Granular cell myoblastoma of the common bile duct treated by biliary drainage and surgery.

A young Caucasian woman is described in whom obstructive jaundice was caused by a granular cell myoblastoma of the common bile duct. She was treated by percutaneous transhepatic biliary drainage for 10 days, before radical removal. Granular cell myoblastomas are benign lesions of disputed histogenesis, rare among biliary neoplasms, the excision of which is curative.     

Cartilage biomarkers in ankylosing spondylitis: relationship to clinical variables and treatment response

OBJECTIVE: Ankylosing spondylitis (AS) is a progressive disease in which chronic inflammation can lead to extensive new bone formation throughout the spine. At present, few measures of the activity or extent of the disease are available. In this study, we sought to determine whether markers of cartilage synthesis and degradation could provide such quantitative measures. METHODS: Serum samples from 23 patients receiving infliximab treatment for AS were obtained at baseline and at weeks 2, 6, 14, and 22. Patients were stratified with respect to joint involvement and baseline levels of inflammatory markers, and responders were defined according to the Assessments in Ankylosing Spondylitis 20% criteria. Serial measurements of interferon-gamma, tumor necrosis factor alpha, transforming growth factor beta (TGFbeta), interleukin-10 (IL-10), and IL-1 were done at each time point. The following biomarkers were measured by enzyme-linked immunosorbent assay: the proteoglycan aggrecan 846 epitope, a marker of cartilage turnover; C-propeptide of type II collagen (CPII), a biosynthesis marker; and the Col2-3/4(long mono) (C2C) and Col2-3/4(short) (C1-2C) neoepitopes, reflecting collagen cleavage of type II collagen and type I/type II collagen, respectively. RESULTS: At baseline, patients with AS demonstrated significant elevations in serum levels of CPII, the 846 epitope, and the CPII-to-C2C (CPII:C2C) ratio (but not C2C or C1-2C) compared with normal controls. Of the biomarkers examined, only CPII:C2C showed a correlation with the C-reactive protein (CRP) level. Among the biomarker-cytokine relationships, TGFbeta demonstrated a trend toward a positive correlation with the 846 epitope. CONCLUSION: In AS, elevated serum levels of CPII and the 846 epitope may be related to biosynthetic turnover of hyaline cartilage and the intervertebral discs but may also reflect progressive bone formation as a result of endochondral ossification. The correlation of the CPII:C2C ratio with CRP suggests that the CPII:C2C ratio might prove to be a useful marker of disease activity in AS.     

Are we negating the benefits of CABG by forgetting secondary prevention?

The objective of the study was to examine medically managed secondary prevention at one year after coronary artery bypass grafting (CABG). In all, 214 consecutive patients undergoing isolated elective CABG seen four weeks preoperatively and one year post-operatively. Preoperative systolic blood pressure averaged 135+/-20 mmHg, which increased to 148+/-25 mmHg (P<0.0001) as did diastolic pressure (81+/-12 to 87+/-13 mmHg; P<0.0001). Anginal symptoms were reported by 45.1% (P<0.0001) although median severity scored lower (4.0 [3.0-5.4] vs 0 [0-2.0]; P<0.0001). Breathlessness decreased from 93% to 64% (P<0.0001) and was scored less severely (4.0 [2.0-5.0] vs 2.0 [0-4.0]; P<0.0001. In all, 88% with postoperative angina reported dyspnoea against 44% of those without (P<0.0001). Calcium antagonist use was more common in patients with angina (27.2% vs 5.1%; P<0.0001), but not nitrates (P=0.8695), diuretics (P=0.4218), digoxin (P=0.2565), beta-blockers (P=0.0820), or ACE inhibitors (P=0.7256). Preoperatively 166 patients (80.2%) took aspirin vs 69.2% afterwards (P=0.0131). Twelve patients (6.5%) received warfarin after operation vs none preoperatively. Two took digoxin (0.97%) preoperatively and 14 (7.7%) postoperatively (P=0.001) for chronic atrial fibrillation. One of these took warfarin. Long-acting nitrate use fell from 63.4% to 15.8% (P <0.0001). Short-acting nitrate use fell similarly (P<0.0001). Preoperatively 37 patients (17.9%) took ACE inhibitors vs 44 postoperatively (24.2%); 39 had not received them before. Preoperatively 48 (23.2%) took diuretics vs 30 (16.5%) postoperatively (P=0.127); 24 had not previously taken diuretics. More patients took HMGCoA inhibitors postoperatively (P=0.0068) and total cholesterol was significantly reduced with a concomitant increase in HDL fraction. Smoking habit was virtually unchanged from 17.8% to 15.1% (P=0.5023). In conclusion: angina was common. Apart from statin prescribing, postoperative secondary prevention measures were poorly applied, less widespread and less effective than preoperatively. The implications are disturbing.     

Current Smoking and Prognosis After Acute ST-Segment Elevation Myocardial Infarction: New Pathophysiological Insights

ObjectivesThe aim of this study was to mechanistically investigate associations among cigarette smoking, microvascular pathology, and longer term health outcomes in patients with acute ST-segment elevation myocardial infarction (MI).BackgroundThe pathophysiology of myocardial reperfusion injury and prognosis in smokers with acute ST-segment elevation MI is incompletely understood.MethodsPatients were prospectively enrolled during emergency percutaneous coronary intervention. Microvascular function in the culprit artery was measured invasively. Contrast-enhanced magnetic resonance imaging (1.5-T) was performed 2 days and 6 months post-MI. Infarct size and microvascular obstruction were assessed using late gadolinium enhancement imaging. Myocardial hemorrhage was assessed with T2* mapping. Pre-specified endpoints included: 1) all-cause death or first heart failure hospitalization; and 2) cardiac death, nonfatal MI, or urgent coronary revascularization (major adverse cardiovascular events). Binary logistic regression (odds ratio [OR] with 95% confidence interval [CI]) with smoking status was used.ResultsIn total, 324 patients with ST-segment elevation MI were enrolled (mean age 59 years, 73% men, 60% current smokers). Current smokers were younger (age 55 ± 11 years vs. 65 ± 10 years, p < 0.001), with fewer patients with hypertension (52 ± 27% vs. 53 ± 41%, p = 0.007). Smokers had better TIMI (Thrombolysis In Myocardial Infarction) flow grade (≥2 vs. ≤1, p = 0.024) and ST-segment resolution (none vs. partial vs. complete, p = 0.010) post–percutaneous coronary intervention. On day 1, smokers had higher circulating C-reactive protein, neutrophil, and monocyte levels. Two days post-MI, smoking independently predicted infarct zone hemorrhage (OR: 2.76; 95% CI: 1.42 to 5.37; p = 0.003). After a median follow-up period of 4 years, smoking independently predicted all-cause death or heart failure events (OR: 2.20; 95% CI: 1.07 to 4.54) and major adverse cardiovascular events (OR: 2.79; 95% CI: 2.30 to 5.99).ConclusionsSmoking is associated with enhanced inflammation acutely, infarct-zone hemorrhage subsequently, and longer term adverse cardiac outcomes. Inflammation and irreversible myocardial hemorrhage post-MI represent mechanistic drivers for adverse long-term prognosis in smokers. (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction. [BHF MR-MI]; NCT02072850)     

Long-term effects of raloxifene on bone mineral density, bone turnover, and serum lipid levels in early postmenopausal women: three-year data from 2 double-blind, randomized, placebo-controlled trials

BACKGROUND: In postmenopausal women, raloxifene hydrochloride has favorable effects on bone and lipid metabolism and does not stimulate reproductive tissues. The studies reported herein evaluated the long-term (3-year) effects of raloxifene treatment on bone mineral density (BMD), serum lipid levels, and drug tolerability in healthy postmenopausal women. METHODS: A total of 1145 healthy European and North American postmenopausal women aged 45 through 60 years were enrolled in 2 parallel, double-blind, randomized, placebo-controlled trials of identical design and randomly assigned to receive raloxifene hydrochloride, 30, 60, or 150 mg, or placebo daily; all groups received 400 to 600 mg of elemental calcium. Assessments included measurements for BMD by dual-energy x-ray absorptiometry, markers of bone turnover, and serum lipid levels. RESULTS: Lumbar spine BMD changed from baseline to 36 months as follows: placebo (mean percentage change + SE), -1. 32% +0.22%; raloxifene, 30 mg, 0.71% +0.23%; raloxifene, 60 mg, 1. 28% +0.23%; and raloxifene, 150 mg, 1.20% +0.24%. Comparable BMD changes were observed in the hip and total body. Biochemical markers of bone turnover were suppressed by raloxifene to normal premenopausal ranges through 3 years. Serum low-density lipoprotein cholesterol was reduced 7% to 12% below baseline through 3 years. Study withdrawals due to any reason (37%) and withdrawals due to adverse events (14%) were not different among groups. The only significant adverse effect of therapy was hot flashes (25% in the 60-mg raloxifene group vs 18% in the placebo group); hot flashes were typically reported as mild and were not associated with study withdrawal (1.7% for 60-mg raloxifene vs 2.4% for placebo). CONCLUSIONS: Raloxifene preserves BMD at important skeletal sites, lowers serum low-density lipoprotein cholesterol levels, and has a tolerability profile comparable to placebo. These results indicate a favorable benefit-risk profile of raloxifene for long-term use in healthy postmenopausal women. Arch Intern Med. 2000;160:3444-3450.     

Hantavirus pulmonary syndrome in Manitoba.

The first confirmed case of hantavirus pulmonary syndrome in Manitoba was diagnosed in 1999. To define better the risk of exposure to hantaviruses in this area, the clinical features and epidemiological factors pertaining to this case were described, and a serological survey of rodents collected near the patient's residence was undertaken. Small mammals were collected using live traps, were anesthetized via inhalation of isoflurane and were bled. Human and mouse serologies were undertaken using an ELISA to detect hantavirus-specific immunoglobulin G and/or immunoglobulin M antibodies. In addition, a full medical and epidemiological assessment, as well as individual risk factor and exposure analysis, were conducted. A 27-year-old Manitoba woman presented with severe respiratory distress and diffuse bilateral air space disease radiologically. Despite extremely aggressive measures, including mechanical ventilation, antibiotics, fluid management and inotropic support, the patient's condition rapidly deteriorated, and she died 8 h after admission. Hantavirus pulmonary syndrome was confirmed by the detection of immunoglobulin M and immunoglobulin G antibodies to the Sin Nombre virus (SNV) in her sera and by the demonstration of SNV genomic sequences in her lung tissue. Exposure to hantavirus likely occurred in and around the home or in the rural area in which she resided. A total of 252 small mammals, primarily deer mice (Peromyscus maniculatus), were collected from 17 different sites at or near where the patient lived. Antibodies to SNV were detected in 28 of 244 (11.5%) deer mice, which were collected within 9 km of the residence of the fatal case, indicating that these rodents are a significant reservoir for SNV in this area.     

HL-60 cell line was derived from a patient with FAB-M2 and not FAB-M3

The leukemia from which the human cell line HL-60 was derived was classified in 1976 as acute progranulocytic leukemia (APL), although it was recognized to show a number of atypical features. In the ensuing 10 years, the concept of APL and its integral association with t(15;17) has evolved, and the concept of APL as a morphologically recognizable entity has become embodied in the term French-American-British classification M3 (FAB-M3). It is now recognized that not every case of leukemia with a high proportion of progranulocytes can be classified as FAB-M3. We reviewed the light and ultrastructural morphology of the original diagnostic material from this case, and we report that the leukemia from which HL-60 was derived does not conform to the currently recognized entity of FAB-M3 and is more appropriately classified as an acute myeloblastic leukemia with maturation, FAB-M2.     

Radiation exposure to patients and medical personnel during radiofrequency catheter ablation for supraventricular tachycardia.

Radiofrequency catheter ablation is an effective alternative to medical therapy for patients with supraventricular arrhythmias. The purpose of this study was to determine the risks to the patient and to medical personnel due to radiation exposure from fluoroscopy during radiofrequency ablation of supraventricular tachycardia. One hundred eight consecutive patients with Wolff-Parkinson-White syndrome or atrioventricular nodal reentry who underwent the ablation procedure were studied. The ablation procedure was successful in 95% of the patients studied. Preexcitation or supraventricular tachycardia recurred in 5% of the patients during a mean follow-up of 9 +/- 4 months. The mean fluoroscopy time was 50 +/- 31 minutes. An anthropomorphic radiologic phantom was used to determine organ exposure and the effective dose equivalents for the patient and medical personnel. The patient's effective dose equivalent during a representative ablation procedure was 1.7 rems, which is comparable to other invasive cardiovascular procedures. The risk of inducing a fatal cancer from this exposure is 1 chance in 745, which is 1% of the spontaneous risk. The risk of a serious birth defect is 1 chance in 80,000, which is 0.1% of the current incidence of serious birth defects in the United States. The cardiologist who receives the highest exposure among medical personnel, would incur 1.8 mrems per case or 450 mrems per year if 250 procedures were performed. This exposure is 9% of the recommended annual limit. These results demonstrate the efficacy of radiofrequency energy ablation of supraventricular tachycardia and confirm that radiation exposure to patients and medical personnel is within established guidelines.