A religiously-tailored, multilevel intervention in African American churches to increase HIV testing: Rationale and design of the Taking It to the Pews cluster randomized trial.

HIV continues to disproportionately impact African American (AA) communities. Due to delayed HIV diagnosis, AAs tend to enter HIV treatment at advanced stages. There is great need for increased access to regular HIV testing and linkage to care services for AAs. AA faith institutions are highly influential and have potential to increase the reach of HIV testing in AA communities. However, well-controlled full-scale trials have not been conducted in the AA church context. We describe the rationale and design of a 2-arm cluster randomized trial to test a religiously-tailored HIV testing intervention (Taking It to the Pews [TIPS]) against a standard information arm on HIV testing rates among AA church members and community members they serve. Using a community-engaged approach, TIPS intervention components are delivered by trained church leaders via existing multilevel church outlets using religiously-tailored HIV Tool Kit materials and activities (e.g., sermons, responsive readings, video/print testimonials, HIV educational games, text messages) to encourage testing. Church-based HIV testing events and linkage to care services are conducted by health agency partners. Control churches receive standard, non-tailored HIV information via multilevel church outlets. Secondarily, HIV risk/protective behaviors and process measures on feasibility, fidelity, and dose/exposure are assessed. This novel study is the first to fully test an HIV testing intervention in AA churches - a setting with great reach and influence in AA communities. It could provide a faith-community engagement model for delivering scalable, wide-reaching HIV prevention interventions by supporting AA faith leaders with religiously-appropriate HIV toolkits and health agency partners.

Understanding the Scientific Basis of Post-traumatic Stress Disorder (PTSD): Precision Behavioral Management Overrides Stigmatization.

Post-traumatic stress disorder (PTSD) is a severe polygenic disorder triggered by environmental factors. Many polymorphic genes, particularly the genetic determinants of hypodopaminergia (low dopamine function), associate with a predisposition to PTSD as well as substance use disorder. Support from the National Institutes of Health for neuroimaging research and molecular, genetic applied technologies has improved understanding of brain reward circuitry functions that have inspired the development of new innovative approaches to their early diagnosis and treatment of some PTSD symptomatology and addiction. This review presents psychosocial and genetic evidence that vulnerability or resilience to PTSD can theoretically be impacted by dopamine regulation. From a neuroscience perspective, dopamine is widely accepted as a major neurotransmitter. Questions about how to modulate dopamine clinically in order to treat and prevent PTSD and other types of reward deficiency disorders remain. Identification of genetic variations associated with the relevant genotype-phenotype relationships can be characterized using the Genetic Addiction Risk Score (GARS®) and psychosocial tools. Development of an advanced genetic panel is under study and will be based on a new array of genes linked to PTSD. However, for now, the recommendation is that enlistees for military duty be given the opportunity to voluntarily pre-test for risk of PTSD with GARS, before exposure to environmental triggers or upon return from deployment as part of PTSD management. Dopamine homeostasis may be achieved via customization of neuronutrient supplementation "Precision Behavioral Management" (PBM™) based on GARS test values and other pro-dopamine regulation interventions like exercise, mindfulness, biosensor tracking, and meditation.

Occurrence and levels of glyphosate and AMPA in shallow lakes from the Pampean and Patagonian regions of Argentina.

Glyphosate (N-(phosphonomethyl)glycine) is a broad-spectrum systemic herbicide used to kill weeds that compete with commercial crops. In Argentina, the use of glyphosate-based herbicides increased dramatically (up to ∼200,000 tons on 2012) since the introduction of glyphosate-resistant crops, such as transgenic soy and resistant corn, and the adoption of non-till practices in the 1990's. Sallow lakes within the Pampa region may be potentially impacted by continuous herbicide usage. We surveyed 52 shallow lakes from the Pampa region (Buenos Aires Province, Argentina) to assess the occurrence and concentrations of glyphosate and its main degradation product (AMPA). For comparison, we also sampled 24 shallow lakes from an area with no agricultural use of glyphosate (Northern Patagonia). Glyphosate and AMPA were analyzed by UPLC-MS/MS ESI (±) in lake water, suspended particulate matter (SPM), and sediment samples. Within the Pampa region, glyphosate residues were detected in >40% of samples. Glyphosate residues were detected more frequently in sediment and surface water than in SPM samples. The mean (maximum) concentrations of glyphosate were 2.11 (4.52) µg l-1 for surface water; 0.10 (0.13) µg l-1 for SPM and 10.47 (20.34) µg kg-1 for sediment samples, respectively. Whereas, mean (maximum) concentrations of AMPA were 0.84 and (0.90) µg l-1 for surface water; 0.07 (0.07) µg l-1 for SPM; and 22.53 (32.89) µg kg-1 for sediment samples. The herbicide was not detected in samples from the Patagonian region. To our knowledge, this is the first study reporting the occurrence and concentrations of the herbicide in freshwater lakes of Argentina.

Influenza vaccination is safe and effective in patients suffering from fibromyalgia syndrome.

The fibromyalgia syndrome (FMS) is considered to result from the exposure of a genetically susceptible individual to various triggers, such as physical trauma, stress, viral infections etc. A possible role of vaccination in FMS etiology has been suspected. Our objective was to evaluate the efficacy and safety of influenza vaccination in FMS patients. Nineteen FMS patients underwent physical and dolorimetric examinations and answered the fibromyalgia impact questionnaire (FIQ), the widespread pain index (WPI) checklist and the symptoms severity scale (SSS), which are part of the 2010 diagnostic criteria. Thirty-eight healthy subjects were recruited as controls. All participants were vaccinated with the inactivated split virion influenza vaccine. Serum was collected for antibody titration. Six weeks after vaccination, sera were tested by hemagglutination (HI) against A/California (H1N1), A/Perth (H3N2) and B/Brisbane. Humoral response was defined as either a fourfold or greater increase in titer, or an increase from a non-protective baseline level of <1/40 to a level of 1/40. No severe vaccination reactions were observed. No significant change was observed between WPI, SSS and FIQ values before and after vaccination, indicating no worsening of FMS symptoms. Vaccine immunogenicity: Six weeks after vaccination, FMS patients showed a significant increase in geometric mean titers of HI antibody. The rates of sero-protection increased from 22.9% for H1N1 to 89.5% post-vaccination. A significant increase in HI antibody titers was also demonstrated among healthy controls. Influenza vaccination was both safe and effective in FMS patients. In view of these results, FMS patients should be encouraged to undergo influenza vaccination according to the standard WHO recommendations.

Apolipoprotein Gene Polymorphisms (APOB, APOC111, APOE) in the Development of Coronary Heart Disease in Ethnic Groups of Kazakhstan.

BACKGROUND: Previous Analysis of polymorphism of genes associated with the development of coronary heart disease (CHD) reveals that the frequency distribution of genotypes and alleles depends on the ethnic characteristics of the populations under study. Further impetus is derived from the well -established links between alcoholism (high prevalence in Kazakhstan region) and cardiovascular disorders. OBJECTIVES: The purpose of this study was to examine a number of apolipoprotein gene polymorphisms and correlate these alleles with changes of lipid profile in CHD patients of Kazakh and Uyghur nationalities. METHODS: Four-Hundred Forty Eight (448) males of Kazakh and Uyghur nationalities residing in Kazakhstan were evaluated and genotyped. The age range of these subjects was 30-55 years which included both afflicted and controls. Specifically, 161- Kazakhs suffered from myocardial infarction compared to 112 health controls; 80- Uyghurs suffered from CHD compared to 95 health controls. Blood lipid profiles were examined in the total cohort. Genotyping was performed by polymerase chain reaction (PCR) using oligonucleotide primers identifying; ApoB; ApoC111; and APOE gene polymorphisms. RESULTS: Initial screening revealed a significant inter-ethnic difference on the frequency of alleles associated with both the ApoB and APOE genes. We found that the X1 ApoB gene polymorphism is overrepresented in healthy Kazakhs relative to Uyghurs [86.4% in Kazakhs vs. 69.4% in Uyghurs]. Moreover, we found that the E4APOE allele was also overrepresented in healthy Kazakhs relative to Uyghurs [16.8% in Kazakhs vs. 9.5% in Uyghurs]. There was a significant relationship of polymorphisms of APOE such as ApoB and ApoC 111 with the value of lipid indices in Kazakhs. Additionally, we found that the E4 allele of the APOE gene also correlated with the value of lipid indices in Kazakhs. Further evaluation showed that the X2 allele of the ApoB and the S2 allele of the ApoCIII gene significantly associated with the lipid indices of Uyghurs. CONCLUSION: This systematic investigation confirms the association of various alleles of Apolipoprotein gene polymorphisms and contribution to aberrant lipid metabolism. Putatively at least in our population we are proposing that certain gene polymorphisms of Apolipoprotein genes such as ApoB; ApoC111; APOE ; X2 of ApoB; and S2 of ApoCIII differentially represented in either Kazakhs or Uyghurs are genetic markers of hypertriglyceridemia.

Have We Hatched the Addiction Egg: Reward Deficiency Syndrome Solution System™

This article co-authored by a number of scientists, ASAM physicians, clinicians, treatment center owners, geneticists, neurobiologists, psychologists, social workers, criminologists, nurses, nutritionist, and students, is dedicated to all the people who have lost loved ones in substance-abuse and "reward deficiency syndrome" related tragedies. Why are we failing at reducing the incidence of 'Bad Behaviors'? Are we aiming at the wrong treatment targets for behavioral disorders? We are proposing a paradigm shift and calling it "Reward Deficiency Solution System" providing evidence for its adoption.

Pharmacotherapies for Overeating and Obesity.

Obesity has become pandemic, and the annual cost in related illnesses and loss of productivity is already over $100 billion and rising. Research has shown that obesity can and does cause changes in behavior and in the brain itself that are very similar to changes caused by drugs of abuse. While food addiction is not the causal agent of all obesity, it is clear that many people no longer eat to survive, but instead survive to eat. This review considers the importance of the brain's reward system in food intake. The review also examines research developments and current treatments for obesity, including diet and exercise, psychotherapy, surgical interventions, and pharmacotherapies. Finally we discuss alterations in American society that are necessary for change to occur, and the diffculties therein.

Low and Normal IGF-1 Levels in Patients with Chronic Medical Disorders (CMD) is Independent of Anterior Pituitary Hormone Deficiencies: Implications for Treating IGF-1 Abnormal Deficiencies with CMD.

Over time, based on evidence-based medicine, a number of hormonal test levels including IGF-1 had been raised or lowered to meet new criteria standards. In particular, IGF-1 plasma levels have been shown in several studies to be an independent diagnostic tool in Adult Growth Hormone Deficiency (AGHD). Many endocrinology studies link low IGF-1 plasma levels with low levels of other anterior pituitary hormones (i.e., LH, FSH, and TSH). Low IGF-1 is considered by most to be between 84-100 µ/l and numerous studies recommend that raising IGF-1 to high normal range reverses Chronic Medical Diseases (CMD), improves bone mineral density (BMD), and fibromyalgia. Moreover, some studies suggest that low levels of IGF-1 by itself independent of anterior pituitary deficiencies is sufficient to determine AGHD in humans. In order to determine the relationship of low IGF-1 with that of LH, FSH, and TSH levels in subjects with CMD, we evaluated these levels (± SD) in 944 patients. Patients with IGF-1 below 84 µ/l, 100 µ/l, and 150 µ/l were accessed. 9.22% had less than 84 µ/l (SD ± 12.52); 19.9% had less than 100 µ/l (SD ± 9.54); and 51.6 had less than 150 µ/l (SD ± 26.0). Specifically, the percentages found for low LH, FSH, and TSH were only 4.2%, 4.8%, and 6.5%. We conclude that IGF-1 deficiencies occur independent of comorbid deficiencies of LH, FSH, and TSH. Finally, we propose that based on the present investigation, IGF-1 low levels between the range of 84-100 µ/l may be too low to be considered as an independent diagnostic marker to treat AGHD with CMD.

Common Phenotype in Patients with Both Food and Substance Dependence: Case Reports.

The understanding that genes play a significant role in reward dependence and associated behavioral and drug addictions is highlighted in the emergence of Reward Deficiency Syndrome (RDS). Here we show two case reports that unequivocally indicate the definite commonality between food and drug addiction. These human cases not atypically raise the question as to how to treat these two seemingly diverse addictions. We suggest that research directed in an attempt to induce natural activation of dopaminergic reward circuitry as a form of common therapy may indeed be parsimonious.

Dopamine Genetics and Function in Food and Substance Abuse.

Having entered the genomics era with confidence in the future of medicine, including psychiatry, identifying the role of DNA and polymorphic associations with brain reward circuitry has led to a new understanding of all addictive behaviors. It is noteworthy that this strategy may provide treatment for the millions who are the victims of "Reward Deficiency Syndrome" (RDS) a genetic disorder of brain reward circuitry. This article will focus on drugs and food being mutuality addictive, and the role of dopamine genetics and function in addictions, including the interaction of the dopamine transporter, and sodium food. We will briefly review our concept that concerns the genetic antecedents of multiple-addictions (RDS). Studies have also shown that evaluating a panel of established reward genes and polymorphisms enables the stratification of genetic risk to RDS. The panel is called the "Genetic Addiction Risk Score (GARS)", and is a tool for the diagnosis of a genetic predisposition for RDS. The use of this test, as pointed out by others, would benefit the medical community by identifying at risk individuals at a very early age. We encourage, in depth work in both animal and human models of addiction. We encourage further exploration of the neurogenetic correlates of the commonalities between food and drug addiction and endorse forward thinking hypotheses like "The Salted Food Addiction Hypothesis".

Epigenetic Modulation of Mood Disorders.

BACKGROUND: Mood disorders are expressed in many heterogeneous forms, varying from anxiety to severe major clinical depression. The disorders are expressed in individual variety through manifestations governed by co-morbidities, symptom frequency, severity, and duration, and the effects of genes on phenotypes. The underlying etiologies of mood disorders consist of complex interactive operations of genetic and environmental factors. The notion of endophenotypes, which encompasses the markers of several underlying liabilities to the disorders, may facilitate efforts to detect and define, through staging, the genetic risks inherent to the extreme complexity of disease state. AIMS: This review evaluates the role of genetic biomarkers in assisting clinical diagnosis, identification of risk factors, and treatment of mood disorders. METHODS: Through a systematic assessment of studies investigating the epigenetic basis for mood disorders, the present review examines the interaction of genes and environment underlying the pathophysiology of these disorders. RESULTS: The majority of research findings suggest that the notion of endophenotypes, which encompasses the markers of several underlying liabilities to the disorders, may facilitate efforts to detect and define, through staging, the genetic risks inherent to the extreme complexity of the disease states. Several strategies under development and refinement show the propensity for derivation of essential elements in the etiopathogenesis of the disorders affecting drug-efficacy, drug metabolism, and drug adverse effects, e.g., with regard to selective serotonin reuptake inhibitors. These include: transporter gene expression and genes encoding receptor systems, hypothalamic-pituitary-adrenal axis factors, neurotrophic factors, and inflammatory factors affecting neuroimmune function. Nevertheless, procedural considerations of pharmacogenetics presume the parallel investment of policies and regulations to withstand eventual attempts at misuse, thereby ensuring patient integrity. CONCLUSIONS: Identification of genetic biomarkers facilitates choice of treatment, prediction of response, and prognosis of outcome over a wide spectrum of symptoms associated with affective states, thereby optimizing clinical practice procedures. Epigenetic regulation of primary brain signaling, e.g., serotonin and hypothalamic-pituitary-adrenal function, and factors governing their metabolism are necessary considerations. The participation of neurotrophic factors remains indispensable for neurogenesis, survival, and functional maintenance of brain systems.

Neurogenetic Impairments of Brain Reward Circuitry Links to Reward Deficiency Syndrome (RDS): Potential Nutrigenomic Induced Dopaminergic Activation.

Work from our laboratory in both in-patient and outpatient facilities utilizing the Comprehensive Analysis of Reported Drugs (CARD)(™) found a significant lack of compliance to prescribed treatment medications and a lack of abstinence from drugs of abuse during active recovery. This unpublished, ongoing research provides an impetus to develop accurate genetic diagnosis and holistic approaches that will safely activate brain reward circuitry in the mesolimbic dopamine system. This editorial focuses on the neurogenetics of brain reward systems with particular reference to genes related to dopaminergic function. The terminology "Reward Deficiency Syndrome" (RDS), used to describe behaviors found to have an association with gene-based hypodopaminergic function, is a useful concept to help expand our understanding of Substance Use Disorder (SUD), process addictions, and other obsessive, compulsive and impulsive behaviors. This editorial covers the neurological basis of pleasure and the role of natural and unnatural reward in motivating and reinforcing behaviors. Additionally, it briefly describes the concept of natural dopamine D2 receptor agonist therapy coupled with genetic testing of a panel of reward genes, the Genetic Addiction Risk Score (GARS). It serves as a spring-board for this combination of novel approaches to the prevention and treatment of RDS that was developed from fundamental genomic research. We encourage further required studies.

Ureteroarterial fistula.

Ureteral-iliac artery fistula (UIAF) is a rare life threatening cause of hematuria. The increasing frequency is attributed to increasing use of ureteral stents. A 68-year-old female presented with gross hematuria. She had prior low anterior resection for rectal cancer and a retained ureteral stent. CT abdomen and pelvis showed a large recurrent pelvic mass and a retained stent. The patient underwent cystoscopy which showed a normal bladder. Upon removal of the stent, brisk bleeding was noted coming from the ureteral orifice. Antegrade pyelogram was done which revealed a UIAF. Angiography was done and a covered stent was placed. Multiple treatment options are available. All must consider management of the arterial and ureteral side. The arterial side may be addressed by primary open repair, embolization with extra-anatomic vascular reconstruction, or endovascular stenting. The ureter can be managed with nephroureterectomy, ureteral reconstruction, placement of a nephrostomy tube, or ureteral stenting. Being minimally invasive, we believe that endovascular stenting should be the preferred therapeutic option as it also corrects the source of bleeding while preserving distal blood flow.

A case series investigating acceptance and commitment therapy as a treatment for previously treated, unremitted patients with anorexia nervosa.

The aim of the present study was to evaluate the effectiveness of Acceptance and Commitment Therapy (ACT) for treatment of anorexia nervosa (AN) using a case series methodology among participants with a history of prior treatment for AN. Three participants enrolled; all completed the study. All participants had a history of 1-20 years of intensive eating disorder treatment prior to enrollment. Participants were seen for 17-19 twice-weekly sessions of manualized ACT. Symptoms were assessed at baseline, post-treatment and 1-year follow-up. All participants experienced clinically significant improvement on at least some measures; no participants worsened or lost weight even at 1-year follow-up. Simulation modelling analysis (SMA) revealed for some participants an increase in weight gain and a decrease in eating disorder symptoms during the treatment phase as compared to a baseline assessment phase. These data, although preliminary, suggest that ACT could be a promising treatment for subthreshold or clinical cases of AN, even with chronic participants or those with medical complications.

Contrasted patterns of age-specific reproduction in long-lived seabirds.

While the number of studies providing evidence of actuarial senescence is increasing, and covers a wide range of taxa, the process of reproductive senescence remains poorly understood. In fact, quite high reproductive output until the last years of life has been reported in several vertebrate species, so that whether or not reproductive senescence is widespread remains unknown. We compared age-specific changes of reproductive parameters between two closely related species of long-lived seabirds: the small-sized snow petrel Pagodroma nivea, and the medium-sized southern fulmar Fulmarus glacialoides. Both are sympatric in Antarctica. We used an exceptional dataset collected over more than 40 years to assess age-specific variations of both breeding probability and breeding success. We found contrasted age-specific reproductive patterns between the two species. Reproductive senescence clearly occurred from 21 years of age onwards in the southern fulmar, in both breeding probability and success, whereas we did not report any decline in the breeding success of the snow petrel, although a very late decrease in the proportion of breeders occurred at 34 years. Such a contrasted age-specific reproductive pattern was rather unexpected. Differences in life history including size or migratory behaviour are the most likely candidates to account for the difference we reported in reproductive senescence between these sympatric seabird species.

Neural and psychological predictors of treatment response in irritable bowel syndrome patients with a 5-HT3 receptor antagonist: a pilot study.

BACKGROUND: Symptom improvement in irritable bowel syndrome (IBS) treatment trials varies widely, with only 50-70% of patients qualifying as responders. Factors predicting treatment responsiveness are not known, although we have demonstrated that symptom improvement with the 5-HT3R antagonist alosetron is correlated with reduced amygdala activity. AIM: To determine whether neural activity during rectal discomfort or psychological distress predicts symptom improvement following treatment with alosetron. METHODS: Basal psychological distress and neural activity (15O PET) during uncomfortable rectal stimulation were measured in 17 nonconstipated IBS patients who then received 3 weeks of alosetron treatment. RESULTS: Greater symptom improvement was predicted by less activity in bilateral orbitofrontal cortex (OFC) and medial temporal gyrus during pre-treatment scans. Lower levels of interpersonal sensitivity predicted greater symptom improvement and were positively related to activity in left OFC. Connectivity analysis revealed a positive relationship between activity in the left OFC and right amygdala. CONCLUSIONS: Irritable bowel disease symptom improvement with 5-HT3R antagonist alosetron is related to pre-treatment reactivity of the left OFC, which may be partially captured by subjective measures of interpersonal sensitivity. The left OFC may fail to modulate amygdala response to visceral stimulation, thereby diminishing effectiveness of treatment. Psychological factors and their neurobiological correlates are plausible predictors of IBS treatment outcome.

Emergency percutaneous coronary intervention (PCI) for the care of patients with ST-elevation myocardial infarction (STEMI).

There is general consensus that emergency percutaneous coronary intervention (PCI) is the preferred treatment for patients with ST-elevation myocardial infarction (STEMI), so long as it can be delivered in a timely fashion, by an experienced' operator and cardiac catheterization laboratory (CCL) team. STEMI is both a functional and structural issue. Although it has been recognized since the work of pioneering cardiologists and surgeons in Spokane, Washington, that approximately 88% of patients presenting within 6 hours of onset of STEMI have an occluded coronary artery, it is the pathophysiology of myocardial necrosis, and the varied consequences of necrosis that characterize STEMI. Accordingly, experience' of both primary operator and cardiac catheterization laboratory (CCL) crew, in performing an emergency PCI for STEMI, are as much a function of experience with the treatment of complex MI patients, as experience with coronary intervention. Rapidly achieving normal coronary artery flow, at both the macro and micro vascular levels, is the recognized key to aborting the otherwise progressive wavefront' of myocardial necrosis. The time urgency of decisions (Time is muscle') make emergency PCI for patients with on-going necrosis, more like emergency room (ER) care, than like most in-hospital or outpatient care. In general, most patients with acute coronary syndromes (ACS) are currently thought to have plaque rupture and/or erosion with subsequent thrombosis and embolization. Consequences of thrombo-embolism, such as slow flow' or no-reflow' are in addition to, the structural (anatomic) considerations of PCI in stable patients (such as ostial location; bifurcation involvement; heavy calcification; tortuosity of lesion or access to it; length of disease; caliber of infarct-artery; etc.). Good quality studies have provided strong support for the specific added value of glycoprotein IIb/IIIa inhibitors (especially abciximab), dual antiplatelet therapy (the addition of the thienopyridine, clopidogrel, to aspirin use), and bare-metal stents (BMS), for a broad range of STEMI patients. The added value of drug-eluting stents (DES) to bare-metal stents (BMS), primarily in terms of reducing restenosis and repeat revascularization, is supported by several randomized trials, and a number of registries, despite its being off-label' from a regulatory standpoint. The recognition of late stent thrombosis (LST) has raised additional issues, in choosing between these two options for specific STEMI patients. The added value of a number of other mechanical approaches to coronary thrombus, such as thrombus removal devices, and/or distal protection, are more controversial, and perhaps, patient specific. Whether intravascular ultrasound guidance (IVUS) for stent use should be used for the majority, or even a specific minority, of STEMI patients, is also controversial; late-stent thrombosis provides a counter-point. The advantages of developing a network approach to STEMI care, so as to optimize the number of patients receiving timely reperfusion, have been demonstrated in Prague, Denmark, and Minneapolis, among many places. The benefits of both bivalirudin (anti-thrombin drug with efficacy against clot-bound thrombin, which does not appear to stimulate platelets) and abciximab (glycoprotein IIb/IIIa inhibitor which is antibody to platelet receptors), as PCI adjuncts generally, and for STEMI patients, in particular, are supported by multiple trials. The specific choice of administering the bolus dose of either, or both, drugs via intra-coronary (IC) injection follows the precedents' of IC thrombolytics, and IC small-vessel vasodilators for no-reflow', but it has not been tested by prospective, randomized trials. Although rapid reperfusion is the first objective, one cannot ignore the other components of the oxygen delivery chain, and the importance of each of these components to on-going delivery of oxygen to all vital organs. A balance must be struck between doing those control' things which serve to stabilize other vital components of the oxygen-delivery chain, without digressing too long from the job of re-establishing brisk coronary flow. The clinical and angiographic heterogeneity of STEMI patients and the array of available therapeutic approaches make it impossible to obtain specific randomized trial direction for many of the clinical decisions in an individual emergency PCI for STEMI. There are a range of reasonable/ appropriate therapeutic choices for a given emergent PCI performed by multiple experienced and competent operators. The treatment of STEMI, and high-risk non-STEMI, patients, by means of emergent PCI, is among the most challenging and rewarding arenas in contemporary medicine.

Bioequivalence study of two fluoxetine capsule formulations in healthy Middle Eastern volunteers.

OBJECTIVE: To assess the bioequivalence of two fluoxetine hydrochloride capsule (20 mg) formulations (Fluoxicare capsule from Pharmacare Ltd., Chemicals and Cosmetics, Ramallah, Palestine, as test formulation, and Prozac from Eli Lilly Ltd., Basingstoke, UK, as reference formulation). DESIGN AND METHODS: The study was conducted open with a randomized 2-period crossover design and a 6-week washout period. Participants were 24 healthy male volunteers aged 18-28 years, divided into 2 groups of 12 subjects. One group was given the originator drug (reference formulation), and the other was given the test formulation. Blood samples were obtained at baseline and at 14 time points during the interval 0-96 hours after drug administration. The concentrations of the samples were assayed spectrophotometrically at 220 nm using a Shimadzu 160 A UV-visible spectrometer. We calculated the plasma concentration-time curve (AUC), maximum plasma concentration (Cmax), and time of maximum plasma concentration (tmax) for each subject. Logarithmic transformation of the AUC and Cmax was used for the statistical analyses and to assess the bioavailability of the two formulations, using analyses of variance (ANOVA) and Satherwait t-tests for unequal variances. The ANOVA performed of tmax in Cmax, and in AUC provided the appropriate intra-subject variance estimates to evaluate the 90% confidence intervals for the differences between study variables after administration of the test and reference formulations. Statistical analyses were conducted on AUC 0-4 as the extrapolated part of the AUC, a truncated area approach was adapted. RESULTS: The mean pharmacokinetic parameters for both of the drugs under study were as follows: Cmax = 61.24 (+/- 12.96) ng/ml for the test formulation, and for the reference formulation Cmax = 61.39 (+/- 14.1) ng/ml, the effects were statistically equivalent. The tmax for the test formulation was 8.25 (+/- 1.7) and 7.33 (+/- 0.96) for the reference formulation. The area under the curve to infinity (AUC 0-infinity (ng, day/ml)) for the test formulation and for the reference formulation were 293.02 (+/- 52.69) and 296.15 (+/- 61.69), respectively. CONCLUSIONS: The two formulations had equivalent pharmacokinetic parameters, were well-tolerated, and their relative bioavailability was 98.94%.

Intracerebral hemorrhage in pregnancy: frequency, risk factors, and outcome.

OBJECTIVE: To describe the frequency, risk factors, and outcome of intracerebral hemorrhage (ICH) in pregnancy and the postpartum period using a large database of US inpatient hospitalizations. METHODS: The authors obtained data from an administrative dataset, the Nationwide Inpatient Sample, which includes approximately 20% of all discharges from non-Federal hospitals, for the years 1993 through 2002. Women aged 15 to 44 years with a diagnosis of ICH were selected from the database for analysis, and within this group patients coded as pregnant or postpartum were identified. Using US Census data, estimates were made of the rates of ICH in pregnant/postpartum and non-pregnant women. Rates of various comorbidities in patients with pregnancy-related ICH were compared to the rates found in the general population of delivering patients using multivariate logistic regression to identify independent risk factors for pregnancy-related ICH. RESULTS: The authors identified 423 patients with pregnancy-related ICH, which corresponded to 6.1 pregnancy-related ICH per 100,000 deliveries and 7.1 pregnancy-related ICH per 100,000 at-risk person-years (compared to 5.0 per 100,000 person-years for non-pregnant women in the age range considered). The increased risk of ICH associated with pregnancy was largely attributable to ICH occurring in the postpartum period. The in-hospital mortality rate for pregnancy-related ICH was 20.3%. ICH accounted for 7.1% of all pregnancy-related mortality recorded in this database. Significant independent risk factors for pregnancy-related ICH included advanced maternal age (OR 2.11, 95% CI 1.69 to 2.64), African American race (OR 1.83, 95% CI 1.39 to 2.41), preexisting hypertension (OR 2.61, 95% CI 1.34 to 5.07), gestational hypertension (OR 2.41, 95% CI 1.62 to 3.59), preeclampsia/eclampsia (OR 10.39, 95% CI 8.32 to 12.98), preexisting hypertension with superimposed preeclampsia/eclampsia (OR 9.23, 95% CI 5.26 to 16.19), coagulopathy (OR 20.66, 95% CI 13.67 to 31.23), and tobacco abuse (OR 1.95, 95% CI 1.11 to 3.42). CONCLUSION: Intracerebral hemorrhage (ICH) accounts for a substantial portion of pregnancy-related mortality. The risk of ICH associated with pregnancy is greatest in the postpartum period. Advanced maternal age, African American race, hypertensive diseases, coagulopathy, and tobacco abuse were all independent risk factors for pregnancy-related ICH.

Malignant eccrine spiradenoma of the vulva: a case report and review of the literature.

Malignant eccrine spiradenoma is a rare skin tumor of sweat gland origin. We present the first reported case of this tumor in the female genitalia. Due to the rarity of this tumor, there has yet to be an established standard of care. The present case is that of a 41-year-old woman with malignant eccrine spiradenoma of the periclitoral region. She had an 18-month history of a recurrent, painful mass adjacent to the clitoris. Her diagnosis was made after excision of the cystic tumor. The patient then underwent a partial radical vulvectomy with bilateral sentinel lymph node sampling. As malignant eccrine spiradenoma is a rare tumor, no standard care exists for treatment and postoperative management. Based on our review of the literature, wide local excision appears to be the preferred initial treatment. Furthermore, adjuvant chemotherapy and/or radiation does not seem to improve survival in patients with advanced or recurrent cancer. Although lymph node sampling and/or lymphadenectomy is frequently reported in the treatment of this tumor, hematogenous metastasis can also occur. Therefore, these patients require close postoperative follow-up for recurrent disease.