acid, ischaemic heart disease, and blood pressure. We used genetic instruments to investigate body mass index as a potentially confounding factor in observational associations, and saw a causal effect on uric acid levels. Every four unit increase of body mass index saw a rise in uric acid of 0.03 mmol/L (95% confidence interval 0.02 to 0.04), and an increase in risk of hyperuricaemia of 7.5% (3.9% to 11.1%).
By contrast with observational findings, there is no strong evidence for causal associations between uric acid and ischaemic heart disease or blood pressure. However, evidence supports a causal effect between body mass index and uric acid level and hyperuricaemia. This finding strongly suggests body mass index as a confounder in observational associations, and suggests a role for elevated body mass index or obesity in the development of uric acid related conditions.
Cites: Stroke. 2006 Jun;37(6):1503-716675740
Cites: JAMA. 2000 May 10;283(18):2404-1010815083
Cites: Ann Epidemiol. 2007 Jul;17(7):511-317466535
Cites: JAMA. 2007 Jul 18;298(3):299-30817635890
Cites: J Am Coll Cardiol. 2007 Nov 27;50(22):2173-9518036459
Cites: Am J Hum Genet. 2008 Jan;82(1):139-4918179892
67Ga imaging of non-Hodgkin's lymphoma is useful for evaluating the presence of viable tumour in a residual mass after treatment. However, we have frequently seen gallium uptake in the pulmonary hila without other evidence of lymphoma. To study the significance of this finding, 79 patients with intermediate grade non-Hodgkin's lymphoma were reviewed. Thirty-seven (47%) had abnormal hilar gallium uptake. Twenty-three of these could be fully evaluated, and only five (22%) had hilar lymphoma. A pattern of bilateral, symmetric hilar uptake was seen in 19 patients, but only one had evidence of lymphoma. In 15 cases, this pattern was seen only on single photon emission computed tomography (SPECT). The aetiology of this uptake remains unknown. It is not treatment related, as 12 patients had hilar gallium uptake prior to chemotherapy. Unless confirmed by other methods, hilar gallium uptake should not be attributed to lymphoma, and should not influence patient management.
Germline mutations of BRCA1 and BRCA2 predispose individuals to a high risk of breast and ovarian cancer, and elevated risk of other cancers, including those of the pancreas and prostate. BRCA2 mutation carriers may have increased risk of uveal melanoma (UM) and cutaneous melanoma (CM), but associations with these cancers in BRCA1 mutation carriers have been mixed. Here, we further assessed whether UM and CM are associated with BRCA1 or BRCA2 by assessing the presence, segregation and reported/predicted pathogenicity of rare germline mutations (variant allele frequency
The purpose of this study was to examine the factors which affect the level of fatigue among patients participating in clinical trials in which this symptom had been assessed with the EORTC QLQ-C30. Data were assembled from 2390 patients in ten clinical trials in which the QLQ-C30 had been used to assess baseline and on-study quality of life. The relationship between the level of fatigue reported by the patients on the fatigue scale of this questionnaire and patient and disease characteristics was assessed in univariate and multivariate cross-sectional analyses. In addition, changes in fatigue scores were compared in a longitudinal analysis among patients on two arms of an anti-emetic trial whose emesis control was markedly different. Baseline fatigue levels differed substantially among patients taking part in the different trials. Factors associated with greater fatigue severity on univariate analysis included: female gender, presence of metastatic disease, and poorer performance status. In addition, on multivariate analyses the oldest patients were found to have less fatigue, as were patients with breast cancer, while patients with ovarian and lung cancer experienced greater fatigue. Patients on the arm of the anti-emetic trial in which emesis was better controlled showed significantly less increase in fatigue after receiving chemotherapy. The fatigue scale of the QLQ-C30 appears to provide a useful approach to assessing this important symptom. The relationships found between fatigue and patient and disease characteristics need further exploration as does the degree to which the QLQ-C30 fully captures this dimension of quality of life.
A cohort of 4,163 persons reported to the nationwide Swedish Cancer Registry by reason of hyperparathyroidism was followed for up to 22 completed years (24,593 person-years of observation). The occurrence of malignant disease manifested after parathyroid surgery was investigated through computerized linkage to the entire Cancer Registry. During the entire period, the hyperparathyroidism patients suffered malignant diseases significantly more often than the background population (relative risk (RR) = 1.6, 95% confidence interval (CI) 1.5-1.8). Even if all cases with malignant diseases detected at the same time as hyperparathyroidism or during the first year after parathyroid surgery were eliminated, a significantly increased risk remained for the following years (RR = 1.4, 95% CI 1.2-1.6). A significantly increased relative risk of developing gastrointestinal cancers, endocrine tumors, kidney carcinomas, and mammary carcinomas was found. During the first postoperative year, an increased surveillance of the cohort is likely to have contributed to the increased risk, but detection bias is considered unlikely to be the only explanation for the higher risk during all subsequent years. The findings indicate that hyperparathyroidism either promotes later development of malignant tumors or that this condition and certain malignant diseases have etiologic factors in common.
Effects of age and training on myocardial Na+/Ca2+ exchange were examined in young sedentary (YS; 14-15 mo), aged sedentary (AS; 27-31 mo), and aged trained (AT; 8- to 11-wk treadmill run training) male Fischer Brown Norway rats. Whole heart performance and isolated cardiocyte Na+/Ca2+ exchange characteristics were measured. At the whole heart level, a small but significant slowing of late isovolumic left ventricular (LV) relaxation, which may be indicative of altered Na+/Ca2+ exchange activity, was seen in hearts from AS rats. This subtle impairment in relaxation was not observed in hearts from AT rats. At the single-cardiocyte level, late action potential duration was prolonged, resting membrane potential was more positive, and overshoot potential was greater in cardiocytes from AS rats than from YS rats (P
In 1969, a health survey was offered to all inhabitants of a town district in Sweden. A clinical examination was carried out, and among other variables, a measurement was made of serum calcium. The same procedure was repeated in 1971. From these two investigations a cohort of 176 individuals (1.1%) with sustained hypercalcemia was identified who could be followed during the subsequent 15 years. Comparisons were made with an age- and sex-matched control group from the same health survey. Survival was significantly lower in the hypercalcemic cohort than in the control group. This reduction was related to the degree of hypercalcemia and apparently mainly due to diseases of the circulatory organs. There was no marked deterioration of renal function, and although there was in some patients a moderate progression of the hypercalcemia, none developed a hypercalcemic crisis during 15 years of follow-up. In consecutively referred patients with primary hyperparathyroidism, psychiatric disturbances of mainly a depressive character were found upon detailed analysis within a majority of the patients, and parathyroid surgery resulted in a clear improvement in mental health.
In the study presented here 26 recent Danish clinical isolates of prolyliminopeptidase (PIP)-negative Neisseria gonorrhoeae were phenotypically and genotypically characterized to investigate whether one or more PIP-negative strains are circulating in the Danish community. The profiles of these isolates were compared with those of three isolates from a recent outbreak of PIP-negative N. gonorrhoeae infection in the UK. Twenty-five of the Danish isolates and all three UK isolates had similar antibiograms and were designated serovar IB-4. Genotypic characterization by pulsed-field gel electrophoresis, porB1b gene sequencing, and opa-typing revealed that these isolates were indistinguishable or closely related. The results indicate that at least one PIP-negative N. gonorrhoeae strain is currently circulating in the Danish community, and this strain is indistinguishable from the one that caused an outbreak in the UK.
The purpose of this study was to evaluate the prevalence of urinary tract symptoms in a population-based cohort of 109 young adult patients with Type 1 diabetes mellitus with onset at 9.0% did not have significantly more treated UTIs than those with HbA1c