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

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).

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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Management of Severe COPD Reviewed
Laurie Barclay, MD, Hien T. Nghiem, MD

April 20, 2010 Various strategies and recommendations to treat patients with severe chronic obstructive pulmonary disease (COPD) are provided in a clinical review published in the April 15 issue of the New England Journal of Medicine.

"The sentinel clinical feature of severe ...COPD is dyspnea on exertion," writes Dennis E. Niewoehner, MD, from the Pulmonary Section, Veterans Affairs Medical Center in Minneapolis, Minnesota. "Its onset is usually insidious, and it may progress to severe disability over a period of years or decades. Other common symptoms include cough, sputum production, wheezing, and chest congestion." The typical clinical manifestations of advanced COPD result from severe airflow obstruction, which can be confirmed by spirometry. Although physical findings may include a barrel-shaped chest, inspiratory retraction of the lower ribs (Hoover's sign), a prolonged expiratory phase, and use of the accessory muscles of respiration, these findings are sometimes absent even in patients with severe COPD.

Failure to confirm COPD with spirometry often leads to misdiagnosis. However, spirometry is a poor guide for decision making regarding treatment continuation or modification in an individual patient. Spirometric evidence of airflow obstruction is defined as a ratio of the postbronchodilator forced expiratory volume in 1 second (FEV1) to a forced vital capacity of less than 0.70.

Overall severity of COPD can be classified based on FEV1 percentage of the predicted normal value, as well as on clinical criteria, such as the degree of breathlessness caused by specific tasks and the frequency of exacerbations. Exacerbations often require medical visits and hospitalizations, causing a dramatic increase in healthcare costs. The relative risk for treatment failure (defined as no resolution or clinical deterioration) is lowered by approximately 50% when antibiotics are used for COPD exacerbations. Antibiotics are most effective in patients who have cough productive of purulent sputum.

Complications of severe COPD include pulmonary hypertension and cor pulmonale resulting from chronic hypoxemia and hypercapnia. Severe COPD is also associated with an elevated risk for cardiovascular disease, osteoporosis, lung cancer, depression, and other systemic diseases.

Management Strategies
Management should include patient education during the initial visit, which should focus on the signs and symptoms of a severe exacerbation and the need for prompt recognition and treatment. The most important aspect of management is smoking cessation, which should be addressed at every visit, as long as the patient continues smoking.

Pharmacotherapy may include an inhaled long-acting
â2-agonist, an inhaled long-acting anticholinergic agent, and/or an inhaled corticosteroid. The long-acting â2-agonists salmeterol and formoterol offer at least 12 hours of sustained bronchodilation, whereas the inhaled long- acting anticholinergic agent tiotropium is effective for at least 24 hours.

Drugs from 2 of these 3 classes should be combined for patients with severe, exacerbation-prone COPD. Because they lower the relative risk for a severe exacerbation by 15% to 20%, these medications should be continued even if they do not provide symptomatic relief. Adverse events of long-acting bronchodilators are typically mild.

For rescue use, a short-acting bronchodilator should be given. Albuterol or other short-acting
â2-adrenergic agonist and ipratropium bromide, a short-acting anticholinergic agent, may be used alone or combined. Patients should be instructed regarding proper inhaler technique. The faster onset of action of albuterol vs ipratropium bromide may give patients more rapid relief. Long-term oxygen therapy should be prescribed and used for 18 hours or more each day if arterial oxygen saturation is 88% or lower at rest in a stable clinical state.


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The Curious Case of a Child Who Looked Like a Spotted Dog
Ronald M. Cyr, MD

Case Report
In the early part of August 1841, I was requested to attend the wife of an innkeeper, in labour with her eighth child. She was a strong, healthy woman, aged about forty-seven. The os uteri was dilated to the size of half a crown [the Crown was a silver coin measuring 39 mm in diameter and worth 5 Shilling (1 £ = 20 Shilling)]; membranes unruptured; vertex presentation. The labor being tedious, it was necessary to rupture the membranes, which, from their toughness, and not yielding to the fingernail, was effected by a quill. There was much mental excitement during the greater part of the labor.

Fearing cerebral congestion, and from the rigid state of the os uteri and the perineum, it was almost decided that venesection [phlebotomy] should be had recourse to. Though repeatedly told all was right, she persisted in a contrary opinion. As her pains increased, so did her ideas, that her child was like the spotted dog by which she had been frightened in the kitchen; as it was always before her eyes, night and day. (These were the words of the patient.) She had scarcely uttered those words, when, by a powerful contraction of the uterus, a fine full-grown female child was expelled.

Before the child was taken from under the bedclothes, the patient distinctly said these words in the presence of the nurse and a second attendant "My child is marked like Troughton's dog (the spotted), and at the back of the neck where the black one held it." On bringing the child to the light, such was the fact; only three or four spots about the size of a sixpence on the face, the rest of the body beautifully marked with black spots varying from the size of a pea to that of a sixpence, with the exception of the back of the neck, which had a brown black appearance covered with hairs, extending about two inches and a half across the neck and shoulders, and one inch and a half down the back. It appears from the patient's statement, that about the period of her third month of pregnancy, she was crossing the kitchen with a pint of beer, when a black dog and a spotted terrier, then lying under the table, began to fight close to her feet; and in the fright turning round, she saw the black dog seize the other by the back of the neck: a chillness came over her, and she felt ill all the day.

What is singular, her last two children were born marked from mental impressions made (as she believed) about the third month of each pregnancy; therefore, she was more convinced that she was to have a spotted child this time. The child is living, and very much admired. The spotted dog frequently passes my house; many persons call at the inn for a pint of beer as an excuse to see the rare spotted lass.


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Hormone Therapy for Menopause Reviewed CME/CE
Laurie Barclay, MD, Penny Murata, MD

April 8, 2010 Women must be informed of the potential benefits and risks of all treatment options for menopausal symptoms and concerns and should receive individualized care, according to a review of the role of perimenopausal hormone therapy published in the April issue of Obstetrics & Gynecology.

"With the first publication of the results of the Women's Health Initiative (WHI) trial in 2002, the use of HT [hormone therapy] declined dramatically," write Jan L. Shifren, MD, and Isaac Schiff, MD, from Harvard Medical School and Massachusetts General Hospital in Boston. "Major health concerns of menopausal women include vasomotor symptoms, urogenital atrophy, osteoporosis, cardiovascular disease, cancer, cognition, and mood.... Given recent findings, specifically regarding the effect of the timing of HT initiation on coronary heart disease [CHD] risk, it seems appropriate to reassess the clinician's approach to menopause in the wake of the recent reanalysis of the WHI."

Many therapeutic options are currently available for management of quality of life and health concerns in menopausal women. Treatment of vasomotor hot flushes and associated symptoms is the main indication for hormone therapy, which is still the most effective treatment of these symptoms and is currently the only US Food and Drug Administrationapproved option. For healthy women with troublesome vasomotor symptoms who begin hormone therapy at the time of menopause, the benefits of hormone therapy generally outweigh the risks.

However, hormone therapy is associated with a heightened risk for coronary heart disease. Based on recent analyses, this higher risk is attributable primarily to older women and to those who reached menopause several years previously. Hormone therapy should not be used to prevent heart disease, based on these analyses. However, this evidence does offer reassurance that hormone therapy can be used safely in otherwise healthy women at the menopausal transition to manage hot flushes and night sweats.

Although hormone therapy may help prevent and treat osteoporosis, it is seldom used solely for this indication alone, particularly if other effective options are well tolerated. Short-term treatment with hormone therapy is preferred to long-term treatment, in part because of the increased risk for breast cancer associated with extended use. The lowest effective estrogen dose should be given for the shortest duration required because risks for hormone therapy increase with advancing age, time since menopause, and duration of use.

Low-dose, local estrogen therapy is recommended vs systemic hormone therapy when only vaginal symptoms are present. Alternatives to hormone therapy should be recommended for women with or at increased risk for disorders that are contraindications to hormone therapy use. These include breast or endometrial cancer, cardiovascular disease, thromboembolic disorders, and active hepatic or gallbladder disease.

In addition to estrogen therapy, progestin alone, and combination estrogen-progestin therapy, there are several nonhormonal options for the treatment of vasomotor symptoms. Lifestyle interventions include reducing body temperature, maintaining a healthy weight, stopping smoking, practicing relaxation response techniques, and receiving acupuncture. Although efficacy greater than placebo is unproven, nonprescription medications that are sometimes used for treatment of vasomotor symptoms include isoflavone supplements, soy products, black cohosh, and vitamin E.

There are several nonhormonal prescription medications sometimes used off-label for treatment of vasomotor symptoms, but they are not approved by the Food and Drug Administration for this purpose. These drugs, and their accompanying potential adverse effects, include the following :
  • Clonidine, 0.1-mg weekly transdermal patch, with potential adverse effects including dry mouth, insomnia, and drowsiness.
  • Paroxetine (10 - 20 mg/day, controlled release 12.5 - 25 mg/day), which may cause headache, nausea, insomnia, drowsiness, or sexual dysfunction.
  • Venlafaxine (extended release 37.5 - 75 mg/day), which is associated with dry mouth, nausea, constipation, and sleeplessness.
  • Gabapentin (300 mg/day to 300 mg 3 times daily), with possible adverse effects of somnolence, fatigue, dizziness, rash, palpitations, and peripheral edema.

"Women must be informed of the potential benefits and risks of all therapeutic options, and care should be individualized, based on a woman's medical history, needs, and preferences," the review authors write. "For women experiencing an early menopause, especially before the age of 45 years, the benefits of using HT until the average age of natural menopause likely will significantly outweigh risks. The large body of evidence on the overall safety of oral contraceptives in younger women should be reassuring for those experiencing an early menopause, especially given the much lower estrogen and progestin doses provided by HT formulations."

Dr. Shifren serves as a scientific advisory board member for the New England Research Institutes. She has been a research study consultant for Eli Lilly & Co and Boehringer Ingelheim and has received research support from Proctor & Gamble Pharmaceuticals.


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Physical activity in pregnancy: a qualitative study of the beliefs of overweight and obese pregnant women
Zoe Weir, Judith Bush, Stephen C Robson, Catherine McParlin, Judith Rankin, Ruth Bell

Whilst there has been increasing research interest in interventions which promote physical activity during pregnancy few studies have yielded detailed insights into the views and experiences of overweight and obese pregnant women themselves. The qualitative study described in this paper aimed to: (i) explore the views and experiences of overweight and obese pregnant women; and (ii) inform interventions which could promote the adoption of physical activity during pregnancy.

The study was framed by a combined Subtle Realism and Theory of Planned Behaviour (TPB) approach. This enabled us to examine the hypothetical pathway between beliefs and physical activity intentions within the context of day to day life. The study sample for the qualitative study was chosen by stratified, purposive sampling from a previous study of physical activity measurements in pregnancy.

Research participants for the current study were recruited on the basis of Body Mass Index (BMI) at booking and parity. Semi-structured, in-depth interviews were conducted with 14 overweight and obese pregnant women. Data analysis was undertaken using a Framework Approach and was informed by TPB.

Results Healthy eating was often viewed as being of greater importance for the health of mother and baby than participation in physical activity. A commonly cited motivator for maintaining physical activity during pregnancy is an aid to reducing pregnancy-related weight gain. However, participants often described how they would wait until the postnatal period to try and lose weight. A wide range of barriers to physical activity during pregnancy were highlighted including both internal (physical and psychological) and external (work, family, time and environmental). The study participants also lacked access to consistent information, advice and support on the benefits of physical activity during pregnancy.

Conclusions Interventions to encourage recommended levels of physical activity in pregnancy should be accompanied by accessible and consistent information about the positive effects for mother and baby. More research is required to examine how to overcome barriers to physical activity and to understand which interventions could be most effective for overweight/obese pregnant women. Midwives should be encouraged to do more to promote activity in pregnancy.


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