Responses to Norepinephrine of Normal and "Ischemic" Canine Purkinje Fibers are Consistent with Activation of Different α1-Receptor Subtypes

α₁-Receptor Subtype Stimulation of Purkinje Fibers. Introduction: Previously we found that WB4101 (WB) 10^-7 M competitively blocks three α₁-adrenergic receptor-effector responses: the increase in normal automaticity occurring in Purkinje fibers (PF) at high membrane potentials: the increase in abnormal automaticity occurring in PF at depolarized membrane potentials; and the prolongation of PF action potential duration. These observations are consistent with two different hypotheses: (1) WB blocks a single α₁-receptor subtype, which subserves different effector pathways; and (2) WB blocks different receptor subtypes, eacb of which subserves an independent patbway. The aim of this study was to test both hypotheses. Methods and Results: We used standard microelectrode techniques to study the concentration-dependent actions of three α₁-adrenoreceptor blockers (WB (α_1A?α_1D], 5-methylurapidil [5-MU] [α_1A, ?α_1D], and UK52,046 [nonselective]) on norepinephrine (NK) effects in normal PF and in PF depolarized with a simulated ischemic solution ([K⁺]_o= 10 mM; pO₂ < 20 mmHg; pH 6.8; maximum diastolic potential -60 ± 1 mV). In normally polarized PF, concentration-dependent actions of all blockers on both the positive cbronotropic response and the prolongation of action potential duration completely coincide. In contrast, the response to NE of abnormal automaticity in “ischemic” PF differs from normals: there is a bigh sensitivity to WB and 5-MU and no response to UK52,046. Conclusions: (1) A single receptor subtype appears responsible for botb the α₁-induced prolongation of repolarization and the positive chronotropic effect in normal PF. (2) Two different receptor subtypes may be responsible for the α₁-induced effects on automaticity in normal and ischemic fibers. It is likely that the latter one is α_1A, and that consideration of antiarrhythmic therapy with α₁-adrenergic blockers should focus on this subtype as a potential target.     

Chylous ascites in cirrhosis: A case report and review of the literature

Chylous ascites is an uncommon clinical entity which results from the accumulation of fat, predominantly chylomicrons, in the ascitic fluid. Conventional treatment methods are unsatisfactory. A patient is reported with chylous ascites associated with cirrhosis and portal hypertension in whom the ascites, the renal insufficiency and the fluid and electrolyte disturbances were corrected by the insertion of a Denver peritoneovenous shunt.     

Mode of Onset of Malignant Ventricular Arrhythmias in Idiopathic Ventricular Fibrillation

Mode of Onset of Idiopathic VF. Introduction : The mode of onset of malignant ventricular arrhythmias (ventricular tachycardia [VT] or ventricular fibrillation [VF] has been well described in patients with organic heart disease and in patients with the long QT syndromes. Less is known about the mode of onset of VF in patients with out-of-hospital VF who have no evidence of organic heart disease or identifiable etiology.
Methods and Results : We reviewed the ECGs of all our patients with Idiopathic VF. Documentation of the onset of spontaneous arrhythmias was available for 22 VK episodes in 9 patients (6 men and 3 women; age 41 ± 16 years). In all instances, spontaneous VF followed a rapid polymorphic VT, which was initiated by premature ventricular complexes (PVCs) with very short coupling intervals. The PVC initiating VF had a coupling interval of 302 ± 52 msec and a prematurity index of 0.4 ± 0.07. These PVCs occurred within 40 msec of the peak of the preceding T wave. Pause-dependent arrhythmias were never observed.
Concltision : Cardiac arrest among patients with idiopathic VF has a very distinctive mode of onset. Documentation of a polymorphic VT that is not pause dependent is of diagnostic value.     

'Original antigenic sin', T cell memory, and malaria sporozoite immunity: an hypothesis for immune evasion

Prior to any exposure to malaria, most adults have T cells specific for malaria parasites and various malaria proteins. The protein for which this has been shown more than any other is the circumsporozoite protein (CSP) of Plasmo-dium falciparum. These T cells can be present in high frequency and appear to have arisen through exposure to other (non-malaria) organisms. Although T cells are thought to provide protection against sporozoites, these T cells specific for cross-reactive organisms are clearly unable to protect against malaria, and may be preferentially expanded following exposure to malaria sporozoites. Thus, cross-reactive organisms have the potential to skew the repertoire of sporozoite-induced T cells and affect the induction of protective immunity. This is analogous to the concept of 'original antigenic sin' whereby prior exposure to one strain of influenza virus was shown to be able to divert the antibody response to a second challenging strain to focus on the shared (cross-reactive) epitopes.     

Prevention of Spontaneous Sustained Ventricular Tachycardia in the Postinfarction Dog by Left Stellate Ganglionectomy

Suppression of Sustained VT by Left Stellectomy. Holter monitoring and ventricular pacing were used to examine control, right stellate ganglionectomy, and left stellate ganglionectomy treatment groups, 6-24 hours after left anterior descending coronary artery ligation in dogs. In nine of 27 controls (33%), spontaneous ventricular triplets (358 ± 8 beats/min) initiated sustained monomorphic ventricular tachycardia (386 ± 16 beats/min), followed by ventricular fibrillation at 12.6 ± 1.4 hours. Ventricular pacing produced sustained monomorphic ventricular tachycardia in 13 of 18 survivors (73%) at 24 hours. Left but not right stellectomy performed 15 minutes before coronary artery ligation reduced the incidence of spontaneous sustained monomorphic ventricular tachycardia (2 of 27, 7%, P = 0.06; 7 of 27, 26%, P = 0.50, respectively) and reduced the maximal ventricular triplet rate (332 ± 12, P <0.05 and 358 ± 10 beats/min, respectively, P = NS vs control). Neither left nor right stellectomy altered the incidence of ventricular triplets during the 6-24 hour period (153 ± 58 and 222 ± 55/hour, respectively, vs control, 177 ± 59/hour, P = NS) nor prevented pacing-induced sustained monomorphic ventricular tachycardia in the survivors at 24 hours (20 of 24, 75%; and 16 of 20, 80%, P = NS). The data demonstrate that left but not right stellectomy reduces spontaneous sustained ventricular tachycardia and ventricular fibrillation during the 6-24 hour period following coronary artery ligation in the dog. Left stellectomy reduces the triggers for sustained monomorphic ventricular tachycardia (rapid ventricular triplets) without altering the underlying reentrant substrate for sustained ventricular tachycardia.     

REDIRECTING T LYMPHOCYTE SPECIFICITY USING T CELL RECEPTOR GENES

Redirecting T cells by transferring T cell receptor (TCR) genes from tumor-associated antigen (TAA)-reactive T cell clones into human peripheral blood lymphocytes (PBL) has therapeutic potential for the treatment of diseases, including cancer. T cell specificity can be altered using retroviruses encoding TCR &#102 and TCR &#103 chain genes, or chimeric immunoglobulin (cIg) genes containing signaling domains of CD3 &#145 or Fc &#108 RI- &#110. This review evaluates recent studies using TCRs and cIgs to redirect T cell specificity and discusses some of the technical and biological hurdles that need to be addressed before these approaches can be successfully used to treat patients.     

Attachment in African American and European American older adults: The roles of early life socialization and religiosity

The significance of attachment relationships in later life has recently emerged as an important topic of study. Yet little attention has focused on attachment dynamics among older minority adults. This paper extends the literatures on ethnicity, attachment, and later life by examining attachment patterns in two large community-dwelling samples of older (65 + years) African American (n=671) and European American (n=447) adults. Data gathered during face-to-face interviews included demographic information, adult attachment, early rearing experiences, and current religiosity. Hierarchical regression analyses revealed that adult attachment dimensions were differentially predicted by childhood socialization patterns and current religiosity. Significant ethnic differences in relations between adult attachment and childhood socialization practices also were found. The results highlight the importance of examining contextual differences in attachment in later life.