Resting heart rate and incident heart failure and cardiovascular mortality in older adults: role of inflammation and endothelial dysfunction: the PROSPER study.

AIMS: Resting heart rate is a promising modifiable cardiovascular risk marker in older adults, but the mechanisms linking heart rate to cardiovascular disease are not fully understood. We aimed to assess the association between resting heart rate and incident heart failure (HF) and cardiovascular mortality, and to examine whether these associations might be attributable to systemic inflammation and endothelial dysfunction. METHODS AND RESULTS: We studied 4084 older adults aged 70-82 years with known cardiovascular risk factors or previous cardiovascular disease, without pre-existing HF or beta-blockers in the PROSPER study. Over a 3.2-year follow-up period, we examined incident HF hospitalization and cardiovascular mortality according to resting heart rate, along with C-reactive protein (CRP), interleukin-6 (IL-6), tissue plasminogen activator (tPA), and von Willebrand factor (vWf). Mean heart rate was 67 b.p.m. for men and 70 b.p.m. for women. CRP, IL-6, tPA, and vWf levels were all positively correlated with heart rate. After multivariate adjustment, heart rate was associated with HF hospitalization [hazard ratio (HR) 1.78 for highest vs. lowest distribution third, 95% confidence interval (CI) 1.21-2.63, P= 0.003] and cardiovascular mortality (HR 1.74, 95% CI 1.23-2.47, P= 0.002). Further adjustment for both IL-6 and vWf levels decreased HR to 1.60 (95% CI 1.08-2.38, P= 0.020) for HF and to 1.50 (95% CI 1.04-2.15, P= 0.028) for cardiovascular mortality. CONCLUSION: Increased heart rate is associated with increased systemic inflammation and endothelial dysfunction. These factors are likely to contribute to, but do not fully explain, the risk of HF and cardiovascular death associated with increased heart rate in older age.

Nemaline myopathy revealed by respiratory failure in adults

Most forms of myopathy may involve the respiratory muscles and progress to respiratory failure. However, the diagnosis of myopathy is seldom considered in an adult patient with no history of muscle disease and presenting with respiratory failure. Nemaline myopathy (NM) is a rare disorder characterized by symmetrical diffuse muscle weakness and rod-like nemaline bodies in muscle fibers. Respiratory muscle involvement is a major determinant of mortality in congenital NM, but is rare in late onset NM. Here, we report that acute or chronic respiratory failure may be caused by NM in subjects with no known history of muscle disease. Adult-onset NM was diagnosed in a 67-year-old woman with chronic respiratory insufficiency. Late onset childhood NM was revealed by respiratory failure in twin sisters aged 31. The diagnosis was established by muscle biopsy and electron microscopy (and mutations in the nebulin gene in the two sisters). Long-term clinical improvement was obtained with non-invasive ventilation (NIV) in the three patients. In conclusion, respiratory failure in an adult patient with no known history may correspond to NM with diaphragm involvement. Long-term outcome may be favorable with NIV.

Swiss Interdisciplinary Management Programme for Heart Failure (SWIM-HF): a randomised controlled trial study of an outpatient inter-professional management programme for heart failure patients in Switzerland.

PRINCIPLES: International guidelines for heart failure (HF) care recommend the implementation of inter-professional disease management programmes. To date, no such programme has been tested in Switzerland. The aim of this randomised controlled trial (RCT) was to test the effect on hospitalisation, mortality and quality of life of an adult ambulatory disease management programme for patients with HF in Switzerland.METHODS: Consecutive patients admitted to internal medicine in a Swiss university hospital were screened for decompensated HF. A total of 42 eligible patients were randomised to an intervention (n = 22) or usual care group (n = 20). Medical treatment was optimised and lifestyle recommendations were given to all patients. Intervention patients additionally received a home visit by a HF-nurse, followed by 17 telephone calls of decreasing frequency over 12 months, focusing on self-care. Calls from the HF nurse to primary care physicians communicated health concerns and identified goals of care. Data were collected at baseline, 3, 6, 9 and 12 months. Mixed regression analysis (quality of life) was used. Outcome assessment was conducted by researchers blinded to group assignment.RESULTS: After 12 months, 22 (52%) patients had an all-cause re-admission or died. Only 3 patients were hospitalised with HF decompensation. No significant effect of the intervention was found on HF related to quality of life.CONCLUSIONS: An inter-professional disease management programme is possible in the Swiss healthcare setting but effects on outcomes need to be confirmed in larger studies.

Secretory IgA in human serum.

Secretory component (SC) was detected by the radioactive single radial diffusion technique in nearly all sera examined. The SC was shown to be associated with polymeric serum IgA. The mean level of secretory IgA (SIgA) in normal sera from India, Africa and Europe was about 0.03 to 0.04 mg/ml. The mean level was elevated in patients with a variety of disorders involving secretory surfaces (e.g., acute bacterial enterocolitis or respiratory tract carcinoma), but also in disorders with no known involvement of secretory surfaces. The highest levels were seen in lactating women, with a mean level five times higher than that in the general population. SIgA was also found at lower levels in cord serum, serum from breast-fed newborns and serum from children 3 to 10 years old.

Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts.

BACKGROUND: American College of Cardiology/American Heart Association guidelines for the diagnosis and management of heart failure recommend investigating exacerbating conditions such as thyroid dysfunction, but without specifying the impact of different thyroid-stimulation hormone (TSH) levels. Limited prospective data exist on the association between subclinical thyroid dysfunction and heart failure events. METHODS AND RESULTS: We performed a pooled analysis of individual participant data using all available prospective cohorts with thyroid function tests and subsequent follow-up of heart failure events. Individual data on 25 390 participants with 216 248 person-years of follow-up were supplied from 6 prospective cohorts in the United States and Europe. Euthyroidism was defined as TSH of 0.45 to 4.49 mIU/L, subclinical hypothyroidism as TSH of 4.5 to 19.9 mIU/L, and subclinical hyperthyroidism as TSH <0.45 mIU/L, the last two with normal free thyroxine levels. Among 25 390 participants, 2068 (8.1%) had subclinical hypothyroidism and 648 (2.6%) had subclinical hyperthyroidism. In age- and sex-adjusted analyses, risks of heart failure events were increased with both higher and lower TSH levels (P for quadratic pattern <0.01); the hazard ratio was 1.01 (95% confidence interval, 0.81-1.26) for TSH of 4.5 to 6.9 mIU/L, 1.65 (95% confidence interval, 0.84-3.23) for TSH of 7.0 to 9.9 mIU/L, 1.86 (95% confidence interval, 1.27-2.72) for TSH of 10.0 to 19.9 mIU/L (P for trend <0.01) and 1.31 (95% confidence interval, 0.88-1.95) for TSH of 0.10 to 0.44 mIU/L and 1.94 (95% confidence interval, 1.01-3.72) for TSH <0.10 mIU/L (P for trend=0.047). Risks remained similar after adjustment for cardiovascular risk factors. CONCLUSION: Risks of heart failure events were increased with both higher and lower TSH levels, particularly for TSH ≥10 and <0.10 mIU/L.

Renal failure after high-dose methotrexate in a child homozygous for MTHFR C677T polymorphism

We report the case of an 11-year-old female treated for mediastinal T-cell lymphoma who presented renal failure following the second cycle of high-dose methotrexate (HDMTX). Because of life threatening plasma methotrexate (MTX) levels, carboxypeptidase G2 (CPDG2) was administered resulting in a dramatic decrease within 1 hr. The patient recovered from renal failure and no other side effects were observed. Homozygosity for the methylentetrahydrofolate reductase (MTHFR) C677T polymorphism diagnosed by molecular genetic analysis was the only explanation for this toxicity.

Effect of oral calcium carbonate on aortic calcification in apolipoprotein E-deficient (apoE-/-) mice with chronic renal failure.

BACKGROUND: In chronic kidney disease (CKD) patients, the intake of calcium-based phosphate binders is associated with a marked progression of coronary artery and aortic calcification, in contrast to patients receiving calcium-free phosphate binders. The aim of this study was to reexamine the role of calcium carbonate in vascular calcification and to analyse its effect on aortic calcification-related gene expression in chronic renal failure (CRF). METHODS: Mice deficient in apolipoprotein E underwent either sham operation or subtotal nephrectomy to create CRF. They were then randomly assigned to one of the three following groups: a control non-CRF group and a CRF group fed on standard diet, and a CRF group fed on calcium carbonate enriched diet, for a period of 8 weeks. Aortic atherosclerotic plaque and calcification were evaluated using quantitative morphologic image processing. Aortic gene and protein expression was examined using immunohistochemistry and Q-PCR methods. RESULTS: Calcium carbonate supplementation was effective in decreasing serum phosphorus but was associated with a higher serum calcium concentration. Compared with standard diet, calcium carbonate enriched diet unexpectedly induced a significant decrease of both plaque (p<0.05) and non-plaque-associated calcification surface (p<0.05) in CRF mice. It also increased osteopontin (OPN) protein expression in atherosclerotic lesion areas of aortic root. There was also a numerical increase in OPN and osteoprotegerin gene expression in total thoracic aorta but the difference did not reach the level of significance. Finally, calcium carbonate did not change the severity of atherosclerotic lesions. CONCLUSION: In this experimental model of CRF, calcium carbonate supplementation did not accelerate but instead decreased vascular calcification. If our observation can be extrapolated to humans, it appears to question the contention that calcium carbonate supplementation, at least when given in moderate amounts, necessarily enhances vascular calcification. It is also compatible with the hypothesis of a preponderant role of phosphorus over that of calcium in promoting vascular calcification in CRF.

Wipe sampling procedure coupled to LC-MS/MS analysis for the simultaneous determination of 10 cytotoxic drugs on different surfaces.

A simple wipe sampling procedure was developed for the surface contamination determination of ten cytotoxic drugs: cytarabine, gemcitabine, methotrexate, etoposide phosphate, cyclophosphamide, ifosfamide, irinotecan, doxorubicin, epirubicin and vincristine. Wiping was performed using Whatman filter paper on different surfaces such as stainless steel, polypropylene, polystyrol, glass, latex gloves, computer mouse and coated paperboard. Wiping and desorption procedures were investigated: The same solution containing 20% acetonitrile and 0.1% formic acid in water gave the best results. After ultrasonic desorption and then centrifugation, samples were analysed by a validated liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in selected reaction monitoring mode. The whole analytical strategy from wipe sampling to LC-MS/MS analysis was evaluated to determine quantitative performance. The lowest limit of quantification of 10 ng per wiping sample (i.e. 0.1 ng cm(-2)) was determined for the ten investigated cytotoxic drugs. Relative standard deviation for intermediate precision was always inferior to 20%. As recovery was dependent on the tested surface for each drug, a correction factor was determined and applied for real samples. The method was then successfully applied at the cytotoxic production unit of the Geneva University Hospitals pharmacy.

Investigation and monitoring of rock slope instabilities in Norway by terrestrial laser scanning

Long-range Terrestrial Laser Scanning (TLS) is widely used in studies on rock slope instabilities. TLS point clouds allow the creation of high-resolution digital elevation models for detailed mapping of landslide morphologies and the measurement of the orientation of main discontinuities. Multi-temporal TLS datasets enable the quantification of slope displacements and rockfall volumes. We present three case studies using TLS for the investigation and monitoring of rock slope instabilities in Norway: 1) the analysis of 3D displacement of the Oksfjellet rock slope failure (Troms, northern Norway); 2) the detection and quantification of rockfalls along the sliding surfaces and at the front of the Kvitfjellet rock slope instability (Møre og Romsdal, western Norway); 3) the analysis of discontinuities and rotational movements of an unstable block at Stampa (Sogn og Fjordane, western Norway). These case studies highlight the possibilities but also limitations of TLS in investigating and monitoring unstable rock slopes.

Sub-acute delayed failure of subthalamic DBS in Parkinson's disease: the role of micro-lesion effect.

OBJECTIVE: To study delayed failure after subthalamic nucleus (STN) deep brain stimulation in Parkinson's disease (PD) patients. METHODS: Out of 56 consecutive bilaterally STN-implanted PD patients, we selected subjects who, after initial clinical improvement (1 month after surgery), lost benefit (delayed failure, DF). RESULTS: Five patients developed sub-acutely severe gait disorders (DF). In 4/5 DF patients, a micro-lesion effect, defined as improvement without stimulation, was observed; immediate post-operative MRI demonstrated electrode located above or behind to the STN. CONCLUSIONS: Patients presenting micro-lesion effect should be carefully monitored, as this phenomenon can mask electrodes misplacement and evolution in DF