Implantable Transvenous Pacing Leads:

With the dawn of a new millennium, physicians' demands for very thin transvenous leads able to be positioned in nontraditional sites like the Bachmann's bundle, the high and mid-right ventricular septum, and the His bundle have created new and exciting challenges for lead engineers. Bipolar leads can now be as thin and reliable as unipolar leads. Cathode electrodes are very small, porous, and demonstrate high impedance. To optimize stimulation thresholds, steroid-eluting passive- and active-fixation electrodes have become popular for use in the atrium and ventricle. To create thin lead body diameters, new insulation and conductor materials and lead body designs are necessary. Hybrid medical materials having the best features of silicone rubber and polyurethane will allow for reliable insulation. Conductor cables instead of helical coils permit strong thin diameter leads to be designed. Transvenous lead implantation using the traditional stylet may not be possible with thin diameter leads, necessitating the use of sophisticated workstations using steerable catheters to guide these new active-fixation leads to selective sites in the right heart. The pacing lead of the future may be very different from the one used today. Ironically, it will have features and implantation techniques similar to the transvenous leads designed prior to the use of the stylet. We are now approaching full circle in lead development, retracing the footprints of the early implanters of three and a half decades ago. (PACE 2004; 27[Pt. II]:887–893)     

Dangerous liaison: sexually transmitted allergic reaction to Brazil nuts.

Brazil nuts are the second most frequent cause of nut allergy in the United Kingdom. We report the case of a 20-year-old woman with documented Brazil nut allergy who developed widespread urticaria and mild dyspnea after intercourse with her boyfriend who had earlier consumed Brazil nuts. Skin prick testing with the boyfriend's semen after Brazil nut consumption confirmed significant reactivity whereas a sample before nut consumption was negative. We believe this to be the first case of a sexually transmitted allergic reaction.     

Modification to improve efficiency of sampling schedules for BA/BE testing of FDC anti-tuberculosis drugs.

SETTING: The assessment of rifampicin (RMP) containing fixed-dose combination (FDC) formulations using in vivo bioequivalence testing is widely accepted. It would be advantageous for both the drug regulatory authorities and drug manufacturers, for optimum minimum blood testing time intervals that encompass all anti-tuberculosis active constituents in the FDC to be established. OBJECTIVE: To determine the optimum blood sampling schedule for testing novel FDC anti-tuberculosis drugs, isoniazid, RMP, pyrazinamide and ethambutol DESIGN: The results of 12 different single-dose, two-way cross-over designs are presented. The studies determined the bioavailability and bioequivalence of RMP-containing FDCs, and conformed with the requirements of the South African national drug regulatory authority for each of the active constituents. RESULTS: The pharmacokinetic parameters to determine bioavailability and the Hauschke method to determine bioequivalence revealed that a six-point time protocol, namely 0, 1, 2, 4, 6 and 8 h, provides a good approximation of the area under the curve, and that an 11-point time protocol of 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6 and 8 h provided information comparable to the conventional 15 time-points for FDCs containing up to four drugs. CONCLUSION: The findings provide concrete economic benefit and convenience for quality assurance testing of existing and novel FDCs.     

The role of still-frame parametric imaging in magnetic resonance assessment of left ventricular wall motion by non-cardiologists.

BACKGROUND: Cardiac magnetic resonance (MR) images are often reviewed by non-cardiologists who are not trained in the interpretation of regional left ventricular (LV) function. We hypothesized that the use of still-frame parametric MR images of wall motion could aid in the assessment of regional LV function. METHODS: Dynamic, electrocardiogram-gated, steady-state free precession (FIESTA) short-axis images were obtained in 6 to 10 slices in 18 consecutive patients. Each loop was used to automatically generate a still-frame image, in which each pixel is assigned a value equal to the amplitude of cyclic variation in local intensity, resulting in higher intensity in pixels that change between blood and tissue during the cardiac cycle. The dynamic images were reviewed by an expert cardiologist who provided gold standard grades for regional wall motion and by four radiologists. Then the radiologists reviewed and graded the same MR images in combination with parametric images. Grades assigned to each segment in the two sessions were compared with the gold standard. RESULTS: According to expert interpretation, 6 patients had normal wall motion, and 12 had wall motion abnormalities. Parametric images showed a bright band in the area spanned by endocardial motion, with reduced brightness and thickness in areas of hypokinesis. The agreement between the radiologists' grades and the gold standard significantly improved by adding parametric images (from 77% to 81%), which also resulted in reduced interobserver variability (from 52% to 33%). CONCLUSIONS: Still-frame parametric images aid in the assessment of regional wall motion by non-cardiologists who are required to interpret cardiac images.     

Inhibition and reversal of platelet-rich arterial thrombus in vivo: direct vs. indirect factor Xa inhibition

BACKGROUND/OBJECTIVE: The efficacy of a direct factor (F)Xa inhibitor, ZK-807834, was compared with indirect inhibition by enoxaparin for inhibition and deaggregation of acute platelet-rich thrombi in a well-characterized porcine carotid injury model. METHODS: A crush injury was performed on a randomly chosen carotid artery and the thrombus allowed to propagate for 30 min. Pigs then received intravenous drug for 35 min: ZK-807834-Dose 1 (40 microg kg(-1) bolus + 1.5 microg kg(-1) min(-1) infusion, n=6); ZK-807834-Dose 2 (20 microg kg(-1) bolus + 0.75 microg kg(-1) min(-1) infusion; n=6); enoxaparin (1 mg kg(-1) bolus; n=6); or saline (n=6). Five minutes after drug initiation, the contralateral artery was injured. Thrombus size was monitored by scintillation detection of autologous 111In-platelets. RESULTS: The prothrombin time ratio was 2.2 +/- 0.1; 1.4 +/- 0.3; 1.2 +/- 0.9 and 1.1 +/- 0.2, respectively. ZK-807834-Dose 1 significantly inhibited carotid platelet deposition (525 +/- 226 x 10(6) cm(-2); P = 0.008), whereas ZK-807834-Dose 2 (2325 +/- 768) and enoxaparin (1236 +/- 383) were not different from saline (2776 +/- 642). Thrombus deaggregation was greatest for animals receiving ZK-807834-Dose 1 (473 +/- 185). Neither ZK-807834-Dose 2 (1588 +/- 480) nor enoxaparin (1618 +/- 686) was different from saline control (2222 +/- 598). CONCLUSIONS: Direct FXa inhibition with ZK-807834, at a prothrombin time ratio of 2.2, effectively inhibits thrombosis and promptly deaggregates thrombi induced by arterial injury. In contrast, indirect FXa inhibition with enoxaparin was ineffective.     

Thrombotic occlusion of the common carotid artery (CCA) in acute ischemic stroke treated with intravenous tissue plasminogen activator (TPA)

Although common carotid artery (CCA) occlusions are rare, acute clinical presentations vary from mild to devastating strokes primarily due to tandem occlusions in the intracranial arteries. Three patients with acute CCA occlusions were treated with systemic tissue plasminogen activator (TPA). Blood pressures were kept at the upper limits allowed with TPA therapy with fluid balance and the 'head-down' position. Recanalization occurred in intracranial vessels only. Marked early neurological improvement occurred in two of three patients. CCA occlusions should not be considered contra-indication to systemic thrombolysis.     

Theory-based predictors of condom use among university students in the United States and South Africa.

This study compared the predictive value of the theory of planned behavior in university students in South Africa (N = 251) and the United States (N = 160) who completed an anonymous self-administered questionnaire. Multiple regression analyses revealed that condom use and intention were significantly predicted by positive condom attitude, subjective norm, self-efficacy, and attending university in South Africa. Significant interactions between country and predictors indicated that subjective norm predicted condom use and intention more strongly in the American sample than in the South African sample; attitude predicted intention more strongly in the American sample than in the South African sample; but self-efficacy predicted intention more strongly in the South African sample than in the American sample. The theory of planned behavior may provide a useful framework for interventions to reduce South African students' risk of HIV/and sexuality transmitted diseases. Such interventions should especially focus on building self-efficacy to use condoms.     

Non-alcoholic fatty liver disease, the metabolic syndrome and the risk of cardiovascular disease: the plot thickens.

Non-alcoholic fatty liver disease (NAFLD) affects a substantial proportion of the general population and is frequently associated with many features of the metabolic syndrome (MetS). Currently, the importance of NAFLD and its relationship with the MetS is being increasingly recognized, and this has stimulated an interest in the possible role of NAFLD in the development of atherosclerosis. Recent studies have reported the association of NAFLD with multiple classical and non-classical risk factors for cardiovascular disease (CVD). Moreover, there is a strong association between the severity of liver histopathology in NAFLD patients and greater carotid artery intima-media thickness and plaque, and lower endothelial flow-mediated vasodilation (as markers of subclinical atherosclerosis) independent of obesity and other MetS components. Finally, it has recently been demonstrated that NAFLD is associated with an increased risk of all-cause death and predicts future CVD events independently of other prognostic factors, including MetS components. Overall, therefore, the evidence from these recent studies strongly emphasizes the importance of assessing the global CVD risk in patients with NAFLD. Moreover, these novel findings suggest a more complex picture and raise the possibility that NAFLD, as a component of the MetS, might not only be a marker but also an early mediator of CVD.