Kidney in old age.

Epidemiological studies have shown that chronic kidney disease (CKD) is a major health problem especially in an older population. Given the growing segment of the elderly population and the important implication of renal disease on health care, this review discusses the structural and functional changes of the ageing kidney and the underlying mechanisms of age-dependent injury. The implications of these changes in daily clinical practice and the management of CKD is also briefly overviewed.

Microarray analysis of newly synthesized RNA in cells and animals.

Current methods to analyze gene expression measure steady-state levels of mRNA. To specifically analyze mRNA transcription, we have developed a technique that can be applied in vivo in intact cells and animals. Our method makes use of the cellular pyrimidine salvage pathway and is based on affinity-chromatographic isolation of thiolated mRNA. When combined with data on mRNA steady-state levels, this method is able to assess the relative contributions of mRNA synthesis and degradation/stabilization. It overcomes limitations associated with currently available methods such as mechanistic intervention that disrupts cellular physiology, or the inability to apply the techniques in vivo. Our method was first tested in serum response of cultured fibroblast cells and then applied to the study of renal ischemia reperfusion injury, demonstrating its applicability for whole organs in vivo. Combined with data on mRNA steady-state levels, this method provided a detailed analysis of regulatory mechanisms of mRNA expression and the relative contributions of RNA synthesis and turnover within distinct pathways, and identification of genes expressed at low abundance at the transcriptional level.

Transvenous left ventricular lead implantation with the EASYTRAK lead system: the European experience.

Several independent studies suggest that resynchronization therapy--achieved by left- or biventricular pacing--improves hemodynamics in heart failure patients with interventricular conduction disturbances. Delivery of this new therapy in an effective and minimally invasive manner presents technical challenges, as transvenous access to the left ventricle is required. Since 1999, a novel over-the-wire approach combining standard pacing lead and angioplasty technology has been evaluated in several European countries. This new left ventricular lead, the EASYTRAK system (Guidant, St. Paul, MN), has been clinically evaluated in 2 phases. The first phase was a clinical investigation to obtain the CE-mark (i.e. European Commission approval). The second phase, which started immediately after the CE-mark was obtained, consisted of a postmarket surveillance called the European registry. This article reports on the results of the pre-CE-mark clinical investigation and the preliminary results of the European registry (first 150 patients). During the pre-CE-mark clinical investigation of the EASYTRAK system, lead performance was assessed in 36 successfully implanted patients. The patients had indications for VVI-pacing, symptoms of heart failure and significant left ventricular dysfunction. The left ventricular lead was implanted in conjunction with a conventional right ventricular lead and a new heart failure device (CONTAK TR, Guidant, Brussels, Belgium). Lead measurements (threshold, sensing, and impedance) were performed at implant and subsequent follow-ups. The stimulation thresholds at 0.5 msec impulse width were acceptable, although (as expected) slightly higher than with standard right ventricular pacing leads: 1.39 +/- 1.15 V at implant, 1.72 +/- 1.26 V at predischarge, 1.54 +/- 0.88 V at 2 weeks, 1.38 +/- 0.80 V at 6 weeks, and 1.24 +/- 0.73 V at 12 weeks. R-wave and impedance measurements were stable over time. A revision of the EASYTRAK lead was required in 3 patients. No perforations were observed. During the second phase of the European registry, 150 implants were attempted in 63 centers from November 1999 to January 2000. The EASYTRAK was implanted with a pulse generator offering, in addition to resynchronization therapy, either tachycardia monitoring (CONTAK TR) or implantable cardioverter defibrillator therapy (CONTAK CD), depending on the patient indication. Over half of the centers involved had not previously implanted the EASYTRAK system. Total implant success rate was 83% (135/150), skin-to-skin duration of the implant was 169 +/- 81 minutes (range, 53-480 minutes), with a clear learning curve. Once the coronary sinus was found, the implant success rate was 92%. One lead dislodgment and 2 cases of phrenic nerve stimulation were reported. We conclude that the new EASYTRAK lead design for transvenous left ventricular lead implantation seems to be a suitable and safe tool for delivering resynchronization therapy to heart failure patients.

First experience with an automatic sensing algorithm in single-lead VDD stimulation.

UNLABELLED: An "Autosensing" algorithm available in SSI(R) and DDR(R) pacemakers automatically adapts the device's sensitivity to changing intracardiac signals. The atrial sensing function of this algorithm was tested for the first time with a VDD pacing system in which large variations of the atrial signal may occur because the atrial electrodes float in the atrial blood pool. METHODS: 15 patients with a VDD pacing system were studied (Unity 292-07, lead 425; Sulzer Intermedics). The atrial sensing threshold was measured, and the atrial sensitivity was programmed with a 2:1 safety margin. The autosensing algorithm and sensitivity profile were temporarily activated, and an ambulatory ECG with continuous marker annotation was recorded. All patients underwent a 30-minute daily life activities protocol. A beat-to-beat analysis of the ambulatory ECG was correlated with the changes in atrial sensitivity. RESULTS: The algorithm changed the baseline sensitivity from 0.57 +/- 0.23 mV during the test to 0.39 +/- 0.20 mV after the final rest period (P < 0.05). During the test 12.6 +/- 10.2 adaptations of the sensitivity occurred (range 0-33). In eight patients atrial undersensing occurred in 4.4% +/- 7.5% of the cycles (4-458 unsensed P waves). In these patients, the algorithm continuously adjusted the sensitivity towards more sensitive values, operating 19.1 +/- 18.3 changes compared with 5.4 +/- 7.3 changes in patients without undersensing (P = 0.009). Oversensing did not occur. CONCLUSION: The autosensing algorithm effectively optimized atrial sensitivity in VDD pacing. In patients with atrial undersensing the algorithm continuously remained near the most sensitive settings, thus reacting as intended. A faster sensitivity adjustment of the system would be desirable.

The patient alert system--pilot study of built-in warning systems for pacemakers.

Malfunction of a pacing system can be life-threatening for a pacemaker-dependent patient. It would be desirable for implantable pulse generators to have a built-in automatic warning system capable of alerting the patient as soon as a potentially dangerous disorder is detected. In this study, seven patients (mean age, 72.6 +/- 10.7 years) with slow, chronic atrial fibrillation underwent implantation of a dual-chamber pulse generator with a custom-made "alert electrode" connected to the atrial port of the pulse generator to stimulate the underlying pectoral muscle. The muscle was temporarily stimulated while the pacemaker was in VVIR mode. The lowest amplitude sufficient to alert the patient (perception threshold) was 1.6 +/- 0.58 V at 0.45 ms during implantation and 1.2 +/- 0.5 V at 0.45 ms chronically. In a second phase, alerts outside of the office were issued using a special software routine capable of delivering stimuli at programmable date and time.

Serum activity induces Schwann cell proliferation in vitro.

The present series of experiments demonstrate that a polypeptide activity present in rat serum induces a proliferative response in cultured rat Schwann cells. Schwann cells in multi-well tissue culture plates were incubated in medium containing 10% heat-inactivated fetal bovine serum and serial dilutions of normal rat serum, and control preparations were incubated in the same culture medium without rat serum. Rates of cell proliferation were assayed by measuring DNA incorporation of tritiated thymidine using liquid scintillation counting. A prominent dose-dependent proliferative response was observed among Schwann cells incubated with rat serum and rat plasma dilutions as compared to controls; this activity is abolished by heat inactivation and by proteolytic digestion, and was not affected by dialysis against a cellulose ester membrane that excludes molecules larger than 10,000 daltons. In contrast, no increase in DNA uptake of tritiated thymidine was observed when astrocyte and oligodendrocyte cultures were incubated with serial dilutions of rat serum. No proliferative effect was observed when rat Schwann cells were incubated with a dilution of standard adult bovine serum. These results suggest there is an intravascular plasma polypeptide with a molecular weight greater than 10,000 daltons that specifically stimulates Schwann cell proliferation, and it is proposed that this factor may be the mitogen responsible for the Schwann cell proliferative response known to occur after nerve injury.