Elevated Heart Rate: A “New” Cardiovascular Risk Factor?

A number of epidemiologic studies and several experimental lines of research point to high heart rate as a main risk factor for cardiovascular disease. However, translating research into clinical practice has been a challenge throughout medical history. From the present symposium, it appears clear that this is particularly the case for heart rate. The complex nature of atherogenesis makes it difficult to establish the role of a putative risk factor because of the correlations and complex interactions among factors. The pathogenetic mechanisms for the connection of resting heart rate with atherosclerosis and cardiovascular morbidity have been elaborated extensively in the chapter papers of this symposium, suggesting that there is a causal relationship between heart rate and cardiovascular mortality. The benefit of heart rate reduction has been proved in patients with coronary artery disease or congestive heart failure. Until now it has been difficult to determine whether modulation of heart rate is beneficial also in patients free of cardiac diseases. This concern, however, does not in any fashion suggest that health care professionals should pay less attention to this clinical variable. The impressive amount of available epidemiologic data show support for the continued effort to raise awareness of the clinical importance of resting heart rate among health care professionals.     

Non‐smoking‐related chronic obstructive pulmonary disease: A neglected entity?

Chronic obstructive pulmonary disease (COPD) is an increasing cause of morbidity and mortality worldwide, and it has been strongly correlated to tobacco smoking. While a number of studies have concentrated on smokers only, recent published data demonstrate that at least one fourth of patients with COPD are non-smokers, and that the burden of COPD in non-smokers is also higher than previously believed. Risk factors of COPD in non-smokers may include genetic factors, long-standing asthma, outdoor air pollution (from traffic and other sources), environmental smoke exposure (ETS), biomass smoke, occupational exposure, diet, recurrent respiratory infection in early childhood, tuberculosis and so on. In Asian region, indoor/outdoor air pollution and poor socioeconomic status may play important roles in the pathogenesis of non-smoking-related COPD. The prevalence of COPD among never smokers varies widely across nations. Such a variation may arise from several aspects, including study design, definition of COPD, diagnostic criteria, age and gender distribution of the studied population, local risk factors and socioeconomic status. More investigations and efforts are required to elucidate the involved factors and their shared contributions to non-smoking-related COPD so as to achieve better estimation and reduction of the burden of this neglected entity worldwide.     

Host-microbiome interaction in Crohn’s disease: A familiar or familial issue?

An impaired interaction between the gut and the intestinal microbiome is likely to be the key element in the pathogenesis of Crohn’s disease (CD). Family studies have provided invaluable information on CD pathogenesis and on its etiology. Relatives share the same genetic risk of developing the disease as affected subjects. Relatives also exhibit similar features relating to their host-microbiome interaction, namely genetic variants in loci involved in detecting bacteria, a greater sero-reactivity to microbial components, and an impaired intestinal permeability. The burden of environmental factors such as cigarette smoking and dysbiosis also seems to be particularly relevant in these genetically predisposed subjects. Diet is emerging as an important factor and could account for the changing epidemiology of CD in recent years. Despite the pivotal role of genetics in the disease’s pathogenesis (especially in familial CD), screening tests in healthy relatives cannot be recommended.     

A Unique Interaction of IVS-I-1 (G>A) (HBA2: c.95+1G>A) with Hb Adana (HBA2: c.179G>A) Presenting as Transfusion-Dependent α-Thalassemia

Abstract

Nondeletional α-globin mutations are known to cause more serious clinical effects than deletional ones. A rare IVS-I-1 (G>A) (HBA2: c.95+1G>A) donor splice site mutation interferes with normal splicing of pre mRNA and results in activation of a cryptic splice site as well as a frameshift mutation. Hb Adana [HBA2: c.179G>A (or HBA1)] is a highly unstable variant hemoglobin (Hb) resulting from a mutation at codon 59 on the HBA2 or HBA1 gene, recognized to cause severe α-thalassemia (α-thal) syndromes. We report a unique case of compound heterozygosity for these two mutations in a 9-year-old boy who presented with a Hb level of 5.3?g/dL and hepatomegaly at the age of 15?months. He required regular blood transfusions in view of a Hb level of <7.0?g/dL and failure to thrive. He had thalassemic red cell indices and peripheral blood film. The Hb electrophoresis only showed a raised Hb F level (3.3%) and a pre run peak but the Hb H inclusion test was negative. His father had thalassemic red cell indices but a normal Hb level. His mother had almost normal Hb levels and red cell indices. Hb Adana involving the HBA2 gene was detected by mutiplex amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) in the proband and his father. DNA sequencing of the HBA2 gene confirmed the IVS-I-1 mutation in the proband and his mother. This case highlighted the unique interaction of the IVS-I-1 mutation with Hb Adana in a young Malay boy presenting with transfusion-dependent α-thal.     

Plasticity of Addiction: A Mesolimbic Dopamine Short‐Circuit?

The development of drug addiction progresses along a continuum from acute drug use to compulsive use and drug seeking behavior. Many researchers have focused on identifying the physiological mechanisms involved in drug addiction in order to develop effective pharmacotherapies. Neuroplasticity, the putative mechanism underlying learning and memory, is modified by drugs of abuse and may contribute to the development of the eventual addicted state. Innovative treatments directly targeting these drug‐induced changes in brain reward components and circuits may be efficacious in reducing drug use and relapse.     

A New Aγ-Globin Chain Variant: Hb F-Sykesville MD [Aγ113(G15)Val → Ile; HBG1: c.340G>A] Detected in a Caucasian Baby

Abstract

The total number of hemoglobin (Hb) variants currently included in the globin gene server database is 1626 (November 12 2014), of which 131 are fetal Hb variants. These variants are observed as two different subunits of fetal Hb, ^Gγ- and ^Aγ-globin chains. Of the 131 documented fetal Hb variants, 73 are ^Gγ- and 58 are ^Aγ-globin chain variants. Although they are easily detected at birth, as the quantity of γ chains progressively decreases over the first few months of life, they are essentially undetectable after 6 months of age. In this report we discuss the molecular characteristics and diagnostic criteria of a new ^Aγ chain variant that was detected during newborn screening and named Hb F-Sykesville MD [^Aγ113(G15)Val?→?Ile; HBG1: c.340G>A].     

The “Nondipper” Elderly: A Clinical Entity or a Bias?

Objectives: To determine the prevalence of nondipper (ND) blood pressure profile in the elderly and to ascertain whether the ND pattern of ambulatory blood pressure in the elderly is an artifact or represents a specific clinical entity.
Design: Cross-sectional, observational study.
Setting: Cardiovascular diagnostic center, division of geriatrics, secondary care, institutional practice.
Participants: Sixty-five consecutive community-dwelling elderly hypertensive patients referred to the cardiovascular center.
Measurements: The patients underwent actigraphy and ambulatory blood pressure monitoring and completed a sleep assessment questionnaire. Patients were divided based on the night-time decrease in blood pressure (>10%: "dippers" (n=19); <10%: "NDs" (n=46)).
Results: Nondippers displayed poorer quality of sleep, as demonstrated objectively by actigraphic data; they obtained a higher mean score±standard deviation on the sleep questionnaire (4.6±2.9 vs 3.0±1.1, P =.030) and were taking more benzodiazepines (33.1% vs 10.7%, P =.035), indicating that their usual sleep quality was worse than that of dippers. Multivariate analysis showed a strong correlation between nondipper profile and quality of sleep and also with comorbidity, total number of drugs being taken, and pulse pressure.
Conclusion: Actigraphy demonstrates impaired sleep in the nondipper elderly. Nevertheless, the nondipping pattern seems independent of the discomfort of cuff-inflation during the night and occurs in association with higher comorbidity and polypharmacy; therefore, it cannot be considered a "bias," but is related to detrimental clinical conditions that should be studied in depth.     

Peroxisome proliferator-activated receptor-γ 34C&gt;G polymorphism and colorectal cancer risk: A meta-analysis

AIM: To investigate the association between peroxisome proliferator-activated receptor-γ (PPAR-γ ) gene polymorphism 34 C&gt;G and colorectal cancer (CRC),a meta-analysis review was performed in this report.METHODS: A systematic literature search and selection of eligible relevant studies were carried out.Nine independent studies with a total number of 4533 cases and 6483 controls were included in the meta-analysis on the association between polymorphism 34 C&gt;G and CRC.RESULTS: There was no evidence for the as...     

Heparin‐induced thrombocytopenia in myeloproliferative disorders: A rare or under‐diagnosed complication?

Patients with myeloproliferative disorders (MPD) are prone to develop thrombotic complications and thus frequently receive heparin. Surprisingly heparin-induced thrombocytopenia (HIT) has been rarely reported in MPD and is potentially under-diagnosed due to the relatively high platelet count. We report three patients with MPD who developed HIT; all presented with a relative fall of platelet counts (although without an absolute thrombocytopenia), thrombosis or skin necrosis and a positive test for HIT antibodies (particle gel immunoassay). Risk factors for developing HIT in our patients were exposure to unfractionated heparin, a recent surgical procedure and female gender. We review the literature on HIT in MPD and discuss the diagnosis of HIT in the absence of an absolute thrombocytopenia.     

Description of a rare β-globin gene mutation,IVS-II-848 (C>A) (HBB: c.316-3C>A) in association with IVS-I-1 (G>A) (HBB: c.92 + 1G>A), observed in a Syrian family: a case report

Abstract

β-Thalassemia (β-thal) is a hereditary and heterogeneous group of disorders caused by mutations on the β-globin gene that result in the reduced or non production of β-globin chains. We report a rare β-globin mutation, IVS-II-848 (C>A) (HBB: c.316-3C>A), which was found in a female Syrian patient. This mutation was associated with the IVS-I-1 (G>A) (HBB: c.92+1G>A) mutation, and the genotype is a compound heterozygote for IVS-I-1(G>A)/IVS-II-848(C>A). This combination was found for the first time in Syria.