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.

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.

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.

[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.

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.

Effects of a novel guanylate cyclase inhibitor on nitric oxide-dependent inhibitory neurotransmission in canine proximal colon.

1. Previous studies suggested that nitric oxide (NO) may cause hyperpolarization and relaxation of canine colonic smooth muscle by both cGMP-dependent and cGMP-independent mechanisms. This hypothesis was tested using 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), a novel inhibitor of NO-stimulated guanylate cyclase. 2. In the presence of histamine (30 microM), atropine and indomethacin (both at 1 microM), electrical field stimulation of intrinsic neurons (EFS; 5 Hz) produced inhibition of phasic contractile activity that is due to NO synthesis. ODQ caused a concentration-dependent block of this response (10 nM to 10 microM). 3. Inhibitory junction potentials (IJPs) due to NO synthesis were recorded from muscle cells located near the myenteric border of the circular muscle layer, using intracellular microelectrodes. IJPs were abolished by ODQ (1-10 microM). 4. EFS (10-20 Hz) produced frequency-dependent inhibition of electrical slow waves recorded from cells located near the submucosal surface of the circular muscle layer. This inhibition is due to NO synthesis, and it was abolished by ODQ (1-10 microM). 5. Hyperpolarization and relaxation produced by an NO donor, sodium nitroprusside, were abolished by ODQ pretreatment (1-10 microM). In contrast, inhibitory responses to 8-Br-cGMP (1 mM) were unaffected by ODQ. 6. ODQ alone (1-10 microM) had no significant effect on spontaneous electrical or phasic contractile activity. In tissues pre-treated with L-NAME (300 microM), ODQ decreased the amplitude of spontaneous or histamine-stimulated phasic contractile activity. 7. These results suggest that electrical and mechanical effects of endogenously released and exogenously applied NO in canine colon are largely due to cGMP synthesis by ODQ-sensitive soluble guanylate cyclase. No evidence to support a direct (cGMP-independent) mechanism of NO action was found. ODQ also appears to cause a non-specific inhibition of muscle contractile activity; however, this effect does not contribute to block of NO-dependent effects.

Functional evidence for a glibenclamide-sensitive K+ channel in rat ileal smooth muscle.

The motor activity of gastrointestinal smooth muscle is closely related to the membrane potential. Controlling the membrane potential via modulation of K+ channels is essential for the action of neurotransmitters on smooth muscle. In the present study the effect of the K+ channel activator, lemakalim, on longitudinal smooth muscle of the rat ileum was investigated. Segments of rat ileum were stimulated by the muscarinic receptor agonist, carbachol (10(-6) M). Lemakalim (10(-10) to 3 x 10(-5) M) induced a dose-dependent inhibition of the carbachol-induced contraction. This inhibitory effect of lemakalim was not modified by neural blockade with tetrodotoxin (10(-6) M, n = 9). Glibenclamide (10(-7) to 10(-5) M), a specific blocker of ATP-dependent K+ channels antagonized dose dependently the relaxant effect of lemakalim (IC50: 3.4 x 10(-6) M, n = 11, P < 0.001). In contrast, apamin (10(-7) M, n = 9, n.s.) and charybdotoxin (10(-7) M, n = 9, n.s.), specific blockers of Ca2+-dependent K+ channels and the non-specific K+ channel blocker, tetraethylammonium (10(-4) to 10(-1) M), had no influence on the inhibitory effect of lemakalim. Contractions induced by the Ca2+ channel activator, Bay-K-8644, were completely inhibited by lemakalim (10(-5) M, n = 12). This inhibitory effect was also selectively antagonized by glibenclamide (10(-5) M). Potential non-adrenergic non-cholinergic (NANC) inhibitory mediators like ATP, nitric oxide (NO) or neurotensin showed no sensitivity to glibenclamide. These functional data indicate that the relaxant effect of lemakalim is due to a specific activation of glibenclamide-sensitive K+ channels, which in turn can modulate the activity of dihydropyridine-sensitive (voltage-dependent) Ca2+ channels. A physiological or pathophysiological role of the glibenclamide-sensitive K+ channels in intestinal smooth muscle is discussed; however, they seem not to be involved in the effect of the NANC inhibitory mediators tested.

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).

Stent-supported angioplasty of an ostial left main stenosis following replacement of the ascending aorta with reimplantation of the coronary arteries.

We describe a patient who underwent replacement of the descending aorta with reimplantation of the coronary arteries for acute type II aortic dissection and developed iatrogenic left main stem stenosis 1 year after operation. The patient was successfully treated by stent implantation in the left main stem.

Thrombocytopenia in patients with rheumatoid arthritis on long-term treatment with low dose methotrexate.

We reviewed the records of 315 patients with rheumatoid arthritis (RA) treated with low-dose methotrexate (MTX) and evaluated the conditions contributing to thrombocytopenia. Thirteen out of 315 patients with RA presented with low platelet counts (< or = 100,000/mm3). The age of these patients (51 +/- 12.6 years) did not correlate with thrombocytopenia (r = 0.211, p > 0.05). Thrombocytopenia resulted from coadministration of MTX and NSAID or multiple drug interactions. We observed a significant (r = 0.48, p < 0.05) increase of discontinuation of NSAID's but not of MTX therapy (r = 0.42, p > 0.05) with a mounting weekly dosage of MTX (12.5 +/- 5 mg orally). There was a significant correlation between this weekly dosage of MTX coadministered on the same day with NSAID and thrombocytopenia (r = 0.6, p < 0.05). In most cases (9/13) MTX was not or just temporarily withdrawn. Three of the remaining patients had multiple drug interactions. Reintroduction of low dose MTX treatment in patients having had thrombocytopenia could be performed safely, if thrombocytopenia occurred as a result of concomitant application of MTX and NSAID and no other multiple drug interactions. Preferably, MTX and NSAID should be given to these risk patients on separate days or intervals considering half time clearance of NSAIDs. This procedure has prevented the reoccurrence of thrombocytopenia and controlled further drug interactions of NSAIDs and MTX in our patients.

Thrombocytopenia in patients with rheumatoid arthritis on long-term treatment with low dose methotrexate.

We reviewed the records of 315 patients with rheumatoid arthritis (RA) treated with low-dose methotrexate (MTX) and evaluated the conditions contributing to thrombocytopenia. Thirteen out of 315 patients with RA presented with low platelet counts (< or = 100.000/mm3). The age of these patients (51 +/- 12.6 years) did not correlate with thrombocytopenia (r = 0.211, p > 0.05). Thrombocytopenia resulted from coadministration of MTX and NSAID or multiple drug interactions. We observed a significant (r = 0.48, p < 0.05) increase of discontinuation of NSAID's but not of MTX therapy (r = 0.42, p > 0.05) with a mounting weekly dosage of MTX (12.5 +/- 5 mg orally). There was a significant correlation between this weekly dosage of MTX coadministered on the same day with NSAID and thrombocytopenia (r = 0.6, p < 0.05). In most cases (9/13) MTX was not or just temporarily withdrawn. Three of the remaining patients had multiple drug interactions. Reintroduction of low dose MTX treatment in patients having had thrombocytopenia could be performed safely, if thrombocytopenia occurred as a result of concomitant application of MTX and NSAID and no other multiple drug interactions. Preferably, MTX and NSAID should be given to these risk patients on separate days or intervals considering half time clearance of NSAIDs. This procedure has avoided the reoccurrence of thrombocytopenia and controlled further drug interactions of NSAIDs and MTX in our patients.

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.

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.

[Differential therapy of osteoporosis]. / Differentialtherapie der Osteoporose.

In the past decade, we observed progress in the differential diagnosis of osteoporosis, mainly because of advanced radiological and laboratory procedures, including new bone markers. Loss of bone can also be related to primary and secondary forms of osteoporosis. Consequently, secondary osteoporosis (and osteomalacia) should be treated primarily according to the original disease. Although etiopathology of primary osteoporosis is still unclean differential therapy should be applied to the different subgroups (juvenile, postmenopausal, and senile osteoporosis). Furthermore, even patients of the same age and sex can be at risk for osteoporosis or have definite osteoporosis. This can be differentiated in "low or high turnover osteoporosis" and should be diagnosed and treated as described. Conjugated estrogens in combination with progesterone decrease the rate of endometrial carcinoma and have been established to be very effective in the treatment of high turnover osteoporosis and patients at high risk of developing manifest osteoporosis. In combination with calcium (1 g/day) total doses of estrogen can be reduced to 0.3 g/day. The same applies for the treatment of low turnover (mostly manifest) osteoporosis with fluoride. Daily doses of fluoride can be decreased from 80 mg sodium fluoride to 50g in combination with calcium. These reductions of daily fluoride doses decreases the rate of side effects and allows longer control periods, provided that bone measurements demonstrate a beneficial long-term effect. The control periods depend on the sensitivity of the bone density measurements. Special indications, modifications, alterations and additions of further drugs are discussed for the individual patient.

[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.