Safety and efficacy of recombinant human erythropoietin treatment of anaemia associated with multiple myeloma in haemodialysed patients

Recombinant human erythropoietin (rHuEpo) was used to treat the anaemia of four haemodialysed patients (3 males, 1 female) with advanced multiple myeloma; the type of serum M component was IgG kappa in all cases. During the 6-month period preceding rHuEpo therapy the patients received multiple blood transfusions (range 4-22 units of packed red cells per patient). After the first month of treatment haematocrit increased from 23±3 (SD) to 32±4% and during the last 3 months the maintenance dose of rHuEpo was 143±37 U/kg per week to achieve a mean haematocrit of 35±1%. After introduction of rHuEpo, blood transfusions were no longer required and the patients reported an improvement in wellbeing. No apparent worsening of multiple myeloma has been observed over the treatment period ranging from 5 to 34 months (cumulative duration of treatment 55 months). Anti-hypertensive therapy was started in one case and increased in two patients. We conclude that rHuEpo appears to be effective and safe in treating anaemia associated with multiple myeloma in patients requiring haemodialysi

Blood pressure changes after renal denervation at 10 European expert centers

We did a subject-level meta-analysis of the changes (Δ) in blood pressure (BP) observed 3 and 6 months after renal denervation (RDN) at 10 European centers. Recruited patients (n=109; 46.8% women; mean age 58.2 years) had essential hypertension confirmed by ambulatory BP. From baseline to 6 months, treatment score declined slightly from 4.7 to 4.4 drugs per day. Systolic/diastolic BP fell by 17.6/7.1 mm Hg for office BP, and by 5.9/3.5, 6.2/3.4, and 4.4/2.5 mm Hg for 24-h, daytime and nighttime BP (P0.03 for all). In 47 patients with 3- and 6-month ambulatory measurements, systolic BP did not change between these two time points (P0.08). Normalization was a systolic BP of <140 mm Hg on office measurement or <130 mm Hg on 24-h monitoring and improvement was a fall of 10 mm Hg, irrespective of measurement technique. For office BP, at 6 months, normalization, improvement or no decrease occurred in 22.9, 59.6 and 22.9% of patients, respectively; for 24-h BP, these proportions were 14.7, 31.2 and 34.9%, respectively. Higher baseline BP predicted greater BP fall at follow-up; higher baseline serum creatinine was associated with lower probability of improvement of 24-h BP (odds ratio for 20-μmol l(-1) increase, 0.60; P=0.05) and higher probability of experiencing no BP decrease (OR, 1.66; P=0.01). In conclusion, BP responses to RDN include regression-to-the-mean and remain to be consolidated in randomized trials based on ambulatory BP monitoring. For now, RDN should remain the last resort in patients in whom all other ways to control BP failed, and it must be cautiously used in patients with renal impairment

Relation of 24-hour urinary caffeine and caffeine metabolite excretions with self-reported consumption of coffee and other caffeinated beverages in the general population.

Caffeine intake is generally estimated by self-reported consumption, but it remains unclear how well self-report associates with metabolite urinary excretion. We investigated the associations of self-reported consumption of caffeinated drinks with urinary excretion of caffeine and its major metabolites in an adult population. We used data from the population-based Swiss Kidney Project on Genes in Hypertension (SKIPOGH) study. Consumption of caffeinated coffee, decaffeinated coffee and other caffeinated beverages was assessed by self-administered questionnaire. Quantification of caffeine, paraxanthine, theobromine and theophylline was performed by ultra-high performance liquid chromatography tandem mass spectrometry in 24-h urine. Association of reported consumption of caffeinated drinks with urinary caffeine derived metabolites was determined by quantile regression. We then explored the association between urinary metabolite excretion and dichotomized weekly consumption frequency of caffeinated coffee, with Receiver Operator Characteristic (ROC) analysis. In the present analysis, we included 598 individuals (52% women, mean age =46 ± 17 years). Self-reported caffeinated coffee intake was positively associated with 24-h urinary excretions of paraxanthine, theophylline and caffeine (p < 0.001), whereas reported intakes of decaffeinated coffee and other caffeinated beverages showed no association. In ROC analysis, optimal discrimination between individuals consuming less than one caffeinated coffee/week, vs. at least one coffee, was obtained for 24-h urinary paraxanthine (Area Under Curve (AUC) = 0.868, 95% Confidence Interval (CI) [0.830;0.906]), with slightly lower performance for theophylline and caffeine, whereas theobromine did not allow any discrimination. Our results suggest that reported consumption of caffeinated coffee is positively associated with 24-h urinary excretion of caffeine, paraxanthine, and theophylline, and may be used as a marker of caffeine intake for epidemiological studies

Sociodemographic, behavioral and genetic determinants of allostatic load in a Swiss population-based study.

Allostatic load (AL) is a marker of physiological dysregulation which reflects exposure to chronic stress. High AL has been related to poorer health outcomes including mortality. We examine here the association of socioeconomic and lifestyle factors with AL. Additionally, we investigate the extent to which AL is genetically determined. We included 803 participants (52% women, mean age 48±16years) from a population and family-based Swiss study. We computed an AL index aggregating 14 markers from cardiovascular, metabolic, lipidic, oxidative, hypothalamus-pituitary-adrenal and inflammatory homeostatic axes. Education and occupational position were used as indicators of socioeconomic status. Marital status, stress, alcohol intake, smoking, dietary patterns and physical activity were considered as lifestyle factors. Heritability of AL was estimated by maximum likelihood. Women with a low occupational position had higher AL (low vs. high OR=3.99, 95%CI [1.22;13.05]), while the opposite was observed for men (middle vs. high OR=0.48, 95%CI [0.23;0.99]). Education tended to be inversely associated with AL in both sexes(low vs. high OR=3.54, 95%CI [1.69;7.4]/OR=1.59, 95%CI [0.88;2.90] in women/men). Heavy drinking men as well as women abstaining from alcohol had higher AL than moderate drinkers. Physical activity was protective against AL while high salt intake was related to increased AL risk. The heritability of AL was estimated to be 29.5% ±7.9%. Our results suggest that generalized physiological dysregulation, as measured by AL, is determined by both environmental and genetic factors. The genetic contribution to AL remains modest when compared to the environmental component, which explains approximately 70% of the phenotypic variance

Seasonal variation of carbon monoxide in northern Japan: Fourier transform IR measurements and source-labeled model calculations

Tropospheric carbon monoxide (CO) was measured throughout 2001 using groundbased Fourier transform IR (FTIR) spectrometers at Moshiri 44.4N and Rikubetsu 43.5N) observatories in northern Japan, which are separated by 150 km. Seasonal and day-to-day variations of CO are studied using these data, and contributions from various CO sources are evaluated using three-dimensional global chemistry transport model (GEOS-CHEM) calculations. Seasonal maximum and minimum FTIR-derived tropospheric CO amounts occurred in April and September, respectively. The ratio of partial column amounts between the 0–4 and 0–12 km altitude ranges is found to be slightly greater in early spring. The GEOS-CHEM model calculations generally reproduce these observed features. Source-labeled CO model calculations suggest that the observed seasonal variation is caused by seasonal contributions from various sources, in addition to a seasonal change in chemical CO loss by OH. Changes in meteorological fields largely control the relative importance of various source contributions. The contributions from fossil fuel (FF) combustion in Asia and photochemical CO production have the greatest yearly averaged contribution at 1 km among the CO sources (31% each). The Asian FF contribution increases from winter to summer, because weak southwesterly wind in summer brings more Asian pollutants to the observation sites. The seasonal variation from photochemical CO production is small (±17% at 1 km), likely because of concurrent increases (decreases) of photochemical production and loss rates in summer (winter), with the largest contribution between August and December. The contribution from intercontinental transport of European FF combustion CO is found to be comparable to that of Asian FF sources in winter. Northwesterly wind around the Siberian high in this season brings pollutants from Europe directly to Japan, in addition to southward transport of accumulated pollution from higher latitudes. The influences are generally greater at lower altitudes, resulting in a vertical gradient in the CO profile during winter. The model underestimates total CO by 12–14% between March and June. Satellite-derived fire-count data and the relationship between FTIR-derived HCN and CO amounts are generally consistent with biomass burning influences, which could have been underestimated by the model calculations

Prevalence and determinants of chronic kidney disease in the Swiss population.

QUESTIONS UNDER STUDY: The prevalence of chronic kidney disease (CKD) is increasing worldwide, corresponding to an increased risk of cardiovascular disease. The latest study on prevalence of CKD involving the three linguistic regions of Switzerland dates back to 2002-2003 and definitions have changed since then. We aimed to assess the current prevalence and determinants of CKD in the Swiss general population. METHODS: We analysed the data of 1353 participants from a cross-sectional population-based survey performed in 2010-2012 in the three linguistic regions of Switzerland. The prevalence of CKD and the derived cardiovascular risk categories were assessed according to the Kidney Disease - Improving Global Outcomes (KDIGO) 2012 classification, using estimated glomerular filtration rate (GFR; CKD-Epidemiological Collaboration equation) and albuminuria level. Multivariate logistic regression was used to analyse factors associated with CKD. RESULTS: We included 660 men and 693 women, equally distributed in four age categories (15-29, 30-44, 45-59 and over 60 years). The overall prevalence of CKD was 10.4%. The prevalence in the low, moderate, high and very high risk KDIGO categories were 89.6%, 8.4%, 1.6% and 0.5%, respectively. The prevalence of CKD was similar in all linguistic regions. In multivariate analysis, female gender, older age, diabetes and uric acid were independently associated with CKD in persons ≥45 y. In younger participants, diabetes and lower educational level were associated with CKD. CONCLUSIONS: In the general Swiss population, CKD affects one in ten adults. Subjects older than 60 years, as well as patients with diabetes and hypertension, show a high prevalence of CKD. Systematic screening may be recommended in this population

Reference intervals for the urinary steroid metabolome: The impact of sex, age, day and night time on human adult steroidogenesis.

Urinary steroid metabolomics by GC-MS is an established method in both clinical and research settings to describe steroidogenic disorders. However, population-based reference intervals for adults do not exist. We measured daytime and night time urinary excretion of 40 steroid metabolites by GC-MS in 1128 adult participants of European ancestry, aged 18 to 90 years, within a large population-based, multicentric, cross-sectional study. Age and sex-related patterns in adjacent daytime and night time urine collections over 24 hours were modelled for each steroid metabolite by multivariable linear mixed regression. We compared our results with those obtained through a systematic literature review on reference intervals of urinary steroid excretion. Flexible models were created for all urinary steroid metabolites thereby estimating sex- and age-related changes of the urinary steroid metabolome. Most urinary steroid metabolites showed an age-dependence with the exception of 6β-OH-cortisol, 18-OH-cortisol, and β-cortol. Reference intervals for all metabolites excreted during 24 hours were derived from the 2.5th and 97.5th percentile of modelled reference curves. The excretion rate per period of metabolites predominantly derived from the adrenals was mainly higher during the day than at night and the correlation between day and night time metabolite excretion was highly positive for most androgens and moderately positive for glucocorticoids. This study gives unprecedented new insights into sex- and age-specificity of the human adult steroid metabolome and provides further information on the day/night variation of urinary steroid hormone excretion. The population-based reference ranges for 40 GC-MS-measured metabolites will facilitate the interpretation of steroid profiles in clinical practice

Increased Cardiovascular Reactivity to Acute Stress and Salt-Loading in Adult Male Offspring of Fat Fed Non-Obese Rats

Diet-induced obesity in rat pregnancy has been shown previously to be associated with consistently raised blood pressure in the offspring, attributed to sympathetic over-activation, but the relative contributions to this phenotype of maternal obesity versus raised dietary fat is unknown. Sprague-Dawley female rats were fed either a control (4.3% fat, n = 11) or lard-enriched (23.6% fat, n = 16) chow 10 days prior to mating, throughout pregnancy and lactation. In conscious adult (9-month-old) offspring cardiovascular parameters were measured (radiotelemetry). The short period of fat-feeding did not increase maternal weight versus controls and the baseline blood pressure was similar in offspring of fat fed dams (OF) and controls (OC). However, adult male OF showed heightened cardiovascular reactivity to acute restraint stress (p<0.01; Δ systolic blood pressure (SBP) and Δheart rate (HR)) with a prolonged recovery time compared to male OC. α1/β-adrenergic receptor blockade normalised the response. Also, after dietary salt-loading (8%-NaCl ad libitum for 1 week) male OF demonstrated higher SBP (p<0.05) in the awake phase (night-time) and increased low/high frequency ratio of power spectral density of HR variability versus OC. Baroreflex gain and basal power spectral density components of the heart rate or blood pressure were similar in male OF and OC. Minor abnormalities were evident in female OF. Fat feeding in the absence of maternal obesity in pregnant rats leads to altered sympathetic control of cardiovascular function in adult male offspring, and hypertension in response to stressor stimuli