An Atypical Cause of Gastrointestinal Bleeding
Nicolai Wennike, MRCP(UK); Tim Battcock, MBChB, FRCP; Andrew J. Bell, MA, MB, FRCP, FRCPath

Background
A 53-year-old man who was diagnosed with multiple myeloma (IgAê) 18 months ago is admitted to the hospital via the emergency department (ED) with a 1-week history of melena, hematemesis, and lethargy. There is no associated weight loss, abdominal pain, dysphagia, or history of upper gastrointestinal (GI) hemorrhage. The patient has no risk factors for peptic ulcer disease, does not drink alcohol or smoke, and is not regularly taking any medications (including no recent nonsteroidal anti-inflammatory drugs [NSAIDs] or steroid use). He has no allergies of note, and his family history and social history are unremarkable. Other than multiple myeloma, which resulted in spinal cord compression that required radiotherapy (with full resolution of symptoms), the patient has no significant past medical history. He has not needed chemotherapy to date. On direct questioning, he does not describe any symptoms suggestive of active multiple myeloma and organ involvement.

On presentation, the patient appears clinically well, with no evidence of anemia, jaundice, lymphadenopathy, or peripheral signs of GI disease. He is hemodynamically stable, with a pulse of 90 bpm, blood pressure of 150/70 mm Hg (with no postural blood pressure drop), and a urine output of approximately 30 mL/hr. On examination, there is no evidence of active GI bleeding, his abdomen is soft and without any peritonitis or organomegaly, and a rectal examination shows evidence of melena, with no masses and a normal-sized prostate. His respiratory examination is unremarkable, with a clear chest and no evidence of aspiration pneumonia. The cardiac and neurologic examinations reveal nothing of significance.

The initial laboratory examinations show a hemoglobin of 8.5 g/L (0.85 g/dL); a low mean corpuscular volume (79 fL), with an iron deficiency picture; a normal international normalized ratio of 1.0; and mild dehydration, with urea nitrogen 10.1 mmol/L (28.29 mg/dL), creatinine 160 Gmol/L (1.81 mg/dL), sodium 136 mmol/L (136 mEq/L), and potassium 3.9 mmol/L (3.9 mEq/L). Liver tests showed a normal screen with alanine aminotransferase 30 U/L, albumin 40g/L (4 g/dL), alkaline phosphatase 50 U/L, and bilirubin 12 Gmol/L (0.70 mg/dL). The patient is treated with intravenous fluid and 2 units of blood. He remains hemodynamically stable and is subsequently able to undergo an esophagogastroduodenoscopy (see Figure 1).

Discussion
Biopsies of the polyps taken at the time of the endoscopy showed evidence of multiple myeloma type IgA ê. Multiple myeloma is a debilitating malignancy that is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. First documented in 1848, multiple myeloma is a disease characterized by a clonal proliferation of malignant B cells in the bone marrow (in which the predominant cell type is plasma cells) that results in an overabundance of monoclonal paraprotein. It is predominantly a disease of the elderly (median age: 60 years), with an incidence of 9.5 per 100,000 population and a slight male predominance.

It is the second most common hematologic cancer (10%), representing 1% of all cases of cancer; despite new advances,multiple myeloma still carries a poor prognosis, with a median survival of 2-3 years. The pathophysiology of multiple myeloma is that of a chromosomal translocation between the immunoglobulin heavy-chain gene (on the 14th chromosome, locus 14q32) and an oncogene (often 11q13, 4p16.3, 6p21, 16q23, or 20q11). This mutation results in dysregulation of the oncogene, which is thought to be an important initiating event in the pathogenesis of myeloma. The result of this mutation is proliferation of a plasma cell clone and genomic instability that leads to further mutations and translocations. The chromosome 14 abnormality is observed in about 50% of all myeloma cases; the other 50% of cases result from a deletion of (parts of) the 13th chromosome. The resulting plasma cells produce cytokines (especially interleukin [IL]-6) that cause osteopenia and create an environment for malignant cells to thrive.

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Vitamin D Supplementation and Cancer Prevention
Thomas L. Lenz, PharmD, MA, PAPHS

Abstract
It is estimated that approximately 1 billion people worldwide have blood concentrations of vitamin D that are considered suboptimal . Much research has been conducted over the past 30 years linking low vitamin D serum concentrations to both skeletal and nonskeletal conditions, including several types of cancers, cardiovascular disease, diabetes, upper respiratory tract infections, all-cause mortality, and many others. Several observational studies and a few prospectively randomized controlled trials have demonstrated that adequate levels of vitamin D can decrease the risk and improve survival rates for several types of cancers including breast, rectum, ovary , prostate, stomach, bladder, esophagus, kidney, lung, pancreas, uterus, non-Hodgkin lymphoma, and multiple myeloma.

Individuals with serum vitamin D concentrations less than 20 ng/mL are considered most at risk, whereas those who achieve levels of 32 to 100 ng/mL are considered to have sufficient serum vitamin D concentrations. Vitamin D can be obtained from exposure to the sun, through dietary intake, and via supplementation. Obtaining a total of approximately 4000 IU/d of vitamin D3 from all sources has been shown to achieve serum concentrations considered to be in the sufficient range. Most individuals will require a dietary supplement of 2000 IU/d of vitamin D3 to achieve sufficient levels as up to 10 000 IU/d is considered safe. Vitamin D3 is available as an over-the-counter product at most pharmacies and is relatively inexpensive, especially when compared with the demonstrated benefits.

Introduction
It is well known that a causal link exists between severe vitamin D deficiency and rickets in children and the bone disease osteomalacia in adults. It is also well known that vitamin D insufficiency is associated with osteoporosis, a decrease in muscular strength, and increased fall risk. It is less well known, however , that a low serum concentration of vitamin D is also associated with several other diseases and conditions. It is estimated that 1 billion people worldwide have vitamin D deficiency or insuffiency.[1] Patients ranging from children to elderly are affected by vitamin D deficiency. One study showed that 48% of white preadolescent girls had deficient blood levels of vitamin D.[2] Another study reported that more than half of postmenopausal women taking medication for osteoporosis had suboptimal blood levels of vitamin D.[3] Several other studies report that from 40% to 100% of community-living elderly men and women in both the United States and Europe have deficient levels of vitamin D.[1] The estimated cost to our society of vitamin D deficiency is reported to be between $100 and $200 billion per year.[4]

The recent number of medical publications on the topic of vitamin D is astounding. A PubMed search of the previous 10 years alone using the term "vitamin D" resulted in 17 399 publication displays . The newly appreciated associations between low vitamin D levels and diseases include glucose intolerance, diabetes mellitus, metabolic syndrome, cardiovascular disease, myocardial infarction, hypertension, obesity, heart failure, myopathy, inflammatory bowel disease, multiple sclerosis, psoriasis, tuberculosis, upper respiratory tract infections, polycystic ovarian syndrome, and even all-cause mortality.[5,6] In addition, a great deal of research has been conducted linking low vitamin D levels with several types of cancers. A follow-up PubMed search of the previous 10 years using the terms "vitamin D AND cancer" resulted in 2870 publication displays, of which two-thirds were published in the past 5 years. The purpose of this article is to briefly reviewthe physiology behind vitamin D, provide an overview of key research linking vitamin D intake with decreased cancer risk, and present the current recommendations for vitamin D intake.

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Ready-to-eat Cereal Breakfasts are Associated with Improved Nutrient Intake and Dietary Adequacy but Not Body Mass Index in Black Adolescents
Improved Nutrient Intake and Dietary Adequacy but Not Body Mass Index

Brandy M. Williams; Carol E. O'Neil, PhD, MPH, LDN, RD; Debra R. Keast, PhD; Susan Cho, PhD; Theresa A. Nicklas, DrPH

Abstract
The goal of this study was to determine whether nutrient intake, dietary adequacy, and weight status were associated with type of breakfast consumption: skipping breakfast, consuming ready-to-eat cereal (RTEC) at breakfast, or consuming other types of foods at breakfast. Data from black adolescents 13 to 18 years of age (n = 988) participating in the 19992002 National Health and Nutrition Examination Survey were used in a secondary data analysis. Thirty-seven percent of black adolescents skipped breakfast, 19% consumed RTEC at breakfast, and44% consumed other breakfasts.

RTEC breakfast and other breakfast consumers had higher mean energy intakes than breakfast skippers (P .05). After adjusting for genderand energy intake, RTEC breakfast consumers had higher intakes of thiamin, riboflavin, niacin , folate, calcium, phosphorus, magnesium, iron, zinc, potassium, and vitamins A, B6 , and B12 than breakfast skippers and other breakfast consumers (P .05). RTEC breakfast consumers had the highest mean adequacy ratio, followed by other breakfast consumers, then breakfast skippers (P .05). Those consuming RTEC at breakfast had lower mean body mass index (P .05) and waist circumference (P .05) than breakfast skippers; however, there was no difference between those consuming RTEC and other breakfasts. If confirmed in prospective studies, consuming a breakfast meal with RTEC may be a useful strategy to encourage in black adolescents as a way to improve nutrient intake and dietary adequacy without increasing weight .

Introduction
Adolescence is a time of rapid growth and development, making this a period of nutritional vulnerability. At the same time, adolescents demonstrate increasing control over their own food choices[1,2] and may make poor dietary choices.[3,4] Discretionary fat and added sugars make up more than 40% of total energy intake in the diet of adolescents.[3] Black adolescents may be especially vulnerable to poor diets because they are less likely than white adolescents to meet dietary recommendations for several essential nutrients.[57]

Skipping breakfast is an example of a poor dietary practice commonly seen in adolescents.[8] Although breakfast has been called the most important meal of the day, it is the meal that is skipped most frequently.[9,10 ] Black adolescents tend to skip breakfast more often than their white counterparts. [11 13] The importance of breakfast is underscored because regular consumption of breakfast is associated with improved cognition [14 ] and nutrient intake in adolescents. Skipping breakfast may result in inadequate nutrient intake that is not compensated for at other times during the day.[15 ] Skipping breakfast is also associated with lower energy intake but higher body mass index (BMI).[8,9,16 ,17 ]

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Exercise in the Prevention and Treatment of Adolescent Depression: A Promising but Little Researched Intervention
Andrea L. Dunn, PhD; Philippe Weintraub, MD

Abstract:
Despite a dramatic increase in the number of treatment studies for adolescent major depressive disorder in the past 15 years, the majority being clinical trials of medications and cognitive behavioral therapy, response rates have been modest and remission rates low. Moreover, most positive responders posttreatment have many residual symptoms, significant functional impairment, and high rates of relapse. There is a need for the development of new, more effective interventions to treat this severe, chronic condition that usually persists into adulthood with poor long-term outcomes. Findings from preliminary treatment studies suggest that exercise may have the potential to be efficacious as a monotherapy or as part of a combined treatment for adolescent major depressive disorder.

This review summarizes the findings and analyzes the design flaws of randomized trials of exercise to treat adolescent depression, offering recommendations on how to design more methodologically sound studies with an emphasis on subjectselection criteria; issues related to control conditions , types of diagnostic interviews, and measures needed to establish the diagnosis of depression; types of exercise treatments; and appropriate outcome measures. Future studies of exercise to treat and prevent adolescent major depressive disorder need to be comparable to state-of-the-art treatment studies of pharmacotherapy and cognitive behavioral therapy in this population to more accurately determine its efficacy and potential public health benefits.

Introduction
Adolescent depression is a major public health problem in the United States and throughout the world. [1-11 ] Major depressive disorder (MDD) in teens is common with point prevalence rates of 3% to 9%.[12- 15] In the United States, it is estimated that by the time adolescents reach adulthood, 25% of them will have experienced at least one episode of MDD.[2] Recent studies show a secular increase in its prevalence, [16 ] and many serious youth problems such as suicide,[17 ,18 ] substance abuse,[19 ] cigarette smoking,[20 ] teen pregnancy,[21 ] impaired psychosocial functioning,[22] and school failure[23 ] have been linked to untreated depression.

Moreover, adolescent depression has been shown to be a chronic condition persisting into adulthood with multiple recurrences and significant morbidity.[24 ,25 ] Therefore, successful treatment of teen depression is important not only in reducing the suffering, morbidity, and mortality from the disorder but also in preventing the development of other adverse long-term psychosocial and health outcomes.

Most of the research on this illness has been for adolescent MDD, but even subsyndromal depression is linked to significant functional impairment and an increased risk of developing MDD. For example , in a prospective study of more than 2000 adolescents,[22] teens with subthreshold depressive symptoms showed significantly greater functional impairment compared with teens diagnosed with conduct disorder . Thus, adolescents with subclinical symptoms of depression represent an equally important intervention target to prevent worsening of symptoms and to improve functional outcomes.[26 -28 ]

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The Role of Aspirin in Cardiovascular Disease Prevention inWomen
Jordan Hopkins, MD; Marian Limacher, MD

Abstract
Cardiovascular disease is the nation's number one killer of women. Through its actions on platelet inhibition, aspirin is an effective agent for primary and secondary cardiovascular disease prevention and for use with cardiac interventions. However, the evidence for aspirin's effectiveness in women differs by age and indication compared to men. As primary prevention, low dose aspirin is recommended for women over age 65 to reduce the risk of myocardial infarction and stroke while younger women at high risk for stroke may benefit from aspirin.

Aspirin has benefits in other selected patient groups, including diabetics and patients presenting with ST segment elevation myocardial infarction (STEMI), non-ST segment elevation myocardial infarction acute coronary syndrome (NSTEMI /ACS), peripheral arterial disease, stroke, coronary artery bypass graft (CABG), and percutaneous coronary intervention (PCI ). Alternative platelet therapy using dipyridamole or clopidogrel, alone orwith aspirin, provides some improved efficacy for reduction in recurrent events for NSTEMI, ASC and PCI, although bleeding risks may be greater. However, dual antiplatelet therapy is not currently recommended for primary prevention in even high risk subjects. Despite the evidence base and guidelines, the use of aspirin in women remains suboptimal and warrants improved provider and patient awareness.

Introduction
Cardiovascular disease (CVD) remains the leading cause of death for both men and women in the United States. [1] Although CVD has previously been considered a disease primarily affecting men, more women than men die from CVD in the United States each year.[1,2] More US women will die from CVD this decade than from all other causes combined.[3] Furthermore, CVD appears to carry a higher mortality rate in women than in men, particularly for younger women with myocardial infarction (MI). [4,5] Factors that may explain this disparity include the advanced age of onset for CVD in women versus men, as well as additional comorbidities, socioeconomic issues, and referral patterns.[6] Fortunately, overall CVD mortality has declined steadily since 1970, although the decline for women has lagged behind the rate of decline for men with coronary heart disease (CHD).[7] Based on data from the Nurses' Health Study, the incidence of CVD in women fell 31% from 1992 to 1994 compared to the rates of CVD from 1980 to 1982.[8] This decrease has been accomplished in large part by recognition and modification of cardiac risk factors through lifestyle modifications such as tobacco avoidance and also through improvements in blood pressure, cholesterol , and glycemic control. Indeed, recent estimates suggest that 44% of the decline in CVD is due to control of risk factors comparedto 47% attributed to treatment advances. [9]

Prevention, diagnosis, and treatment advancements have spurred the development and frequent updates of practice guidelines regarding CVD. With the recognition of the importance of CVD as a cause of morbidity and mortality in women, national authorities have directed increasing attention to appropriate assessment of primary and secondary risk of CVD in women. The 2007 update of guidelines for CVD prevention in women reaffirms that traditional CVD risk factors impart significant risk for women ( Table 1 ) while providing several distinct recommendations for women.[10 ] In particular, women younger than age 65 are possible candidates for aspirin use to prevent stroke but are not considered candidates for the use of aspirin for the primary prevention of CHD ( Table 2 ).[10 ]

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Advancing the Prevention and Control of Hypertension
Lisa Terre, PhD

Abstract
Hypertension is on a worrisome public health trajectory. This review discusses some key contributing dynamics as well as considerations for progress toward the prevention and control of hypertension and its comorbidities.

Introduction
The past decade has witnessed a proliferation of evidence-based practice guidelines for the prevention and control of hypertension. Yet its prevalence has only multiplied, with no signs of leveling off any time soon.[1,2] Despite being a key driver of physician visits, medication prescriptions, and countless cardiometabolic complications, hypertension remains suboptimally controlled for many patients, with socioeconomically and culturally disenfranchised groups being disproportionately affected. Put simply, hypertension is on a worrisome public health trajectory.[19]

Fortunately, the scramble for solutions has given rise to several innovative lines of inquiry. To its credit , this new crop of research has started yielding clues about some novel areas that deserve more attention. Taken together , these emerging findings have extended the focus beyond an exclusive emphasis on biological influences toward a wider-angled perspective that conceptualizes blood pressure dyscontrolas a final common pathway leading from a tangled web of biological, psychological , and social processes.[912 ] Tellingly, many of these mediators begin to exert their influences very early in the developmental process.

The Developmental Context
Accumulating evidence now indicates that the early family milieu may profoundly influence lifelong hypertension risk. For instance, early life stress has been implicated in a cascade of cardiometabolic vulnerabilities that tilt the odds toward hypertension through an intricate network of biopsychosocial mechanisms.[13 21]

To cite one of many interrelated pathways, a history of childhood adversities (including harsh parenting, family conflict or instability, and limited resources) can leave a negatively biased emotional residue that increases the likelihood of experiencing distressing emotions throughout life, which in turn heightens myriad cardiovascular risks both near and long term, including involvement in health-detrimental lifestyles (eg, physical inactivity, central adiposity, and obesity),[1012 ,22 26 ] medication nonadherence,[12] and a trail of physiological sequelae (eg, endothelial dysfunction, arterial stiffness) that further up the ante for subsequent cardiovascular events.[23,2528 ]

Of course, the actual complexity of these biopsychosocial relationships belies any simple effort at exposition. Because of the individualized nature of these transactionalnetworks, other biopsychosocial configurations also can confer risk. Illustratively, considerable evidence has suggested that prenatal and early postnatal nutrition may heighten downstream cardiometabolic hazards.[13 15 ,17 ,19 ,20 ] Likewise, maternal hypertension may compromise interuterine growth with adverse repercussions on child cognitive abilities and motor skills,[21 ] which in turn may constrain potential capacities for self-regulation .[21 ,29 ]

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