Giant cell arteritis: Involvement of intracranial arteries.
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Aged↗
Biomedical subjects
Dylan V Miller
Publications and source records attributed to Dylan V Miller.
Impact of transforming growth factor-beta1 on atrioventricular node conduction modification by injected autologous fibroblasts in the canine heart.
BACKGROUND: Atrioventricular (AV) nodal ablation for management of atrial fibrillation (AF) is irreversible and requires permanent pacemaker implantation. We hypothesized that as an alternative, implantation of autologous fibroblasts in the perinodal region would focally modify AV nodal conduction and that this modulation would be enhanced by pretreatment with transforming growth factor-beta1 (TGF-beta1), a stimulant of fibroblasts. METHODS AND RESULTS: Skin biopsies were taken from 12 mongrel dogs, and derived fibroblasts were dissociated and grown in culture for 2 weeks. Multiple injections (0.25 mL) were made through an 8F NOGA catheter along the fast/slow AV nodal pathways as guided by an electroanatomic mapping system. Seven dogs received fibroblasts alone (1x10(6) cells/mL), 7 dogs received TGF-beta1 (5 microg), 4 dogs received fibroblasts and TGF-beta1 (1x10(6) cells/mL+5 microg), and 4 dogs received saline only. AV node function was assessed at baseline and after 4 weeks. Saline (80 mL) with assigned therapy (0.25 mL per injection) was injected into the peri-AV nodal region in each dog. At baseline, the AH interval (66+/-3 ms) and the average RR interval (331+/-17 ms) in pacing-induced AF were similar in each cohort. The increase in AH interval in normal sinus rhythm was longer after fibroblast (23+/-4 versus 5+/-5 ms; P=0.05) and fibroblast plus TGF-beta1 (50+/-5 versus 5+/-5 ms; P<0.001) injections than with saline alone, with similar findings during high right atrium and distal coronary sinus pacing. The AH interval was not significantly increased after TGF-beta1 injections. The AH interval was significantly longer after fibroblast plus TGF-beta1 injections than with either therapy (TGF-beta1 or fibroblasts) alone. The RR interval during AF was increased in dogs that received fibroblasts alone (110+/-36 versus -41+/-34 ms) and to a greater extent with the addition of TGF-beta1 (294+/-108 versus -41+/-34 ms). No AV block was seen in any cohort at 4 weeks. Labeled fibroblasts that expressed vimentin were identified in all dogs that received cell injections at 4 weeks. CONCLUSIONS: AV nodal modification can be achieved with injected fibroblasts without the creation of AV block. The effect on AV node conduction is substantially enhanced by pretreatment of fibroblasts with TGF-beta1. These data have therapeutic potential for the management of rapid ventricular rate during AF without pacemaker implantation.
Animals↗
Diagnostic features of cardiac hemangioma on cardiovascular magnetic resonance, a case report.
Cardiac hemangiomas are benign cardiac tumors that account for 5-10% of all benign tumors of the heart (Grebenc ML, Rosado de Christenson ML, Burke AP, Green CE, Galvin JR. Radiographics 2000; 20(4): 1073-1103). They occur in any cardiac location, including the pericardium (Brodwater B, Erasmus J, McAdams HP, Dodd L. J Comput Assist Tomogr 1996; 20(6): 954-956). Magnetic resonance imaging (MRI) has an excellent contrast resolution and multiplanar capability to allow optimal evaluation of myocardial infiltration, pericardial involvement and/or extracardiac extension (Brown JI, Barakos JA, Higgins CB. J Thorac Imaging 1989; 4(2): 58-64). This is a case report of cardiac hemangioma involving the ventricular septum with radiological and pathological correlation. It illustrates the capability of the MRI to non-invasively detect histological and flow characteristics of the tumor.
Contrast Media↗
Endothelial and smooth muscle cell populations in a decellularized cryopreserved aortic homograft (SynerGraft) 2 years after implantation.
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Aortic Valve↗
Surgical pathology of noninfectious ascending aortitis: a study of 45 cases with emphasis on an isolated variant.
BACKGROUND: Aortitis is emerging as an important cause of ascending aortic aneurysm in the elderly. Its features have not been described in a surgical population. DESIGN: Retrospective clinicopathologic review of 45 cases of active noninfectious aortitis among 513 consecutive ascending aortic resections (1985 to 1999). METHODS: Clinical data were collected from medical records. Histopathologic features were recorded during review of slides stained with hematoxylin-eosin and Verhoeff-van Gieson. Cases were categorized by predefined clinical criteria. Clinicopathologic features were compared among groups, with emphasis on unsuspected aortitis without systemic arteritis. RESULTS: The 2 largest groups were isolated aortitis (47%) and giant cell arteritis (31%). Other aortitis groups included Takayasu (14%), rheumatoid (4%), and unclassified (4%). Patients with isolated aortitis and giant cell arteritis were generally women (80%; mean age 73 y). All 6 with Takayasu arteritis were women (mean age 26). Although giant cell arteritis and isolated aortitis were histologically indistinguishable, their clinical courses differed substantially. Among 21 patients with isolated aortitis (2 treated with corticosteroids), only 10% later developed aortic aneurysms. In contrast, of 14 patients with giant cell arteritis (11 treated with corticosteroids), 21% subsequently developed aneurysms (P=0.09). CONCLUSIONS: Aortitis primarily affected women. Patients with isolated aortitis and giant cell arteritis were generally older than 50 years and, by definition, those with Takayasu arteritis were younger. In patients with isolated aortitis, outcomes were generally good, despite the absence of anti-inflammatory therapy. Accordingly, a conservative approach may be warranted for managing this subset of patients with aortitis.
Aged↗
The development of a fluorescence in situ hybridization assay for the detection of dysplasia and adenocarcinoma in Barrett's esophagus.
The goal of this study was to identify a set of fluorescence in situ hybridization probes for the detection of dysplasia and adenocarcinoma in patients with Barrett's esophagus. We examined 170 brushing specimens from 138 patients with Barrett's esophagus or a history of Barrett's esophagus using fluorescence in situ hybridization with probes to 5p15, 5q21-22, centromere 7, 7p12, 8q24.12-13, centromere 9, 9p21, centromere 17, 17p13.1, 17q11.2-12, 20q13.2, and centromere Y. Receiver-operator curves were used to determine the sensitivity and specificity of various four-probe combinations for detecting low-grade dysplasia, high-grade dysplasia, and esophageal adenocarcinoma. Endoscopic biopsy results were used as the gold standard. Numerous four-probe combinations provided a similarly high sensitivity and specificity. Of these, a set consisting of probes to 8q24, 9p21, 17q11.2, and 20q13.2 was found to have a sensitivity and specificity, respectively, of 70% and 89% for low-grade dysplasia, 84% and 93% for high-grade dysplasia, and 94% and 93% for esophageal adenocarcinoma. This probe set was chosen for future prospective clinical evaluations based on its high sensitivity and specificity, its ability to distinguish adenocarcinoma and high-grade or low-grade dysplasia from lesser diagnostic categories, and the favorable signal quality for each of the probes.
Adenocarcinoma↗
Wegener's granulomatosis presenting as renal mass: a case for nephron-sparing surgery.
Wegener's granulomatosis (WG) is a systemic disease well recognized by physicians. The upper and lower respiratory symptoms associated with the disease are easily recognized; however, its presentation as a solid renal mass is underappreciated. We present a case of a 61-year-old man who presented with a 5.2-cm renal mass diagnosed as WG after nephron-sparing surgery. The patient presented with mild symptoms suggestive of WG, but the antineutrophil cytoplasmic antibody test was negative. The renal mass and concerns about possible malignancy obscured the diagnosis of WG. This case illustrates that WG should be considered in the differential diagnosis of solid renal masses.
Diagnosis, Differential↗
Thymoma arising within cardiac myxoma.
Hematopoietic, glandular, and mesenchymal elements can be found within cardiac myxomas; ectopic endocrine tissues and "thymic rests" have also rarely been described. Atrial tumors (one right and one left) from 2 patients (a 69-year-old man and a 77-year-old woman) were encountered among the atrial myxoma cases in one of the author's consultation files. Both tumors were comprised of classic cardiac myxoma (with characteristic rings and syncytial chains of myxoma cells in a loose myxoid matrix) and cellular thymoma-like elements (characterized by a lobulated sheet-like growth of epithelioid spindle cells admixed with small lymphocytes punctuated by vessels with prominent perivascular spaces). Neither patient had evidence of thymoma elsewhere. Immunophenotypically, the thymoma-like component reacted strongly with antibodies to keratins (AE1/AE3, Cam 5.2, wide spectrum, CK19, CK7) and CD57 and weakly with antibodies to CD31, CD34, and calretinin. This intermediate phenotypic expression of both epithelial and vascular antigens likely reflects the multipotential nature of the cells comprising this lesion. The most likely explanation for this extremely unusual finding is neoplastic transformation of thymic rests within a myxoma.
Aged↗
Mechanisms of phrenic nerve injury during radiofrequency ablation at the pulmonary vein orifice.
BACKGROUND: The phrenic nerve can be injured with radiofrequency energy delivery. Nevertheless, the mechanisms of injury are unknown. This study was undertaken to examine phrenic nerve tissue temperatures during ablation at the pulmonary vein (PV) orifice, assess the temperature dependence of injury, and to delineate the possible mechanisms of untoward nerve effects. METHODS: Ten dogs underwent ablation at the right superior PV (RSPV) orifice. Phrenic nerve temperatures were assessed with implanted thermocouples overlying the endocardial ablation site. Using an 8-mm ablation catheter tip, energy was titrated to 50 degrees C and incremented by 5 degrees C for 120 seconds. RESULTS: Phrenic nerve capture was achieved in nine (90%) dogs after thermocouple implantation. A RSPV orifice tissue temperature >60 degrees C occurred in 32 (84%) of energy deliveries with a power of 34 +/- 22 W. In three (33%) dogs, this resulted in nerve dysfunction (maximum nerve temperature: 41 degrees C, 41 degrees C, and 91 degrees C) with histology consistent with acute thermal injury. In four additional dogs, 17 energy deliveries were made directly to the phrenic nerve using a novel in situ model. In 5 (29%) energy deliveries, nerve function was impacted immediately by the generated current, with resolution simultaneous with discontinuing radiofrequency. Transient phrenic nerve injury occurred in all dogs at a temperature of 47 +/- 3 degrees C (range: 43-53 degrees C) after 38 +/- 32 seconds (range: 20-120 seconds). After termination of the energy delivery, nerve function returned in 15(88%) during 30 seconds of postablation pacing. In two (12%) ablation attempts, nerve recovery was delayed (>3 minutes). Permanent injury occurred in all dogs after 92 +/- 83 seconds (range: 20-280 seconds) of additional energy delivery at a temperature of 51 +/- 6 degrees C (range: 45-65 degrees C). CONCLUSION: Phrenic nerve injury can be more common than anticipated with RF ablation at the RSPV orifice. Relatively low tissue temperatures can injure the nerve. Immediate nerve effects suggest a second mechanism of nerve dysfunction related to electrical current. Transient nerve effects occur prior to permanent damage, providing an opportunity to discontinue energy delivery before permanent injury.
Animals↗
Rhabdomyosarcoma arising in the hand or foot: a clinicopathologic analysis.
Rhabdomyosarcomas (RMS) arising at different anatomic sites have distinct clinicopathologic features that affect prognosis and outcome. RMS arising in the extremities generally have a worse prognosis. Case reports and anecdotal experience suggests the possibility that RMS of the hand or foot (RMSHF) may behave even more aggressively than RMS elsewhere in the extremities. This study describes clinicopathologic features and outcome of RMSHF. Charts and pathologic material from RMSHF cases from institutional files over a 32-year interval were reviewed. Additional cases from published reports and series over a 42-year interval were identified by a MEDLINE search. Pertinent clinicopathologic features for each case were compiled. Survival analysis and other data from these patients were compared with previously reported statistics in the literature for RMS at other anatomic sites, including elsewhere in the extremities. Six patients from the institutional files and 46 from published reports were identified. A number of adverse prognostic indicators were observed in the majority of these patients including alveolar morphology (86%) and distant metastasis at presentation (63%). Despite the aggressive nature of these tumors, the majority were smaller than 5 cm (61%). A propensity was observed for metastases to unusual sites such as breast, ovary, testis, pancreas, and kidney. The median survival was 19 months, and the 5-year survival was 27%. While these may reflect a constellation of findings related to site, it is also possible that alveolar histology is the main influence. RMSHF can present as a very small primary tumor with clinically evident or occult metastatic disease. Whether this reflects the location, the predominantly alveolar histologic type, or a molecular genetic subtype will require further analysis. Patients presenting with RMSHF should be thoroughly evaluated for occult metastases at the time of diagnosis and followed closely throughout treatment for subsequent involvement of unusual sites.
Adolescent↗
Histiocytes containing immunoglobulin crystals in the urine of a patient with IgA kappa plasmacytoma of the bladder.
Exfoliative cytology specimens from patients with plasma cell dyscrasias are rarely diagnostic, though there are reports of neoplastic plasma cells observed in pleural fluid and urine. Immunoglobulin concretions or crystals associated with neoplastic plasma cell populations have been well described. These crystals may be found within plasma cell nuclei or cytoplasm, extracellularly, or within cells of histiocytic lineage where they are presumably derived by phagocytosis. To the best of our knowledge, this is the first report of immunoglobulin crystals within histiocytes in the urine of a patient with plasmacytoma. A 61-year-old male underwent routine cystoscopy and urine collection to evaluate hematuria. The bladder biopsy demonstrated IgA kappa-producing plasmacytoma. Urine cytopsin preparations did not contain plasma cells, but there were histiocytic cells with degenerative nuclei and eccentrically located cytoplasmic spherical refractile hyaline crystals thought to be immunoglobulin crystals. This was supported by immunocytochemical staining.
Crystallization↗
Surgical pathology of infected aneurysms of the descending thoracic and abdominal aorta: clinicopathologic correlations in 29 cases (1976 to 1999).
Infected aortic aneurysms are uncommon, and only rarely have their surgical pathological features been described. Clinical and histopathologic features were evaluated in patients undergoing surgical repair of infected aneurysms of the descending thoracic or abdominal aorta over a 24-year period. Findings were compared with observations (primarily from autopsy studies) from the previous 25-year period (1950 to 1975) and other more recent reports. Of the 29 patients in our study, 79% were men, 90% had risk factors for atherosclerosis, and 72% had an identifiable risk or source of infection. Fever was present in 76%, and abdominal or back pain was seen in 66%. Among the 20 cases with an identifiable causative organism, staphylococcus accounted for 30%, streptococcus for 20%, salmonella for 20%, Escherichia coli for 15%, and other organisms for 15%. Aneurysms were saccular in 59% and infrarenal in 42%, and had a mean diameter of 5.6 cm. Microscopically, 6 patterns were recognized: acute inflammation superimposed on severe chronic atherosclerosis (55%), atherosclerosis with chronic inflammation (20%), acute inflammation without atherosclerosis (7%), chronic adventitial inflammation (7%), pseudoaneurysm formation (7%), and necrotizing granulomatous inflammation (4%). Special stains for organisms were positive in only 38% of the cases. Pathological findings of this series of surgical specimens spanning the fourth quarter of the twentieth century were not appreciably different from those described in autopsy series from the preceding years, although the causative microorganisms and agents used to treat them, preoperative diagnostic modalities, and surgical approaches have evolved.
Aged↗
Utilizing Nottingham Prognostic Index in microarray gene expression profiling of breast carcinomas.
We report a novel approach to gene expression profiling using the Nottingham Prognostic Index (NPI) to stratify 26 patients with invasive breast carcinoma. As an aggregate index of parameters reflecting metastatic potential, growth rate, and genetic instability the NPI has distinct advantages over other clinicopathologic features used to segregate breast cancer patients. As a continuous variable it offers a responsive and sensitive means of modeling a continuum of clinical aggressiveness. Using RNA extracted from 26 tumors and cDNA microarrays with 23 343 unique genetic elements, 84 genes and expressed sequence tags were identified whose expression patterns correlated with NPI. Differential expression by immunohistochemistry (IHC) was also observed for two of three genes evaluated by this method. Correlation was determined by the Spearman rank correlation method with null distribution analysis. Among the 84 genetic elements were seven previously implicated in neoplastic progression (including the two demonstrating differential expression by IHC), 11 without specific cancer association but localized to chromosomal sites whose loss or gain has been identified in cytogenetic studies of breast carcinoma, and 73 not previously associated with breast carcinoma. Collectively, the expression patterns of these 84 elements have potential to distinguish high and low NPI patient samples. These data add support to the assertion that prognostic groups of breast carcinoma are reflected in distinguishable expression profiles of a limited set of genes.
Adult↗
Transfusion of apheresis PLTs from IgA-deficient donors with anti-IgA is not associated with an increase in transfusion reactions.
BACKGROUND: Passive transfer of antibodies through transfusion has been reported to cause adverse consequences. Approximately 1 in 700 individuals of Northern European ancestry lack IgA with up to 40 percent reported as having anti-IgA. Whether these antibodies when passively transfused were associated with reactions was examined. STUDY DESIGN AND METHODS: Records were reviewed to identify IgA-deficient (<0.05 mg/dL detectable IgA) apheresis PLT donors with anti-IgA. Transfusion outcomes of products from these donors were compared to outcomes of control transfusions from donors who were not IgA-deficient. RESULTS: Four IgA-deficient donors with anti-IgA donated a total of 25 apheresis PLT products transfused to 22 recipients. Of the transfused products, 1 (4.0%) was associated with fever that was classified as unrelated to transfusion. In the control group, 60 donors donated 78 apheresis PLT products transfused to 56 recipients. Among these, an allergic reaction was identified (1.3%). The reaction rates between both groups were not different whether the single event in the anti-IgA group was considered a reaction (chi-squared value 0.735, p = 0.3914) or considered unrelated to transfusion (chi-square value 0.324, p = 0.5694). CONCLUSION: The transfusion of products containing anti-IgA does not appear to be associated with a greater frequency of reactions.
Adolescent↗
Fatal coronary artery disease after unrelated donor bone marrow transplantation.
Several factors are responsible for the occurrence of cardiac complications after bone marrow transplantation (BMT). These factors include the cardiotoxic effects of radiation therapy, antineoplastic and immunosuppressive drugs, abnormal immunologic reactions associated with graft-vs-host disease, and infectious agents. We report the case of a 45-year-old woman with T-cell prolymphocytic leukemia and no prior risk factors for coronary artery disease in whom sudden cardiac death occurred 2 1/2 years after allogeneic BMT from an unrelated male donor. Autopsy revealed severe 3-vessel coronary disease with grade 4/4 stenosis. This process was primarily nonatherosclerotic, with intimal hyperplasia of undetermined etiology. Furthermore, fluorescence in situ hybridization to identify the donor Y chromosome with simultaneous immunofluorescence labeling of smooth muscle actin suggested the presence of donor cells that transformed into myocytes. Coronary artery disease is an important, albeit rare, complication of BMT. Donor hematopoietic cells may contribute to its pathogenesis.
Bone Marrow Transplantation↗
Smooth muscle cells in human coronary atherosclerosis can originate from cells administered at marrow transplantation.
Atherosclerosis is the major cause of adult mortality in the developed world, and a significant contributor to atherosclerotic plaque progression involves smooth muscle cell recruitment to the intima of the vessel wall. Controversy currently exists on the exact origin of these recruited cells. Here we use sex-mismatched bone marrow transplant subjects to show that smooth muscle cells throughout the atherosclerotic vessel wall can derive from donor bone marrow. We demonstrate extensive recruitment of these cells in diseased compared with undiseased segments and exclude cell-cell fusion events as a cause for this enrichment. These data have broad implications for our understanding of the cellular components of human atherosclerotic plaque and provide a potentially novel target for future diagnostic and therapeutic strategies.
Adult↗
Subtractive hybridization identifies a novel predicted protein mediating epithelial cell invasion by virulent serotype III group B Streptococcus agalactiae.
Group B Streptococcus agalactiae bacteria (group B streptococci [GBS]) are the most common cause of serious bacterial infection in newborn infants. The majority of serotype III-related cases of neonatal disease are caused by a genetically related subgroup of bacteria, restriction fragment digest pattern (RDP) type III-3, suggesting that these strains possess unique genes contributing to virulence. We used genomic subtractive hybridization to identify regions of genomic DNA unique to virulent RDP type III-3 GBS strains. Within one of these III-3-specific regions is a 1,506-bp open reading frame, spb1 (surface protein of group B streptococcus 1). A mutant type III GBS strain lacking Spb1 was constructed in virulent RDP type III-3 strain 874391, and the interactions of the wild-type and spb1 isogenic mutant with a variety of epithelial cells important to GBS colonization and infection were compared. While adherence of the spb1 isogenic mutant to A549 respiratory, C2Bbe1 colonic, and HeLa cervical epithelial cells was slightly lower than that of the 874391 strain, invasion of the Spb1(-) mutant was significantly reduced with these cell lines compared to what was seen with 874391. The defect in epithelial invasion was corrected by supplying spb1 in trans. These observations suggest that Spb1 contributes to the pathogenesis of neonatal GBS infection by mediating internalization of virulent serotype III GBS and confirm that understanding of the population structure of bacteria may lead to insights into the pathogenesis of human infections.
Amino Acid Sequence↗
Case report: acute spontaneous Achilles tendon rupture in a patient with giant cell arteritis.
We report a case of a 69-yr-old previously healthy man with acute spontaneous Achilles tendon rupture and severe tendonitis, which occurred after 2 weeks of steroid therapy for newly diagnosed giant cell arteritis. The Achilles tendon rupture was treated conservatively and the tendonitis resolved incrementally with steroid dose reduction. The patient made a complete recovery. In view of the widespread use of steroids in practice, this novel case presentation has important clinical implications. The tendon rupture early in the course of high-dose steroid therapy expands the understanding of this adverse reaction, which was previously reported only with long-term steroid therapy. The severe tendonitis responded to steroid therapy reduction suggesting a dose correlation. This report adds to a sole previous report of a spontaneous Achilles tendon rupture associated with giant cell arteritis.
Achilles Tendon↗