Nonischemic heart failure in diabetes mellitus

PURPOSE OF REVIEW: Diabetic patients with heart failure have a poor prognosis. Although it has been demonstrated in animal models that metabolic maladaptation plays a pivotal role in contractile dysfunction of the heart, the understanding of 'diabetic cardiomyopathy' and its treatment in humans remains incomplete. RECENT FINDINGS: Epidemiological studies show that structural changes in the left ventricle can be demonstrated before onset of clinical diabetes. Diastolic dysfunction is the earliest manifestation that is associated with increasing level of serum-free fatty acids and worsening glycemic control. Spectroscopic and histologic evidence in the human myocardium indicates a maladaptive metabolic response in diabetes, characterized by intramyocellular triglyceride accumulation. Studies also suggest a link between myocardial isoform switching, calcium homeostasis and altered metabolism in the development of heart failure. However, treatment directed at deranged metabolic control in diabetes is effective only in animals, and not in humans. SUMMARY: Although clinical studies suggest the existence of 'diabetic cardiomyopathy', it is still difficult to prove causality. However, animal models and human studies suggest that systemic metabolic derangements may lead to metabolic, functional and structural maladaptation of the heart. The exact mechanisms of heart failure in diabetes remain elusive.     

Significance of Cryptosporidium as an aetiology of acute infectious diarrhoea in elderly Indians

OBJECTIVE: To explore the significance of Cryptosporidium isolation in elderly Indian with acute infectious diarrhoea and its clinical correlates. DESIGN: A hospital-based clinico-aetiological study of 120 patients aged 60 years or older, 25 adults younger than 60 years and 25 children up to age 14 with acute diarrhoea, and 57 apparently healthy elderly individuals. RESULTS: Cryptosporidium was isolated in 22 older patients with diarrhoea (18.3%) and was highly significant (P < 0.01) compared with healthy age-matched controls. Of these patients 66% had a history of close contact with animals. Most (68%) Cryptosporidium infections occurred during the rainy season. Among the elderly patients 17% suffered from vomiting and abdominal pain, 31% were febrile; none were severely dehydrated. Stools numbered three to nine per day with duration of 5-17 days. Stool leucocytes were <6/hpf and no RBCs were seen. Isolation of Cryptosporidium in older persons was associated with diabetes mellitus (22.7%), tuberculosis (9.0%), malignancy (4.5%) and coronary artery disease (4.5%). CONCLUSION: Cryptosporidium is an important cause of diarrhoea in elderly Indians, especially those with close contact with animals. The infection has a mild clinical course, is self-limiting and does not cause dysenteric stool. Its effect on nutrition requires further study.     

Phosphatidylinositol 3-kinase and protein kinase C contribute to the inhibition by interleukin 6 of phosphoenolpyruvate carboxykinase gene expression in cultured rat hepatocytes

The participation of phosphatidylinositol 3-kinase (PI3-kinase), protein kinase C, and mitogen-activated protein kinase (MAP-kinase) in the inhibition by interleukin 6 (IL-6) and insulin of phosphoenolpyruvate carboxykinase (PCK) gene expression was investigated in cultured rat hepatocytes. IL-6 or insulin inhibited the glucagon-stimulated increase in PCK messenger RNA (mRNA) by about 70%. In the presence of either the PI3-kinase inhibitor, wortmannin, or the protein kinase C inhibitor, GF109203x, the inhibition by IL-6 was only about 40%, although it was abolished with both inhibitors in combination. Wortmannin alone but not GF109203x prevented the inhibition by insulin of glucagon-stimulated PCK gene expression. The MAP-kinase pathway inhibitor, PD98059, did not affect IL-6 or insulin inhibition of PCK mRNA increase. When chlorophenylthio-cyclic 3',5' adenosine monophosphate (CPT-cAMP) was used instead of glucagon, IL-6 or insulin inhibited the increase in PCK mRNA by 75% and 85%, respectively. The inhibition by IL-6 was only about 50% in the presence of either wortmannin or GF109203x alone but was abolished with the combination of both inhibitors. The inhibition by insulin was only about 50% in the presence of GF109203x and was abolished by wortmannin. The inhibitors did not affect the inhibition by IL-6 or insulin of the glucagon-stimulated increase in cAMP. It is concluded that the inhibition by IL-6 of PCK gene expression involved both PI3-kinase and protein kinase C, whereas the inhibition by insulin required only PI3-kinase. The inhibition occurred downstream from cAMP formation. Hence, IL-6 and insulin may share, in part, common signal transduction pathways in the inhibition of PCK gene expression.     

Unique Kir2.x properties determine regional and species differences in the cardiac inward rectifier K+ current

The inwardly rectifying potassium (Kir) 2.x channels mediate the cardiac inward rectifier potassium current (I(K1)). In addition to differences in current density, atrial and ventricular I(K1) have differences in outward current profiles and in extracellular potassium ([K+]o) dependence. The whole-cell patch-clamp technique was used to study these properties in heterologously expressed Kir2.x channels and atrial and ventricular I(K1) in guinea pig and sheep hearts. Kir2.x channels showed distinct rectification profiles: Kir2.1 and Kir2.2 rectified completely at potentials more depolarized than -30 mV (I approximately 0 pA). In contrast, rectification was incomplete for Kir2.3 channels. In guinea pig atria, which expressed mainly Kir2.1, I(K1) rectified completely. In sheep atria, which predominantly expressed Kir2.3 channels, I(K1) did not rectify completely. Single-channel analysis of sheep Kir2.3 channels showed a mean unitary conductance of 13.1+/-0.1 pS in 15 cells, which corresponded with I(K1) in sheep atria (9.9+/-0.1 pS in 32 cells). Outward Kir2.1 currents were increased in 10 mmol/L [K+]o, whereas Kir2.3 currents did not increase. Correspondingly, guinea pig (but not sheep) atrial I(K1) showed an increase in outward currents in 10 mmol/L [K+]o. Although the ventricles of both species expressed Kir2.1 and Kir2.3, outward I(K1) currents rectified completely and increased in high [K+]o-displaying Kir2.1-like properties. Likewise, outward current properties of heterologously expressed Kir2.1-Kir2.3 complexes in normal and 10 mmol/L [K+]o were similar to Kir2.1 but not Kir2.3. Thus, unique properties of individual Kir2.x isoforms, as well as heteromeric Kir2.x complexes, determine regional and species differences of I(K1) in the heart.     

HIV pre-exposure prophylaxis (PrEP) awareness and acceptability among trans women: a review

ABSTRACT

Transgender (trans) women are disproportionally burdened by the HIV epidemic due to complex structural, psychosocial and biological factors. HIV pre-exposure prophylaxis (PrEP) is a biomedical prevention approach for people at substantial risk of acquiring HIV. This literature review assessed awareness, willingness to use, and barriers and facilitators for PrEP acceptability among trans women. A search was conducted through five databases and included studies with primary data and disaggregate results for trans women. Of 255 retrieved citations, 17 met the inclusion criteria and were included. Low to moderate knowledge about PrEP was observed among studies. However, willingness to use PrEP was predominantly high. Frequent barriers to PrEP acceptability included concerns about side effects, cost, hormone therapy, adherence, PrEP-related stigma and interaction with healthcare workers. Facilitators included perceived reduction of HIV risk, fear of HIV/AIDS and reduced dependence on partners. Findings suggest elevated interest in PrEP and highlight important barriers and facilitators that should be specifically addressed to optimize PrEP uptake and use among this highly vulnerable population.     

Cholinergic atrial fibrillation: I(K,ACh) gradients determine unequal left/right atrial frequencies and rotor dynamics

OBJECTIVE: We tested the hypothesis that left atrial (LA) myocytes are more sensitive to acetylcholine (ACh) than right atrial (RA) myocytes, which results in a greater dose-dependent increase in LA than RA rotor frequency, increased LA-to-RA frequency gradient and increased incidence of wavelet formation during atrial fibrillation (AF). METHODS AND RESULTS: AF was induced in seven Langendorff-perfused sheep hearts in the presence of ACh (0.1-4.0 microM) and studied using optical mapping and bipolar recordings. Dominant frequencies (DFs) were determined in optical and electrical signals and phase movies were used to identify rotors and quantify their dynamics. DFs in both atria increased monotonically with ACh concentration until saturation, but the LA frequency predominated at all concentrations. Rotors were also seen more often in the LA, and although their life span decreased, their frequency and number of rotations increased. Patch-clamp studies demonstrated that ACh-activated potassium current (I(K,ACh)) density was greater in LA than RA sheep myocytes. Additionally, ribonuclease protection assay demonstrated that Kir3.4 and Kir3.1 mRNAs were more abundant in LA than in RA. CONCLUSIONS: A greater abundance of Kir3.x channels and higher I(K,ACh) density in LA than RA myocytes result in greater ACh-induced speeding-up of rotors in the LA than in the RA, which explains the ACh dose-dependent changes in overall AF frequency and wavelet formation.     

Single center experience on dosing and adverse events of recombinant factor seven use for bleeding after congenital heart surgery

There are limited data on the relationship between the administered dose of recombinant factor seven (rFVIIa) and the development of adverse clinical outcomes after congenital heart surgery. This single institution case series reports on dosing, adverse events, and blood product usage after the administration of rFVIIa in the congenital heart surgery patient population. A retrospective review identified 16 consecutive pediatric patients at an academic, free-standing, children’s hospital who received rFVIIa to curtail bleeding following congenital heart surgery between April 2004 and June 2012. Patients were assessed for survival to hospital discharge versus in-hospital mortality and the presence or absence of a major neurological event during inpatient hospitalization. The median age at surgery was 6.8 months (range: 3 days–42 years). Seven patients (44%) survived to hospital discharge and nine patients (56%) died. The cause of mortality included major neurological events (44%), uncontrolled bleeding (33%), and sepsis (23%). Eight patients (50%) required extracorporeal membrane oxygenation support following congenital heart surgery. The median cumulative rFVIIa dose administered was 97 mcg/kg, and the median cumulative amount of blood products administered was 452 ml/kg. In conclusion, this case series underscores the need to prospectively evaluate the effect that rFVIIa has on patient survival and the incidence of adverse events, including thrombotic and major neurological events, in congenital heart surgery patients. Ideally, a randomized, multicenter study would provide the sufficient numbers of patients and events to test these relationships.     

A prospective,multi-centre,observational study to examine kidney disease progression in adults with chronic kidney disease – CKDOD - Study design and preliminary results

Background

The objective of this article is to describe the organisation of an international, clinical registry, the Chronic Kidney Disease Observational Database (CKDOD), the processes of enrolling patients and entering data and preliminary results to date.

Design

The Chronic Kidney Disease Observational Database (CKDOD) is designed to assess the association between different factors with a known influence on chronic kidney disease (CKD) progression as well as treatment strategies such as dietary modifications, blood pressure control and pharmacological interventions in Asian countries (India, China, Malaysia and Thailand). The only inclusion criterion is the presence of CKD stage 2 or higher as defined by the KDIGO guidelines. Demographic and clinical information are collected by a standardised electronic questionnaire, available in English and Chinese. The data are transferred to the CKDOD database either by e-mail or via web access. All data are checked for consistency and missing values.Collection of data started in September 2011 and by April 2015, data on 1323 individual patients had been submitted. The mean age at inclusion was 57?±?14 years, 67 % were male and 36 % were diabetic. The baseline estimated glomerular filtration rate was 26 ml/min/1.73 m². Of all enrolled patients, 324 (24 %) received ketoanalogue supplementation during at least one recorded visit.

Discussion

The CKDOD is a very large and comprehensive data repository, currently focused in subjects recruited from Asia. The database is expected to provide important long-term information on CKD progression, nutritional and metabolic derangements that accompany CKD progression and treatment strategies to ameliorate progression and complications of CKD.

Trial Registration

Clinical Trial Registry – India: CTRI/2012/06/002743; 25th July 2012

     

Electrolyte and hemodynamic changes following percutaneous left atrial appendage ligation with the LARIAT device

Journal of Interventional Cardiac Electrophysiology - The left atrial appendage (LAA) is a well-known source of atrial natriuretic peptide (ANP) and therefore plays an important role in...