Biomedical subjects

Daniel Walsh

Publications and source records attributed to Daniel Walsh.

7 recordsLinked to original sources

PubMed2006

Preoperative profiling of symptomatic breast cancer by diagnostic core biopsy.

BACKGROUND: Precise preoperative profiling of breast tumors could facilitate fuller consideration of (neo)adjuvant therapies. METHODS: Diagnostic core biopsy (DCB) accuracy in profiling the primary tumor was prospectively studied in 95 patients with operable breast cancer. The histological type and grade (hematoxylin and eosin staining) and membrane receptor status (semiquantitative immunohistochemistry for estrogen [ER] and progesterone [PR] receptors, as well as Her-2 antigen expression) were assigned by the DCB before surgery. These measures were then compared with those of the definitive surgical specimen available after operation. RESULTS: DCB correctly ascribed tumor type and grade and ER, PR, and Her-2 receptor status in most cases (correlating exactly in 97.5%, 77%, 68%, 71%, and 60%, respectively) with at least moderate concordance (weighted kappa, >.41). When miscategorized, DCB consistently tended to upscore the receptor stain intensity compared with the surgical specimen (22%, 19%, and 27% had higher ER, PR, and Her-2 categorical scores, respectively). ER H-scores correlated best in specimens that stained strongly (224.4 +/- 3 vs. 215.5 +/- 5) and were significantly higher on DCB in those that stained either moderately (195.6 +/- 8.2 vs. 156.8 +/- 5.1; P < .0001) or weakly (157.1 +/- 24.8 vs. 81.4 +/- 4; P = .02). DCB accurately identified all tumors with clinically important ER and Her-2 expression. Furthermore, it promoted three patients into the therapeutically significant range of ER (n = 1) or Her-2 (n = 2) expression. ER negativity on DCB (n = 25) indicated a high-grade tumor (88%), although 11 (44%) patients also overexpressed Her-2. Significant Her-2 expression (n = 16) on DCB predicted the tumor as being poorly differentiated (80%) and both ER and PR negative (67%). CONCLUSIONS: DCB accurately profiles clinically relevant measures of primary tumor cell differentiation. It also reliably categorizes patients with regard to (neo)adjuvant therapy before radical surgery is attempted.

Adult↗

PubMed2006

Comparison of embolization protection device-specific technical difficulties during carotid artery stenting.

BACKGROUND: Embolic protection devices (EPDs) consisting of an internal carotid artery (ICA) filter or balloon occlusion are typically used during carotid artery stenting (CAS). This study compares the technical difficulties encountered using these two types of EPD. METHODS: A retrospective review was conducted of patients undergoing CAS using a balloon occlusion EPD (balloon group: PercuSurge GuardWire) or filter EPD (filter group: Accunet, AngioGuard, or FilterWire). Complications were defined as minor stroke, National Institutes of Health (NIH) stroke scale <3; major stroke, NIH stroke scale > or =3; transient ischemic attack (TIA), reversible focal neurologic impairment; technical, reversible neurologic compromise during EPD deployment, inability to cross lesion, ICA spasm requiring treatment, EPD-related factors that prolonged CAS. RESULTS: CAS (n = 141) was performed in 133 patients (82% men) with a mean age of 72 of years. Comorbidities included diabetes, 35%; coronary artery disease, 75%; hypertension, 82%; and renal insufficiency, 15%. Indication was previous cerebrovascular accident in 10%, TIA in 29%, and asymptomatic >80% stenosis in 61%. Primary lesions were treated in 83% vs restenosis in 17%. The 30-day event rate was 1.4% major stroke, 2.1% minor stoke, 1.4% myocardial infarction, and 0.7% death. The overall combined 30-day stroke, death, and myocardial infarction rate was 5.6%. The 30-day stroke and death rate was 4.0% in the balloon group (n = 99) and 4.6% in the filter group (n = 42, P = .51). EPD-related technical difficulties occurred in 15% of the balloon group and 31% of the filter group (P < .05). Technical difficulties included a 10% incidence of reversible neurologic compromise during balloon deployment compared with 0% in the filter group (P = .002) and 12% incidence of inability to cross the lesion before predilation in the filter group compared with 0% in the balloon group (P = .001). CONCLUSIONS: During CAS, both balloon occlusion and filter devices provide acceptable results and appear complimentary. Filters can be used preferentially to avoid a 10% incidence of reversible neurologic compromise associated with balloon occlusion, except in critically narrowed or tortuous lesions when balloon occlusion may be preferred because of a 12% need for unprotected predilatation with filters.

Aged↗

PubMed2006

AIDS and non-AIDS diffuse large B-cell lymphomas express different antigen profiles.

Based on gene expression profiling, diffuse large B-cell lymphomas arising in immunocompetent patients can be divided into germinal center and activated B-cell types. Since little is known about acquired immunodeficiency syndrome associated diffuse large B-cell lymphomas, we tested whether the protein expression of germinal center and activated B-cell markers differed between acquired immunodeficiency syndrome (AIDS) vs non-AIDS diffuse large B-cell lymphomas. We immunohistochemically stained tissue microarrays of 39 de novo diffuse large B-cell lymphomas: 12 AIDS associated and 27 non-AIDS, with germinal center (BCL6, CD10, CyclinH) and activated B-cell markers (MUM1, CD138, PAK1, CD44, BCL2). We scored each case for percent positive cells (0-19%=0; 20-49%=1; 50-100%=2). The activated B-cell and germinal center summation scores of each case were used as (x, y) coordinate data points to construct two-dimensional contour-frequency plots. The contour plot of non-AIDS diffuse large B-cell lymphomas showed two distinct clusters: a cluster with a high germinal center phenotype (cluster 1) and a cluster with a high activated B-cell phenotype (cluster 3). In contrast, the AIDS-related diffuse large B-cell lymphomas formed a single aggregate (cluster 2) (P=0.02, Fisher exact test). When the contour plots of the AIDS-related and the non-AIDS cases were superimposed, cluster 2 of the AIDS cases expressed an intermediate germinal center/activated B-cell phenotype compared to clusters 1 and 3 of the non-AIDS diffuse large B-cell lymphomas. Our results confirm that non-AIDS diffuse large B-cell lymphomas segregate into two groups with either germinal center or activated B-cell phenotype. We report the new finding that the AIDS status of the patient predicts the immunophenotype of the diffuse large B-cell lymphomas.

Adult↗

PubMed2005

Germinal center and activated b-cell profiles separate Burkitt lymphoma and diffuse large B-cell lymphoma in AIDS and non-AIDS cases.

Morphologic features of Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) overlap. No single phenotypic marker or molecular abnormality is pathognomonic. We tested a panel of 8 germinal center (GC) and activated B-cell (ABC) markers for their ability to separate BL and DLBCL. We diagnosed 16 BL and 39 DLBCL cases from 21 patients with AIDS and 34 without AIDS based on traditional morphologic criteria, Ki-67 proliferative index, and c-myc rearrangement (fluorescence in situ hybridization). After immunohistochemically staining tissue microarrays of BL and DLBCL for markers of GC (bcl-6, CD10, cyclin H) and ABC (MUM1, CD138, PAK1, CD44, bcl-2), we scored each case for the percentage of positive cells. Hierarchical clustering yielded 2 major clusters significantly associated with morphologic diagnosis (P < .001). For comparison, we plotted the sum of the GC scores and ABC scores for each case as x and y data points. This revealed a high-GC/low-ABC group and a low-GC/high-ABC group that were associated significantly with morphologic diagnosis (P < .001). Protein expression of multiple GC and ABC markers can separate BL and DLBCL.

Adolescent↗

PubMed2004

Early results of carotid stent placement for treatment of extracranial carotid bifurcation occlusive disease.

OBJECTIVE: The purpose of this study was to review the initial results of carotid artery angioplasty with stenting (CAS) performed by vascular surgeons to treat bifurcation occlusive disease. Most patients were selected for CAS if they had indications for endarterectomy (CEA) but were considered at high risk for surgery. METHODS: Since December 2000, 74 carotid arteries in 69 patients underwent CAS, with distal balloon embolization protection in 96%. Mean patient age was 72 years; 82% of patients were men. Indications for CAS included asymptomatic disease (62%), transient ischemic attack (TIA; 23%), and cerebrovascular accident (15%). Mean internal carotid artery diameter stenosis was 82%. CAS was chosen over CEA because of cardiac (49%) or pulmonary (4%) comorbid conditions, hostile neck (25%), distal extent of disease (6%), and contralateral cranial nerve injury (1%). CAS was performed in 15% patients who were good surgical candidates, because of patient preference. Pathologic conditions were primary atherosclerosis (81%), recurrent carotid stenosis (18%), and dissection (1%). Procedures were transfemoral in 95% of cases and transcarotid in 5%. In 30% of cases the contralateral carotid artery had 80% or greater stenosis or was completely occluded. RESULTS: Technical success was achieved in 96% of cases. There were no deaths, no major strokes, one minor stroke (National Institutes of Health Stroke Scale, 3), and one TIA (neurologic event rate, 2.6%). The single minor stroke resolved completely by 1 month. One patient (1.3%) had a perioperative myocardial infarction. Transient neurologic changes occurred in 8% of patients during the protection balloon inflation, and all resolved with deflation. Bradyarrhythmia requiring pharmacologic treatment occurred in 14% of patients. At mean follow-up of 6 months there have been two instances of recurrent stenosis greater than 50% as noted at duplex scanning. During the same period, 266 carotid CEAs were performed, with a neurologic event rate of 0.8% (major stroke, 0.4%; no minor strokes; TIA, 0.4%) and a myocardial infarction rate of 3%. Combined stroke and death rate was 1.3% in patients who underwent CAS and 0.5% in patients who underwent CEA. CONCLUSION: CAS with cerebral protection can be performed safely in patients at high surgical risk, with low perioperative morbidity and mortality. The durability of the procedure must be determined with longer follow-up.

Aged↗

PubMed2004

Managing the megacity for global sustainability: the new york metropolitan region as an urban biosphere reserve.

The UNESCO World Network of Biosphere Reserves (WNBR), while not originally conceived to include urban areas, was intended to include sites representing all significant ecosystems with the goal of support for sustainable development locally and globally. Drawing on the example of the New York Metropolitan Region (NYMR), which has a population of 21.4 million, it is argued here that the eventual inclusion of the largest of the world's cities in WNBR not only is within the logic of the biosphere reserve concept, but would also benefit the network and its goals. The ecological significance of the NYMR, its role as a driver for global environmental change, as well as the efforts under way in the city to improve urban environmental management and governance are all examined. Potential added value to the WNBR of including megacities such as the NYMR is considered, in particular, regarding the sharing of best practices, lessons learned, and the strengthening of links between megacities and their global natural resource bases.

City Planning↗

PubMed2003

Understanding the effects of the polymer support on reaction rates and kinetics: knowledge toward efficient synthetic design.

Solid-phase organic synthesis (SPOS) has an ever-expanding role in the field of organic synthesis. Partially out of difficulty, and partially from the rapid speed of progress, few basic studies on the role of the physical structure of the resin have been undertaken, and the dissemination of the existing knowledge has been slow. Major advances have been made in the understanding of the many factors that govern a SPOS reaction's performance as a function of the choice of solid support.

Amides↗