Primary AL-amyloidosis, ulcerative colitis and collagenous colitis in a 57-year-old woman: a case study

A 57-year-old woman with AL-amyloid deposits in the heart, gastrointestinal tract and the liver developed ulcerative colitis, which was treated with glucocorticosteroids and 5-aminosalicylic acid, with good response. The AL-amyloidosis was successfully treated with high-dose chemotherapy and autologous stem-cell transplantation. The patient was in good clinical condition for 18 months after treatment, until she developed diarrhea, which was found to be due to collagenous colitis. Two years after treatment of amyloidosis, the patient is in excellent condition, the symptoms of heart failure have stabilized and no adverse effects of the treatment regime have been observed. The bowel diseases are in clinical remission.     

Doppler tissue imaging in congestive heart failure patients due to diastolic or systolic dysfunction: a comparison with Doppler echocardiography and the atrio-ventricular plane displacement technique

BACKGROUND: Doppler tissue imaging (DTI) is an echocardiographic technique by which regional contractility, relaxation properties and time intervals are obtained easily. DTI has been reported to be relatively pre-load independent and could, in comparison with the commonly used mitral pulse wave Doppler (MPWD) method, be of clinical interest for identification of patients with diastolic dysfunction. The atrio-ventricular plane displacement (AVPD) method is an established technique to assess left ventricular systolic function. AIMS: To determine the pulsed Doppler DTI-pattern in patients with heart failure and to examine whether it has a similar capacity as MPWD and AVPD to diagnose diastolic dysfunction. METHODS: We studied 15 controls without congestive heart failure (CHF), 15 patients with diastolic (EF>45%+CHF) and 15 patients with systolic (EF<35%+CHF) left ventricular dysfunction and CHF. RESULTS: The DTI maximal velocities during systole (s), early filling wave (e) and atrial filling wave (a), decrease with reduced left ventricular ejection fraction, r=0.75, r=0.56 and r=0.66 (P<0.001) and regional isovolumetric contraction and intraventricular relaxation time measured by DTI are prolonged, r=0.59 and r=0.73, respectively (P<0.001). The 15 patients with diastolic heart failure were identified by MPWD or DTI but only 11 by AVPD with 8, 10 and 9 false-positive, respectively (P<0.01, P<0.05 and NS). CONCLUSIONS: Regional DTI show a consistent pattern in patients with left ventricular dysfunction and heart failure. Regional DTI has similar accuracy as MPWD in identifying diastolic heart failure patients and is superior to the AVPD technique. DTI may be a useful diagnostic tool in diastolic heart failure patients.     

From the Cover: Plexin D1 determines body fat distribution by regulating the type V collagen microenvironment in visceral adipose tissue

Genome-wide association studies have implicated PLEXIN D1 (PLXND1) in body fat distribution and type 2 diabetes. However, a role for PLXND1 in regional adiposity and insulin resistance is unknown. Here we use in vivo imaging and genetic analysis in zebrafish to show that Plxnd1 regulates body fat distribution and insulin sensitivity. Plxnd1 deficiency in zebrafish induced hyperplastic morphology in visceral adipose tissue (VAT) and reduced lipid storage. In contrast, subcutaneous adipose tissue (SAT) growth and morphology were unaffected, resulting in altered body fat distribution and a reduced VAT:SAT ratio in zebrafish. A VAT-specific role for Plxnd1 appeared conserved in humans, as PLXND1 mRNA was positively associated with hypertrophic morphology in VAT, but not SAT. In zebrafish plxnd1 mutants, the effect on VAT morphology and body fat distribution was dependent on induction of the extracellular matrix protein collagen type V alpha 1 (col5a1). Furthermore, after high-fat feeding, zebrafish plxnd1 mutant VAT was resistant to expansion, and excess lipid was disproportionately deposited in SAT, leading to an even greater exacerbation of altered body fat distribution. Plxnd1-deficient zebrafish were protected from high-fat-diet-induced insulin resistance, and human VAT PLXND1 mRNA was positively associated with type 2 diabetes, suggesting a conserved role for PLXND1 in insulin sensitivity. Together, our findings identify Plxnd1 as a novel regulator of VAT growth, body fat distribution, and insulin sensitivity in both zebrafish and humans.The regional distribution and morphology of adipose tissue (AT) are strong predictors of metabolic disease (1–3). Excess lipid deposition in visceral AT (VAT; adipose associated with visceral organs) is associated with increased susceptibility to insulin resistance and type 2 diabetes (4), whereas expansion of subcutaneous AT (SAT; adipose between muscle and skin) is associated with reduced risk for metabolic disease and is even protective against hyperglycemia and dyslipidemia (4–7). In turn, hypertrophic AT morphology (few large adipocytes) is associated with insulin resistance and AT dysfunction, whereas hyperplastic AT morphology (many small adipocytes) is associated with improved metabolic parameters (4, 7–9). Therefore, the identification of factors that regulate regional distribution and AT morphology could lead to new therapies to treat metabolic disease.Genome-wide association studies have implicated the PLEXIN D1 (PLXND1) locus in waist:hip ratio (a measurement of regional AT distribution) and type 2 diabetes (10). However, a role for Plxnd1 in AT morphology, distribution, and metabolism is unknown. Plxnd1 is a transmembrane receptor that controls the migration, proliferation, and survival of diverse cell types (11). Mutation of Plxnd1 in mouse and zebrafish leads to hypervascularization in many tissues (12, 13), and vascular endothelial cell Plxnd1 modulates extracellular matrix (ECM) synthesis and composition by regulating the collagen receptor, β1-integrin (14). In turn, ECM provides a supportive microenvironment for AT growth and function (15). For example, type V collagens regulate collagen fiber assembly, geometry, and strength (16, 17), are up-regulated during adipogenesis, and can stimulate adipocyte differentiation in vitro (18–20). However, the role of type V collagens during in vivo AT growth is unknown.In this study, we use genetic analysis and in vivo imaging of lipid deposition dynamics in zebrafish to assess the role of Plxnd1 in AT morphology and body fat distribution. Previous studies have shown that zebrafish adipocytes and AT are morphologically, molecularly, and functionally homologous to mammalian white AT (21–26), and like mammals, zebrafish adipocytes accumulate a large cytoplasmic lipid droplet (LD) that facilitates the in vivo identification of adipocytes by fluorescent lipophilic dyes (21, 22, 24–26). Here we determine in zebrafish that Plxnd1 functions through Col5a1 to exert a VAT-specific effect on adipose growth and morphology, resulting in altered body fat distribution and improved insulin sensitivity. In accord, molecular and physiological assessments in humans support a conserved role for PLXND1 in regulation of VAT morphology and insulin sensitivity.     

Long term health care consumption and cost expenditure in systolic heart failure

BackgroundThe prevalence, health care consumption, and mortality increase in elderly patients with heart failure. This study aimed to analyse long term cost expenditure and predictors of health care consumption in these patients.MethodsWe included 208 patients aged 60 years or older and hospitalised with heart failure (NYHA class II–IV and left ventricular systolic dysfunction); 58% were men, mean age 76 years, and mean ejection fraction 0.34. Data on all hospital admissions, discharge diagnoses, lengths of stay, and outpatient visits were collected from the National Board of Health and Welfare. We obtained data of all health care consumption for each individual.ResultsAfter 8–12 years of prospective follow up 72% were dead (median survival 4.6 years). Main drivers of health care expenditure were non-cardiac (40%) and cardiac (29%) hospitalizations, and visits to primary care centres (16%), and hospital outpatient clinics (15%). On average, health care expenditures were € 36,447 per patient during follow up. The average yearly cost per patient was about 5,700€, in contrast to the estimated consumption of primary and hospital care in the general population: € 1,956 in 65–74 year olds and € 2,701 in 75–84 year olds. Poor quality of life (Nottingham Health Profile) was the strongest independent predictor of total health care consumption and costs (p < 0.001; by multivariate analyses).ConclusionHealth care costs in chronic systolic heart failure are at least two-fold higher than in the general population. Quality of life is a strong independent predictor of health care consumption.     

Primary AL-amyloidosis,ulcerative colitis and collagenous colitis in a 57-year-old woman: a case study

A 57-year-old woman with AL-amyloid deposits in the heart, gastrointestinal tract and the liver developed ulcerative colitis, which was treated with glucocorticosteroids and 5-aminosalicylic acid, with good response. The AL-amyloidosis was successfully treated with high-dose chemotherapy and autologous stem-cell transplantation. The patient was in good clinical condition for 18 months after treatment, until she developed diarrhea, which was found to be due to collagenous colitis. Two years after treatment of amyloidosis, the patient is in excellent condition, the symptoms of heart failure have stabilized and no adverse effects of the treatment regime have been observed. The bowel diseases are in clinical remission.