Angiotension-converting enzyme gene I/D polymorphism in patients with angina and normal coronary arteriograms

A polymorphism of the human angiotensin-converting enzyme (ACE) gene has been identified in which the insertion (I) rather than the deletion (D) variant is associated with lower circulating and tissue ACE activity. ACE I allele is associated with resistance and endurance performance. Skeletal muscle metabolic efficiency is reduced in patients with heart failure and is improved by ACE inhibition. Profound muscle fatigue is a predominant and debilitating symptom in a proportion or patients with angina and normal coronary arteriograms (ANCA), and we postulated that the gene D allele might be associated with the presence of fatigue in ANCA patients. We studied 33 consecutive patients with typical ANCA who completed a validated fatigue questionnaire, and found an excess of the D allele frequency in patients with the highest fatigue scores compared to those with the lowest (64% vs. 36%; p=0.027).     

Stereotactic Magnetic Resonance Guidance for Anatomically Targeted Ablations of the Fossa Ovalis and the Left Atrium

INTRODUCTION: Targets for radiofrequency ablation (RFA) of atrial fibrillation are increasingly being selected based on anatomic considerations. Because fluoroscopy provides only limited information about the relationship between catheter positions and cardiac structures, we evaluated whether stereotactic catheter guidance might facilitate anatomical catheter navigation and RFA to the great vessels, the fossa ovalis and the left atrium (LA). METHODS AND RESULTS: An electromagnetic catheter's position system was superimposed on three-dimensional (3D) MR images using fiducial markers. This allowed the dynamic display of the catheter position on the true anatomy of previously acquired MRI in real-time. To assess the reproducibility of RFA, repeat ablations were created at the identical anatomic site in the inferior vena cava (IVC) in 5 swine. Average distance of the repeated ablations was 4.4 +/- 2.4 mm.In five swine the catheter was anatomically guided with the MRI to the fossa ovalis and a single RFA was performed. On the pathological specimen all ablation sites were located within the fossa ovalis with an average distance of 3.9 +/- 2.1 mm from its center. In two of the experiments the ablation catheter was passed into the left atrium and anatomically targeted ablation performed in the lateral wall of the left atrial appendage. Catheter location and ablation site were confirmed by autopsy and histology. CONCLUSION: Real-time display of the catheter position on 3D-MRI allows anatomically targeted catheter navigation and RFA in the IVC, the fossa ovalis, and the left atrium. This may facilitate anatomically based interventions like septal puncture or pulmonary vein ablation and decrease fluoroscopy times.     

Chronic Pancreatitis and the Hepatobiliary System

Alcohol-induced chronic pancreatitis involving the head of pancreas may have profound effects on the hepatobiliary system. The natural history, complications, and management of the syndrome are presented, using selected cases to emphasize important features. Chronic pancreatitis can cause mechanical obstruction to both the distal common bile duct and the proximal pancreatic duct. In the common bile duct this will result in proximal dilatation above the stenosis with bile stasis. Possible sequelae are ascending cholangitis, cholecystitis, biliary calculi formation, and secondary biliary cirrhosis. The mechanical effects of stricture of the proximal pancreatic duct may exacerbate pancreatic dysfunction. The clinicopathological spectrum of chronic pancreatitis with biliary obstruction encompasses three clinical types–"transient,""recurrent." and "persistent." The widespread effects of the syndrome are evident from the involvement of pancreas, proximal pancreatic duct, papilla of Vater, liver, peripheral biliary tree, common bile duct, gallbladder, and reticuloendothelial system. Essential to management is surgery which should be considered when there is objective evidence of obstruction to the common bile duct. Choledochoduodenostomy is the preferred type of operation. If dilatation is mild and jaundice transient, conservative therapy with careful observation is advocated.     

Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma

Bortezomib, a proteasome inhibitor with efficacy in multiple myeloma, is associated with thrombocytopenia, the cause and kinetics of which are different from those of standard cytotoxic agents. We assessed the frequency, kinetics, and mechanism of thrombocytopenia following treatment with bortezomib 1.3 mg/m2 in 228 patients with relapsed and/or refractory myeloma in 2 phase 2 trials. The mean platelet count decreased by approximately 60% during treatment but recovered rapidly between treatments in a cyclic fashion. Among responders, the pretreatment platelet count increased significantly during subsequent cycles of therapy. The mean percent reduction in platelets was independent of baseline platelet count, M-protein concentration, and marrow plasmacytosis. Plasma thrombopoietin levels inversely correlated with platelet count. Murine studies demonstrated a reduction in peripheral platelet count following a single bortezomib dose without negative effects on megakaryocytic cellularity, ploidy, or morphology. These data suggest that bortezomib-induced thrombocytopenia is due to a reversible effect on megakaryocytic function rather than a direct cytotoxic effect on megakaryocytes or their progenitors. The exact mechanism underlying bortezomib-induced thrombocytopenia remains unknown but it is unlikely to be related to marrow injury or decreased thrombopoietin production.     

Spontaneous free perforation of the small intestine in Crohn's disease.

Spontaneous free perforation of the small intestine is a rare but often dramatic event in the clinical course of Crohn's disease. Fifteen new cases of spontaneous free perforation of the small intestine--nine female patients and six male patients--were discovered in a series of 1000 consecutively evaluated patients with Crohn's disease seen during a period spanning 20 years, for an estimated frequency of 1.5%. Spontaneous free perforation was the presenting clinical feature of Crohn's disease in nine (60%) of the newly discovered cases. Most perforations were located in the ileum rather than in the jejunum, and there were no duodenal free perforations. One patient with extensive intestinal disease presented with concomitant free perforations of the jejunum and ileum, while a second patient had two free ileal perforations that developed independently, separated by about six years. No perforations were the result of a superimposed malignant process, ie, adenocarcinoma or lymphoma. There have been no mortalities, and the subsequent clinical course of these patients has been limited to a minority requiring corticosteroid or immunosuppressive medications, or further surgical resections.     

Identifying Stage B colorectal cancer patients at high risk of tumor recurrence and death

PURPOSE: This study was designed to determine clinical and pathologic variables associated with poor outcome following resection of Stage B colorectal cancer. METHODS: This was a retrospective study of 117 patients with Stage B cancer who underwent curative surgery and survived the postoperative period. Fourteen clinical and pathologic features were studied. Clinical data were extracted from a prospective colorectal cancer database, and histologic slides were retreived and examined by a pathologist blinded as to clinical details and outcome. RESULTS: After a median follow-up period of 8.2 years, bowel obstruction was significantly related to a poor prognosis (log-rank test; P=0.03). Extensive necrosis (P =0.01) and perineural invasion (P = 0.03) were also associated with decreased survival. Vascular invasion was associated with poor long-term outcome in the subgroup of patients with rectal (P =0.07) but not colonic (P =0.57) cancer. Multivariate regression analysis identified both tumor necrosis (P =0.01) and perineural invasion (P =0.03) as independently related to outcome. CONCLUSION: Further study of prognostic indicators might result in an algorithm to distinguish Stage B cases at high risk of tumor recurrence and death. Such patients could be included in future trials of adjuvant therapies.Presented in part at the meeting of the American Gastroenterological Association, Boston, Massachusetts, May 16 to 19, 1993. Published in abstract form in Gastroenterology 1993;104:A432.     

Recent developments on the role of Clostridium difficile in inflammatory bowel disease

Clostridium difficile （CD）, specifically its toxins, have been implicated as a risk factor for exacerbation of the inflammatory process in up to 5% of patients with ulcerative colitis or Crohn’s disease. Typical evidence of colonic changes with CD infection, including pseudomembranous exudate, are often not present; however, a severe clinical course may result, including precipitation of toxic colitis and toxic megacolon. Recently, hypervirulent CD strains have been reported raising concern for a more severe disease process in patients with underlying inflammatory bowel disease.Moreover, small bowel involvement or CD enteritis has been increasingly described, usually in those with a history of a prior colectomy or total proctocolectomy for prior severe and extensive inflammatory bowel disease. Finally, refractory or treatment-resistant pouchitis may occur with CD infection.     

Adult celiac disease followed by onset of systemic lupus erythematosus

BACKGROUND: Celiac disease has been associated with autoimmune disease (eg, autoimmune thyroiditis) and the appearance of different autoantibodies (eg, antidouble-stranded DNA). Conversely, tissue transglutaminase antibodies have been detected in autoimmune disorders, including systemic lupus erythematosus (SLE), but cases of celiac disease with SLE have been only rarely recorded. METHODS: In this study, 246 patients with biopsy-defined celiac disease were evaluated for a prior diagnosis of SLE on the basis of American Rheumatological Association-defined clinical and serologic parameters. RESULTS: There were 6 patients with celiac disease and SLE, or 2.4%, including 4 females and 2 males. Their mean age at diagnosis of celiac disease was 44.7 years and SLE 50 years. In all patients, the diagnosis of SLE was established from 2 years to more than 10 years after the diagnosis of celiac disease, with a mean of 5.3 years. The celiac disease in all 6 patients responded to a gluten-free diet with histologic normalization of the small intestinal biopsies. Despite this small bowel biopsy response, SLE appeared later in the clinical course of the celiac disease. CONCLUSIONS: This study suggests that SLE occurs far more frequently in biopsy-defined celiac disease than is currently appreciated, and detection may be more likely if the period of clinical follow-up of the celiac disease is prolonged.     

Acupuncture for Chronic Pain: Update of an Individual Patient Data Meta-Analysis

Despite wide use in clinical practice, acupuncture remains a controversial treatment for chronic pain. Our objective was to update an individual patient data meta-analysis to determine the effect size of acupuncture for 4 chronic pain conditions. We searched MEDLINE and the Cochrane Central Registry of Controlled Trials randomized trials published up until December 31, 2015. We included randomized trials of acupuncture needling versus either sham acupuncture or no acupuncture control for nonspecific musculoskeletal pain, osteoarthritis, chronic headache, or shoulder pain. Trials were only included if allocation concealment was unambiguously determined to be adequate. Raw data were obtained from study authors and entered into an individual patient data meta-analysis. The main outcome measures were pain and function. An additional 13 trials were identified, with data received for a total of 20,827 patients from 39 trials. Acupuncture was superior to sham as well as no acupuncture control for each pain condition (all P?<?.001) with differences between groups close to .5 SDs compared with no acupuncture control and close to .2 SDs compared with sham. We also found clear evidence that the effects of acupuncture persist over time with only a small decrease, approximately 15%, in treatment effect at 1 year. In secondary analyses, we found no obvious association between trial outcome and characteristics of acupuncture treatment, but effect sizes of acupuncture were associated with the type of control group, with smaller effects sizes for sham controlled trials that used a penetrating needle for sham, and for trials that had high intensity of intervention in the control arm. We conclude that acupuncture is effective for the treatment of chronic pain, with treatment effects persisting over time. Although factors in addition to the specific effects of needling at correct acupuncture point locations are important contributors to the treatment effect, decreases in pain after acupuncture cannot be explained solely in terms of placebo effects. Variations in the effect size of acupuncture in different trials are driven predominantly by differences in treatments received by the control group rather than by differences in the characteristics of acupuncture treatment.

Impact of Preoperative Prealbumin on Outcomes After Cardiac Surgery

Background: Preoperative malnutrition is increasingly prevalent in patients undergoing cardiac surgery. Although prealbumin is a widely used indicator of nutrition status, its use in the preoperative assessment of patients undergoing cardiac surgery is not well defined. The purpose of this study is to determine the impact of preoperative prealbumin levels on outcomes after cardiac surgery. Materials and Methods: Data were prospectively gathered from February 2013 to July 2013 on 69 patients undergoing cardiac surgery. Prealbumin levels were obtained within 24 hours of surgery. Patients were divided into 2 groups based on a prealbumin cutoff value of 20 mg/dL. Results: Of the 69 patients, 32 (46.4%) had a preoperative prealbumin ≤20 mg/dL. There was no correlation between prealbumin levels and body mass index (r = ?0.13, P = .28). Likewise, there was no correlation between preoperative albumin and prealbumin levels (r = 0.09, P = .44). Nine of 32 (28.1%) patients with low preoperative prealbumin levels had postoperative infections compared with 2 of 37 (5.4%) patients with high prealbumin levels (P = .010). Patients with low prealbumin levels also had increased risk of postoperative intubation for >12 hours (P = .010). Conclusions: Patients undergoing cardiac surgery with preoperative prealbumin levels of ≤20 mg/dL have an increased risk for postoperative infections and the need for longer mechanical ventilation. If feasible, nutrition optimization of such patients may be considered prior to cardiac surgery.