Christopher W. T. Miller

Antimicrobial implications of vitamin D

Evidence exists that vitamin D has a potential antimicrobial activity and its deficiency has deleterious effects on general well-being and longevity. Vitamin D may reduce the risk of infection through multiple mechanisms. Vitamin D boosts innate immunity by modulating production of anti-microbial peptides (AMPs) and cytokine response. Vitamin D and its analogues via these mechanisms are playing an increasing role in the management of atopic dermatitis, psoriasis, vitiligo, acne and rosacea. Vitamin D may reduce susceptibility to infection in patients with atopic dermatitis and the ability to regulate local immune and inflammatory responses offers exciting potential for understanding and treating chronic inflammatory dermatitides. Moreover, B and T cell activation as well as boosting the activity of monocytes and macrophages also contribute to a potent systemic anti-microbial effect. The direct invasion by pathogenic organisms may be minimized at sites such as the respiratory tract by enhancing clearance of invading organisms. A vitamin D replete state appears to benefit most infections, with the possible noteworthy exception of Leishmaniasis. Antibiotics remain an expensive option, and misuse of these agents results in significant antibiotic resistance and contributes to escalating health care costs. Vitamin D constitutes an inexpensive prophylactic option and possibly therapeutic product either by itself or as a synergistic agent to traditional antimicrobial agents. This review outlines the specific antimicrobial properties of vitamin D in combating a wide range of organisms. We discuss the possible mechanisms by which vitamin D may have a therapeutic role in managing a variety of infections.

Acceptability of Mobile Phone Technology for Medication Adherence Interventions among HIV-Positive Patients at an Urban Clinic.

Mobile phone technology is increasingly used to overcome traditional barriers limiting access to care. The goal of this study was to evaluate access and willingness to use smart and mobile phone technology for promoting adherence among people attending an urban HIV clinic. One hundred consecutive HIV-positive patients attending an urban HIV outpatient clinic were surveyed. The questionnaire evaluated access to and utilization of mobile phones and willingness to use them to enhance adherence to HIV medication. The survey also included the CASE adherence index as a measure of adherence. The average age was 46.4 (SD = 9.2). The majority of participants were males (63%), black (93%), and Hispanic (11.4%) and reported earning less than

Meta-analysis of the efficacy and safety of prazosin versus placebo for the treatment of nightmares and sleep disturbances in adults with posttraumatic stress disorder

10,000 per year (67.3%). Most identified themselves as being current smokers (57%). The vast majority reported currently taking HAART (83.5%). Approximately half of the participants reported some difficulty with adherence (CASE < 10). Ninety-six percent reported owning a mobile phone. Among owners of mobile phones 47.4% reported currently owning more than one device. Over a quarter reported owning a smartphone. About 60% used their phones for texting and 1/3 used their phone to search the Internet. Nearly 70% reported that they would use a mobile device to help with HIV adherence. Those who reported being very likely or likely to use a mobile device to improve adherence were significantly more likely to use their phone daily (P = 0.03) and use their phone for text messages (P = 0.002). The vast majority of patients in an urban HIV clinic own mobile phones and would use them to enhance adherence interventions to HIV medication.

Molecular defects in the mannose binding lectin pathway in dermatological disease: Case report and literature review.

ABSTRACT Although sleep disturbances occur commonly in patients with posttraumatic stress disorder (PTSD) and are associated with adverse outcomes and increased suicidality, they are often inadequately addressed by antidepressant medications. Objective: This review aims to assess whether prazosin reduces nightmares, sleep disturbances, and illness severity in adults with PTSD. Method: Electronic databases (PubMed, PsycINFO) were searched in September 2014 for randomized controlled trials in adults. Search terms included posttraumatic stress disorder, prazosin, nightmares, and sleep disturbance. Included studies used prazosin and provided objective outcome data related to nightmares and/or sleep quality. Results: Six studies (191 participants) met the criteria for inclusion. Prazosin was more effective than placebo in improving nightmares (standardized mean difference [SMD] = 1.022, 95% confidence interval [CI] [0.41, 1.62], p = .001), sleep quality (SMD = 0.93, 95% CI [−0.02, 1.88], p = .054; and SMD = 1.14, 95% CI [0.24, 2.03], p = .01), and illness severity (SMD = 1.20, 95% CI [0.79, 1.61], p = .001, with no significant effect on systolic (SMD = −0.01, 95% CI [−0.40, 0.37], p = .94) or diastolic (SMD = 0.30, 95% CI [−0.09, 0.68], p = .154) blood pressure. Conclusion: PTSD-related nightmares, sleep disturbances, and overall illness severity showed a significant response to treatment with prazosin. With careful dose titration, prazosin was well tolerated and had no significant sustained effect on blood pressure.

Exercise-induced anaphylaxis: a serious but preventable disorder.

Mannose-binding lectin (MBL) and the Mannose-binding lectin-associated serine proteases (MASPs) are an essential aspect of innate immune responses that probably play an important but understudied role in cutaneous function. The MBL-MASP pathway appears to exert its primary role by assisting in the clearance of apoptotic skin cells (thus preventing accumulation and a subsequent autoimmune response) and promoting opsonophagocytosis of invading pathogens, limiting their dissemination. Deficiencies of the pathway have been described and are associated with infectious, autoimmune and vascular complications. However, the role of this pathway in dermatological disease is essentially unexplored. We describe 6 patients presenting with recurrent inflammatory and/or infectious skin conditions who also demonstrated severely low MBL levels. One patient also had a defect in the MASP2 gene. Genotype analysis revealed specific point mutations in the MBL2 promoter in all 6 patients and a variant MASP-2 gene in one patient. Five patients presented recurrent pustular skin infections (cellulitis, folliculitis and cutaneous abscess). A case of Grovers disease and one forme fruste of Behcets syndrome (orogenital ulcers) were also observed. The patients responded to antimicrobial therapy, although in some, recurrence of infection was the rule. It appears that MBL deficiency may contribute to recurrent skin infections and to certain forms of inflammatory skin disease. The mechanisms may relate to the role of this pathway in innate immunity, removal of apoptotic cells and in immune complexes. Further study of MBL pathway defects in dermatological disease is required.

Correlation Between Intrasac Pressure Measurements of a Pressure Sensor and an Angiographic Catheter During Endovascular Repair of Abdominal Aortic Aneurysm

Abstract Described for the first time approximately 30 years ago, exercise-induced anaphylaxis is a rare disorder characterized by development of a severe allergic response occurring after mild-to-strenuous physical activity. This disorder is especially important to recognize with the recent increase in physical activity and health fitness fads. A number of predisposing factors (eg, prior ingestion of particular food groups) linked to exercise-induced anaphylaxis has been outlined over the years. Mechanisms governing the condition are still being unveiled, and it is likely that one mechanism involves mast cell degranulation and inflammatory mediator generation resulting from the biochemical effects of exercise, sometimes in the presence of an ingested allergen such that wheat or shell fish. Clinical manifestations usually occur after around 10 minutes of exercise, and follow a specific sequence, starting with pruritis and widespread urticarial lesions, evolving into a more typical anaphylactic picture with respiratory distress and vascular collapse. Fatality is exceedingly rare, with only one documented case in the literature. There is an overlap of symptoms with other syndromes (such as systemic mastocytosis and cholinergic urticaria), and these should be remembered when establishing a differential. Treatment of exercise-induced anaphylaxis consists of immediate stabilization geared toward the anaphylactic response with epinephrine and antihistamines. The patient needs to be educated on preventive measures and equipped with an epinephrine autoinjector in the event of an emergency. Exercise-induced anaphylaxis remains a potentially serious disorder, and the health care provider should be aware of its clinical features and effective management strategies.

Epigenetic and Neural Circuitry Landscape of Psychotherapeutic Interventions

PURPOSE To establish a correlation between intrasac pressure measurements of a pressure sensor and an angiographic catheter placed in the same aneurysm sac before and after its exclusion by an endoprosthesis. METHODS Patients who underwent endovascular abdominal aortic aneurysm repair and received an EndoSureTM wireless pressure sensor implant between March 19 and December 11, 2004 were enrolled in the study. Simultaneous readings of systolic, diastolic, mean, and pulse pressure within the aneurysm sac were obtained from the catheter and the sensor, both before and after sac exclusion by the endoprosthesis (Readings 1 and 2, respectively). Intrasac pressure measurements were compared using Pearson’s correlation and Student’s t test. Statistical significance was set at p<0.05. RESULTS Twenty-five patients had the pressure sensor implanted, with simultaneous readings (i.e., recorded by both devices) obtained in 19 patients for Reading 1 and in 10 patients for Reading 2. There was a statistically significant correlation for all pressure variables during both readings, with p<0.01 for all except the pulse pressure in Reading 1 (p<0.05). Statistical significance of pressure variations before and after abdominal aortic aneurysm exclusion was coincident between the sensor and catheter for diastolic (p>0.05), mean (p>0.05), and pulse (p<0.01) pressures; the sole disagreement was observed for systolic pressure, which varied, on average, 31.23 mmHg by the catheter (p<0.05) and 22 mmHg (p>0.05) by the sensor. CONCLUSION The excellent agreement between intrasac pressure readings recorded by the catheter and the sensor justifies use of the latter for detection of post-exclusion abdominal aortic aneurysm pressurization.

Development of Tinnitus at a Low Dose of Sertraline: Clinical Course and Proposed Mechanisms.

The science behind psychotherapy has garnered considerable interest, as objective measures are being developed to map the patients subjective change over the course of treatment. Prenatal and early life influences have a lasting impact on how genes are expressed and the manner in which neural circuits are consolidated. Transgenerationally transmitted epigenetic markers as well as templates of enhanced thought flexibility versus evasion can be passed down from parent to child. This influences gene expression/repression (impacting neuroplasticity) and kindling of neurocircuitry which can perpetuate maladaptive cognitive processing seen in a number of psychiatric conditions. Importantly, genetic factors and the compounding effects of early life adversity do not inexorably lead to certain fated outcomes. The concepts of vulnerability and resilience are becoming more integrated into the framework of “differential susceptibility,” speaking to how corrective environmental factors may promote epigenetic change and reconfigure neural templates, allowing for symptomatic improvement. Psychotherapy is one such factor, and this review will focus on our current knowledge of its epigenetic and neurocircuitry impact.

Self-Limited Kleptomania Symptoms as a Side Effect of Duloxetine

Introduction. Serotonin is involved in filtering of auditory stimuli. Cochlear input is processed through complex interactions between serotonergic, glutamatergic, and GABAergic neurotransmitter systems. Options for treatment of tinnitus include selective serotonin reuptake inhibitors (SSRIs); however in rare instances this symptom may occur as a side effect of this class of medications. Case Presentation. A 50-year-old woman developed bilateral tinnitus after several weeks of being treated with sertraline 50 mg. She had been on a long-standing daily dose of aspirin 325 mg which had been discontinued shortly before starting sertraline. Medical work-up was negative for her symptom. Shortly after discontinuation of the medication, her tinnitus subsided completely. Discussion. Tinnitus is a rare side effect of sertraline and may be related to particular distribution of serotonin receptor subtypes within the auditory system, and serotonergic agents may reinforce or desensitize the activity of different receptors. Also, there may be a priming effect of salicylate agents on the auditory system, predisposing particular patients to be more sensitive to how auditory stimuli are processed.

Topiramate as Monotherapy or Adjunctive Treatment for Posttraumatic Stress Disorder: A Meta-Analysis: Topiramate as Treatment for PTSD

Introduction. Impulse control disorders (ICDs) have been described as a side effect of dopamine agonists, frequently used in neurodegenerative conditions affecting the nigrostriatal pathway. Serotonin-norepinephrine reuptake inhibitors (e.g., duloxetine) have dose-dependent differential affinity for monoaminergic transporters, inhibiting the dopamine transporter at higher doses, thus increasing availability of synaptic dopamine, with the potential for similar impulse control side effects. Case Presentation. A 19-year-old Asian-American female with a history of depression developed new-onset stealing behaviors after an increase in her dose of duloxetine from 60 mg to 90 mg; she described these actions as “compulsive” and irresistible, later experiencing either relief or guilt, features compatible with an ICD. Her symptoms eventually subsided with continued use of 90 mg of duloxetine. Discussion. To the knowledge of the authors, this is the first report of a patient developing new-onset ICD behaviors after being placed on a higher dose of duloxetine, which can inhibit the dopamine transporter and cause difficulty with impulse control. The self-resolving nature of the symptoms may result from compensatory upregulation of dopamine transporters, increasing reuptake of dopamine. Asian populations may be at a higher risk due to the frequent occurrence of CYP2D6 polymorphisms, which decrease the conversion of duloxetine to its inactive metabolites.