Associations between sleep complaints, suicidal ideation and depressive symptoms among adolescents and young adults in Greece.

Depression prevalence increases significantly during adolescence/early adulthood. Depression in youth may present suicidal ideation, while suicide represents the leading cause of death in this age group. Moreover, adolescents/young adults frequently report sleep complaints that may partially be due to depressive symptoms. Studies on the associations between depression, sleep complaints and suicidality in this age group are limited. We aimed to examine associations between depressive symptoms, sleep complaints and suicidal ideation in a large (n = 2771), representative sample of adolescents (age: 15-17 years, n = 512) and young adults (age: 18-24 years, n = 2259) from the general population in Greece. A telephone structured questionnaire was administered. Depressive symptoms were assessed using the modified Patient Health-7 questionnaire score, while presence of suicidal ideation and sleep complaints were assessed using the ninth and third question of Patient Health-9 questionnaire, respectively. Mediation logistic regression analysis revealed significant direct paths from depressive symptoms to sleep complaints (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.19-1.24; OR 1.21, 95% CI 1.18-1.24) and suicidal ideation (OR 1.18, 95% CI 1.14-1.22; OR 1.18, 95% CI 1.14-1.22), as well as sleep complaints and suicidal ideation (OR 1.82, 95% CI 1.32-2.50; OR 1.91, 95% CI 1.33-2.76) in the total group and in young adults, respectively, but not among adolescents. Moreover, we detected a significant indirect effect of depressive symptoms on suicidal ideation mediated by sleep complaints (18.8%) in young adults. These findings support the hypothesis that treatment of sleep disturbances among youth with depression may independently further reduce suicidal risk.

Unveiling the longitudinal association between short sleep duration and the incidence of obesity: the Penn State Cohort.

OBJECTIVE: Several epidemiologic, longitudinal studies have reported that short sleep duration is a risk factor for the incidence of obesity. However, the vast majority of these studies used self-reported measures of sleep duration and did not examine the role of objective short sleep duration, subjective sleep disturbances and emotional stress. DESIGN: Longitudinal, population-based study. SUBJECTS: We studied a random sample of 815 non-obese adults from the Penn State Cohort in the sleep laboratory for one night using polysomnography (PSG) and followed them up for a mean of 7.5 years. Subjective and objective measures of sleep as well as emotional stress were obtained at baseline. Obesity was defined as a body mass index (BMI) ≥30 kg/ m(-2). RESULTS: The incidence of obesity was 15% and it was significantly higher in women and in individuals who reported sleep disturbances, shorter sleep duration and higher emotional stress. Significant mediating effects showed that individuals with subjective sleep disturbances who developed obesity reported the shortest sleep duration and the highest emotional stress, and that subjective sleep disturbances and emotional stress were independent predictors of incident obesity. Further analyses revealed that the association between short sleep duration, subjective sleep disturbances and emotional stress with incident obesity was stronger in young and middle-age adults. Objective short sleep duration was not associated with a significantly increased risk of incident obesity. CONCLUSION: Self-reported short sleep duration in non-obese individuals at risk of developing obesity is a surrogate marker of emotional stress and subjective sleep disturbances. Objective short sleep duration is not associated with a significant increased risk of incident obesity. The detection and treatment of sleep disturbances and emotional stress should become a target of our preventive strategies against obesity.

7th International Immunoglobulin Conference: Mechanisms of action.

Although intravenous immunoglobulin (IVIg) is widely used for replacement therapy in immunodeficiencies and to treat autoimmune and inflammatory diseases, its mechanisms of action are not fully understood. Examination of immunoglobulin (Ig) receptors, including the Fc-gamma receptors (FCγRs) and the neonatal Fc receptor, have revealed genetic variations that are linked to autoimmune diseases and to the efficacy of IVIg treatment. However, the beneficial effect of IVIg encompasses multiple mechanisms of action. One of these is scavenging of activated complement fragments, such as C3a, C5a, C3b and C4b, by infused Ig molecules. This interaction prevents binding of complement fragments to their receptors on target cells, thus attenuating the immune damage. Additionally, anti-inflammatory effects may be facilitated by IgA via specific receptors and/or complement scavenging. Glycosylation of both the Fc- and Fab-fragments has also been implicated in the anti-inflammatory action of IVIg. Although there is evidence to support a role for sialylated IgG glycovariants in mediating the effect of IVIg, evidence from animal models of inflammatory disease suggest that sialylation may not be a critical factor. However, an increase in IgG glycosylation has been observed following IVIg treatment in Guillain-Barré syndrome patients, and this has been associated with improved clinical outcomes.

7th International Immunoglobulin Conference: Mechanisms of action.

The mechanism of action by which therapeutic administration of intravenous immunoglobulin (IVIg) is able to provide a beneficial effect in autoimmune and inflammatory diseases is not yet fully understood, but current research is providing some answers. Signalling via receptors that interact with immunoglobulin (Ig) is crucial, and genetic polymorphisms of the Fc receptors have clear links to disease and also appear to influence the outcome of IVIg treatment. Glycosylation of the IgG, Fc- or Fab-fragments has a role in enhancing or blocking the pro- and anti-inflammatory effector functions. In addition, and independently of Fc receptors and glycosylation, Fc fragment and the constant domain of the Fab fragment contain binding sites for activated complement fragments that mediate complement-scavenging based immunomodulation. Although IgG Fc sialylation may not be critical for IVIg activity, research in some diseases suggests that it is associated with improved clinical outcomes. Therefore, further investigation of how IgG and IgA receptor expression and regulation affects the outcome of IVIg treatment may further clarify the mechanisms behind IVIg, and provide valuable guidance for future treatment paradigms.

Ventral hernia repair with synthetic mesh in a contaminated field: a systematic review and meta-analysis.

PURPOSE: The use of mesh in ventral hernia repair becomes especially challenging when associated with a contaminated field. Permanent synthetic mesh use in this setting is currently debated and this discussion is yet to be resolved clinically or in the literature. We aim to systematically assess postoperative outcomes of non-absorbable synthetic mesh (NASM) used in ventral hernia repair in the setting of contamination. METHODS: A literature search of PubMed, Embase, Scopus, Cinahl, and Cochrane Library identified all articles from 2000-2020 that examined the use of NASM for ventral hernia repair in a contaminated field. Postoperative outcomes were assessed by means of pooled analysis and meta-analysis. Qualitative analysis was completed for all included studies using a modified Newcastle-Ottawa scale. RESULTS: Of 630 distinct publications and 104 requiring full review, this study included 17 articles published between 2007 and 2020. Meta-analysis demonstrated absorbable mesh was associated with more HR (OR 1.89, 1.15-3.12, p = 0.008), SSO (OR 1.43, 0.96-2.11, p = 0.087), SSI (OR 2.84, 1.85-4.35, p < 0.001), and unplanned reoperation (OR 1.99, 1.19-3.32, p = 0.009) compared to NASM. CONCLUSION: The use of NASM for ventral hernia repair in a contaminated field may be a safe alternative to absorbable mesh, as evidenced by lower rates of postoperative complications. This review counters the current clinical paradigm, and additional prospective randomized controlled trials are warranted.

An audit of cervical cytology in HIV-positive women.

OBJECTIVE: To investigate whether a cohort of human immunodeficiency virus-positive (HIV+) women were having annual cervical cytology as recommended by the English National Health Service cervical screening programme (NHSCSP) guidelines. METHODS: An audit of cervical cytology in an HIV+ cohort of 187 women by obtaining their last cervical cytology result and recall from local cytology services. RESULTS: Of the 187 women in the audit, two were ineligible, leaving 185 women, 167 (90.3%) of whom were aged 25-64 years and eligible for screening. Of the 185 women, 126 (68.1%) had a cytology history, 50 (27%) had never had cervical cytology and nine (4.9%) had inadequate details to ascertain whether or not they had a cytology history. Of the 126 with a cytology record, 34 (27%) had a current cytological abnormality, which was low grade in 25 (19.8%) and high grade in nine (7.1%). Among women aged 25-64 years attending the clinic, these percentages were significantly higher than expected for England as a whole (P < 0.001). Of 126 women with a cytology record, 29 (23%) were overdue for their recall date and of these the previous test was abnormal in 14 (48.3%). Cytology tests were taken within the community setting in 61 (48.4%), whereas 65 (51.6%) were seen either at an HIV sexual health clinic or were under colposcopy follow-up. Of 91 women with negative cytology only 50 (54.9%) were recommended for repeat in 12 months. CONCLUSION: This audit demonstrates a high rate of cytological abnormalities among HIV+ women compared with the screening population at large. Implementation of NHSCSP guidelines has been difficult and requires improved care pathways between HIV clinics, primary care and laboratories.

Intravenous immunoglobulins--understanding properties and mechanisms.

High-dose intravenous immunoglobulin (IVIg) preparations are used currently for the treatment of autoimmune or inflammatory diseases. Despite numerous studies demonstrating efficacy, the precise mode of action of IVIg remains unclear. Paradoxically, IgG can exert both pro- and anti-inflammatory activities, depending on its concentration. The proinflammatory activity of low-dose IVIg requires complement activation or binding of the Fc fragment of IgG to IgG-specific receptors (FcgammaR) on innate immune effector cells. In contrast, when administered in high concentrations, IVIg has anti-inflammatory properties. How this anti-inflammatory effect is mediated has not yet been elucidated fully, and several mutually non-exclusive mechanisms have been proposed. This paper represents the proceedings of a session entitled 'IVIg--Understanding properties and mechanisms' at the 6th International Immunoglobulin Symposium that was held in Interlaken on 26-28 March 2009. The presentations addressed how IgG may affect the cellular compartment, evidence for IVIg-mediated scavenging of complement fragments, the role of the dimeric fraction of IVIg, the anti-inflammatory properties of the minor fraction of sialylated IgG molecules, and the genetic organization and variation in FcgammaRs. These findings demonstrate the considerable progress that has been made in understanding the mechanisms of action of IVIgs, and may influence future perspectives in the field of Ig therapy.

Differential effects of earthquakes on patients with bipolar disorder versus schizophrenia: Findings from Crete, Greece, 2008-2010.

Electromagnetic radiation influences in many ways humans and animals, while earthquakes are known to be related with electromagnetic phenomena. We recently showed that large earthquakes reduced admissions of psychiatric patients, whereas small earthquakes were associated with increased number of admissions. Our aim was to examine the effect of seismic-related electromagnetic activity on two chronic and severe psychiatric disorders varying in terms of etiology and treatment, i.e. bipolar disorder and schizophrenia. Retrospective data concerning monthly admission rates of patients diagnosed with schizophrenia or bipolar disorder in the Psychiatric Unit of the University Hospital of Heraklion, Crete, Greece between 2008 and 2010 were analyzed in relation to the number of earthquakes with small (≥2) or larger magnitude in the Crete region in Greece. Results showed a marked reduction of acute admissions during a storm of large earthquakes, which was greater in patients with bipolar disorder (91.2%) than schizophrenia patients (52.4%). In addition there was a significant increase of admissions during a period of frequent small earthquakes, primarily among patients with bipolar disorder. The results suggest that electrostatic fields that accompany large earthquakes may have a protective effect on psychiatric disorders, particularly on bipolar disorder. These findings are consistent with the ameliorating effect of electromagnetic fields used in Electroconvulsive therapy (ECT) and Transcranial Magnetic Stimulation (TMS) in patients with bipolar disorder. Future studies focusing on the underlying mechanisms may lead to more specific treatments of psychiatric disorders.

Selective effects of CPAP on sleep apnoea-associated manifestations.

BACKGROUND: Visceral adiposity and obstructive sleep apnoea (OSA) may be independently associated with daytime sleepiness/low performance, insulin resistance, hypercytokinaemia, and/or hypertension. The objectives of this study are to simultaneously test these associations at baseline and after 3 months of continuous positive airway pressure (CPAP) therapy. MATERIALS AND METHODS: Sixteen obese men with OSA; 13 non-apnoeic, obese controls, and 15 non-obese controls were monitored in the sleep laboratory for four consecutive nights. Objective measures of daytime sleepiness and performance, serial 24 h plasma measures of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), TNF receptor 1 (TNF-r1) and adiponectin, fasting blood glucose and insulin, visceral adiposity and blood pressure were obtained. Sleep apnoeics were re-assessed using the same protocol after 3 months of CPAP. RESULTS: At baseline, IL-6, TNF-r1, and insulin resistance were highest in OSA patients, intermediate in obese controls, and lowest in non-obese controls (P < 0.05). Visceral fat was significantly greater in sleep apnoeics than obese controls and predicted insulin resistance and IL-6 levels, whereas OSA predicted TNF-r1 levels (P < 0.05). CPAP decreased daytime sleepiness and blood pressure (P < 0.05), but did not affect fasting glucose or insulin or around the clock adiponectin, IL-6, TNF-alpha, or TNF-r1 levels. CONCLUSIONS: In obese sleep apnoeics, visceral fat is strongly associated with insulin resistance and inflammation. CPAP decreases sleepiness and moderates hypertension but does not affect visceral adiposity, insulin resistance, hypoadiponectinaemia or hypercytokinaemia, all of which are independent risk factors for cardiovascular disease and diabetes.

Factors associated with repeat diagnosis of syphilis in genitourinary medicine (GUM) clinic attendees in the North East of England, 2002-2014.

This study aimed to identify factors associated with repeat syphilis infection in North East England, in order to inform local prevention and control opportunities. We undertook a case-case study comparing individuals diagnosed with single or multiple episodes of syphilis infection within genitourinary medicine (GUM) clinics in NE England (12 clinics serving a population of 2.5 million). Study cases were verified as having had true re-infection by a GUM clinician (using serological and/or clinical parameters) and control cases (3 per case) frequency matched to cases by age and year of presentation. The odds of exposure to sexual behavioural and clinical factors were compared for cases and control cases using stepwise multivariable logistic regression. We included 66 cases and 235 control cases. The majority of cases (62/66) and control cases (165/235) were men who had sex with men (MSM). Data were missing for 0-64% of cases across different variables. Following multivariable analysis HIV seropositivity (OR 23.3, 95% CI 4.32-125.9), failure to attend follow-up (OR 4.63, 95% CI 1.11-19.31), stage of infection and deprivation were associated with re-infection ( p < 0.001). In this study, HIV seropositivity and failure to attend follow-up were associated with re-infection with syphilis. Actions targeted at these groups may help to reduce ongoing transmission.

Hypothalamic-pituitary-adrenal axis activity in obese men with and without sleep apnea: effects of continuous positive airway pressure therapy.

CONTEXT: Previous studies on the association between the hypothalamic-pituitary-adrenal axis activity and sleep apnea (SA) and obesity are inconsistent and/or limited. OBJECTIVE: In this study, we evaluated the activity of the hypothalamic-pituitary-adrenal axis in nonpsychologically distressed obese subjects with and without SA and examined the impact of continuous positive airway pressure (CPAP) in SA patients. DESIGN AND PARTICIPANTS: In study I, four-night sleep laboratory recordings and serial 24-h plasma measures of cortisol were obtained in 45 obese men with and without apnea and nonobese controls. Sleep apneic patients were reassessed after 3 months of CPAP use. In study II, 38 obese men with and without sleep apnea and nonobese controls were challenged with ovine CRH administration after four nights in the sleep laboratory. RESULTS: The sleep patterns were similar between obese and nonobese controls. Twenty-four-hour plasma cortisol levels were highest in nonobese controls, intermediate in obese apneic patients, and lowest in obese controls (8.8 +/- 0.4 vs. 8.1 +/- 0.3 vs. 7.5 +/- 0.3 microg/dl, P < 0.05). CPAP tended to reduce cortisol levels in the apneic patients (difference -0.7 +/- .4 microg/dl, P = 0.1). CRH administration resulted in a higher ACTH response in both obese groups, compared with nonobese controls; the three groups were not different in cortisol response. CONCLUSIONS: Nonpsychologically distressed, normally sleeping, obese men had low cortisol secretion. The cortisol secretion was slightly activated by SA and returned to low by CPAP use. The low cortisol secretion in obesity through its inferred hyposecretion of hypothalamic CRH might predispose the obese to sleep apnea.

High-dose intravenous immunoglobulin exerts its beneficial effect in patients with dermatomyositis by blocking endomysial deposition of activated complement fragments.

In patients with dermatomyositis (DM) the earliest lesion is microvasculopathy mediated by deposition of C5b-C9 membranolytic attack complex (MAC) on intramuscular capillaries. This leads sequentially to muscle ischemia, necrosis of muscle fibers, and muscle weakness. High-dose intravenous immunoglobulin (IVIG), which can modulate complement-dependent tissue damage in animal models, has been shown to be effective in the treatment of patients with DM. We used an in vitro C3 uptake assay to examine 55 coded sera from 13 patients with DM and 5 patients with other non-complement-mediated neuromuscular diseases, before and after treatment with IVIG or placebo. Patients with active DM had a significantly higher baseline C3 uptake compared with the others (geometric mean 12,190 vs 3,090 cpm). Post-IVIG but not post-placebo sera inhibited the C3 uptake, without depleting the complement components, by 70.6-93.4%. The maximum inhibition of C3 uptake occurred within hours after IVIG infusion, started to rebound 2 d later, and reached pretreatment levels after 30 d. The serum levels of SC5b-9 complex production were high at baseline but normalized after IVIG therapy. Repeat biopsies from muscles of improved patients showed disappearance of C3b NEO and MAC deposits from the endomysial capillaries and restoration of the capillary network. We conclude that IVIG exerts its beneficial clinical effect by intercepting the assembly and deposition of MAC on the endomysial capillaries through the formation of complexes between the infused immunoglobulins and C3b, thereby preventing the incorporation of activated C3 molecules into C5 convertase. These findings provide the first serological and in situ evidence that IVIG modulates complement attack in a human disease.

Mechanism of therapeutic effect of high-dose intravenous immunoglobulin. Attenuation of acute, complement-dependent immune damage in a guinea pig model.

Studies were performed in in vitro and in vivo models to assess the effect of intravenous immunoglobulin (IVIG) on the development of acute complement-mediated tissue damage. IVIG significantly increased the duration of survival and frequently prevented the death of guinea pigs injected with anti-Forssman antiserum to cause lethal Forssman shock; no control animal treated with albumin and/or maltose vehicle survived. The most pronounced effect was achieve by delivering IVIG as one slow injection at 1,800 mg/kg 3 h before Forssman shock was elicited. Infusion of guinea pig IgG at the same dosage was similarly protective. A strong positive correlation was found between IgG plasma levels and survival time in guinea pigs treated with graded doses of IVIG. Therapy itself did not affect C3 and C4 levels nor the capacity to activate these components. In vitro studies showed almost complete inhibition of C3 uptake onto IgG-sensitized erythrocytes using serum from an IVIG-treated animal. We suggest that supraphysiologic levels of IVIG act in part by preventing active C3 fragments from binding to target cells. Infusion of high dose IVIG may be a rational approach to modulating acute, complement-dependent tissue damage in a variety of diseases in man.

Randomized trial of a hospital-based exercise training program after acute myocardial infarction: cardiac autonomic effects.

OBJECTIVES: This study sought to determine whether a moderate intensity supervised exercise training program, performed immediately after an uncomplicated acute myocardial infarction, improves recovery in cardiac autonomic function compared with standard advice about activity at home. BACKGROUND: Exercise training has beneficial effects on cardiac autonomic function and may improve prognosis after acute myocardial infarction. METHODS: Thirty-nine male and 10 female patients, mean (+/-SE) age 57 +/- 1 years, with an uncomplicated acute myocardial infarction were randomized to either a 6-week moderate intensity supervised hospital-based exercise training program (exercise group) or to an unsupervised low intensity home walking program (control group). Outcome measures included changes in baroreflex sensitivity (phenylephrine bolus method) and heart rate variability (24-h Holter monitoring) and the endurance time at 85% of peak oxygen consumption. RESULTS: At baseline, there were no significant differences in left ventricular ejection fraction (57 +/- 2% vs. 53 +/- 2%), frequency of anterior infarction (27% vs. 18%) and peak creatine kinase (1,256 +/- 170 vs. 2,599 +/- 295 IU) between the exercise and control groups. Baroreflex sensitivity (10.5 +/- 1.0 vs. 8.4 +/- 1.2 ms/mm Hg) and time domain measures of heart rate variability were also similar. After completion of the program, the exercise group exercised for a median of 15 min (interquartile range 12 to 25) at a workload of 104 +/- 7 W compared with 7 min (interquartile range 3.5 to 12) at a workload of 89 +/- 8 W in the control group (p < 0.01). There were significant (p < 0.001) improvements in baroreflex sensitivity and heart rate variability for the 49 patients combined but no differences between the exercise and control groups. Baroreflex sensitivity improved by 3.4 +/- 1.0 and 1.7 +/- 1.0 ms/mm Hg and the standard deviation of 24-h RR intervals by 36 +/- 6 and 40 +/- 10 ms, respectively (p > 0.1). CONCLUSIONS: A hospital-based exercise training program increased endurance capacity but did not improve recovery of cardiovascular antonomic function after uncomplicated acute myocardial infarction.

In vitro effects of skin lipid extracts on skin bacteria in relation to age and acne changes.

Skin lipid extracts of 185 persons of different age were tested in vitro against single representatives of skin bacteria: Staphylococcus aureus, S. epidermidis, Propionibacterium acnes, P. granulosum and Corynebacterium sp. in order to find differences in their inhibitory effects. Percentages of the extracts inhibiting the first 4 bacteria were nearly the same (about 20%) while corynebacteria were inhibited by only 3 extracts. Extracts showing these properties were isolated mainly from adolescents with acne changes, young adults, about 20 yr old, and from children 8--10 yr old, but not from elderly people. The age-related differences in growth inhibition may be related to known differences in relative composition of the sebum constituents according to age. Forty-two extracts of acne patients and healthy adults and adolescents showed an inverse effect in vitro: they enhanced bacterial growth. Growth enhancement was demonstrated only for P. granulosum.

A rapid FPLC method for purification of the third component of human and guinea pig complement.

A method is described for the purification of human and guinea pig C3 from small amounts of serum. This procedure requires only two steps--polyethylene glycol (PEG) precipitation and fast protein liquid chromatography (FPLC) Mono Q HR 10/10 ion exchange chromatography. The protocol takes less than two hours to complete and yields 4-6 mg of purified C3. Similar results, in terms of antigenic and functional recovery, were obtained for both human and guinea pig components. About 67% of C3 antigen was recovered from eluted fractions with fully preserved specific activity. Isolated C3 was over 95% pure as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography; this level of purity was confirmed by the absence of any observable contamination as assessed by immunoelectrophoresis using high titer anti-whole human serum. This method allows rapid and reproducible purification of fully active human or guinea pig C3 on a daily basis.

Increased in vitro uptake of the complement C3b in the serum of patients with Guillain-Barré syndrome, myasthenia gravis and dermatomyositis.

To examine the role of complement in certain autoimmune neuromuscular diseases, we used an in-vitro quantitative complement uptake assay that allows measurement of the capacity of patients' sera to deposit fragments of the third complement component onto sensitized targets. C3 uptake was significantly higher in patients with active dermatomyositis, Guillain-Barré syndrome and myasthenia gravis, compared to inclusion body myositis and controls. The in-vitro C3 uptake assay supports the role of C3b neoantigen and Membranolytic Attack Complex deposition in the target tissues and may be a useful tool to monitor disease activity in patients with complement-mediated neurological disorders.

Safety of slow pathway ablation in patients with atrioventricular node reentrant tachycardia and a long fast pathway effective refractory period.

Radiofrequency catheter ablation is an accepted primary therapy for atrioventricular (AV) node reentrant tachycardia (AVNRT). There is concern that slow pathway ablation in patients with a long anterograde fast pathway effective refractory period (ERP) may potentially impair subsequent node conduction. Eighteen patients (14 women; age 53 +/- 20 years) with symptomatic AVNRT, whose fast pathway ERP at baseline was > or = 500 ms, underwent slow pathway ablation. Their outcome was compared with 24 consecutive control patients (17 women; age 42 +/- 17 years) who underwent ablation for AVNRT whose fast pathway ERP at baseline was <500 ms (controls). Slow pathway ablation was successful in 16 patients (90%). One patient had inadvertent fast pathway ablation. In a second patient the slow pathway could not be ablated because of recurrent transient AV block. Ablation was successful in all patients in the control group. Transient AV block related to current application occurred in 4 patients (22%) versus 1 control (4%) (p = 0.07). After ablation, the AV node refractory period increased in patients (368 +/- 68 to 428 +/- 92 ms, p = 0.02) and in controls (282 +/- 35 to 336 +/- 55 ms, p <0.0001), but the fast pathway ERP shortened in both groups (patients: 558 +/- 63 to 428 +/- 92 ms, p = 0.003; controls: 356 +/- 53 to 336 +/- 55 ms, p = 0.05). Furthermore, the slope of the regression line relating to shortening of the fast pathway ERP to the baseline ERP was markedly steeper in patients compared with controls (1.9 vs 0.4, p <0.0001). The shortening of the fast pathway ERP was greater in patients compared with controls (122 +/- 130 vs 21 +/- 50 ms, p = 0.001). During a mean follow-up of 18 +/- 11 months, 1 patient with severe coronary artery disease died suddenly 2 years after ablation. There was no recurrence of clinical tachycardia, and none of the patients developed symptoms of bradycardia or required permanent pacing. Thus, slow pathway ablation in patients with AVNRT and a long fast pathway ERP is safe and effective.

Effect of phenylephrine infusion on atrial electrophysiological properties.

OBJECTIVE: To determine the effect of changes in autonomic tone induced by phenylephrine infusion on atrial refractoriness and conduction. DESIGN: Left and right atrial electrophysiological properties were measured before and after a constant phenylephrine infusion designed to increase sinus cycle length by 25%. SUBJECTS: 20 patients, aged 53 (SD 6) years, undergoing electrophysiological study for investigation of idiopathic paroxysmal atrial fibrillation (seven patients) or for routine follow up after successful catheter ablation of supraventricular tachycardia (13 patients). MAIN OUTCOME MEASURES: Changes in left and right atrial effective refractory periods, atrial activation times, and frequency of induction of atrial fibrillation. RESULTS: Phenylephrine (mean dose 69 (SD 18) mg/min) increased mean blood pressure by 22 (12) mm Hg (range 7 to 44) and lengthened sinus cycle length by 223 (94) ms (20 to 430). Left atrial effective refractory period lengthened following phenylephrine infusion from 250 (25) to 264 (21) ms (P < 0.001) but there was no significant change in right atrial effective refractory period: 200 (20) v 206 (29), P = 0.11. There was a significant relation between the effect of phenylephrine on sinus cycle length and on right atrial refractoriness (r = 0.6, P = 0.005) with shortening of right atrial refractoriness in patients with the greatest prolongation in sinus cycle length. During phenylephrine infusion, the right atrial stimulus to left atrial activation time at the basic pacing cycle length of 600 ms was unchanged, at 130 (18) v 131 (17) ms, but activation delay with a premature extrastimulus increased: 212 (28) v 227 (38) ms, P = 0.002. Atrial fibrillation was induced by two of 58 refractory period measurements at baseline and by 12 of 61 measurements during phenylephrine infusion (P < 0.01). Phenylephrine increased the difference between left and right atrial refractory periods by 22.8 (19.4) ms in the five patients with induced atrial fibrillation after phenylephrine compared to 0.9 (16.2) ms in the 13 patients without induced atrial fibrillation after phenylephrine infusion (P = 0.02). CONCLUSIONS: Phenylephrine infusion increased left atrial refractoriness and intra-atrial conduction delay following a premature right atrial extrastimulus. Induction of atrial fibrillation during phenylephrine infusion was associated with non-uniform changes in atrial refractoriness. These data support the concept that changes in autonomic tone may precipitate atrial fibrillation in susceptible individuals.