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.     

Study of microcirculatory flow variations by laser Doppler velocimetry after cutaneous application of nitrated derivatives in normal subjects]

The local microcirculatory effect of percutaneous nitrate derivatives was evaluated by determining flux by laser Doppler in 10 controls. The application of Lenitral cream under the recording probe produced a rapid (within a mean of 6.7 min) elevation in the flux, reaching a maximum in 20 min and returning to baseline values in 55 minutes. This vasodilatory effect was maximal in the richly vascularized zones, but remained limited to the site of application of the nitrate derivatives, being undetectable even at a short distance from the application zone.     

Efficacy of lumiracoxib in relieving pain associated with knee osteoarthritis: a 6‐week,randomized, double‐blind,parallel‐group study

Aim: The aim of the current study was to assess the efficacy, safety, and tolerability of lumiracoxib 200 mg once daily (o.d.) in relieving osteoarthritis (OA) knee pain in patients in China, Taiwan, and South Korea. Methods: Patients of either sex (aged ≥ 18 years) with symptomatic, primary OA of the knee for ≥ 3 months were eligible for inclusion if they had OA pain intensity of ≥ 40 mm (100 mm visual analogue scale [VAS]) in the target knee joint during the previous 24 h. Patients were required to undergo regular non‐steroidal anti‐inflammatory drug therapy for ≥ 6 weeks. After 3–7 days of screening, patients were randomized (1 : 1) to receive either lumiracoxib 200 mg o.d. or celecoxib 200 mg o.d. The primary efficacy comparison between the study groups was overall OA pain intensity (VAS) in the target knee after 6 weeks of treatment. Results: The mean overall OA pain intensity (VAS) in the target knee after 6 weeks decreased from 60.6 mm to 35.7 mm and 60.5 mm to 36.1 mm in the lumiracoxib and celecoxib groups, respectively. Both study groups showed similar results in terms of improvement in both patient's and physician's global assessment of disease activity and functional health status. The percentage of adverse events (AEs) in the lumiracoxib and celecoxib groups (40.3% and 37.9%, respectively) was similar, as was the proportion of treatment‐related AEs (21.0% and 18.2%, respectively). Conclusions: Lumiracoxib 200 mg o.d. provided effective and well‐tolerated pain relief similar to that achieved with celecoxib 200 mg o.d. in knee OA patients.     

Selecting antibodies to detect HER2 overexpression by immunohistochemistry in invasive mammary carcinomas.

There is an increasing clinical demand for HER2 analysis in breast cancer, especially since the release of trastuzumab. The authors assessed the ability of immunohistochemistry to detect HER2 overexpression in invasive mammary carcinomas (IMC) using five antibodies. Paraffin-embedded samples of 86 IMCs (T2N0) were used to compare the immunohistochemical overexpression of HER2 using two polyclonal antibodies (HercepTest [DAKO] and A0485 [DAKO]) and three monoclonal antibodies (CB11 from two different laboratories, Biogenex and Novocastra, and 4D5 [Genentech]). All immunostainings were scored according to the FDA-approved HercepTest recommendations. The HercepTest-positive cases were compared with gene amplification by FISH (Oncor Inform, Ventana). The HercepTest was positive in 31 of the 86 cases (36.1%). The DAKO antibody A0485 was positive in 25 of the 66 (37.8%). Monoclonal antibody 4D5 was positive in only 15 of the 86 cases (17.4%). There was almost total agreement in results between the two CB11 antibodies: 25 of the 86 positive cases (29.1%). All cases positive for CB11 or 4D5 were HercepTest positive. Most of the HercepTest 2+ cases were negative when using either monoclonal antibody. FISH was positive in 19 of the 20 HercepTest 3+ cases and negative in 5 HercepTest 2+ cases. Three CB11-2+ cases showed no amplification by FISH. In three FISH-positive cases the immunohistochemistry showed no overexpression by all antibodies used. These findings suggest that immunohistochemistry may be used reliably as a primary methodology for evaluating HER2; however, the use of polyclonal antibodies may not be adequate to assess HER2 overexpression. CB11, regardless of the manufacturer (Biogenex or Novocastra), showed better concordance with FISH (kappa=0.83) than did the polyclonal antibodies.     

Changes in spinal cord injury-induced gene expression in rat are strain-dependent.

BACKGROUND AND CONTEXT: The functional recovery of animals subject to experimental spinal cord injury (SCI) is dependent on the injury model as well as the species and strain of animal used. Previous studies have shown differences in rates and degree of recovery between rats of different strains. PURPOSE: We sought to explore the hypothesis that differences in gene expression are associated with differences in functional recovery. STUDY DESIGN/SETTING: Laboratory study involving cohorts of three different strains of rat. METHODS: We used the Impactor device to produce identical spinal cord contusion injuries in groups of Long Evans, Sprague-Dawley, and Lewis rats (10 each). The functional recovery of animals was assessed using the Basso, Beattie, and Bresnahan rating scale. Six weeks after injury, rats were killed and the spinal cords were harvested for deoxyribonucleic acid microarray analysis. Changes in gene expression compared with intraspecies controls (3 each) were assessed at the region of injury and at a rostral segment of the spinal cord. Selected genes were also studied with real-time polymerase chain reaction. RESULTS: We found that different strains tended to exhibit different patterns of functional recovery. There were differences between the strains in terms of gene expression. CONCLUSIONS: These results emphasize the importance of testing novel therapies for SCI in a variety of animal species before introduction into human trials. Further research into the influence of several gene products on functional recovery is needed.     

Fertilization and early embrology: Monozygotic twinning in the human is associated with the zona pellucida architecture

Six cases of identical twin pregnancies which occurred in 2163cycles of in-vitro fertilization during a 3 year period arereported. Monozygosity was confirmed when the number of fetusesexceeded the number of embryos replaced (n = 4) or when twoconcepti were observed in a single amniotic sac (n = 2). Eachof the reported pregnancies resulted from replacement of embryoseither with naturally thin zonae pellucida or embryos whosezonae had been breached during micromanipulation for assistedfertilization (subzonal sperminsertion) or assisted hatching.That such cases exclusively gave rise to monozygosity suggestsa link between the physical state of the zona pellucida, hatching,and generation of identical twins.     

Intraarterial 5-FU-infusion and simultaneous radiotherapy as palliative treatment of recurrent rectal cancer.

Palliative treatment of recurrent rectal cancer remains to be a challenge. From 1989 to 1991 13 patients with recurrent rectal cancer were treated with intraarterial infusion of 5-Fluorouracil and simultaneous radiotherapy in a palliative intent. Seven patients had received postoperative adjuvant radiotherapy with 56 to 60 Gy. Three patients had been treated with systemic chemotherapy. Radiotherapy of the recurrence was performed with 19.8 to 30.6 Gy in the pre-irradiated patients and with 50.4 to 59.4 Gy in the others. One complete remission, three partial remissions and nine minor responses were observed. Three patients had complete pain relief after the treatment, in the remaining patients major pain reduction was achieved. Palliation lasted from three to twelve months (median: five months). Our results indicate that locoregional chemo- and radiotherapy are a effective modality in recurrent rectal cancer.     

Epilepsie im Kindesalter: Wann kann die antiepileptische Therapie abgesetzt werden?

Zusammenfassung Der richtige Zeitpunkt für das Absetzen der Antiepileptika (AE) im Kindesalter ist unbekannt. Anl?sslich ihrer Jahrestagung haben die Mitglieder des K?nigsteiner Arbeitskreises (KA) eigene und publizierte Absetzstrategien diskutiert. Da Studien zu diesem Thema rar und widersprüchlich sind, wurde beschlossen, die Diskussionsergebnisse im Sinne einer Meinungs?u?erung zu publizieren. Bei Neugeborenen besteht übereinstimmung, AE innerhalb von 2 bis 12 Wochen nach dem letzten Anfall abzusetzen. Bei BNS-Epilepsie wird Vigabatrin nach 6 bis 12 und Sultiam nach 6 bis 36 Monaten abgesetzt. Nach erfolgreicher Steroidtherapie setzt die Mehrheit des KA die AE-Therapie für zwei Jahre fort. Für die Rolando-Epilepsie sind 1 bis 3 Jahre Anfallsfreiheit ausreichend, auch wenn fokale Spike-Waves persistieren. Im Falle einer symptomatisch fokalen Epilepsie ist die Grunderkrankung mitentscheidend für das Absetzen. Die Behandlung der Absencen-Epilepsie kann nach zwei Jahren beendet werden, w?hrend bei myoklonisch- astatischer Epilepsie meist eine 2- bis 5-j?hrige Anfallsfreiheit vorausgesetzt wird. Konsens besteht darüber, dass die Juvenile- Myoklonus-Epilepsie ein sehr hohes Rückfallrisiko birgt. Dennoch ziehen einzelne neurop?diatrische Mitglieder einen Absetzversuch nach 2- bis 3-j?hriger Anfallsfreiheit in Betracht. Die überwiegende Mehrheit des KA führt aber bei gesicherter Diagnose keinen Absetzversuch durch. Bezüglich der Absetzgeschwindigkeit wird ein langsames (3 bis 12 Monate) Ausschleichen favorisiert. Nur zwei Mitglieder praktizieren ein rascheres Absetzen (<3 Monaten). Das EEG spielt für die Entscheidung eine untergeordnete Rolle und bleibt auf bestimmte Epilepsieformen (z. B. Absencen-Epilepsie) beschr?nkt. Das vorliegende Papier gibt die Meinung des KA wieder und eignet sich nicht im Sinne einer Leitlinie. Für die Entscheidung AE abzusetzen, ist immer eine individuelle Abw?gung von Grunderkrankung, Epilepsieform und psychosozialen Umst?nde erforderlich.      

Endogenous and recombinant erythropoietin levels decline in human amniotic fluid and fetal plasma in vitro at 37 degrees C.

OBJECTIVE: To determine the in vitro stability of endogenous and recombinant erythropoietin (EPO) incubated at 37 degrees C in amniotic fluid (AF) and fetal plasma. STUDY DESIGN: Endogenous and recombinant EPO in AF, fetal plasma and phosphate buffer were incubated in vitro for 21 days at 37 degrees C. Serial aliquots were analyzed for EPO and the rates of EPO decline were compared within and between groups. RESULTS: Endogenous and recombinant EPO declined significantly in plasma and AF at 37 degrees C. Endogenous EPO displayed a similar linear rate of decline in AF and plasma, with nearly 70% of the initial hormone concentration remaining at 21 days. Recombinant EPO incubated in buffer did not change. CONCLUSIONS: Using the rate of decline in endogenous EPO we observed, EPO levels measured in AF or plasma within 21 days of fetal demise can be extrapolated back to the level likely present at fetal death.