Focal segmental glomerular sclerosis among patients infected with hepatitis C virus.

This study describes the occurence of hepatitis C virus (HCV) infection in the setting of focal segmental glomerular sclerosis (FSGS). All patients with the pathologic diagnosis of idiopathic FSGS between 1992 and 1996 at the University of Washington Hospitals were examined using a retrospective cohort study design. FSGS was determined by renal biopsy in the absence of secondary causes. Demographic, laboratory, and outcome data were collected in a standardized fashion. Six patients (50%) were infected with HCV. Patients with HCV infection and FSGS were primarily Black (67%), hypertensive (100%), had a history of intravenous drug abuse (83%), and had normal liver enzymes. Those with HCV infection and a history of IVDA appeared clinically and histologically similar to previously described cases of 'heroin nephropathy'. We demonstrate that there is a high prevalence of HCV infection in our population of patients with idiopathic FSGS. Although this may simply reflect an epiphenomenon, we propose that HCV infection may play a role in the development of FSGS in a predisposed host.

The Ib phase of ventricular arrhythmias in ischemic in situ porcine heart is related to changes in cell-to-cell electrical coupling. Experimental Cardiology Group, University of North Carolina.

BACKGROUND: This study was designed to test the hypothesis that the loss of cell-to-cell electrical interaction during ischemia modulates the amplitude of ischemia-induced TQ-segment depression (ie, the injury potential) and the occurrence of ventricular fibrillation (VF) during the so-called Ib phase of ventricular arrhythmias. METHODS AND RESULTS: Regional ischemia was induced by 60 minutes of mid-left anterior descending coronary artery ligation in open-chest swine (n = 10). Cell-to-cell electrical uncoupling was defined as the onset of the terminal rise in whole-tissue resistivity (Rt). Local activation times and TQ-segment changes (injury potential) were determined from unipolar electrograms. Extracellular K+ ([K+]e) and pH (pHe) were measured with plunge-wire ion-selective electrodes. VF occurred in 6 of 10 pigs during regional no-flow ischemia between 19 and 30 minutes after the arrest of perfusion. The occurrence of VF was positively correlated to the onset of cell-to-cell electrical uncoupling (R2 = .885). Cell-to-cell electrical uncoupling superimposed on changes of [K+]e and pHe contributed to the failure of impulse propagation between 19 and 30 minutes after the arrest of perfusion. During ischemia, maximum TQ-segment depression was -10 mV at 19 minutes, after which TQ-segment depression slowly recovered. The onset of the TQ-segment recovery was correlated to the second rise in Rt (R2 = .886). CONCLUSIONS: In the regionally ischemic in situ porcine heart, loss of cell-to-cell electrical interaction is related to the occurrence of VF and changes in the amplitude of the injury current. Cellular electrical uncoupling contributes to failure of impulse propagation in the setting of altered tissue excitability as a result of elevated [K+]e and low pHe. These data indicate that Ib arrhythmias and ECG changes during ischemia are influenced by the loss of cell-to-cell electrical interaction.

Marked activation delay caused by ischemia initiated after regional K+ elevation in in situ pig hearts.

BACKGROUND: Conduction mediated by the slow inward (Ca2+) current occurs in vitro under specific experimental conditions but has not been documented in ventricular muscle in vivo during regional myocardial ischemia, perhaps because certain constituents of ischemia (including hypoxia and acidosis) may inhibit the Ca2+ current in this setting. We hypothesized that slow conduction mediated by the Ca2+ current could occur during acute ischemia in situations in which the extracellular K+ rise was more marked relative to the degree of acidosis, as may occur at ischemic boundaries. METHODS AND RESULTS: In open-chest, anesthetized swine, an arterial shunt from the carotid artery to the mid-left anterior descending coronary artery was created through which a solution of KCl was infused to raise extracellular K+ ([K+]e) to approximately 9.4 mmol/L before the initiation of ischemia, which we termed "K(+)-modified ischemia." Ischemia initiated at a normal [K+]e ("unmodified ischemia") resulted in a mean activation delay in the center of the ischemic zone of 55 +/- 26 milliseconds after 5 minutes of ischemia and a decrease in epicardial longitudinal conduction velocity from 53 to 21 cm/s before the onset of conduction block. K(+)-modified ischemia resulted in a mean activation delay in the center of the ischemic zone of 181 +/- 8 milliseconds and a decrease in epicardial longitudinal conduction to less than 10 cm/s. K(+)-modified ischemia was associated with ventricular fibrillation in 85% of episodes compared with 28% of episodes of unmodified ischemia (P < .01). Verapamil prevented the occurrence of marked activation delay during K(+)-modified ischemia, producing local activation block following a maximum activation delay of 74 +/- 25 milliseconds. In two experiments, responses mediated by the slow inward current were produced by regional K+ elevation to 15 to 16 mmol/L, followed by concomitant regional administration of epinephrine (10(-7) mol/L). Regional [K+]e elevation alone to this level resulted in local activation block following a maximum activity delay of 70 to 80 milliseconds, whereas administration of epinephrine in combination with high [K+]e resulted in return of local activation with an activation delay of 160 to 180 milliseconds (ie, similar to that during K(+)-modified ischemia). CONCLUSIONS: Compared with unmodified ischemia, K(+)-modified ischemia resulted in marked activation delay and a high incidence of ventricular fibrillation. Based on measurements of longitudinal conduction velocity, the inhibitory effect of verapamil, and the results of experiments with high [K+]e plus epinephrine, we conclude that the marked activation delay during K(+)-modified ischemia represents conduction mediated by the slow inward current. Because the conditions produced by K(+)-modified ischemia (high [K+]e with minimal acidosis) are similar to conditions in and near ischemic border regions, we hypothesize that responses mediated by the slow inward current may occur in such regions during unmodified ischemia and may participate in the development of reentrant arrhythmias.

Effect of rate on changes in conduction velocity and extracellular potassium concentration during acute ischemia in the in situ pig heart.

INTRODUCTION: The purpose of our study was to determine if the slowing of longitudinal intraventricular conduction in the in situ porcine heart during acute regional no-flow ischemia was rate dependent. Further, we investigated whether any rate dependence could be correlated to a rate-dependent component of the ischemia-induced rise in extracellular potassium concentration, [K+]e. METHODS AND RESULTS: We studied in situ hearts in nine anesthetized open chest pigs in which acute no-flow ischemia was induced by occlusion of the left anterior descending coronary artery. To determine the effects of steady-state rate on the slowing of conduction and rise in [K+]e during ischemia, we varied the rate of stimulation during sequential occlusions from 90 to 150 beats/min. Longitudinal conduction velocity was determined by unipolar electrodes embedded in a plaque that was sutured to the epicardial surface in the center of the ischemic zone. Myocardial [K+]e was determined simultaneously by potassium-sensitive electrodes placed at or within 1 to 2 mm of the epicardium in close proximity to the activation recording electrodes. Conduction velocity decreased more rapidly at the more rapid rates of stimulation although the reduction in conduction velocity occurring prior to the onset of conduction block was similar at both rates. The potassium change was not rate dependent and rose at the same rate regardless of the rate of stimulation. CONCLUSION: Our study demonstrates that the steady-state rate-dependent component of the slowing of intraventricular conduction induced by acute ischemia in the in situ porcine heart occurs in the absence of a rate-dependent component in the rise of [K+]e. Between rates of 90 and 150 beats/min, the rate dependence of the conduction slowing may be attributed to one or more potassium-independent factors such as the rate-dependent changes in resting membrane potential, in Vmax of the action potential upstroke, and in cell-to-cell uncoupling, which have been observed in other models of acute ischemia.

Local myocardial biochemical and ionic alterations during myocardial ischaemia and reperfusion.

Acute myocardial ischaemia and reperfusion result in a series of inhomogeneous metabolic, ionic and neurohumoral events that explain the associated mechanical and electrical events, including cardiac death. The time course of the hydrolysis of high energy phosphates, the rise in extracellular potassium and the fall in intracellular and extracellular pH induced by acute no-flow ischaemia have been well characterised. However, the time course of the changes in intracellular sodium, calcium and magnesium levels is less clear. It appears that the changes in intracellular calcium may be pivotal to many of the biochemical and electrophysiological changes produced by the abrupt cessation of coronary arterial inflow and the associated interruption of venous washout. Consequently, agents that modify the handling of calcium by the sarcolemma and the sarcoplasmic reticulum have a significant impact on many of the metabolic, ionic and electrical abnormalities characterising acute ischaemia and reperfusion.

Selective attention in hemispatial neglect.

To determine how increasing demands on visual selective attention affect the symptoms of hemispatial neglect, we studied patients with right hemispheric lesions on a cancellation task requiring various degrees of focused attention. In the target only condition, the patients were to cancel all stimuli. In the target-nontarget condition, discriminating targets from nontargets did not require close scrutiny, whereas in the target-foil condition, discriminating targets from foils required greater attention to detail. Our findings indicate that increasing demands on visual selective attention adversely affect both exploration of the left side of space and visual discrimination.

Pupil-sparing oculomotor palsy from midbrain hemorrhage.

Pupil-sparing oculomotor nerve palsy generally results from extraaxial lesions, but it has also been seen with intraaxial infarcts and tumors. This report of a midbrain hemorrhage in a 64-year-old man supports the idea of selective interference with widely separated oculomotor nerve fascicles as the mechanism for intraaxial pupil-sparing oculomotor nerve palsies.

Dopamine agonist therapy for neglect in humans.

Lesions of ascending dopaminergic pathways induce neglect in animals. Apomorphine, a dopamine receptor agonist, decreases the magnitude of neglect in rats with cortical lesions. We treated two patients with 15 mg of bromocriptine daily for 3 to 4 weeks, one with chronic (longer than 6 months) and one with relatively more acute disabling neglect. Tests for neglect that significantly improved on therapy and worsened after its withdrawal included line, letter, and geometric figure cancellation tasks. Neither patient noted any untoward effects. Based on this open trial of dopamine agonist therapy in humans with neglect, larger controlled studies may be warranted.

A comparison of acetaminophen and rimantadine in the treatment of influenza A infection in children.

Rimantadine was compared with acetaminophen in a double-blind randomly assigned therapeutic trial in 63 children presenting with influenzal symptoms. Forty-nine of the children were proven to have influenza A by culture on presentation. Forty-three of the cultures, 88%, were influenza A/H1N1 strains. Both drugs were well tolerated. Rimantadine lowered the amount of virus shed in the first 2 days after initiation of therapy. Clinical resolution of illness was not different between the two therapeutic modalities. In individuals who shed virus for 4 days, strains recovered on the last day were relatively resistant to rimantadine.

Resolution of gumma with steroid therapy.

Antibiotic usage has rendered neurosyphilis uncommon, and cerebral gummas are rare. Reduced awareness of cerebral gummas and abolition of serologic screening can delay diagnosis of this treatable disease. Diagnostic confusion between syphilitic and nonsyphilitic cerebral mass lesions can be increased by apparent resolution of a gumma during steroid therapy. Such an occurrence in a young woman emphasizes the need for serologic testing for syphilis in diagnosing cerebral mass lesions. A trial of conservative therapy using penicillin (with or without prednisone) should be considered for patients with intracerebral mass lesions and positive serologic findings.