Arrhythmogenic right ventricular dysplasia and sudden cardiac death in Croatians' young athletes in 25 years

The paper deals with the sudden cardiac death during training in male athletes in Croatia. The data are a part of a retrospective study dealing with 67 sudden death due to physical activity in men in Croatia during 25 years: from January 1, 1986 to December 31, 2010. Two of them suddenly died during training due to malignant ventricular arrhythmia because of the arrhythmogenic right ventricular dysplasia. First was a short trails runner aged 24, with no any previous physical discomforts, who suddenly collapsed and died during training. The second was a soccer player aged 13, with no any previous physical discomfort, who suddenly collapsed and died during training. A sudden cardiac death due to physical exercise in young athletes in Croatia suffered of arrhythmogenic right ventricular dysplasia reached 0.07/ 100.000 yearly (p = 0.00000), in all young athletes suffered of heart diseases reached 0.19/100 000 (p = 0.00005), and in the total male population aged 15-40 engaged in sports and recreational physical exercise: 0.71/100.0000 (p = 0.00001).     

The breadth, but not the magnitude, of circulating memory B cell responses to P. falciparum increases with age/exposure in an area of low transmission

Background

Malaria caused by Plasmodium falciparum remains a major cause of death in sub-Saharan Africa. Immunity against symptoms of malaria requires repeated exposure, suggesting either that the parasite is poorly immunogenic or that the development of effective immune responses to malaria may be impaired.

Methods

We carried out two age-stratified cross-sectional surveys of anti-malarial humoral immune responses in a Gambian village where P. falciparum malaria transmission is low and sporadic. Circulating antibodies and memory B cells (MBC) to four malarial antigens were measured using ELISA and cultured B cell ELISpot.

Findings and Conclusions

The proportion of individuals with malaria-specific MBC and antibodies, and the average number of antigens recognised by each individual, increased with age but the magnitude of these responses did not. Malaria-specific antibody levels did not correlate with either the prevalence or median number of MBC, indicating that these two assays are measuring different aspects of the humoral immune response. Among those with immunological evidence of malaria exposure (defined as a positive response to at least one malarial antigen either by ELISA or ELISPOT), the median number of malaria-specific MBC was similar to median numbers of diphtheria-specific MBC, suggesting that the circulating memory cell pool for malaria antigens is of similar size to that for other antigens.     

Early recognition of sudden cardiac arrest in athletes during sports activity

Introduction

Sudden cardiac arrest (SCA) in athletes is an unexpected life-threatening event, which is often not recognised early and cardiopulmonary resuscitation (CPR) is not always initiated immediately. We describe key features to rapidly recognise non-traumatic SCA in athletes during sports activity.

Methods

We reviewed videos and images of athletes suffering from non-traumatic SCA during sports activity. We searched Google images, Google videos and YouTube.com using the keywords ‘sudden cardiac death athlete’ and ‘resuscitation athlete’. We analysed (1) the athlete’s performance before syncope, (2) the athlete’s performance at the start of syncope, (3) the position of the body, and (4) the athlete’s facial expressions before CPR. We analysed our data by describing these four features to answer our research question.

Results

We analysed the sequence of events in six well-known soccer players in whom a camera-witnessed non-traumatic SCA occurred during their athletic activity. All six athletes showed no changes before syncope. Four became unstable while standing and unexpectedly collapsed falling on their back. Two suddenly ‘dropped dead’ and fell face down. All six had their eyes wide open with a fixed gaze and fixed pupils.

Conclusions

Sudden unexpected loss of consciousness in an athlete in action and a fixed gaze eye position are key features of SCA. Immediate cardiac massage should follow. The described features to immediately recognise SCA in athletes during sports activity should be taught to everyone involved in athletic activity leading to earlier recognition of SCA followed by earlier CPR.

     

Omega-3 consumption and sudden cardiac death in schizophrenia

People with schizophrenia show a two- to three-fold increased risk to die prematurely. Mortality is accounted for by a combination of factors (patients’ life style, suicide, premature cardiovascular disease, metabolic syndromes and, not so often mentioned, sudden death). The cause of sudden death in schizophrenia is unknown, but cardiac arrhythmia plays a potential role. Patients with schizophrenia are at high risk for cardiovascular disease, and some antipsychotics may be associated with cardiovascular adverse events (e.g., electrocardiograph QT interval prolongation), suggesting that this could lead to sudden cardiac death. Animal and clinical studies have shown that omega-3 fatty acids could be useful in the prevention and treatment of schizophrenia. As omega-3 fatty acids have been considered a cardioprotector agent, reducing cardiac arrhythmias and hence sudden cardiac deaths and given their relative safety and general health benefits, our update article summarizes the knowledge by the possible positive effects of omega-3 supplementation and fish consumption against sudden cardiac death in patients with schizophrenia. However, fish species should be selected with caution due to contamination with toxic methylmercury.     

Severe Childhood Malaria Syndromes Defined by Plasma Proteome Profiles

Background

Cerebral malaria (CM) and severe malarial anemia (SMA) are the most serious life-threatening clinical syndromes of Plasmodium falciparum infection in childhood. Therefore it is important to understand the pathology underlying the development of CM and SMA, as opposed to uncomplicated malaria (UM). Different host responses to infection are likely to be reflected in plasma proteome-patterns that associate with clinical status and therefore provide indicators of the pathogenesis of these syndromes.

Methods and Findings

Plasma and comprehensive clinical data for discovery and validation cohorts were obtained as part of a prospective case-control study of severe childhood malaria at the main tertiary hospital of the city of Ibadan, an urban and densely populated holoendemic malaria area in Nigeria. A total of 946 children participated in this study. Plasma was subjected to high-throughput proteomic profiling. Statistical pattern-recognition methods were used to find proteome-patterns that defined disease groups. Plasma proteome-patterns accurately distinguished children with CM and with SMA from those with UM, and from healthy or severely ill malaria-negative children.

Conclusions

We report that an accurate definition of the major childhood malaria syndromes can be achieved using plasma proteome-patterns. Our proteomic data can be exploited to understand the pathogenesis of the different childhood severe malaria syndromes.     

Perspectives for malaria vaccination

The need for vaccines to relieve the current global resurgence of malaria is apparent. Immunity is specific for each species of human malaria and for each stage in the life cycle. Once protective immunogens have been identified for one species, the homologous molecules in other species may lead to protection. The usefulness of a particular immunogen will be determined, in part, by its antigenic diversity in the population and the potential for boosting during natural infection. Successful immunization with malarial antigens may require adjuvants to induce effective, long-lived immunity. If different vaccines become available against each stage in the life cycle, then the composition of a particular vaccine may be tailored for different objectives: protection for short periods (for example, during epidemics and for tourists), decrease in disease and death, and malaria eradication.     

Serological responses and immunity to superinfection with avian malaria in experimentally-infected Hawaii amakihi

Six of seven Hawaii Amakihi (Hemignathus virens) with chronic malarial infections had no increases in peripheral parasitemia, declines in food consumption, or loss of body weight when rechallenged with the homologous isolate of Plasmodium relictum 61 to 62 days after initial infection. Five uninfected control amakihi exposed at the same time to infective mosquito bites developed acute infections with high parasitemias. Reductions in food consumption and loss of body weight occurred in all control birds and three of these individuals eventually died. When surviving birds were rechallenged >2 yr later with either the same parasite isolate or an isolate of P. relictum collected on the island of Kauai, all individuals were immune to superinfection. Chronically infected birds developed antibodies to a common suite of malarial antigens ranging in size from 22 to 170 kDa that were detectable as early as 8 days post infection on immunoblots of SDS-polyacrylamide gels. Antibodies to this suite of malarial antigens persisted as long as 1,248 days after initial infection and were consistently detectable at times when parasites were not easily found by microscopy on Giemsa-stained blood smears. The immunoblotting method that is described here appears to be an effective technique for identifying birds with chronic, low-intensity malarial infections when circulating parasites are not easily detectable by microscopy. Hawaiian honeycreepers that are capable of recovering from acute infections develop concomitant immunity to superinfection, making them functionally immune in areas where malaria transmission has become endemic.     

Hypertrophic cardiomyopathy and sudden cardiac death due to physical exercise in Croatia in a 27-year period

The paper deals with the sudden cardiac death during physical exercise in males in Croatia. The data are a part of a retrospective study dealing with 69 sudden death due to physical activity in men in Croatia during 27 years: from January 1, 1984 to December 31, 2010. Three of them suddenly died during training and two of them died during recreational physical exercise, probably because of malignant ventricular arrhythmia due to hyperthrophic cardiomyopathy. One had an obstructive form of hypertrophic cardiomyopathy with i.v. septum of 40 mm and four had a non-obstructive forms of hyperthrophic cardiomyopathy with left ventricular wall of 18-20-22-25 mm. First athlete was a short trails runner, aged 24, with no any previous physical discomforts, who suddenly collapsed and died during training. The second athlete was a soccer player aged 18, with no any previous physical discomfort, who suddenly collapsed and died during training. The third aged 15, was a school boy, basketball player, with no any previous physical discomfort, who collapsed and died during training. Two aged 25 and 34, were with no physical discomfort during exercise and died suddenly during recreational soccer games. A sudden cardiac death due to physical exercise in young athletes in Croatia suffered of hyperthropic cardiomyopathy reached 0.06/100 000 yearly (p = 0.00000) in 27 years, in teenagers 0.26/100 000 (p = 0.00226), in teenagers suffered of hypertrophic cardiomyopathy reached 0.10/100 000 (p = 0.00000), in all young athletes suffered of other heart diseases reached 0.19/100 000 (p = 0.00005), and in the total male population aged 15 or more, engaged in sports and recreational physical exercise: 0.71/100.0000 (p = 0.00001).     

Sudden death during ambulatory monitoring.

Three patients with ischaemic heart disease died suddenly while being monitored with an ambulatory tape recorder. Two had terminal ventricular fibrillation initiated by paired bidirectional ventricular ectopic beats against a background of scattered ectopic activity; both had had ventricular tachycardia during routine treadmill exercise testing in the week before death. The third patient developed bizarre ventricular complexes followed by asystole. Sudden death may be due to ventricular fibrillation initiated by paired ventricular ectopic beats with changing morphology, or asystole following bizarre ventricular complexes. Exercise testing may have an important predictive value.     

Community study of the causes of "natural" sudden death.

Three hundred and fifty cases of "natural" sudden death within six hours of onset of symptoms in people ranging in age from 18 to 69 years in Wandsworth were studied using a detailed necropsy protocol to determine the cause of death. Sudden death occurred in 28 (8%) Asians and blacks, but because of the small number they were excluded from the study, leaving 322 cases. Ischaemic heart disease accounted for 189 (59%) of the 322 sudden deaths (155 (65%) men; 34 (41%) women) and no proportional increase in instantaneous compared with non-instantaneous sudden death was found. Non-ischaemic cardiac disease was the cause of sudden death in 24 cases (7.5%). Non-cardiac disease included pulmonary emboli, aortic aneurysms, and intracerebral haemorrhage and caused 89 (27.6%) deaths. Alcohol was the cause of nine deaths (2.8%) and in 11 (3.4%) cases (six men and five women) no cause of death was found. This study shows that although ischaemic heart disease is the single largest cause of sudden natural death there are other major causes.     

Circadian variation of abnormal heart beats in an elderly population and their relation to sudden cardiac death.

The relationships between the circadian variation of abnormal heart beats and the circadian variation in sudden cardiac death warrant further discussion for the high correlations demonstrated here are difficult to ignore. In the healthy group abnormal beats showed a high correlation of their circadian variation with that of sudden cardiac death which is independent of heart rate. As a result the conclusion that the relationship of the circadian variations of abnormal heart beats and sudden cardiac death is merely dependent on a mutual dependence on activity is not supported here. The present data illustrates a strong association between arrhythmias and sudden cardiac death. The relationship of sudden cardiac death with abnormal heart beats demonstrated here, however, cannot confirm a causal role of the latter on the former for both may be responding to circadian variations of some underlying mechanism such as ischemia. Additionally the population studied here, although relatively comparable in terms of living conditions and other significant factors, was not strictly age-matched with those from the sudden cardiac death study warranting further caution in interpreting the association demonstrated here. The results from the unhealthy group, although somewhat limited, indicate that cardiovascular morbidity may alter the relationship of sudden cardiac death and abnormal heart beats. Such a result could be explained by the presence of other forms of heart disease which could be responsible for sudden cardiac death in the unhealthy group. An interesting question to ask concerning the data presented above is whether or not significant circadian variations in in the frequency of abnormal heart beats could have been demonstrated when exogenous factors such as meal times and activity were altered. The data on in hospital sudden cardiac death indicates that the circadian variation in sudden cardiac death is significantly altered by the radical changes in routine which accompany hospitalization. If the relationship between the circadian variation of sudden cardiac death and abnormal heart beats is as strong as the results presented here indicate, it is likely that the alteration of such exogenous factors would also change the circadian variation of abnormal heart beats. The results of the present study indicate that both the circadian variation in abnormal heart beats, and its relationship to sudden cardiac death, warrant further study.     

Complement receptor 1 and the molecular pathogenesis of malaria

Malaria is a pathogenic infection caused by protozoa of the genus plasmodium. It is mainly confined to sub-Saharan Africa, Asia and South America. This disease claims the life of over 1.5 to 2.7 million people per year. Owing to such a high incidence of malarial infections, there is an urgent need for the development of suitable vaccines. For the development of ideal vaccines, it is essential to understand the molecular mechanisms of malarial pathogenesis and the factors that lead to malaria infection. Genetic factors have been proposed to play an important role in malarial pathogenesis. Complement receptor 1 (CR1) is an important host red blood cell protein involved in interaction with malarial parasite. Various polymorphic forms of CR1 have been found to be involved in conferring protection or increasing susceptibility to malaria infections. Low-density allele (L) of CR1 gave contradictory results in different set of studies. In addition, Knops polymorphic forms Sl (a(+)) and McC (a) have been found to contribute more towards the occurrence of cerebral malaria in malaria endemic regions compared to individuals with Sl (a(-)) / McC (a/b) genotype. This article reviews the research currently going on in this area and throws light on as yet unresolved mysteries of the role of CR1 in malarial pathogenesis.     

Genetic determinants of QT interval variation and sudden cardiac death

Electrocardiographic QT interval prolongation or shortening is a risk factor for sudden cardiac death. The study of Mendelian syndromes in families with extreme long and short QT interval duration and ventricular arrhythmias has led to the identification of genes encoding ion channel proteins important in myocardial repolarization. Rare mutations in such ion channel genes do not individually contribute substantially to the population burden of ventricular arrhythmias and sudden cardiac death. Only now are studies systematically testing the relationship between common variants in these genes--or elsewhere in the genome--and QT interval variation and sudden cardiac death. Identification of genetic variation underlying myocardial repolarization could have important implications for the prevention of both sporadic and drug-induced arrhythmias.     

Heterogeneous capillary recruitment among adjoining alveoli

Pulmonary capillaries recruit when microvascular pressure is raised. The details of the relationship between recruitment and pressure, however, are controversial. There are data supporting 1). gradual homogeneous recruitment, 2). sudden and complete recruitment, and 3). heterogeneous recruitment. The present study was designed to determine whether alveolar capillary networks recruit in a variety of ways or whether one model predominates. In isolated, pump-perfused canine lung lobes, fields of six neighboring alveoli were recorded with video microscopy as pulmonary venous pressure was raised from 0 to 40 mmHg in 5-mmHg increments. The largest group of alveoli (42%) recruited gradually. Another group (33%) recruited suddenly (sheet flow). Half of the neighborhoods had at least one alveolus that paradoxically derecruited when pressure was increased, even though neighboring alveoli continued to recruit capillaries. At pulmonary venous pressures of 40 mmHg, 86% of the alveolar-capillary networks were not fully recruited. We conclude that the pattern of recruitment among neighboring alveoli is complex, is not homogeneous, and may not reach full recruitment, even under extreme pressures.     

Three-dimensional structure of heat shock protein 90 from <Emphasis Type="Italic">Plasmodium falciparum</Emphasis>: molecular modelling approach to rational drug design against malaria

We have recently implicated heat shock protein 90 from Plasmodium falciparum (PfHsp90) as a potential drug target against malaria. Using inhibitors specific to the nucleotide binding domain of Hsp90, we have shown potent growth inhibitory effects on development of malarial parasite in human erythrocytes. To gain better understanding of the vital role played by PfHsp90 in parasite growth,we have modeled its three dimensional structure using recently described full length structure of yeast Hsp90.S equence similarity found between PfHsp90 and yeast Hsp90 allowed us to model the core structure with high confidence. The superimposition of the predicted structure with that of the template yeast Hsp90 structure reveals an RMSD of 3.31 Angstrom. The N-terminal and middle domains showed the least RMSD (1.76 Angstrom) while the more divergent C-terminus showed a greater RMSD (2.84 Angstrom) with respect to the template. The structure shows overall conservation of domains involved in nucleotide binding, ATPase activity, co-chaperone binding as well as inter-subunit interactions. Important co-chaperones known to modulate Hsp90 function in other eukaryotes are conserved in malarial parasite as well. An acidic stretch of amino acids found in the linker region, which is uniquely extended in PfHsp90 could not be modeled in this structure suggesting a flexible conformation. Our results provide a basis to compare the overall structure and functional pathways dependent on PfHsp90 in malarial parasite. Further analysis of differences found between human and parasite Hsp90 may make it possible to design inhibitors targeted specifically against malaria.     

Malaria transmission and morbidity

Stable malaria endemicity is maintained over a wide range of transmission intensities in sub-Saharan Africa. This paper considers variations in the clinical manifestations and their consequences with differences in transmission intensity. Epidemiological approaches to malarial disease have concentrated on two clinical syndromes, severe malarial anaemia and cerebral malaria. Within an area the mean age of children with severe malarial anaemia is always lower than that of those with cerebral malaria. In areas of higher malaria transmission children, on average, encounter malaria at a younger age and the mean age of clinical cases is lower. Malarial anaemia tends therefore to be relatively more important under high transmission settings and cerebral malaria tends to gain in importance under lower transmission settings. In a number of studies the total load of malaria morbidity, whether measured as none severe malaria in the community or as severe malaria admitted to hospital, is low under stable low transmission conditions but is at its highest under moderate intensities of transmission. Thereafter it reaches a plateau, or even falls, at the highest transmission intensities. It is not known whether the same is true for mortality in communities living under different transmission settings. Possible implications for changes in patterns of morbidity and mortality following interventions which lower malaria transmission are discussed. It is concluded that such interventions should play an important role in integrated malaria control programmes but that these should involve concomitant introduction of other interventions, in order to minimise the possible risks of a reduced effect as the immune response of the population re-equilibrates in the face of reduced challenge.     

Sudden cardiac death: what should we tell the family?

The sudden unexpected death of a child or a young person can have enormous implications for the surviving family members in addition to the immediate shock, sadness and sense of loss. The sudden loss of a sibling without any prior medical history may confront the family members with the question whether the sudden death was caused by a genetic condition and the fear that other family members may suffer the same fate.     

Hyperreactive malarious splenomegaly (tropical splenomegaly syndrome)

Hyperreactive malarious splenomegaly (HMS), formerly known as tropical splenomegaly syndrome (TSS), was recognized some 20 years ago as an entity distinct from the splenic enlargement resulting directly from malarial parasitaemia. Its basis appears to be a disturbance in the T-lymphocyte control of the humoral response to recurrent malaria, possibly linked to particular HLA Class II antigens. Gross overproduction of IgM antibodies leads to the formation of high molecular weight immune complexes, persistent gross splenomegaly recurrent episodes of profound anaemia and increased susceptibility to infections. Those with gross disease experience a high mortality, which constitutes a major public health problem in communities where the syndrome affects a majority of adults.