Sudden cardiac death in the adolescent population: a narrative review.

Background: Death from unexpected circulatory arrest within 60 min of onset of symptom is known as sudden cardiac death (SCD). In spite of the advancement in treatment and prevention strategies, SCD remains the most common cause of death worldwide especially in the young. Main body: This review focuses on highlighting how different cardiovascular diseases contribute to SCD. We discuss the clinical symptoms that the patient experience prior to sudden cardiac arrest and the treatment strategies including pharmacological and surgical treatment. Conclusions: We conclude that since there are many causes of SCD and very few treatment options, prevention strategies, early detection, and resuscitation of those at greatest risk is important.

Decision making process, programmatic and logistic impact of the transition from a single-dose vial to a multi-dose vial of the 13-valent pneumococcal vaccine in Benin.

BACKGROUND: Benin, a country eligible for Gavi support, changed the presentation of the 13-valent pneumococcal vaccine (PCV13) from the single-dose vial (SDV) to the multi-dose vial (MDV). The present work aims to evaluate the process of making this decision as well as programmatic and logistic impacts. METHODS: WHO protocol for post-introduction evaluation (PIE) was used. Programmatic impact was evaluated by comparing PCV13 coverage and dropout rates with a comparator vaccine administered simultaneously over similar 6-month periods prior to and after the transition. This impact was also appreciated from observation of multi-dose vial management practices during immunization sessions. Logistic impact was measured from the analysis of storage capacities, waste management and vaccine losses. RESULTS: Decision to move to PCV13 MDV was taken at EPI level. Activities planned to support this switch were partially implemented. Impact on vaccination coverage and PCV13 dropout rates in relation with the transition to PCV13 MDV was not detected. The study found that 63% of the health staff surveyed knew and applied WHO's multidose vial policy (MDVP). Vaccines opened vials were found in 83% of health facilities visited. PCV13 MDV (37%) was one of the 3 main vaccines found with open vials in health facility refrigerators. Vaccination risky practices were observed during immunization sessions in 83% of health facilities. The main risky practice was the lack of indication of the date and hour of opening vials (56%). There was a reduction of the volume occupied by vaccines at central store by 47%. Net storage volume per fully immunized child (FIC) decreased from 69.5 to 41 m3. PCV13 MDV allows for 40% reduction in the amount of waste produced by vaccination. PCV13 open vial loss rate has increased from 3 to 7%. CONCLUSION: Benin's experience in transition to an MDV presentation of PCV13 reveals the need for better preparation and planning.

Prevention of spontaneous bleeding in dogs with haemophilia A and haemophilia B.

Dogs with haemophilia A or haemophilia B exhibit spontaneous bleeding comparable with the spontaneous bleeding phenotype that occurs in humans with severe haemophilia. The phenotypic and genotypic characteristics of haemophilic dogs have been well-described, and such dogs are suitable for testing prophylactic protein replacement therapy and gene transfer strategies. In dogs with haemophilia, long-term effects on spontaneous bleeding frequency (measured over years) can be used as an efficacy endpoint in such studies. Although complete correction of coagulopathy has not been achieved, published data show that prophylactic factor replacement therapy and gene transfer can markedly reduce the frequency of spontaneous bleeding in haemophilic dogs. Further studies are currently ongoing.

Confined detection volume of fluorescence correlation spectroscopy by bare fiber probes.

A fiber-tip-based near-field fluorescence correlation spectroscopy (FCS) has been developed for confining the detection volume to sub-diffraction-limited dimensions. This near-field FCS is based on near-field illumination by coupling a scanning near-field optical microscope (SNOM) to a conventional confocal FCS. Single-molecule FCS analysis at 100 nM Rhodamine 6G has been achieved by using bare chemically etched, tapered fiber tips. The detection volume under control of the SNOM system has been reduced over one order of magnitude compared to that of the conventional confocal FCS. Related factors influencing the near-field FCS performance are investigated and discussed in detail. In this proof-of-principle study, the preliminary experimental results suggest that the fiber-tip-based near-field FCS might be a good alternative to realize localized analysis at the single-molecule level.

[Bone densitometry in inflammatory rheumatic diseases : Characteristics of the measurement site and disease-specific factors]. / Knochendichtemessungen bei entzündlich-rheumatischen Erkrankungen : Besonderheiten der Messorte und krankheitsspezifische Einflussfaktoren.

Bone densitometry should be performed earlier in patients with inflammatory arthritis, since factors such as inflammation and drug therapy, in particular treatment with glucocorticoids, have an important impact on the development of osteoporosis. DXA (Dual energy X-ray Absorptiometry) is considered the gold standard for bone densitometry. According to the German guidelines for osteoporosis, bone densitometry plays a crucial role in the choice of therapy.In patients with rheumatoid arthritis, measurement of peripheral bone (forearm) density in addition to lumbar spine and hip is recommended, since local bone loss is pathognomonic for this disease. DXA measurements of the hand enable the diagnosis of juxtaarticular osteoporosis at an earlier stage; however, this has not yet been established in routine practise.Bone measurement in patients with ankylosing spondylitis can be performed in the lumbar spine and the hip at disease onset. In systemic lupus erythematosus, bone loss is more frequent in patients with high inflammatory activity. Patients with psoriasis arthritis frequently have osteoporosis in the case of a destructive development of the joints.

Associations with subregional BMD-measurements in patients with rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) have bone loss to various degrees at different skeletal sites. The subregional bone mineral density (BMD) of the hand and the correlation of BMD to other regional bone losses, parameters of inflammation or bone resorption was evaluated in 421 patients with RA and controls. RA patients had significantly (P<0.01) lower BMD values in the carpus (0.405+/-0.004 g/cm2), metacarpal joint II (0.318+/-0.036 g/cm2) and metacarpal joint III (0.326+/-0.022 g/cm2) compared to controls. There was no difference in bone density at the lumbar spine or hip. Significant (P<0.001) correlations were found between BMD total of the hand, its subregions, the forearm and hip. Parameters of inflammation correlated significantly (P<0.001) with pyridinolines (r=0.378), desoxypyridinolines (r=0.183), forearm (r=-10, P<0.05), MCP II (r=-0.190, P<0.001), MCP III (r=0.204, P<0.001) and carpus (r=0.191, P<0.001).

Intracellular applications of analytical SERS spectroscopy and multispectral imaging.

The aim of this tutorial review is to give an overview of the state of the art of intracellular applications of analytical SERS spectroscopy. We pay particular attention to nanoparticle-based SERS spectroscopy since this currently dominates the published literature on non-disturbing analysis of live cells. We describe recent advances in this domain due to the development of multispectral imaging and to the combined use of SERRS (surface-enhanced resonance Raman scattering) and fluorescence spectroscopy. Finally, a perspective view is given on the tip-based approaches like tip-enhanced Raman spectroscopy (TERS) which allow micrometric and nanometric resolution.

[The mechanism of bone loss in rheumatoid arthritis. Description based on a case report]. / Mechanismen des Knochenmasseverlustes bei rheumatoider Arthritis. Darstellung anhand einer Kasuistik.

Various factors influencing bone turnover and bone loss in rheumatoid arthritis (RA) are illustrated using the example of a postmenopausal woman with a highly active RA. In particular, the relationships between disease activity, vitamin D metabolism, parathyroid hormone (PTH) levels and calcium metabolism are described. High disease activity is associated with low levels of 25-hydroxycholecalciferol, and especially of 1.25-dihydroxycholecalciferol. Despite vitamin D deficiency, PTH levels were decreased and histomorphometric investigation of the iliac crest biopsy showed severe osteoporosis but no signs of osteomalacia. Suppression of the inflammatory disease activity of RA led to a normalisation of the serum levels of 1.25-dihydroxycholecalciferol and PTH. This was associated with a reduction in the initially increased levels of bone specific alkaline phosphatase to normal values. This case report shows a close relationship between disease activity and bone turnover in RA and indicates that early investigation and therapy of disturbances of bone metabolism in RA are necessary.

Imaging of P-glycoprotein of H69/VP small-cell lung cancer lines by scanning near-field optical microscopy and confocal laser microspectrofluorometer.

Chemoresistance remains the major obstacle to successful therapy of the lung cancer. The multi-drug resistance (MDR) is generally associated with altered expression of drug transporter proteins, such as P-glycoprotein (P-gp). So the distribution of P-gp on the membrane is of great importance to further study the interaction between drug and P-gp. In the present work, the P-gp of the H69/VP small-lung cancer cells was detected using monoclonal antibody UIC2. A secondary goat-anti mouse antibody coupled with biotin was used. The fluorescence emission was detected from a streptavidin-Texas Red. Results were investigated by a homemade scanning near-field optical microscope (SNOM) coupled to a confocal laser microspectrofluorometer (CLMF). Topographical images and localized spectra were obtained at the level of one cell membrane. It was found that the distribution of P-gp is not homogeneous and this observation is basically in accord with the fluorescent images obtained by classical microscopy. The distribution of P-gp would be localized in a higher region on a cell surface. This methodology would also enhance our understanding of MDR under physiological conditions.

[Specialties in therapy of osteoporosis in inflammatory joint disease]. / Besonderheiten der Osteoporose-Therapie bei entzündlich-rheumatischen Erkrankungen.

The therapeutic specialties of osteoporosis in inflammatory rheumatic diseases has gained mounting interest in the last year. The paper describes special aspects of osteoporosis in rheumatoid arthritis, ankylosing spondylitis and systemic lupus erythematodes. The problems of glucocorticoid therapy are discussed intensively with regard to the recently published recommendations for glucocorticoid-induced osteoporosis. Risk factors of osteoporosis and the therapeutic implications are demonstrated intensively as well as the modifications of the recommendations.

[Lyme carditis and symptomatic sinus node dysfunction]. / Symptomatische Sinusknotendysfunktion bei Lyme-Karditis.

Lyme carditis is typically associated with AV nodal conduction abnormalities. We describe the case of a 66 year old female patient, who experienced a series of syncopal attacks after several tick bites two weeks earlier. ECG monitoring revealed recurrent sinus arrest with a maximum pause duration of 8 seconds. After institution of antibiotic therapy for Lyme carditis, sinus node dysfunction resolved rapidly and the patient had no further syncopes. Pacemaker implantation was not necessary. We therefore have to assume that in this patient Lyme carditis was the cause of symptomatic sinus node dysfunction.

PAS inclusions, immunoreactive tenascin and proliferative activity in low-grade chondrosarcomas.

To distinguish between chondrosarcoma (grade 1--borderline histology) and enchondroma, we examined six chondrosarcomas (grade 1--borderline histology) which looked like benign lesions. Their diagnosis, albeit based on clinical, radiologic and pathologic examinations, was not easily reached. Moreover, we examined six enchondromas and 11 chondrosarcomas, the diagnoses of which were straightforward. All cartilaginous tumors were studied, placing emphasis on PAS-positive intracytoplasmic globules. Anti-Ki67 proliferation-associated nuclear antigen antibody and tenascin antibody were applied. The following features were observed in low-grade chondrosarcomas: (1) masses of hyalin and/or myxoid cartilage invading spaces around the tumor, (2) host lamellar bone trabeculae surrounded by cartilage on all sides, (3) tumoral resorption of bone trabeculae. Intracytopasmic hyalin globules (ICG) were more frequently found in malignant than in benign neoplasm (p = 0.042). Moreover, tenascin matrix immunoreactivity was more likely to be observed in benign than in malignant neoplasm (p = 0.029). Ki67 immunoreactivity was more frequent in characterized than in low-grade chondrosarcomas or in enchondromas, where it was null (p = 0.0044).

Melatonin reduces non-adrenergic, non-cholinergic relaxant neurotransmission by inhibition of nitric oxide synthase activity in the gastrointestinal tract of rodents in vitro.

The aim of the present study was to investigate the effects of melatonin on non-adrenergic, non-cholinergic (NANC) relaxant neurotransmission in the gastrointestinal tract, which is mainly mediated by nitrergic and peptidergic mechanisms. Melatonin (10(-7)-10(-3) M) had no effect on the basal tonus of the rat gastric fundus smooth muscle. Relaxant responses following electrical stimulation(40 V; 0.5 ms pulse duration; 10 s stimulation duration) under NANC conditions on a 5-hydroxytryptamine (5-HT, 10(-7) M) contraction plateau were elicited at frequencies in the range of 0.5-16 Hz. Melatonin significantly reduced these inhibitory NANC responses (16 Hz without melatonin: -103 +/- 6.3%; melatonin 10(-5) M: -80.4 +/- 7.5%; melatonin 10(-4) M: -39.1 +/- 17.1%). Intracellular recording was carried out in a mouse colonic preparation. Electrical neural stimulation of the mouse colonic neurons caused biphasic intracellular hyperpolarization in smooth-muscle cells. The initial fast component is apamin-sensitive, and the following slow component is dependent on nitrergic mechanisms, as it is abolished in the presence of NG-nitro-L-arginine (L-NNA). Melatonin significantly reduced the nitric oxide-dependent slow component of neurally transmitted hyperpolarization, whereas the initial fast component was left unchanged. In a synaptosomal preparation of the enteric nervous system of rat intestine, enzymatic nitric oxide synthase (NOS) activity was significantly reduced by melatonin at concentrations ranging from 10(-7) to 10(-4) M (basal preparation including cofactors: 61.2 +/- 9.4 fmol/mg; melatonin 10(-4) M: 39.2 +/- 6.9 fmol/mg). Reverse transcriptase-polymerase chain reaction (RT-PCR) studies were conducted to investigate the melatonin receptors (mt(1), MT(2) and MT(3)) present in the esophagus, stomach and ileum of the rat. The presence of mt1 mRNA expression alone, but not of mRNA expression for MT(2) or MT(3), was demonstrated in the tissues. In conclusion, this study demonstrates that melatonin reduces the functional inhibitory NANC response. It shows that this effect may be the result of a reduction of the nitrergic component of the smooth-muscle inhibitory junction potential (IJP) and related to direct inhibition of NOS activity in enteric synaptosomes. The presence of mt1 receptor transcripts adds supportive evidence for a possible physiological role of melatonin within the enteric nervous system.

Experimental study of the sacroiliac joint micromotion in pelvic disruption.

OBJECTIVE: To measure the sacroiliac (SI) joint micromotion when different ligamentous lesions are created to simulate various degrees of pelvic anteroposterior compression injury. DESIGN: Cadaveric study. MATERIALS AND METHOD: Six SI joints were studied using a special device that made it possible to vary up to 310 N the loads applied on the ischial tuberosity and to measure simultaneously the SI micromotion. RESULTS: SI micromotion increases when the sacrospinous and sacrotuberous ligaments, and even more when the interosseous ligaments, have been sectioned off. In these cases, the stability of the SI joint is not restored by an isolated pubic fixation. CONCLUSION: This microinstability of the SI joint could contribute to the pain and arthritic changes sometimes observed in patients after anteroposterior compression injury. These experimental results could justify a larger spectrum of indications of SI joint fixation, but this should be confirmed by clinical study.

Mechanisms of alpha,beta-methylene atp-induced inhibition in rat ileal smooth muscle: involvement of intracellular Ca2+ stores in purinergic inhibition.

1. In order to investigate purinergic effects on rat ileal smooth muscle, we used alpha,beta-methylene ATP (alpha,beta-MeATP), ATP, ADP and UTP. alpha,beta-Methylene ATP and ATP were the only agonists that caused a concentration-dependent inhibition of carbachol-precontracted smooth muscle. The inhibitory effect of alpha,beta-MeATP was completely blocked by pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (3 x 10(-5) mol/L), a selective antagonist of the P2X > > P2Y receptor. 2. Using reverse transcription-polymerase chain reaction we demonstrated the presence of both, P2X and P2Y receptor mRNA within the rat ileal longitudinal muscle/myenteric plexus layer preparation. 3. The alpha,beta-MeATP-induced inhibition was blocked in a concentration-dependent manner in the presence of the K+ channel blocker apamin, but was unaffected by other K+ channel blockers, such as charybdotoxin (10(-7) mol/L), 4-aminopyridine (10(-4)mol/L), glibenclamide (10(-5) mol/L) and tetraethylammonium (10(-3) mol/L). 4. The alpha,beta-MeATP-induced inhibition was unaffected by pretreatment with atropine (10(-6) mol/L), phentolamine (10(-6) mol/L), propranolol (10(-6) mol/L), nitrendipine (10(-7) mol/L), pertussis toxin (10(-6) mol/L) NG-nitro-L-arginine (3 x 10(-4) mol/L) and tetrodotoxin (10(-6) mol/L), excluding an involvement of adrenergic, cholinergic, neural, nitrinergic or G-protein involvement in purinergic-mediated inhibition. 5. In order to investigate whether the internal Ca2+ stores participated in the inhibitory effect observed, we depleted internal Ca2+ stores with cyclopiazonic acid, a specific Ca2+-ATPase inhibitor. The inhibitory effect of alpha,beta-MeATP was completely abolished after depletion of the intracellular Ca2+ stores. 6. This is in contrast with the effects seen for neurotensin, where neurotensin-induced inhibition was unchanged after depletion of intracellular Ca2+ stores, suggesting at least two different pathways of apamin-sensitive non-adrenergic, non-cholinergic inhibition in rat ileal smooth muscle. 7. According to our results, the inhibitory effect of alpha,beta-MeATP in rat ileum longitudinal smooth muscle is mediated via a P2 purinoceptor, most likely a P2X receptor, involves G-protein-independent activation of an apamin-sensitive K+ channel and requires filled intracellular Ca+ stores.

Serum osteocalcin levels in patients with psoriatic arthritis: an extended report.

The aim of the study was to investigate the rate of bone formation in patients with psoriatic arthritis (PsA) compared to controls and patients with psoriasis vulgaris without PsA (PS). Osteocalcin (OC) and other parameters of bone turnover were measured in 32 patients with PsA and 17 patients with PS and compared to controls (n = 50). Patients with PsA do not generally present with different OC levels (3.0 +/- 1.6 ng/ml), than controls (3.6 +/- 1.17 ng/ml), if disease activity or sex are not considered. Women with PsA had significantly lower OC levels (2.28 +/- 0.44 ng/ml) than female controls (4.11 +/- 1.7 ng/ml) or women with PS (3.0 +/- 0.89 ng/ml). However, mean disease activity (2.27 +/- 1.0 vs 2.95 +/- 0.92) was also significantly lower in women than men. Furthermore, we found a significant correlation between alkaline phosphatase (AP) and OC in all patients with PsA (r = 0.49, P < 0.05). Disease activity of PsA had an influence on OC levels. Patients with no disease activity had lower OC levels (2.2 +/- 0.7 ng/ml) than patients with a high activity (OC 3.92 +/- 1.25, P < 0.05). Similar results were obtained with alkaline phosphatase. In addition, we found a significant correlation between clinical activity and OC (r = 0.38, P < 0.02) and alkaline phosphatase (r = 0.49, P < 0.01). Patients with PsA show a corresponding increase in OC levels. if disease activity is high. The proliferative changes in active PsA may be related to inflammatory mechanisms coupled with bone formation.

Total body and regional bone mineral densitometry (BMD) and soft tissue measurements: correlations of BMD parameter to lumbar spine and hip.

Bone loss in men and women seems to differ according to the skeletal regions or particular areas being evaluated. Dual energy X-ray absorptiometry (DXA) is the method of choice for measuring total body and regional bone mineral area density (BMD). The aim of the study was to evaluate the importance of DXA measurements of total body in relation to lumbar spine and hip in different scan beam designs. In 300 patients, ages 43-80 years, lumbar spine, hip, total body and regional bone mineral area density, and soft tissue measurements were performed on all subjects in the supine position on a QDR 2000 using single beam (SB) and fan beam (FB). Short-term precision errors were 0.7% (SB) and 1.2% (FB) for BMD total of the total body and between 1.2% and 8.0% for soft tissue measurements. All mid-term precision errors of BMD total, right and left leg, and pelvis were below 2.0% with SB and FB, whereas precision errors of thoracic and lumbar spine varied depending on the scan mode being applied. In contrast, all mid-term precision errors of soft tissue measurements were greater (2.6-11.0%). All SB values of BMD and soft tissue measurement were significantly higher than FB values, except for BMD values of the head, thoracic spine, and pelvis. Furthermore, BMD total of the total body scan correlated significantly (P < 0. 001) with all subregional parameters with best "r"-values (0.86-0. 92) for the right and left leg in SB and FB design. In addition, there were excellent correlations (r > 0.94, P < 0.001) between the right and left legs (SB and FB) or arms (SB). There were also highly significant correlations between the lumbar spine (or hip) and total body, being best for the subregional thorax. Our data demonstrate short-and mid-term precision errors of BMD with reproducible results for most areas in SB and FB design, whereas soft tissue measurements vary depending on the area being measured. Furthermore, there is a close relationship between BMD values of total body total and subregional parameters and lumbar spine and hip scans, respectively.

Rebound excitation and alternating slow wave patterns depend upon eicosanoid production in canine proximal colon.

1. We tested the hypothesis that eicosanoid production could be related to the long-duration slow waves that occur after brief periods of inhibitory neurotransmission (rebound excitation) and the alternating patterns of long- and short-duration slow waves observed in the canine proximal colon. 2. Electrical field stimulation of colonic muscles inhibited slow waves during the stimulus and a long-duration slow wave occurred after the stimulus. Indomethacin reduced the post-stimulus response without affecting the inhibitory response. 3. ATP or 2-methylthio-ATP produced post-stimulus rebound responses similar to the response to field stimulation. Indomethacin inhibited the rebound response caused by ATP or 2-methylthio-ATP. 4. Alternating patterns consisting of long- and short-duration slow waves occurred spontaneously in some colonic muscles. These patterns could also be induced with acetylcholine. 5. Indomethacin, acetylsalicylic acid and ibuprofen abolished the alternating pattern and shifted the bimodal distribution of slow wave durations toward an intermediate duration. 6. Patch clamp experiments on isolated colonic myocytes showed that indomethacin blocked L-type Ca2+ currents. The effects of indomethacin on rebound excitation and alternating slow waves were accomplished at concentrations that blocked cyclooxygenase activity without significantly inhibiting L-type Ca2+ currents. 7. The results demonstrate that rebound excitation and alternating slow wave patterns in the canine colon have similar dependence on endogenous eicosanoid production. Rebound excitation may result from reduced production of an inhibitory eicosanoid during inhibitory nerve stimulation, and the alternating pattern may result from oscillations in eicosanoid production as a function of changes in cytoplasmic Ca2+ during long and short slow waves.