Decreased myocardial free fatty acid uptake in patients with idiopathic dilated cardiomyopathy: evidence of relationship with insulin resistance and left ventricular dysfunction

BackgroundResults on myocardial substrate metabolism in the failing heart have been contradictory. Insulin resistance, a common comorbidity in heart failure patients, and medical therapy may modify myocardial metabolism in complex fashions. Therefore, we characterized myocardial oxidative and free fatty acid (FFA) metabolism in patients with idiopathic dilated cardiomyopathy (IDCM) and investigated the contributions of insulin resistance and β-blocker therapy.Methods and ResultsNineteen patients with IDCM (age 58 ± 8 years, ejection fraction 33 ± 8.8%) and 15 healthy controls underwent examination of myocardial blood perfusion, oxidative and FFA metabolism using positron emission tomography and [¹⁵O]H₂O, [¹¹C]acetate and [¹¹C]palmitate, respectively. Echocardiography was used to assess myocardial function, work, and efficiency of forward work. Insulin resistance was calculated using the homeostasis model assessment index (HOMA index) and the degree of β-blockade was estimated with a β-adrenoceptor occupancy test. IDCM patients were characterized by decreased cardiac efficiency (35 ± 2 versus 57 ± 12 mm Hg·L·g⁻¹, P < .0001) and reduced myocardial FFA uptake (5.5 ± 2.0 versus 6.4 ± 1.2 μmol·100 g⁻¹·min⁻¹, P < .05), but the FFA β-oxidation rate constant was not changed. In the patients, myocardial FFA uptake was inversely associated with left ventricular (LV) ejection fraction (r = −0.63, P < .01), indicating that further depression of LV function induces an opposite switch to greater FFA uptake. The FFA β-oxidation rate constant correlated positively with the HOMA index (r = 0.53, P < .05). In patients on β-1 selective β-blockers, β-1 adrenoceptor occupancy correlated inversely with LV work, oxidative metabolism, and FFA uptake; similar relationships were not found in patients on nonselective β-blocker.ConclusionsMyocardial FFA metabolism is reduced in patients with IDCM. However, when LV function is further depressed and insulin resistance manifested, myocardial FFA uptake and oxidation are, in turn, upregulated. These findings may partly explain the discrepancies between previous studies about cardiac metabolism in heart failure.     

Multiple viral infections post‐hematopoietic stem cell transplantation are linked to the appearance of chronic GVHD among pediatric recipients of allogeneic grafts

Olkinuora HA, Taskinen MH, Saarinen‐Pihkala UM, Vettenranta KK. Multiple viral infections post‐hematopoietic stem cell transplantation are linked to the appearance of chronic GVHD among pediatric recipients of allogeneic grafts.
Pediatr Transplantation 2010:14:242–248. © 2009 John Wiley & Sons A/S. Abstract: Delayed immune reconstitution and the ensuing opportunistic infections among children following hematopoietic stem cell transplantation (HSCT) are associated with increased treatment‐related morbidity and mortality (TRM). We retrospectively evaluated the impact of viral infections on the posttransplant recovery of pediatric recipients of stem cell grafts as a reflection of their posttransplant immunoreconstitution in a single institution setting. The case histories of 124 children (during 1/1999‐9/2006) were reviewed for infectious episodes, and correlated with their respective clinical parameters. Patients with a high risk for CMV received prophylaxis, but failures in the prophylaxis were common (40%). 110/124 (89%) of these allogeneic patients had at least one viral reactivation/clinical infection posttransplant. In this group of pediatric patients chronic GVHD (P<0,001) and secondary graft failure were significantly (P=0,001) associated with early (during the first 100 days post HSCT), multiple (≥ 2) viral infections. Our data indicate that viruses are common pathogens among pediatric recipients of allogeneic stem cell grafts. In this group of patients multiple viral infections early on seem to reflect an even more severe degree of immunological derangement in the recipient and identify a group of patients with an increased risk of chronic GVHD and secondary graft failure.     

Alpha-methylated polyamines as potential drugs and experimental tools in enzymology

We describe synthesis of alpha-methylated analogues of the natural polyamines and their use as tools in unraveling polyamine functions. Experiments with alpha-methylated spermidine and spermine revealed that the polyamines are exchangeable in supporting cellular growth. Degradation of the analogues by polyamine oxidase disclosed hidden, aldehyde-guided stereospecificity of the enzyme.     

Decline in suicidal ideation among patients with MDD is preceded by decline in depression and hopelessness

BACKGROUND: Suicidal ideation is likely to represent a phase preceding suicidal acts among most suicidal patients with major depressive disorder (MDD). Factors predicting reversal of the suicidal process are unknown. Our aim was to test the hypothesis that a decline in suicidal ideation is preceded by a decline in hopelessness among patients with MDD. METHOD: Of the 269 Vantaa Depression Study patients with DSM-IV MDD, 103 patients scored > or = 6 points at baseline on the Scale for Suicidal Ideation (SSI). Seventy of these patients were followed-up weekly either until they scored zero points on the SSI, or up to 26 weeks. RESULTS: The median duration for a decline of suicidal ideation to zero was 2.2 months after baseline. The level of baseline suicidal ideation, depressive symptoms, and the presence of any personality disorder predicted duration of suicidal ideation. A decline in both depression (BDI) and hopelessness (HS) independently predicted a decline in suicidal ideation. LIMITATIONS: Due to study design, we do not know if suicidal ideation relapsed after the first time the patient reached zero score in the SSI. CONCLUSIONS: Among patients with major depressive disorder having suicidal ideation, the decline in suicidal ideation is independently predicted by preceding declines in the levels of both depressive symptoms as well as hopelessness. The findings are consistent with possible causal roles of declines in depression and hopelessness in reversing the suicidal process.     

Use of dietary supplements among people living with HIV/AIDS is associated with vulnerability to medical misinformation on the internet

Background  

Use of dietary supplements is common among people living with HIV/AIDS. Because dietary supplements are used in the context of other health behaviors, they may have direct and indirect health benefits. However, supplements may also be associated with vulnerability to medical misinformation and unfounded health claims. We examined use of dietary supplements among people living with HIV/AIDS (PLWH) and the association between use of dietary supplements and believing medical misinformation.     

The FAST in screening for at-risk drinking among middle-aged women

Objective: There is a need for brief methods to screen for at-risk drinking. The FAST is a two-stepped structured questionnaire. In the FAST-1, one question categorizes into three groups: low-risk drinking, potential at-risk drinking or at-risk drinking. In the FAST-2, those with potential at-risk drinking are asked three additional questions. The aim was to study its effectiveness in screening for at-risk drinking among women and to define an optimal cut-off score.

Method: The FAST was validated against the Timeline Followback (TLFB) utilizing data from a health check of a group of 40-year old women (response rate 69.2%; n = 907/1311). The TLFB-based definition of at-risk drinking was consuming ≥140 grams of alcohol weekly (6.1% reported at-risk drinking).

Results and conclusions: Of all women, 54.5% could be correctly classified either as having low-risk or at-risk drinking with the FAST-1. The optimal cut-off score was ≥2 (sensitivity 0.82, specificity 0.86) which is lower than has previously been reported. Only those with a FAST-1 score of one needed further evaluation with the FAST-2. A FAST-2 score of ≥1 resulted in a positive screen for at-risk drinking. The FAST seems to be a valid and feasible method in screening for at-risk drinking among middle-aged women.