David S. Mendelson

A Prospective, Cross-sectional Survey Study of the Natural History of Niemann-Pick Disease Type B

OBJECTIVE. The objective of this study was to characterize the clinical features of patients with Niemann-Pick disease type B and to identify efficacy end points for future clinical trials of enzyme-replacement therapy. METHODS. Fifty-nine patients who had Niemann-Pick disease type B, were at least 6 years of age, and manifested at least 2 disease symptoms participated in this multicenter, multinational, cross-sectional survey study. Medical histories; physical examinations; assessments of cardiorespiratory function, clinical laboratory data, and liver and spleen volumes; radiographic evaluation of the lungs and bone age; and quality-of-life assessments were obtained during a 2- to 3-day period. RESULTS. Fifty-three percent of the patients were male, 92% were white, and the median age was 17.6 years. The R608del mutation accounted for 25% of all disease alleles. Most patients initially presented with splenomegaly (78%) or hepatomegaly (73%). Frequent symptoms included bleeding (49%), pulmonary infections and shortness of breath (42% each), and joint/limb pain (39%). Growth was markedly delayed during adolescence. Patients commonly had low levels of platelets and high-density lipoprotein, elevated levels of low-density lipoprotein, very-low-density lipoprotein, triglycerides, leukocyte sphingomyelin, and serum chitotriosidase, and abnormal liver function test results. Nearly all patients had documented splenomegaly and hepatomegaly and interstitial lung disease. Patients commonly showed restrictive lung disease physiology with impaired pulmonary gas exchange and decreased maximal exercise tolerance. Quality of life was only mildly decreased by standardized questionnaires. The degree of splenomegaly correlated with most aspects of disease, including hepatomegaly, growth, lipid profile, hematologic parameters, and pulmonary function. CONCLUSIONS. This study documents the multisystem involvement and clinical variability of Niemann-Pick B disease. Several efficacy end points were identified for future clinical treatment studies. Because of its correlation with disease severity, spleen volume may be a useful surrogate end point in treatment trials, whereas biomarkers such as chitotriosidase also may play a role in monitoring patient treatment responses.

Case report: Lung disease in World Trade Center responders exposed to dust and smoke: carbon nanotubes found in the lungs of World Trade Center patients and dust samples.

Context After the collapse of the World Trade Center (WTC) on 11 September 2001, a dense cloud of dust containing high levels of airborne pollutants covered Manhattan and parts of Brooklyn, New York. Between 60,000 and 70,000 responders were exposed. Many reported adverse health effects. Case presentation In this report we describe clinical, pathologic, and mineralogic findings in seven previously healthy responders who were exposed to WTC dust on either 11 September or 12 September 2001, who developed severe respiratory impairment or unexplained radiologic findings and underwent video-assisted thoracoscopic surgical lung biopsy procedures at Mount Sinai Medical Center. WTC dust samples were also examined. We found that three of the seven responders had severe or moderate restrictive disease clinically. Histopathology showed interstitial lung disease consistent with small airways disease, bronchiolocentric parenchymal disease, and nonnecrotizing granulomatous condition. Tissue mineralogic analyses showed variable amounts of sheets of aluminum and magnesium silicates, chrysotile asbestos, calcium phosphate, and calcium sulfate. Small shards of glass containing mostly silica and magnesium were also found. Carbon nanotubes (CNT) of various sizes and lengths were noted. CNT were also identified in four of seven WTC dust samples. Discussion These findings confirm the previously reported association between WTC dust exposure and bronchiolar and interstitial lung disease. Long-term monitoring of responders will be needed to elucidate the full extent of this problem. The finding of CNT in both WTC dust and lung tissues is unexpected and requires further study.

Superior Mesenteric Vein Thrombosis After Colectomy for Inflammatory Bowel Disease

AbstractPURPOSE: Thromboembolism is a significant cause of morbidity and mortality in inflammatory bowel disease. Several prothrombotic conditions have been investigated in inflammatory bowel disease. The aim of this study was to evaluate the incidence of symptomatic postoperative superior mesenteric vein thrombosis in inflammatory bowel disease patients undergoing colonic resections and to identify and characterize their clinical presentation. nMETHODS: Between January 1999 and December 2001, 83 consecutive patients undergoing total colectomy for inflammatory bowel disease were studied retrospectively. Patients who developed new-onset postoperative acute abdominal pain were evaluated by CT scan of the abdomen. A complete coagulation profile, including thrombin time, platelet count, protein C, protein S, antithrombin III, homocysteine level, factor V Leiden mutation, plasminogen, and prothrombin G20210A mutation, was obtained in patients diagnosed with superior mesenteric vein thrombosis. nRESULTS: Four patients (4.8 percent; 3 females; 3 patients with ulcerative colitis and 1 with Crohn’s colitis) developed symptomatic postoperative superior mesenteric vein thrombosis. Two of these patients had extension of the clot into the portal vein. Their presenting symptom was abdominal pain, with a median interval of ten days from the index surgery. The hematologic workup was negative in three patients, with one heterozygous for prothrombin G20210A mutation. All patients were treated with systemic anticoagulation for at least six months. One ulcerative colitis patient was diagnosed after abdominal colectomy and underwent an uneventful ileal pouch-anal anastomosis after systemic anticoagulation. nCONCLUSION: Postoperative superior mesenteric vein thrombosis is a more frequent occurrence than previously reported in patients with inflammatory bowel disease. Direct surgical trauma to the middle colic veins, with resulting thrombosis, is likely to be the precipitating factor in a borderline intrinsically hypercoagulable environment. All patients became asymptomatic after systemic anticoagulation and recovered uneventfully.

Pulmonary artery and aortic sarcomas: cross-sectional imaging.

Sarcomas of the major arteries are rare tumors often misdiagnosed due to nonspecific symptomatology. The authors present three cases of pulmonary artery and aortic sarcomas that were initially believed to be more common diseases. Modern imaging techniques including helical computed tomography (CT) and magnetic resonance imaging (MRI) are increasing the frequency of premortem diagnosis of these entities and aided surgical planning.

Breast Imaging in the Era of Big Data: Structured Reporting and Data Mining.

OBJECTIVEnThe purpose of this article is to describe structured reporting and the development of large databases for use in data mining in breast imaging.nnnCONCLUSIONnThe results of millions of breast imaging examinations are reported with structured tools based on the BI-RADS lexicon. Much of these data are stored in accessible media. Robust computing power creates great opportunity for data scientists and breast imagers to collaborate to improve breast cancer detection and optimize screening algorithms. Data mining can create knowledge, but the questions asked and their complexity require extremely powerful and agile databases. New data technologies can facilitate outcomes research and precision medicine.

Imaging Manifestations of Niemann-Pick Disease Type B

OBJECTIVEnThe purpose of this article is to illustrate the various imaging manifestations of Niemann-Pick disease type B using various imaging techniques emphasizing cross-sectional imaging.nnnCONCLUSIONnNiemann-Pick disease type B is a multisystem disease that affects the pulmonary, cardiovascular, abdominal, and skeletal systems. Cross-sectional imaging is well suited for detecting and assessing the various manifestations of this disease, which can be highly suggestive of the diagnosis when seen in combination.

Cardiac abnormalities in patients with diffuse malignant pleural mesothelioma

Many patients with diffuse malignant pleural mesothelioma have dyspnea or chest pain. Cardiac symptomatology is frequently difficult to differentiate from symptoms of pleuropulmonary disease. To better define the clinical characteristics of cardiac involvement in patients with mesothelioma, the electrocardiographic (EKG) and echocardiographic findings in 64 patients with biopsy‐proven malignant pleural mesothelioma were reviewed. A total of 19/64 (30%) patients had autopsy studies available for review. The EKG was abnormal in 55 patients (89%). Over half (60%) had an arrhythmia, including sinus tachycardia (42%), premature atrial and ventricular contractions (13%), atrial fibrillation (3%), and atrial flutter (1%). Over one third (37%) had a conduction abnormality, including bundle branch block (13%), hemiblock (8.5%), and incomplete right bundle branch block (13%). Echocardiography revealed a total of 13 patients with pericardial effusions, two with pericardial thickening, and one with an anterior sonolucent space. Of 19 autopsies, cardiac invasion was found in 14 (74%), with more than half to the pericardium and more than one quarter to the myocardium. It is concluded that: (1) clinical cardiac abnormalities occur in the great majority of patients with malignant pleural mesothelioma, (2) pathologic cardiac invasion occurs in the great majority of patients with pleural mesothelioma, and (3) the EKG and echocardiogram are helpful in differentiating cardiac involvement from progressive pulmonary disease in patients with pleural mesothelioma.

Imaging informatics: essential tools for the delivery of imaging services.

There are rapid changes occurring in the health care environment. Radiologists face new challenges but also new opportunities. The purpose of this report is to review how new informatics tools and developments can help the radiologist respond to the drive for safety, quality, and efficiency. These tools will be of assistance in conducting research and education. They not only provide greater efficiency in traditional operations but also open new pathways for the delivery of new services and imaging technologies. Our future as a specialty is dependent on integrating these informatics solutions into our daily practice.

High Resolution Computed Tomography in Idiopathic Interstitial Pneumonias

In June 2001, using an international multidisciplinary consensus, the American Thoracic Society and European Respiratory Society classified the idiopathic interstitial pneumonias (Am J Respir Crit Care Med 2002;165:277-304). The American Thoracic Society and European Respiratory Society coined the term idiopathic interstitial pneumonias because the diseases in question have both unknown etiologies and various combinations of inflammation and fibrosis within the lung parenchyma. The consensus included the development of a classification standard of the interstitial pneumonias and discussed the role of surgical lung biopsy and bronchoalveolar lavage evaluation. The classification of idiopathic interstitial pneumonias is based on histologic criteria, which correlate to imaging patterns on high-resolution computed tomography. The group of lung diseases under the umbrella of idiopathic interstitial pneumonias includes the following: usual interstitial pneumonia, nonspecific interstitial pneumonia, desquamative interstitial pneumonia, respiratory bronchiolitis interstitial lung disease, acute interstitial pneumonia, cryptogenic organizing pneumonia, and lymphoid interstitial pneumonia.

CT- and computer-based features of small hamartomas

PURPOSEnTo identify characteristic computed tomographic (CT) and computer-derived features of hamartomas manifesting as small pulmonary nodules.nnnMETHODSnIndividuals with a diagnosis of hamartoma were identified among participants in the International Early Lung Cancer Action Program and were included if there thin section CT images that included the entire nodule. The CT findings were reviewed to determine the nodule consistency (solid, part-solid, nonsolid), nodule diameter (average of length and width), shape (round, lobulated, neither) and edge (smooth, not smooth). Computer measures of nodule compactness, sphericity, surface regularity and gradient (change in gray-scale between the nodule and the surrounding parenchyma) were determined. Volume doubling time (VDT) was also determined for those with at least two scans with similar imaging acquisitions.nnnRESULTSnA total of 21 cases of hamartomas that had histologic or cytologic confirmation were identified. The median age was 60 and 12 (57%) were men. Average diameter was 10.7 mm (5-20.7 mm). All were solid in consistency and were described by the radiologist as having either round or lobulated shape with a smooth edge. None had pathognomonic radiologic findings for hamartoma. Computer measures demonstrated that all were compact and spherical, with a regular surface and a sharp margin between the nodule and surrounding parenchyma. Of nine on whom the VDT could be calculated, eight had VDTs longer than 450 days.nnnCONCLUSIONnBoth radiologist and computer derived features of small hamartomas suggest a consistent presentation for these lesions which may be helpful in distinguishing them from other types of nodules.