Validation of a Method for Choice of Pacing Mode in Carotid Sinus Syndrome With or Without Sinus Bradycardia

A new method for selection of the pacing mode in 60 consecutive patients with severe cardie-inhibitory or mixed carotid sinus syndrome was prospectively validated. ODD pacing was preferred for 26 patients with: (1) the cardioinhibitory form and who had symptomatic pacemaker effect; (2) mixed type I form, (cardioinhibitory and vasodepressor) with symptomatic pacemaker effect, ventriculoatrial conduction or orthostatic hypotension; (3) mixed type II; or (4) severe bradycardia. VVI pacing was seiected in the remaining 34 patients without these symptoms. During a 32 ± 10 month follow-up period syncope and severe dizziness persisted in five patients in the VVI group (15%) and in three patients in the ODD group (12%). Symptomatic relief occurred in 87% (52/60) of patients. Minor symptoms persisted in 47% of the VVI group and 42% of the DDD group. No patient developed cardiac insufficiency or intolerance to pacing. During a 2-month duration a single-blind, randomized, cross-over study compared VVI and DDD pacing, 69% of the patients programmed from DDD to VVI suffered more frequent, severe, and intolerable symptoms. (1) Thirty four of 60 patients (57% of the entire group) in whom VVI pacing was satisfactory were identified prior to pacemaker implant. In the remainder, VVI pacing was contraindicated as it produced frequent side effects. (2) The preimplant predictive value that VVI pacing would be successful was 85% for those eventually receiving VVI pacemakers and the preimplant predictive value that VVI pacing would fail was 69% for those who underwent DDD implant.     

The Parotid and the Pancreas

Physiologic, experimental, and clinical studies have been presented concerning the salivary secretion in man and animals with and without pancreatic disease. Further evidence is presented that hoth organs tend to respond to noxious agents, to show a parallelism of secretion, and to display a glandular histologic and fvuictional relationship which may he concordant or inverse.     

The effect on epidermal DNA synthesis of a combination of topical steroid with either dithranol or tar as used for psoriasis

The hairless mouse was used to investigate the effects of a combination of glucocorticosteroid with either dithranol or tar on epidermal DNA synthesis, in order to determine whether such combinations reduce epidermal DNA synthesis more effectively than the single agents. Dithranol alone produced a significant local inhibition of DNA synthesis at concentrations of 0.1% and 0.05% but not at lower concentrations. Dose-response data for dilutions of clobetasol propionate and betamethasone 17-valerate showed progressive diminution of both local and systemic effects with decreasing concentrations. An additive effect was found from combining clobetasol propionate with dithranol and from combining betamethasone 17-valerate with liquor picis carbonis. These combined preparations were tested again after storage for 6 months and 2 months respectively and showed no loss of efficacy. These results lend justification to the use of these combined preparations in the treatment of psoriasis.     

Radiofrequency Catheter Ablation and Modulation of Atrioventricular Conduction in Patients with Atrial Fibrillation

We attempted radiofrequency ablation of the AV junction with a sequential right- and left-sided approach in 78 patients affected by severely symptomatic, drug refractory atrial fibrillation. Stable third-degree A V block was obtained in 99% of cases and, after 3 months, persisted in 92% of cases. Single session, stepwise, radiofrequency modulation of the AV node was attempted in 13 patients with paroxysmal atrial fibrillation. During sinus rhythm, ablation of the slow and fast AV node pathways was performed in order to increase the nodal refractory period or to slow conduction. Clinically successful modulation of AV conduction was achieved in 15% of cases and persisted during a 3-month follow-up. In conclusion. AV junction ablation is a well-established means of treating atrial fibrillation, but implies the implant of a permanent pacemaker. AV node modulation avoids the pacemaker implant, but is efficacious only in a minority of patients. Thus, in patients affected by paroxysmal atrial fibrillation, AV modulation should be attempted first; if this is ineffective. AV ablation can be performed during the same session.     

Obsessive-compulsive disorder in children and adolescents

Children and adults with OCD have similar obsessions and compulsions, as well as a similar response to most psychotherapeutic and pharmacotherapeutic interventions. A large proportion of adults with OCD, perhaps as high as 80%, have their onset during childhood or adolescence. The prevalence estimate of OCD in children is at least 2-4% and an even larger number may have subclinical OCD. Recent gains in OCD research have consisted in differentiating normal ritualistic behavior in children from OCD symptoms, realizing a more systematic assessment of OCD symptoms in children, refuting the impression that OCD in children is a rare condition and developing psychological and pharmacologic treatment strategies. Controlled studies of the phenomenology of OCD in children have been conducted. The vast majority of children with OCD have concurrent neuropsychiatric disorders including mood, tic, other anxiety and neurologic disorders, as well as pervasive developmental disorders. Recent investigations show that risk to relatives for OCD or subthreshold OCD is significantly higher in relatives than controls. Earlier age of onset also seems to be related to degree of familiality of OCD. The management of OCD in children entails an integrated approach of available behavioral, pharmacological, family therapy and supportive interventions. Illness education should be a major component of management and individualized treatment is important. Further research in OCD should serve to improve the prognosis of this mostly chronic condition in children.     

Platelet Gs hypofunction and abnormal morphology resulting from a heterozygous RGS2 mutation

Summary. Background: Regulator of G‐protein signaling (RGS) 2 negatively regulates Gs signaling by inhibiting the activation of adenylyl cyclase (AC). RGS2 mRNA contains four translation initiation sites, leading to four isoforms with different abilities to inhibit AC activity; the largest isoform is the most pronounced inhibitor. A role for RGS2 in platelets is not known. Objective: To describe a heterozygous RGS2 mutation (G23D) in three related patients, leading to Gs hypofunction in their platelets, and to study the mechanism behind the effect of the RGS2 mutation on platelet function and morphology. Methods: Gs signaling was studied ex vivo in platelets and in vitro in transfected cells. Translation initiation was evaluated in vitro, and the interaction of wild‐type and G23D RGS2 with AC was unraveled via immunoprecipitation. Platelet granule content was analyzed with proteomics. Results: The mutation leads to reduced cAMP production after stimulation of Gs‐coupled receptors. The largest RGS2 isoforms, with strong AC inhibitor activity, are enriched when the mutation is present, as compared with wild‐type RGS2. Moreover, the mutation results in a stronger interaction of RGS2 with AC. G23D RGS2 carriers have enlarged, round platelets with abnormal α‐granules. Proteomics of the platelet releasate revealed altered expression of some proteins involved in actin assembly, and carriers seemed to have a reduced platelet shape change. Conclusions: We present the first platelet Gs signaling defect caused by a heterozygous RGS2 variant that results in a unique mutational mechanism, such as the differential use of translation initiation sites resulting in different functional RGS2 isoforms.     

Dominant Frequency Mapping of Atrial Fibrillation: Comparison of Contact and Noncontact Approaches

Introduction: The ability to acquire a dominant frequency (DF) map during atrial fibrillation (AF) instantaneously using noncontact mapping has significant advantages over the current sequential contact mapping approach; however, the relationship between DFs determined from contact bipolar and noncontact unipolar recordings is unknown. We sought to determine the difference between DFs determined using contact bipolar, contact unipolar, noncontact unipolar, and noncontact pseudobipolar recordings. Methods: Sustained AF was induced in 5 canines with 10 weeks of atrial tachy‐pacing at 440 ppm. A noncontact multielectrode array was positioned in the left atrium (LA). Two simultaneous contact signals (unipolar and bipolar) and 3 noncontact signals (unipolar, pseudobipolar, and pseudobipolar Laplacian) were recorded from multiple LA sites. Fourier analysis was performed, and the DFs of contact and noncontact signals were compared. Results: Recordings were obtained from 389 LA locations in 5 canines. The correlation was best between contact bipolar and noncontact QRS‐subtracted unipolar signals (r = 0.58, P < 0.001), and weaker between contact bipolar and noncontact best‐fit pseudobipolar (r = 0.50, P < 0.01) and noncontact Laplacian bipolar (r = 0.49, P < 0.01). There was no significant difference in the mean DFs between contact bipolar and noncontact unipolar signals; however, there was a significant difference in the DFs comparing contact bipolar to noncontact pseudobipolar signals (11.6 ± 1.8 vs 11.2 ± 2.5 Hz; P = 0.004) and a small nonsignificant difference comparing contact bipolar DF and noncontact pseudobipolar Laplacian DF (11.4 ± 1.8 vs 11.1 ± 1.6 Hz; P = NS). Conclusions: We found that estimation of DFs using noncontact mapping is feasible and that QRS‐subtracted noncontact unipolar signals perform better than noncontact pseudobipolar signals at estimating contact bipolar DFs. This has important implications for developing algorithms for noncontact frequency mapping of AF.