P2X(7) receptors are expressed during mouse nephrogenesis and in collecting duct cysts of the cpk/cpk mouse.

BACKGROUND: Purinergic receptors are cell-surface molecules that bind extracellular nucleotides, notably ATP. The P2X family includes seven nonselective ion channels with one member, P2X(7), implicated in cytolytic pore formation and cell death. MATERIALS AND METHODS: We sought P2X(7) expression in mouse nephrogenesis and cpk/cpk renal cyst growth, conditions in which both proliferation and apoptosis are prominent. RESULTS: P2X(7) immunolocalized to condensed metanephric mesenchyme: both proliferation and apoptosis were detected in this compartment, assessed by proliferating cell nuclear antigen expression and propidium iodide-stained pyknotic nuclei respectively. Later in nephrogenesis, P2X(7) was detected in collecting ducts, a pattern persisting to maturity. A mesenchymal to epithelial shift of P2X(7) expression was also documented in ureter development. In cpk/cpk kidneys, P2X(7)-expressing collecting duct cysts dominated histology from two weeks until four weeks after birth, when animals die from uremia. In polycystic kidneys pyknotic nuclei were rarely identified in P2X(7)-expressing epithelia, but were detected between cysts, consistent with a non-apoptotic role for P2X(7) in cyst enlargement. CONCLUSION: P2X(7) is expressed during normal nephrogenesis and in a model of congenital polycystic kidney disease. Further experiments are necessary to define possible functions of P2X(7) in these settings.     

Adverse hemodynamic and clinical effects of encainide in severe chronic heart failure

STUDY OBJECTIVE: To evaluate the hemodynamic effects of the antiarrhythmic drug, encainide, in patients with severe chronic heart failure. DESIGN: Unblinded, before-after study. SETTING: Referral center for patients with heart failure. PATIENTS: Thirty patients with severe chronic heart failure and a left ventricular ejection fraction less than 40%. INTERVENTIONS: Invasive hemodynamic measurements were done (using a balloon-tipped thermodilution catheter) before and for 3 hours after a single oral dose of 50 mg of encainide. MEASUREMENTS AND MAIN RESULTS: Ninety to one hundred and twenty minutes after its administration, encainide produced a significant deterioration in cardiac performance, as reflected by a fall in cardiac index from 2.3 to 1.8 L/min.m2 body surface (mean change 0.5 +/- 0.1; P less than 0.001), a fall in stroke work index from 26 to 18 g.m/m2 (mean change 8 +/- 2; P less than 0.001), and an increase in left ventricular filling pressure from 19 to 22 mm Hg (mean change 3 +/- 2; P less than 0.05). These deleterious hemodynamic effects were accompanied by worsening symptoms of heart failure in 8 of the 30 patients. Serum levels of encainide and its metabolites, O-desmethylencainide and 3-methoxy-O-desmethylencainide, were within the therapeutic range in most patients. CONCLUSIONS: Encainide can cause adverse hemodynamic and clinical effects in patients with severe chronic heart failure.     

Noninvasive Intracranial Cerebral Flow Velocity Evaluation in the Emergency Department by Emergency Physicians

Transcranial Doppler (TCD) is an accepted modality for the evaluation of cerebral blood flow velocities. OBJECTIVES: The purpose of this study was to test the feasibility of bedside TCD measurement in the emergency department (ED) with critically ill, intubated patients. METHODS: A prospective convenience sample of patients presenting to a university hospital over a two-month period underwent TCD evaluation of the middle cerebral artery. Intubated patients with head trauma and any patient requiring tracheal intubation were eligible. A 2-MHz Doppler probe was positioned over the temporal bone to acquire blood flow velocities. An emergency medicine resident and research assistant obtained measurements. Continuous TCD tracings were recorded on a video cassette recorder tape for quality assurance review and data collection. Vital signs and therapeutic interventions were also recorded. Flow velocities were measured in cm/s; the peak Resistance Index (RI) was calculated for each patient. RESULTS: A total of 30 patients were enrolled in the study. Adequate tracings were obtained in 25 patients (83%) without a disruption of resuscitation. Tracings could not be obtained in five patients; they were listed as TCD failures. However, in two of these patients, adequate flow velocity tracings were obtained after resuscitation. Four patients were evaluated during tracheal intubation. One patient was monitored successfully during cardiopulmonary resuscitation. The median time required for data acquisition was 1.9 minutes. The mean highest RI for those who expired was 0.84. For those who survived, the mean highest RI was 0.52. The difference of 0.32 was statistically significant (p = 0.04). CONCLUSIONS: Noninvasive blood flow velocity monitoring of the middle cerebral artery using TCD is feasible in the ED when performed at the bedside on intubated patients with traumatic brain injury and others during tracheal intubation and resuscitation.     

Effect of anticholinergic agents upon acquired nystagmus: a double-blind study of trihexyphenidyl and tridihexethyl chloride

We conducted a randomized, double-blind, crossover trial of two anticholinergic agents--trihexyphenidyl and tridihexethyl chloride (a quaternary anticholinergic that does not cross the blood-brain barrier)--in patients with acquired nystagmus and measured visual acuity and nystagmus before and at the end of 1 month on each medication. Of the 10 patients admitted to the study, only five completed trials of both drugs due to intolerance of medication or intercurrent illness. Of six patients who completed the trial of trihexyphenidyl, only one showed improvement. Of six patients who completed a trial of tridihexethyl chloride, four showed improvement. We conclude that (1) trihexyphenidyl is not a reliable treatment for acquired nystagmus, although occasional patients may benefit; (2) anticholinergic agents may suppress nystagmus by peripheral rather than central mechanisms; and (3) the side effects of anticholinergic agents limit their effectiveness in the treatment of nystagmus.