Health-related quality of life in patients with common rheumatic diseases referred to a university clinic

The aim of the present study was to assess the health-related quality of life (HRQoL) in patients with common rheumatic diseases referred to a rheumatology clinic and to compare it to the HRQoL of the general population. All patients with a new referral to the Department of Rheumatology of the Helsinki University Central Hospital were asked to participate in the study during the period from May 2002 to April 2003. A total of 295 patients with various rheumatic diseases were included in the analysis: 99 patients with rheumatoid arthritis (RA), 47 with arthralgia and fibromyalgia, 43 with other chronic arthritis (spondyloarthritis, psoriatic arthritis, enteropathic arthritis), 44 with osteoarthritis (OA), 22 with active reactive arthritis (ReA), 17 with systemic rheumatic diseases, 9 adults with juvenile idiopathic arthritis (JIA) and 14 with other diagnoses. HRQoL was measured by a disease specific instrument, the Stanford health assessment questionnaire (HAQ) and by a generic instrument, 15D. The mean baseline 15D score of the 295 included patients (0.822, SD 0.114) was significantly lower than of the general population (0.903, SD 0.098). Patients with OA and chronic arthritis reported the poorest HRQoL scores (both 0.810 on a 0-1 scale). In patients with RA and ReA the 15D score improved in a statistically significant and clinically important manner during the 8-month follow-up. Discomfort and symptoms caused by the disease were alleviated in a statistically significant manner in patients with RA as well as in those with arthralgia and fibromyalgia, chronic arthritis, ReA and systemic rheumatic diseases. HAQ score improved significantly in patients with RA, arthralgia and fibromyalgia, and ReA. The HRQoL of patients with common rheumatic diseases at referral to rheumatology clinic is significantly lower than the HRQoL of age-standardized general population. The most affected patients are those with OA, chronic arthritis and RA. A significant improvement in HRQoL with conventional interventions was achieved in patients with RA and ReA.     

Taurocholate Potentiates Ethanol-Induced NF-κB Activation and Inhibits Caspase-3 Activity in Cultured Rat Gastric Mucosal Cells

We have previously shown that ethanol (EtOH) induces protective NF-κB activation in gastric surface epithelial cells. This study investigates the defense systems in rat gastric mucosal cells (RGM-1) exposed simultaneously to EtOH and taurocholate (TC) or acetylsalicylic acid (ASA). Simultaneous exposure to ASA and EtOH increased EtOH-induced caspase-3 activity and decreased cell viability, indicating synergetic damaging action. Simultaneous exposure to TC (5 mM) with EtOH (5%) increased EtOH-induced NF-κB activation, opposing EtOH-induced decrease in cell membrane integrity and in cell viability as shown by decreasing RelA expression with siRNA technique. Low doses of TC decreased the EtOH (5%) induced caspase-3 activity independently from NF-κB pathway and inhibited EtOH-induced decrease in caspase-3 precursor protein levels, also indicating the inhibition of caspase-3 pathway. The TC (5 mM)-induced protection in EtOH exposed tissues seems to have two distinct pathways, inhibition of apoptosis and enhancement of NF-κB signaling.     

Weight control and physical activity in cancer prevention

Overweight and obesity have reached epidemic dimensions worldwide, mainly due to consumption of high energy diets and increased sedentary behaviour. Overweight and insufficient physical activity are clearly associated with cardiovascular diseases and type 2 diabetes. Evidence is also accumulating that they may also increase cancer risk, particularly in the colon, breast and endometrium. This effect seems to be mediated by alterations in the metabolism of endogenous hormones, including sex steroids and insulin, and levels of insulin‐like growth factor(IGF)‐I and IGF‐binding proteins. In light of the beneficial effects of weight control and physical activity for cancer prevention, a healthy lifestyle, keeping a low body weight and exercising most days of the week, is recommended.     

Determination of an ensemble of structures representing the intermediate state of the bacterial immunity protein Im7

We present a detailed structural characterization of the intermediate state populated during the folding and unfolding of the bacterial immunity protein Im7. We achieve this result by incorporating a variety of experimental data available for this species in molecular dynamics simulations. First, we define the structure of the exchange-competent intermediate state of Im7 by using equilibrium hydrogen-exchange protection factors. Second, we use this ensemble to predict Phi-values and compare the results with the experimentally determined Phi-values of the kinetic refolding intermediate. Third, we predict chemical-shift measurements and compare them with the measured chemical shifts of a mutational variant of Im7 for which the kinetic folding intermediate is the most stable state populated at equilibrium. Remarkably, we found that the properties of the latter two species are predicted with high accuracy from the exchange-competent intermediate that we determined, suggesting that these three states are characterized by a similar architecture in which helices I, II, and IV are aligned in a native-like, but reorganized, manner. Furthermore, the structural ensemble that we obtained enabled us to rationalize the results of tryptophan fluorescence experiments in the WT protein and a series of mutational variants. The results show that the integration of diverse sets of experimental data at relatively low structural resolution is a powerful approach that can provide insights into the structural organization of this conformationally heterogeneous three-helix intermediate with unprecedented detail and highlight the importance of both native and non-native interactions in stabilizing its structure.     

Intranasal exposure to Stachybotrys chartarum enhances airway inflammation in allergic mice

RATIONALE: Exposure to building dampness, often associated with growth of microbes such as Stachybotrys chartarum, has been linked to respiratory symptoms. We have shown previously in a murine model that exposure to S. chartarum can induce lung inflammation characterized by infiltration of neutrophils and lymphocytes; this process is regulated by proinflammatory cytokines and leucocyte-attracting chemokines. OBJECTIVES: Because an atopic predisposition may influence the response to microbes, we examined the effects of S. chartarum on allergic mice in an experimental model. BALB/c mice were sensitized to ovalbumin by intraperitoneal injections and exposed for 3 wk to spores of S. chartarum. MEASUREMENTS AND MAIN RESULTS: Numbers of eosinophils and neutrophils were drastically increased in bronchoalveolar fluid from these mice as compared with the ovalbumin-sensitized/challenged mice or those exposed to S. chartarum without ovalbumin sensitization. Histologic sections showed severe granulomatous inflammatory cell infiltrates in all compartments of the lung, including peribronchial, perivascular, and alveolar spaces. The mRNA levels of proinflammatory cytokines interleukin-1beta and tumor necrosis factor alpha and the chemokine CCL3/MIP-1alpha were also markedly increased in the lungs. Despite the enhancement of the pulmonary inflammatory reaction, exposure to S. chartarum spores significantly down-regulated airway hyperresponsiveness and showed a tendency to decrease levels of Th2 cytokines in the lung. CONCLUSION: Exposure to S. chartarum modulates the inflammatory reaction and airway hyperresponsiveness, depending on the allergic status of the exposed mice.     

Relationship of sex hormones to bone geometric properties and mineral density in early pubertal girls

This study aimed to evaluate the associations among serum 17beta-estradiol (E2), testosterone (T), sex hormone-binding globulin (SHBG), bone geometric properties, and mineral density in 248 healthy girls between the ages of 10 and 13 yr old. The left tibial shaft was measured by peripheral quantitative computed tomography (Stratec XCT-2000; Stratec Medizintechnik, GmbH, Pforzheim, Germany). The cortical bone and marrow cavity areas were expressed as proportions of the total tibial cross-sectional area (CSA). Cortical thickness and total volumetric bone mineral density (vBMD) were also determined. These tibial geometric and densitometric measures were correlated against the serum sex hormone concentrations after controlling for age and body size. The results showed that E2 was negatively associated with marrow cavity proportion (r = -0.19, P = 0.003) and positively associated with cortical proportion and thickness and with total vBMD (r = 0.26, P < 0.001; r = 0.25, P < 0.001; and r = 0.23, P < 0.001, respectively). However, T was not associated with these bone variables. On the other hand, SHBG was positively associated with marrow cavity proportion (r = 0.17, P = 0.007) and negatively associated with cortical proportion and thickness and with total vBMD (r = -0.14, P = 0.029; r = -0.16, P = 0.010; and r = -0.18, P = 0.005, respectively). Total bone CSA did not correlate with E2, T, or SHBG. These results suggest that E2 has a positive effect on bone geometric and densitometric development by suppressing bone turnover at the endocortical surface during the early pubertal period, that SHBG plays an opposite role to E2, and that T has no detectable effect.     

Prevention of falls and consequent injuries in elderly people

Injuries resulting from falls in elderly people are a major public-health concern, representing one of the main causes of longstanding pain, functional impairment, disability, and death in this population. The problem is going to worsen, since the rates of such injuries seem to be rising in many areas, as is the number of elderly people in both the developed and developing world. Many methods and programmes to prevent such injuries already exist, including regular exercise, vitamin D and calcium supplementation, withdrawal of psychotropic medication, cataract surgery, professional environment hazard assessment and modification, hip protectors, and multifactorial preventive programmes for simultaneous assessment and reduction of many of the predisposing and situational risk factors. To receive broader-scale effectiveness, these programmes will need systematic implementation. Care must be taken, however, to rigorously select the right actions for those people most likely to benefit, such as vitamin D and calcium supplementation and hip protectors for elderly people living in institutions.     

Carnitine deficiency and L-carnitine supplementation in lysinuric protein intolerance

The aim of the study was to investigate the prevalence and mechanisms of development of carnitine deficiency in patients with lysinuric protein intolerance (LPI). In our cohort of 37 Finnish patients with LPI, 8 (8-52 years of age) have been diagnosed with hypocarnitinemia. Their free and total serum carnitine levels, acyl carnitine profiles, renal function, diet, and medication were compared with the data from 8 age- and sex-matched patients with LPI not treated with carnitine supplementation. In patients with LPI, hypocarnitinemia was strongly associated with female sex, renal insufficiency, and the use of ammonia-scavenging drugs. Of the 8 hypocarnitinemic patients, 3 complained of muscle weakness, and their symptoms disappeared during carnitine supplementation. Oral lysine supplementation did not correct hypocarnitinemia in our patients. The patients with LPI are at considerable risk for carnitine deficiency. Supplementation of hypocarnitinemic LPI patients with oral L-carnitine improved serum total carnitine values, but the ratio of free and total carnitine remained subnormal in all supplemented patients except one. Furthermore, decreased ratio of free and total serum carnitine was common even in LPI patients with normal total serum carnitine concentration.     

Heritability of daytime ambulatory blood pressure in an extended twin design

The present study estimated the genetic influences on ambulatory systolic and diastolic blood pressure, and on hypertensive status derived from ambulatory levels, in a family sample of 535 twins and 257 singleton siblings. This "extended twin design" was used to explicitly test the possibility that results obtained in singleton siblings are different from those obtained in twins. To examine the effects of excluding (medicated) hypertensive subjects, the genetic analyses were first performed under strict exclusion (medication and/or blood pressure >135/85 mm Hg), then without the medicated subjects, and, finally, without any exclusion. For the latter analysis, the untreated blood pressure values in subjects using antihypertensive medication were estimated by augmenting the observed blood pressure by the published efficacy of the specific antihypertensive medication used. No evidence was found for differential means, variances, or covariances of ambulatory blood pressure in singletons compared with twins. This indicates that estimates of heritability of ambulatory blood pressure from twin studies can be generalized to the singleton population. Heritability of hypertension, defined as a mean daytime blood pressure >135/85 mm Hg or antihypertensive medication use, was 61%. Genetic contribution to ambulatory blood pressure was highest when all subjects were included (systolic, 44% to 57%; diastolic, 46% to 63%) and lowest under strict exclusion (systolic, 32% to 50%; diastolic, 31% to 55%). We conclude that exclusion of (medicated) hypertensives removes part of the true genetic variance in ambulatory blood pressure.     

Health-related quality of life of coronary artery bypass grafting and percutaneous transluminal coronary artery angioplasty patients: 1-year follow-up

OBJECTIVES: The aim of the study was to compare the health-related quality of life (HRQoL) of patients undergoing coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA) before the interventions and 6 and 12 months afterward, and to compare their HRQoL also with that of the general population. METHODS: The sample (n = 615) consisted of consecutive coronary artery disease patients treated with elective CABG (n=432) or PTCA (n=183). The baseline data before the treatments were collected by structured interview, the follow-up data mainly by mailed self-administered questionnaires. HRQoL was measured by the 15D. For comparisons, the groups were standardized for differences in socioeconomic and clinical characteristics with a regression analysis. RESULTS: At baseline, the average 15D scores of the patient groups were 0.752 (95 percent confidence interval [CI], 0.743-0.761) in CABG and 0.730 (95 percent CI, 0.716-0.744) in PTCA. After standardization, the difference between the groups was statistically significant but not clinically important. These scores were significantly worse (statistically and clinically) than the score of 0.883 (95 percent CI, 0.871-0.879) in the general population sample matched with the gender and age distribution of the patients. By 6 months, the CABG and PTCA patients had experienced a statistically significant and clinically important improvement to 0.858 (95 percent CI, 0.844-0.872) and 0.824 (95 percent CI, 0.806-0.842), respectively. No significant change took place in either group from 6 to 12 months. CONCLUSIONS: Both CABG and PTCA produces an approximately similar, clinically important improvement in HRQoL in 1-year follow-up.