Dissociative Process and the Depressed Patient

This article postulates a connection between the clinical phenomena of depression and dissociation. In cases of patients presenting with recurrent bouts of depression without apparent causes, rather than positing a purely biological origin of the depressed states, I suggest the presence of an underlying dissociative process triggered by intense shame. Analyzing such shame as a phenomenon of severe self-judgment fueled by hidden, grandiose self-expectations, we can detect the powerful eliminatory force of dissociative process at work. For a self-identity precariously based on inflated standards, ordinary experiences of negative evaluation can become traumatic humiliations. The radical dissociation of such injury produces a state of mind devoid of significant memories, a pervasive sense of meaningless emptiness, and an impoverished sense of self. The treatment of such depressions is based on the recognition that the depression itself is a secondary phenomenon. Retrieving the primary, intolerable not-me experience of shamed humiliation will allow the patient to mourn the loss of great expectations.     

A novel TMEM16A splice variant lacking the dimerization domain contributes to calcium‐activated chloride secretion in human sweat gland epithelial cells

Sweating is an important physiological process to regulate body temperature in humans, and various disorders are associated with dysregulated sweat formation. Primary sweat secretion in human eccrine sweat glands involves Ca²⁺‐activated Cl^? channels (CaCC). Recently, members of the TMEM16 family were identified as CaCCs in various secretory epithelia; however, their molecular identity in sweat glands remained elusive. Here, we investigated the function of TMEM16A in sweat glands. Gene expression analysis revealed that TMEM16A is expressed in human NCL‐SG3 sweat gland cells as well as in isolated human eccrine sweat gland biopsy samples. Sweat gland cells express several previously described TMEM16A splice variants, as well as one novel splice variant, TMEM16A(acΔe3) lacking the TMEM16A‐dimerization domain. Chloride flux assays using halide‐sensitive YFP revealed that TMEM16A is functionally involved in Ca²⁺‐dependent Cl^? secretion in NCL‐SG3 cells. Recombinant expression in NCL‐SG3 cells showed that TMEM16A(acΔe3) is forming a functional CaCC, with basal and Ca²⁺‐activated Cl^? permeability distinct from canonical TMEM16A(ac). Our results suggest that various TMEM16A isoforms contribute to sweat gland‐specific Cl^? secretion providing opportunities to develop sweat gland‐specific therapeutics for treatment of sweating disorders.     

Optimizing implantable cardioverter-defibrillator treatment of rapid ventricular tachycardia: Antitachycardia pacing therapy during charging

BACKGROUND: Previous studies in implantable cardioverter-defibrillator (ICD) patients demonstrated the efficacy and safety of antitachycardia pacing (ATP) for rapid ventricular tachycardias (VT). To prevent shock delay in case of ATP failure, a new feature (ATP during charging) was developed to deliver ATP for rapid VT while charging for shock. OBJECTIVE: The purpose of this study was to determine the efficacy and safety of this new feature. METHODS: In a prospective, nonrandomized trial, patients with standard ICD indication received an EnTrust ICD. VT and ventricular fibrillation (VF) episodes were reviewed for appropriate detection, ATP success, rhythm acceleration, and related symptoms. RESULTS: In 421 implanted patients, 116 VF episodes occurred in 37 patients. Eighty-four (72%) episodes received ATP during or before charging. ATP prevented a shock in 58 (69%) of 84 episodes in 15 patients. ATP stopped significantly more monomorphic (77%) than polymorphic VTs (44%, P = .05). Five (6%) episodes accelerated after ATP but were terminated by the backup shock(s). No symptoms were related to ATP during charging. In four patients, 38 charges were saved by delivering ATP before charging. Of 98 induced VF episodes, 28% were successfully terminated by ATP versus 69% for spontaneous episodes (P <.01). CONCLUSION: Most VTs detected in the VF zone can be painlessly terminated by ATP delivered during charging, with a low risk of acceleration or symptoms. ATP before charging allows delivery of two ATP attempts before shock in the same time that would otherwise be required to deliver only one ATP plus a shock. It also offers potential battery energy savings.     

Host-derived amino acids support the proliferation of symbiotic bacteria

Animals are typically colonized by diverse bacterial symbionts, many of which are commensal and, in numerous cases, even essential for their host’s proper development and growth. In exchange, the host must supply a sufficient array and quantity of nutrients to support the proliferation and persistence of its microbial community. In this investigation, we have examined such a nutritional environment by determining the symbiotic competence of auxotrophic mutants of the bioluminescent bacterium Vibrio fischeri, and have demonstrated that the host squid Euprymna scolopes provides at least 9 aa to the growing culture of symbiotic V. fischeri present in its light-emitting organ. We also collected and analyzed the extracellular fluid from this organ, in which the symbionts reside, and confirmed that it contained significant amounts of amino acids. The combined results suggested that host-derived free amino acids, as well as peptides or proteins, are a source of the amino acids that support the growth of the symbionts. This work describes a technique to sample the symbionts and their surrounding environment without contamination by host tissue components and, in combination with molecular genetic studies, allows the characterization of the nutritional conditions that support a cooperative animal–bacterial symbiosis.     

Hypertension exacerbates the effect of hypercholesterolemia on the myocardial microvasculature

OBJECTIVE: Hypercholesterolemia (HC) and hypertension (HT) are both major risk factors for the development and progression of atherosclerotic heart disease, and their co-existence has been associated with an increased incidence of cardiac events in clinical studies. HC and HT are individually associated with abnormal myocardial vascular function, but whether HT exacerbates the HC-induced myocardial vascular dysfunction remains unclear. METHODS: We studied in pigs the effect of renovascular HT superimposed on diet-induced HC (HC+HT) on myocardial perfusion and microvascular permeability in vivo (using electron-beam computed tomography) in response to cardiac challenge (i.v. adenosine and dobutamine). The involvement of systemic and myocardial tissue oxidative stress in vitro was assessed by oxidizability of LDL, levels of endogenous antioxidants, and tissue activities of radical-scavenger systems. RESULTS: While in normal animals myocardial perfusion increased in response to i.v. adenosine (+36+/-13%, P<0.05), in HC and HT alone the increase was blunted. In HC+HT myocardial perfusion response was further attenuated and significantly lower than normal, and myocardial vascular resistance failed to decrease (+7.6+/-8.8 vs. -21.0+/-5.8%, P=0.02 versus normal). HC+HT also showed blunted response to dobutamine, and augmented increases in microvascular permeability in vivo. These functional abnormalities were associated with increased systemic and myocardial tissue oxidative stress compared to HC or HT alone, and a synergistic decrease in endogenous antioxidant defenses in myocardial tissue. Furthermore, chronic antioxidant vitamin supplementation in combined HC and HT improved myocardial vascular responses. CONCLUSION: HT amplifies the HC-induced myocardial microvascular dysfunction in vivo and increased oxidative stress in vitro. These alterations may potentially play a role in the increased incidence of cardiac events observed when HC and HT co-exist.     

Relationship between angiographic late loss and target lesion revascularization after coronary stent implantation: analysis from the TAXUS-IV trial

OBJECTIVES: We sought to evaluate the relationship between angiographic late loss and clinical outcomes in the drug-eluting stent era. BACKGROUND: The interrelationship between angiographic late loss, binary restenosis, and clinical recurrence (target lesion revascularization [TLR]) after coronary stent implantation has been incompletely evaluated. METHODS: Using the angiographic substudy of the TAXUS-IV trial, in which 1,314 patients with de novo coronary lesions were randomized to either the paclitaxel-eluting TAXUS stent or to its bare-metal equivalent, we defined the relationship between in-stent and analysis segment late loss, the shape of the late loss histogram (variance and skewedness), and nine-month TLR. RESULTS: Late loss by several measures was closely related to TLR (area under the receiver-operator curve >0.90). For individual vessels of the size in this study (2.8 +/- 0.5 mm), the likelihood of TLR did not exceed 5% until analysis segment late loss was >0.5 mm, and did not exceed 10% until late loss was >0.65 mm. At greater late losses, the late loss TLR relationship was steep and nearly linear. For the overall patient cohort, the rate of TLR was related, however, not only to median late loss, but also to measures of its statistical distribution (TLR increased with lack of homogeneous biologic response [greater variance and greater right skewedness]). Similar relationships held for late loss measured within the confines of the stent itself. CONCLUSIONS: Coronary stents result in large lumens with "room" to accommodate up to approximately 0.5 to 0.65 mm of tissue (angiographic analysis segment late loss) before the likelihood of clinical restenosis (TLR) exceeds 5% to 10%. These data have important implications toward understanding the absolute and relative efficacy of drug-eluting stents.     

Improved Detection and Analysis of Sensed and Paced Events in Dual Chamber Pacemakers with Extended Memory Function A Prospective Multicenter Trial in 626 Patients

PATIENTS AND METHODS: This prospective study analyzed the incidence of atrial arrhythmias in a population of 626 patients in 173 medical centers of eleven European countries and Japan with indication for a dual chamber pacemaker system. The accuracy of the new Automatic Interpretation for Diagnosis Assistance (AIDA) program which is included in Chorus pacemakers was evaluated and the AIDA analysis was compared to and proven with Holter monitoring. Data stored in the pacemakers' memories for the first 24 hours (D1) were compared with simultaneously recorded 24-hour surface electrocardiograms, and data stored over the following 28 days (D28) were examined against reported intercurrent symptoms. RESULTS: At D1, atrial arrhythmias were detected by AIDA in 60 of 626 patients (12%), consisting of atrial fibrillation (n = 29), atrial flutter (n = 4), and miscellaneous arrhythmias (n = 17), and closely corroborated by Holter monitoring (sensitivity 93.7%, specificity 94.9%). At D28, 149 of 386 patients (49%) had had episodes of automatic mode switch prompted by atrial arrhythmias. Symptoms were reported by 81 patients (54%), 92 (62%) had no histories of atrial arrhythmias, and 57 patients (38%) were neither symptomatic nor had histories of atrial arrhythmias. An inverse relationship was found between the number of atrial paced events and the occurrence of atrial arrhythmias (p < 0.001). A history of atrial arrhythmias and older age were associated with a higher risk of atrial arrhythmias (p < 0.05). In contrast, gender, hypertension, concomitant heart disease, or type of atrial lead fixation system were not related with the occurrence of atrial arrhythmias. CONCLUSION: AIDA allowed to confirm, or disprove, the occurrence of atrial arrhythmias as a source of symptoms reported during long-term follow-up. It could also be used to examine the efficacy of antiarrhythmic therapy, and be of assistance when weighing the needs for anticoagulation in patients experiencing asymptomatic atrial arrhythmias.     

Effects of oral magnesium therapy on exercise tolerance,exercise-induced chest pain,and quality of life in patients with coronary artery disease

Previous studies have demonstrated that magnesium supplementation improves endothelial function in patients with coronary artery disease (CAD). However, the impact on clinical outcomes, such as exercise-induced chest pain, exercise tolerance, and quality of life, has not been established. In a multicenter, multinational, prospective, randomized, double-blind and placebo-controlled trial, 187 patients with CAD (151 men, 36 women; mean +/- SD age 63 +/- 10 years, range 42 to 83) were randomized to receive either oral magnesium 15 mmol twice daily (Magnosolv-Granulat, total magnesium 365 mg provided as magnesium citrate) (n = 94) or placebo (n = 93) for 6 months. Symptom-limited exercise testing (Bruce protocol) and responses given on quality-of-life questionnaires were the outcomes measured. Magnesium therapy significantly increased intracellular magnesium levels ([Mg]i) in a substudy of 106 patients at 6 months compared with placebo (35.5 +/- 3.7 vs 32.6 +/- 2.9 mEq/L, p = 0.0151). Magnesium treatment significantly increased exercise duration time compared with placebo (8.7 +/- 2.1 vs 7.8 +/- 2.9 minutes, p = 0.0075), and lessened exercise-induced chest pain (8% vs 21%, p = 0.0237). Quality-of-life parameters significantly improved in the magnesium group. These findings suggest that oral magnesium supplementation in patients with CAD for 6 months results in a significant improvement in exercise tolerance, exercise-induced chest pain, and quality of life, suggesting a potential mechanism whereby magnesium could beneficially alter outcomes in patients with CAD.     

The emerging role of microRNAs in regulating immune and inflammatory responses in the lung

Chronic inflammatory diseases of the lung are leading causes of morbidity and mortality worldwide. Many of these disorders can be attributed to abnormal immune responses to environmental stimuli and infections. As such, understanding the innate host defense pathways and their regulatory systems will be critical to developing new approaches to treatment. In this regard, there is increasing interest in the role of microRNAs (miRNAs) in the regulation of pulmonary innate host defense responses and the inflammatory sequelae in respiratory disease. In this review, we discuss recent findings that indicate an important role for miRNAs in the regulation in mouse models of various respiratory diseases and in host defense against bacterial and viral infection. We also discuss the potential utility and limitations of targeting these molecules as anti-inflammatory strategies and also as a means to improve pathogen clearance from the lung.