Recommendations for participation in leisure-time physical activity and competitive sports of patients with arrhythmias and potentially arrhythmogenic conditions. Part II: ventricular arrhythmias, channelopathies and implantable defibrillators.

This consensus paper on behalf of the Study Group on Sports Cardiology of the European Society of Cardiology follows a previous one on guidelines for sports participation in competitive and recreational athletes with supraventricular arrhythmias and pacemakers. The question of imminent life-threatening arrhythmias is especially relevant when some form of ventricular rhythm disorder is documented, or when the patient is diagnosed to have inherited a pro-arrhythmogenic disorder. Frequent ventricular premature beats or nonsustained ventricular tachycardia may be a hallmark of underlying pathology and increased risk. Their finding should prompt a thorough cardiac evaluation, including both imaging modalities and electrophysiological techniques. This should allow distinguishing idiopathic rhythm disorders from underlying disease that carries a more ominous prognosis. Recommendations on sports participation in inherited arrhythmogenic conditions and asymptomatic gene carriers are also discussed: congenital and acquired long QT syndrome, short QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, arrhythmogenic right ventricular cardiomyopathy and other familial electrical disease of unknown origin. If an implantable cardioverter defibrillator is indicated, it is no substitute for the guidelines relating to the underlying pathology. Moreover, some particular recommendations for patients/athletes with an implantable cardioverter defibrillator are to be observed.     

Bilateral spontaneous femoral neck fracture in chronic alcoholism and liver cirrhosis

One case of a double-time, bilateral spontaneous fracture of the femoral neck as a result of a hepatogenic osteopathy is reported. The other reasons for spontaneous fractures are shortly mentioned, the osteopathy in chronic liver disease is examined more closely.     

Adhesion of human platelets to albumin is synergistically increased by lysophosphatidic acid and adrenaline in a donor-dependent fashion.

Lysophosphatidic acid (LPA) and adrenaline are weak platelet activators considered important for thrombus formation, and were previously shown to synergistically increase platelet aggregation. Here we investigate synergistic activation by LPA and adrenaline when measuring platelet adhesion. Platelet-rich plasma from healthy blood donors together with adrenaline and/or LPA were added to protein-coated microplates. Platelets were allowed to adhere and the amount of adhesion detected enzymatically. The LPA and adrenaline combination induced a synergistic increase of platelet adhesion to a normally non-adhesive albumin surface. The degree of synergy varied markedly between individuals; these variations could not be explained by age, gender, blood type or different amounts of platelets, oxidized low-density lipoprotein, insulin or glucose in plasma. There was a trend indicating increased synergistic effect for platelets sensitive to adrenaline stimulation. The synergistic effect was blocked by the alpha2-adrenoceptor antagonist yohimbine and inhibited by the ADP scavenger system creatine phosphate/creatine phosphokinase and antibodies against alphaIIbbeta3. Furthermore, platelets adhering to albumin after adrenaline and LPA treatment expressed P-selectin. In conclusion, LPA and adrenaline act synergistically to increase alphaIIbbeta3-mediated platelet adhesion to albumin, dependent on alpha2-adrenoceptor signalling and platelet secretion. We also confirm that synergistic platelet activation achieved with LPA and adrenaline is highly donor dependent.     

The MTT assay for chemosensitivity testing of human tumors of the central nervous system

In this study we assessed the influence of patient- and drug-specific parameters in the short-term MTT-chemosensitivity assay in 150 primary cell cultures derived from human brain tumors. In 45 patients the MTT assay was directly compared with the CFA (Colony Forming Assay). Resistance was 10-20% higher in the MTT assay than in the CFA, but there was a good agreement in both assays, that more malignant gliomas had a higher in vitro chemosensitivity against ACNU and BCNU. Overall the results demonstrate, that there is no uniform correlation between the in vitro chemosensitivity and the histopathological classification of the tumors, which corresponds well to the clinical situation. On the basis of this study we suggest prospective clinical trials with the MTT assay in human brain tumors.     

Identification of a parathyroid hormone in the fish Fugu rubripes.

A PTH gene has been isolated from the fish Fugu rubripes. The encoded protein of 80 amino acid has the lowest homology with any of the PTH family members. Fugu PTH(1-34) had 5-fold lower potency than human PTH(1-34) in a mammalian cell system. INTRODUCTION: Parathyroid hormone (PTH) is the major hypercalcemic hormone in higher vertebrates. Fish lack parathyroid glands, but there have numerous attempts to identify and isolate PTH from fish. MATERIALS AND METHODS: Polymerase chain reaction (PCR) was performed with primers based on preliminary data from the Joint Genome Institute database. PCR amplification was performed on genomic DNA isolated from Fugu rubripes. PCR products were purified and DNA was sequenced. All sequence was confirmed from more than one independently amplified PCR product. Multiple sequence alignments were carried out, and the percentage of identities and similarities were calculated. An unrooted phylogenetic tree, using all the known PTH and PTH-related protein (PTHrP) amino acid sequences, was determined. Synthetic peptides were tested in a biological assay that measured cyclic adenosine 3',5'-monophosphate formation in UMR106.1 cells. Rabbit polyclonal antisera specific for N-terminal human PTHrP and one rabbit polyclonal antiserum specific for N terminus hPTH were used to test the cross-reactivity with fPTH(1-34) in immunoblots.     

Effects of Ethanol on Human Natural Killer Cell Activity: In Vitro and Acute, Low-Dose In Vivo Studies

Chronic use of ethanol may cause a variety of immunological abnormalities in humans. In this study, we have determined the effects of an acute, low dose of ethanol (0.5 g/kg), administered either intravenously or orally, to normal, nonalcoholic male volunteers, on natural killer cell (NK) activity. We have also examined the effects of a 4-hr incubation with ethanol, in concentrations ranging from 0 to 320 mg/dl, on human NK activity in vitro. NK activity was measured by the ⁵¹Cr release assay technique in all of these studies, using peripheral blood mononuclear cells prepared from blood obtained from healthy, nonalcoholic volunteers. Eight subjects received ethanol in vivo; cells from nine subjects were used for the in vitro studies. Blood ethanol concentrations were determined at multiple time points before and after ethanol administration for the in vivo studies; for the in vitro studies, ethanol concentrations were measured from each assay sample both before and after the incubation period. Gas chromatography was used for determinations of both blood alcohol and medium ethanol concentrations. Results of the in vivo studies showed that a single dose of ethanol (0.5 g/kg), administered either intravenously (with resultant peak blood levels transiently up to 89 mg/dl) or orally (with resultant peak blood levels transiently up to 40 mg/dl at the time of the NK assay), did not alter NK activity. However, results of the in vitro studies showed a significant dose-dependent decrease ( p < 0.001) in NK activity when ethanol exposure was sustained for 4 hr at concentrations of 80 mg/ dl and above. We conclude that one of the possible causes for a higher incidence of certain viral infections and malignant tumors among chronic alcoholics may be due, in part, to this observed direct effect of ethanol on NK cytotoxicity.     

A school curriculum-based exercise program increases bone mineral accrual and bone size in prepubertal girls: two-year data from the pediatric osteoporosis prevention (POP) study.

This 2-year prospective controlled exercise intervention trial in 99 girls at Tanner stage 1, evaluating a school curriculum-based training program on a population-based level, showed that the annual gain in BMC, aBMD, and bone size was greater in the intervention group than in the controls. INTRODUCTION: Most exercise intervention studies in children, evaluating the accrual of BMD, include volunteers and use specifically designed osteogenic exercise programs. The aim of this study was to evaluate a 2-year general school-based exercise intervention program in a population-based cohort of girls at Tanner stage 1. MATERIALS AND METHODS: Forty-nine girls 7-9 years of age in grades 1 and 2 in one school were included in a school curriculum-based exercise intervention program of general physical activity for 40 minutes per school day (200 minutes/week). Fifty healthy age-matched girls in three neighboring schools, assigned to the general Swedish school curriculum of physical activity (60 minutes/week), served as controls. All girls were premenarchal, remaining in Tanner stage 1 during the study. BMC (g) and areal BMD (aBMD; g/cm2) were measured with DXA of the total body (TB), the lumbar spine (L2-L4 vertebrae), the third lumbar vertebra (L3), the femoral neck (FN), and the leg. Volumetric BMD (vBMD; g/cm3) and bone size were calculated at L3 and FN. Total lean body mass and total fat mass were estimated from the total body scan. Height and weight were also registered. Baseline measurements were performed before the intervention was initiated. Follow-up was done after 2 years. RESULTS: No differences between the groups were found at baseline in age, anthropometrics, or bone parameters. The annual gain in BMC was greater in the intervention group than in the controls: L2-L4, mean 3.8 percentage points (p = 0.007); L3 vertebra, mean 7.2 percentage points (p < 0.001); legs, mean 3.0 percentage points (p = 0.07). The intervention group had a greater annual gain in aBMD: total body, mean 0.6 percentage points (p = 0.006), L2-L4, mean 1.2 percentage points (p = 0.02), L3 vertebra, mean 1.6 percentage points (p = 0.006); legs, mean 1.2 percentage points (p = 0.007). There was also a greater mean annual gain in bone size in the L3 vertebra (mean 1.8 percentage points; p < 0.001) and in the FN (mean 0.3 percentage points; p = 0.02). CONCLUSIONS: A general school-based exercise program for 2 years for 7- to 9-year-old girls (baseline) enhances the accrual of BMC and BMD and increases bone size.     

HLA-A24 and survivin: possibilities in therapeutic vaccination against cancer

Recently, it was described that an HLA-A24 restricted peptide derived from the survivin splice variant survivin-2B can be recognized by CD8(+) cytotoxic T-cells. The identification of an HLA-A24 epitope is critical for survivin-based immunotherapy as HLA-24 is the most frequent HLA allele in Asia. Consequently, this survivin-2B epitope is already a target in a clinical study in patients with advanced or recurrent colorectal cancer expressing survivin. However, the splice variant survivin-2B has been described to be pro-apoptotic, and is only expressed at low levels in most malignant tissues. Furthermore, survivin-2B expression are significantly decreased in later tumor stages and inversely correlated with tumor differentiation and invasion. Consequently, survivin is a more general vaccination candidate than the splice variant survivin-2B. Here, we on the basis of spontaneous immune responses in HLA-A24+ cancer patients describes that a HLA-A24-restricted survivin epitopes does indeed exist. Consequently, this epitope is an attractive target for the ongoing survivin-based peptide immunotherapy against cancer.     

Update on transplant pharmacology: sirolimus.

Rapamune (Sirolimus), the latest immunosuppressant agent for solid organ transplants, is prescribed for induction therapy, refractory rejection, steroid withdrawal, and combination therapy. As the use of this agent increases among various transplant populations, it is essential for critical care nurses to be cognizant of the indications, pharmacodynamics, current research findings, side effects, and implications. This knowledge will ultimately improve patient education and outcomes in this ever-growing field of nursing.