Comparative analyses of multi-species sequences from targeted genomic regions.

The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding and conserved non-coding regions, including regulatory elements, and provide insight into the forces that have rendered modern-day genomes. As a complement to whole-genome sequencing efforts, we are sequencing and comparing targeted genomic regions in multiple, evolutionarily diverse vertebrates. Here we report the generation and analysis of over 12 megabases (Mb) of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, including the gene mutated in cystic fibrosis. These sequences show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region. In particular, we identify substantial numbers of conserved non-coding segments beyond those previously identified experimentally, most of which are not detectable by pair-wise sequence comparisons alone. Analysis of transposable element insertions highlights the variation in genome dynamics among these species and confirms the placement of rodents as a sister group to the primates.

Idiopathic enteropathy: an evaluation in rural Iran with an appraisal of nutrient loss.

Idiopathic enteropathy in the rural population of Iran was investigated through evaluation of 100 randomly selected apparently normal subjects. The evaluation included quantitation of the nutrient loss, presence of malabsorption, and small intestinal morphological abnormalities. The results show that: 1) there was no significant loss of major nutrients, 2) severe malabsorption was not present, 3) an enteropathy of unknown etiology was found in nearly one-third of the subjects, and 4) abnormalities in morphology did not necessarily mean presence of malabsorption.

Immunoproliferative small intestinal disease: portrait of a potentially preventable cancer from the Third World.

PURPOSE: To review the recent progress in the understanding of clinical and laboratory characterization as well as management of immunoproliferative small intestinal disease (IPSID). DATA IDENTIFICATION: A literature search was conducted using Index Medicus, MEDLINE (1962 to 1989), and bibliographies of identified relevant articles. STUDY SELECTION: All international comprehensive reviews, reported epidemiologic or immunologic studies, and prospective clinical trials published or abstracted in English were selected. RESULTS OF DATA SYNTHESIS: A high incidence of lymphoma primarily in the gastro-intestinal tract in Third World countries has stimulated enormous epidemiologic and pathogenetic interests globally. IPSID, with a distinctive biologic marker (alpha heavy chain para-protein), affects the young underprivileged population of those countries. The initially benign-appearing antibiotic-responsive immunoproliferative lesions often evolve to fatal high-grade lymphomas. Roles of environmental and host factors in this evolutionary course are emerging. Recently demonstrated malignant potentials form the early onset of pathogenesis have given a new dimension to the traditional management strategy of IPSID. CONCLUSIONS: Epidemiologic, immunologic, and pathogenetic data that have emerged over the last 25-year study of IPSID have improved our understanding about the complexity of infection-immunity-cancer interrelationships, comparable to those that have arisen from the study of the acquired immunodeficiency syndrome. Early detection and institution of antimicrobial-based treatment regimens with judicious and consistent follow-up can save the lives of many young patients whose manpower is badly needed in Third World countries.

Angiosarcoma of the lung with fatal pulmonary hemorrhage.

A patient with fatal pulmonary hemorrhage was found to have angiosarcoma of the lung at postmortem examination. This case, occurring in a man with a prior history of industrial exposure in South African copper mines, is the third well-described primary occurrence of this tumor in the lung.

Primary upper small-intestinal lymphoma and alpha-chain disease. Report of 10 cases emphasizing pathological aspects.

Ten cases of primary upper small-intestinal lymphoma associated with alpha-chain protein in serum were discovered in a prospective study of the sera of patients with immunoproliferative small-intestinal disease (IPSID). Patients were mostly young males presenting with abdominal pain, weight loss, and diarrhea and showing laboratory evidence of carbohydrate, fat, and vitamin B12 malabsorption and hypoalbuminemia. The more frequently encountered pathologic abnormality was a diffusely nodular jejunal mucosa produced by a plasmacytic infiltrate of variable cell maturity involving a varible depth of small bowel wall with or without involvement of the mesenteric or para-aortic-lymph node complex and, in one instance, the liver. A less frequent picture included circumferential ulcerative and constrictive transmural tumors of the upper small intestine produced by a malignant lymphoma with involvement of abdominal lymph nodes. Small-intestinal surface epithelial abnormalities, a dense mantle of mature plasma cells overlying the lymphoma, a pronounced follicular lymphoid hyperplasia adjacent to and at distances from the lymphoma were other features of note in our IPSID cases associated with alpha-chain protein.

AIDS and malignant mesothelioma--is there a connection?

A 35-year-old male homosexual, a former intravenous drug abuser, was found to be human immunodeficiency virus (HIV) positive in 1984. He developed AIDS in 1987 and began treatment with zidovudine in 1989. One year later he developed left apical pleural blebs, a pneumothorax and an exudative pleural effusion. A malignant mesothelioma developed at the pleural blebs in the left apex. He was treated with adriamycin but rapid progression of the malignancy occurred and he died three months later. At autopsy, a malignant mesothelioma, causing respiratory failure and death, was found. The patient had no exposure to asbestos and asbestosis was not present at autopsy. We postulate that the development of malignant mesothelioma was probably related to HIV immune suppression or HIV and/or cytomegalovirus or zidovudine and is a complication of AIDS similar to the development of other malignant neoplasms in patients with AIDS.

Investigation of a new arthrographic contrast agent: Iotrol.

A new nonionic dimer (Iotrol; Schering AG) and diatrizoate meglumine-diatrizoate sodium (Renografin-60; Squibb) were compared as arthrographic agents by injecting these substances into the knees of rabbits. Three experienced arthrographers judged the image quality produced by Iotrol to be superior to that of Renografin-60. Following animal sacrifice, histologic examination of the synovium revealed a significant difference in the inflammatory response evoked by the contrast agents: Iotrol caused less inflammation. In a second group of rabbits, methylprednisolone was subcutaneously injected 24 hours before the arthrographic studies. The methylprednisolone significantly reduced the inflammation in the Renografin-60 subgroup when compared with the nonmedicated counterparts. No significant effect was noted in a like comparison with Iotrol. In addition, the administration of methylprednisolone led to a deterioration of the radiographic images. Based upon our data, we believe Iotrol is superior to Renografin-60 as an arthrographic agent.

Sternocostal joints. Anatomic, radiographic and pathologic features in adult cadavers.

Using radiographic-pathologic correlation, we studied the sternocostal joints derived from 27 consecutive cadavers and one additional cadaver with rheumatoid arthritis. Radiographic findings that were tabulated included joint space narrowing, sternal or costal osteophytes, articular calcification, vacuum phenomena, and the degree of ossification of the costal cartilages. The first sternocostal joint could be classified as either a synchondrosis or synostosis in every instance; however, a joint cavity lateral to the first sternocostal joint represented a normal variation and was seen radiographically in 10 specimens. The second sternocostal joint was synovial in type and intimately related to the manubriosternal joint; cavitation within this joint was present bilaterally in 36% of our specimens. Degenerative changes in the sternocostal articulations were characterized much more frequently by sternal osteophytes than by costal osteophytes or joint space narrowing. Calcification compatible with chondrocalcinosis was observed in two cadavers. Radiographic and pathologic evidence of synovial inflammation was evident in the sternocostal joints of the rheumatoid specimen.

The high signal intensity meniscus of the knee. Magnetic resonance evaluation and in vivo correlation.

This study describes the different appearances of meniscal abnormalities on magnetic resonance (MR) images and correlates macroscopic and histologic findings. Twenty-three of 40 cadaveric menisci with MR signal abnormalities were examined macroscopically; five of the 23 were studied histologically. In addition, MR studies of seven patients (14 menisci) were examined and findings were correlated arthroscopically. Histologic analysis was performed on two of these menisci. The two major findings on MR images were: (1) abnormal, high, centrally located signal intensity within the meniscus and (2) disruption of the peripheral meniscal contour. Macroscopically evident meniscal degeneration correlated well with findings on MR images in all cases. Histologic abnormalities included microcyst formation and separation of collagen bundles. Four menisci with intact outer contour lines on MR images had macroscopically identifiable tears. In addition, two meniscal tears were appreciated only after intra-articular injection of gadolinium-DTPA. We conclude that MR imaging is superior to macroscopic examination as performed by arthroscopy or arthrotomy for the detection of degenerative meniscal lesions. The technique also accurately identifies meniscal tears, a capability that might be enhanced by prior intra-articular injection of MR contrast agents.

Evaluation of the triangular fibrocartilage and the scapholunate and lunotriquetral ligaments in cadavers with low-field-strength extremity-only magnet. Comparison of available imaging sequences and macroscopic findings.

RATIONALE AND OBJECTIVES: The authors assessed the ability of a low-field-strength extremity-only magnet to provide visualization of the triangular fibrocartilage and the scapholunate and lunotriquetral ligaments. METHODS: Twelve human wrists were examined with a 0.2 T extremity-only magnet. T1-weighted spin echo, proton density-weighted, and T2-weighted turbo spin echo, short-tau inversion recovery, and three-dimensional gradient recalled echo images were acquired, and sections of the specimens were then made that corresponded to the magnetic resonance images. Masked imaging analyses were correlated with macroscopic and limited histopathologic findings. RESULTS: Low-field-strength extremity-only magnet allowed consistent visualization of the triangular fibrocartilage and accurate assessment of a small number of complete tears of the triangular fibrocartilage. The scapholunate ligaments in all cases were identified using a combination of imaging sequences. Consistent visualization of the lunotriquetral ligament with a low-field-strength extremity magnet was difficult. CONCLUSIONS: Magnetic resonance imaging with a low-field-strength extremity-only magnet can be used to visualize the triangular fibrocartilage and the scapholunate ligament, but not the lunotriquetral ligament.

The effect of intra-articular gadolinium-DTPA on synovial membrane and cartilage.

This investigation evaluated the potential effect of gadolinium (Gd)-DTPA-dimeglumine on synovial membrane and joint cartilage, using macroscopic, microscopic, and x-ray fluorescent spectroscopic techniques. Thirteen New Zealand white rabbits (26 knees) were used in this study, ten receiving 500 micromolar injections of Gd-DTPA-dimeglumine in their right knees; the remainder of the knees served as controls. One injected knee had minimal joint effusion and one had mild hyperemia. Microscopically four knees exhibited mild focal hyperplasia of the synovium, another three minimal focal mononuclear cell infiltration. X-ray fluorescent spectroscopy demonstrated no evidence of Gd-DTPA-dimeglumine in the synovium or articular cartilage. Neither macroscopic nor microscopic evaluation detected any Gd-DTPA-dimeglumine related effects. Gd-DTPA-dimeglumine was found to be safe for intra-articular injection in this animal model.

Perfluoroctylbromide as a contrast agent for computed tomographic imaging of septic and aseptic arthritis.

Perfluoroctylbromide (PFOB), a perfluorocarbon macrophage-labeling contrast agent, was applied to computed tomographic imaging of septic and aseptic arthritis models in rabbits. Marked enhancement of induced pyarthrosis was observed in both the knee and the sacroiliac joint. Moderate enhancement was noted in tetracycline-induced synovitis of the knee. Sterile synovitis of the sacroiliac joint and simple knee joint effusion showed no enhancement. These results suggest that PFOB is a useful contrast medium for the diagnosis of and distinction between septic and sterile arthritis.

Transverse ligament and its effect on meniscal motion. Correlation of kinematic MR imaging and anatomic sections.

RATIONALE AND OBJECTIVES: To evaluate the effect of the transverse ligament on translation of the menisci. METHODS: Six cadaveric knees were examined by MR imaging inside a positioning device before and after transecting the transverse ligament. The knees were examined at various positions: extension, 30 degrees of flexion, 60 degrees of flexion, and full flexion. Sagittal T1-weighted spin-echo images were generated at each knee position and evaluated for statistical differences with regard to anterior-posterior meniscal excursion. RESULTS: Statistically significant differences in meniscal excursion were found before and after transsecting the transverse ligament for anterior-posterior meniscal motion of the anterior horn of the medial meniscus at 30 degrees of knee flexion. No such significant differences were found, however, at 60 degrees of flexion and full flexion in anterior-posterior meniscal excursion of the anterior or posterior horn of either meniscus before and after transsecting the transverse ligament. CONCLUSIONS: The transverse ligament has a restricting effect on anterior-posterior excursion of the anterior horn of the medial meniscus at lower degrees of knee flexion.

Ventral sacroiliac ligament. Anatomic and pathologic considerations.

RATIONALE AND OBJECTIVES: The ventral sacroiliac ligament (VSL), which bridges the sacroiliac (SI) joint anteriorly, has been described as an important stabilizing structure of the joint, but no data exist regarding its assessment with routine and advanced imaging methods. The authors determine the imaging appearance of the normal and abnormal VSL using close anatomic-histologic-imaging correlation. METHODS: Eight and 10 cadaveric SI joints were examined with magnetic resonance imaging in axial and coronal planes, respectively; and in four computed tomography scanning in both planes was obtained. Anatomic sectioning with histologic correlation at levels corresponding to those of imaging planes was performed. Representative examples of diseases that produce abnormalities of the VSL and connective tissue about the SI joint were reviewed. RESULTS: Magnetic resonance images showed the VSL-anterior capsular complex as a hypointense, linear, or minimally curved structure of approximately 2 mm thickness traversing the SI joint anteriorly. The VSL could not be separated from the anterior joint capsule by imaging studies, but such differentiation by histology could be determined based upon the orientation of its collagen fibers. Any disease process that affects the ligament or the site of ligamentous attachment to bone produces characteristic imaging alterations.

Carcinoembryonic antigen staining in choriocarcinoma.

Choriocarcinoma of the colon presented as life-threatening lower gastrointestinal bleeding and a pathologic femoral fracture in a 42-year-old man. Elevated serum carcinoembryonic antigen (CEA) levels and immunohistochemical positivity for CEA in neoplastic syncytiotrophoblasts were noted, as well as the expected positivity for the beta subunit of human chorionic gonadotropin (beta HCG). Additional cases, including one of two gestational choriocarcinomas and one of four testicular choriocarcinomas studied immunocytochemically for CEA also demonstrated positivity. Although CEA staining is commonly associated with tumors derived from the surface epithelium of the gastrointestinal tract and other organs, its presence in choriocarcinomas should not be interpreted as conclusive evidence of primary origin from these sites.

Non-pulmonary Rhodococcus equi infections in patients with acquired immune deficiency syndrome (AIDS).

Rhodococcus equi, formerly known as Corynebacterium equi, was isolated repeatedly from the blood of two patients with the acquired immune deficiency syndrome (AIDS). Neither of the patients had pneumonia while they were bacteraemic, whereas pneumonia has been present in all previously reported cases of human infection with R equi. One of our patients had diarrhoea and the organism was isolated from a stool culture; the other patient had a large granulomatous soft tissue mass in his pelvis caused by R equi. Both isolates were resistant to penicillin and one produced a beta-lactamase. Both patients were treated with vancomycin but only one recovered.

Aortic valve repair for aortic stenosis in adults.

The stenotic aortic valve was surgically repaired in 48 adults, 21 women and 27 men, aged 38 to 83 years. Five had congenital aortic stenosis (AS), with a mean aortic valve gradient and area of 58 +/- 23 mm Hg (standard deviation) and 0.54 +/- 0.13 cm2, respectively; 32 had senile AS with a mean aortic valve gradient and area of 43 +/- 20 mm Hg and 0.98 +/- 0.41 cm2; and 11 had rheumatic AS with a mean aortic valve gradient and area of 59 +/- 24 mm Hg and 0.47 +/- 0.15 cm2. Only 6 patients underwent isolated aortic valvoplasty, 11 underwent concomitant mitral valve procedure, and 34 underwent concomitant coronary revascularization. Repair consisted of decalcification in 33 patients and decalcification as well as commissurotomy in 15 patients. There were three hospital deaths, none related to the aortic valve. Only 2 patients (both rheumatic) did not improve clinically. During follow-up (mean, 64 +/- 41 months) aortic valve restenosis developed in 24% (10 patients, 3/5 congenital, 4/11 rheumatic, and 3/32 senile) at a mean of 64 +/- 28 months. Postoperative Doppler echocardiographic assessment of 21 patients with senile AS at 1.1 +/- 2.7 and 18.1 +/- 1.4 months showed significantly lower aortic valve gradient and improved area in comparison with preoperative values. At 36 +/- 2.7 months, aortic valve gradient and area were not significantly different than preoperative values, and at 58.5 +/- 2.6 months aortic valve gradient was 1.41 (p = 0.07) times the preoperative value. At 7 years, actuarial freedom from aortic valve-related symptoms of the patients with senile AS was 87%. We conclude that in select patients aortic valve repair results in excellent relief of AS. Late restenosis is expected and more likely to occur in the valves with congenital and rheumatic disease than in those with senile disease.

Computerized tomography of proximal femoral trabecular patterns.

A comprehensive imaging and pathologic investigation utilizing patients and cadaver material was performed in order to identify the normal trabecular pattern of the proximal femur and to assess alterations in this pattern in various disorders. Patients and specimens were studied with computed tomography (CT), including three-dimensional CT image reconstruction in selected cases and plain film radiography. The CT imaging of the proximal femur provides insight into the dynamic state of bone in this region. Despite limited resolution, three-dimensional CT image reconstruction is capable of portraying the concentration and orientation of major trabeculae in the proximal femur. Increased trabecular spacing occurs in osteoporosis and is well depicted by CT. Proliferation and thickening of the most superior subchondral primary compressive trabeculae is an early sign of osteoarthritis. In the region of the calcar femorale, crossing trabeculae, similar to the appearance of an enchondroma or bone infarct, have been described in osteoporosis and osteoarthritis and probably represent unmasking of normally present reinforcing trabeculae. In ischemic necrosis, CT should be considered a useful modality for detection of early or mild alterations and may be valuable in treatment planning.

Alpha-heavy chain disease.

A review of alpha-heavy chain disease (AHCD) emphasizing its histopathology and associated lesions is presented. Unusual clinicopathologic presentations and modern concepts regarding histogenesis of AHCD in the light of recent immunohistochemical findings are discussed. Increasingly reported cases of Burkitt's (or Burkitt-type) lymphoma involving distal small intestine or the ileocecal region in children are noted.

MOHS for head and neck mucosal cancer: report on 111 patients.

Microscopically Oriented Histologic Surgery (MOHS) has been applied to primary epidermoid cancers of the mucosal tissues of the head and neck since 1979. In that time we have treated 170 patients and maintained excellent records, losing no patients to follow-up. One hundred three patients have been followed for 2 years. Of this group, only nine patients have developed local recurrences; three were salvaged, six were not. This presentation reviews the concept of MOHS and its application to head and neck mucosal lesions. The results are analyzed, and conclusions are drawn regarding what we have learned about the biologic behavior of head and neck tumors and the role of MOHS in treating these neoplasms.