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E McGuire

Publications and source records attributed to E McGuire.

At least 19 recordsLinked to original sources
PubMed2001

The schistosome oligosaccharide lacto-N-neotetraose expands Gr1(+) cells that secrete anti-inflammatory cytokines and inhibit proliferation of naive CD4(+) cells: a potential mechanism for immune polarization in helminth infections.

Immunomodulatory oligosaccharides found on helminths also are found in human milk, and both helminths and milk have been shown to be immunosuppressive. We have been examining the immunomodulatory capabilities of two oligosaccharides expressed in milk and on helminth parasites, lacto-N-fucopentaose III and lacto-N-neotetraose (LNnT). In an attempt to dissect mechanisms that lead to Th2 polarization and immune suppression, we examined the early response in mice to the glycoconjugate LNnT-Dextran (LNnT-Dex). We found that injection of LNnT-Dex expanded a cell population, phenotypically defined as Gr1(+)/CD11b(+)/F4/80(+), as early as 2 h after injection. Examination of spontaneous cytokine production showed that this Gr1(+)/F4/80(+) population of cells spontaneously produced low levels of proinflammatory cytokines, but higher levels of IL-10 and TGF-beta ex vivo, compared to peritoneal cells from mice injected with Dex. Gr1(+) cells adoptively suppressed naive CD4(+) T cell proliferation in vitro in response to anti-CD3/CD28 Ab stimulation. Suppression of naive CD4(+) cells involved cell contact and was dependent on IFN-gamma and NO, with a discrete role played by IL-10. Coculture of naive CD4(+)T cells with Gr1(+) suppressor cells did not lead to CD4(+) T cell apoptosis, although it did imprint on naive CD4(+) T cells a response characterized by lower levels of IFN-gamma, coincident with increased IL-13 production. Our results suggest that both human milk and helminth parasites may share a ligand-specific mechanism involved in the generation of anti-inflammatory mediators that suppress Th1-type and inflammatory responses.

Amino Sugars↗
PubMed2001

A schistosome-expressed immunomodulatory glycoconjugate expands peritoneal Gr1(+) macrophages that suppress naive CD4(+) T cell proliferation via an IFN-gamma and nitric oxide-dependent mechanism.

Lacto-N-fucopentaose III (LNFPIII) is found in human milk and on the Th2 driving helminth parasite Schistosoma mansoni. This pentasaccharide drives Th2-type responses in vivo and in vitro when conjugated to a carrier. In an attempt to further understand early events in Th1 to Th2 switching, we examined phenotypic and functional changes in peritoneal cell populations in BALB/c and SCID mice following LNFPIII-dextran injection. We found that i.p. injection with LNFPIII-dextran resulted in rapid (<20 h) expansion of the Gr1(+) subpopulation of F4/80(+)/CD11b(+) peritoneal cells, comprising up to 75% of F4/80(+)/CD11b(+) peritoneal cells compared with 18% in uninjected or dextran-injected mice. Functionally, these cells suppressed anti-CD3- and anti-CD28-induced proliferation of naive CD4(+) T cells. LNFPIII-dextran also expanded functional Gr1(+) suppressor macrophages in SCID mice, demonstrating that expansion and function of suppressor cells did not require T cells. Suppression in both BALB/c and SCID mice was NO and IFN-gamma dependent, as addition of inhibitors of inducible NO synthase (N(G)-monomethyl-L-arginine), as well as anti-IFN-gamma Abs, restored the ability of CD4(+) T cells to proliferate in vitro. Depletion of the F4/80(+) subset of Gr1(+) cells eliminated the suppressive activity of peritoneal exudate cells showing that these cells were macrophages. Thus, LNFPIII-dextran rapidly expands the Gr1(+) suppressor macrophage population in the peritoneal cavities of otherwise naive mice. These Gr1(+) cells suppress proliferation of naive CD4(+) T cells in an NO-dependent mechanism, and may play a regulatory role in the switching of Th1- to Th2-type responses.

Amino Sugars↗
PubMed2001

Penetrating esophageal injuries: multicenter study of the American Association for the Surgery of Trauma.

OBJECTIVE: The purpose of this study was to define the period of time after which delays in management incurred by investigations cause increased morbidity and mortality. The outcome study is intended to correlate time with death from esophageal causes, overall complications, esophageal related complications, and surgical intensive care unit length of stay. METHODS: This was a retrospective multicenter study involving 34 trauma centers in the United States, under the auspices of the American Association for the Surgery of Trauma Multi-institutional Trials Committee over a span of 10.5 years. Patients surviving to reach the operating room (OR) were divided into two groups: those that underwent diagnostic studies to identify their injuries (preoperative evaluation group) and those that went immediately to the OR (no preoperative evaluation group). Statistical methods included Fisher's exact test, Student's T test, and logistic regression analysis. RESULTS: The study involved 405 patients: 355 male patients (86.5%) and 50 female patients (13.5%). The mean Revised Trauma Score was 6.3, the mean Injury Severity Score was 28, and the mean time interval to the OR was 6.5 hours. There were associated injuries in 356 patients (88%), and an overall complication rate of 53.5%. Overall mortality was 78 of 405 (19%). Three hundred forty-six patients survived to reach the OR: 171 in the preoperative evaluation group and 175 in the no preoperative evaluation group. No statistically significant differences were noted in the two groups in the following parameters: number of patients, age, Injury Severity Score, admission blood pressure, anatomic location of injury (cervical or thoracic), surgical management (primary repair, resection and anastomosis, resection and diversion, flaps), number of associated injuries, and mortality. Average length of time to the OR was 13 hours in the preoperative evaluation group versus 1 hour in the no preoperative evaluation group (p < 0.001). Overall complications occurred in 134 in the preoperative evaluation group versus 87 in the no preoperative evaluation group (p < 0.001), and 74 (41%) esophageal related complications occurred in the preoperative evaluation group versus 32 (19%) in the no preoperative evaluation group (p = 0.003). Mean surgical intensive care unit length of stay was 11 days in the preoperative evaluation group versus 7 days in the no preoperative evaluation group (p = 0.012). Logistic regression analysis identified as independent risk factors for the development of esophageal related complications included time delays in preoperative evaluation (odds ratio, 3.13), American Association for the Surgery of Trauma Organ Injury Scale grade >2 (odds ratio, 2.62), and resection and diversion (odds ratio, 4.47). CONCLUSION: Esophageal injuries carry a high morbidity and mortality. Increased esophageal related morbidity occurs with the diagnostic workup and its inherent delay in operative repair of these injuries. For centers practicing selective management of penetrating neck injuries and transmediastinal gunshot wounds, rapid diagnosis and definitive repair should be made a high priority.

Adolescent↗
PubMed2001

Local tumor control with salvage cryotherapy for locally recurrent prostate cancer after external beam radiotherapy.

PURPOSE: We identified variables associated with a positive prostate biopsy after salvage cryotherapy in patients in whom initial external beam radiotherapy for prostate cancer failed to improve our cryotherapy technique, optimize local control and improve our patient selection criteria for salvage cryotherapy. MATERIALS AND METHODS: Between July 1992 and January 1995, 145 patients underwent salvage cryotherapy. Post-cryotherapy sextant prostate biopsies were performed in 107 cases. We evaluated certain variables on univariate and multivariate analysis as predictors of a positive biopsy after cryotherapy, including the type of previous therapy, tumor stage and grade at initial diagnosis, prostate volume, pre-cryotherapy prostate specific antigen (PSA), number of positive biopsy cores before cryotherapy, PSA nadir after cryotherapy, stage and grade of local recurrence, number of cryoprobes, number of freeze-thaw cycles and use of a urethral warming catheter during cryotherapy. RESULTS: Biopsies were positive in 23 cases (21%) after salvage cryotherapy. Variables associated with a positive biopsy on univariate analysis were initial stage, precryotherapy PSA, PSA nadir after cryotherapy, number of cryoprobes, number of freeze-thaw cycles and a history of chemotherapy (p = 0.005, 0.027, 0.001, 0.009, 0.018 and 0.008, respectively). Variables that remained associated with a positive biopsy on multivariate analysis were the number of probes used and post-cryotherapy PSA nadir (p = 0.013 and 0.019, respectively). CONCLUSIONS: Patients with initial clinical stage T1-2N0M0 disease and PSA no more than 10 ng./ml. have a higher rate of negative biopsies after salvage cryotherapy. Therefore, they are better candidates for salvage cryotherapy for locally recurrent prostate adenocarcinoma after external beam radiotherapy. To optimize the potential for local control the technique of salvage cryotherapy should include 2 freeze-thaw cycles and a minimum of 5 cryoprobes. Detectable PSA after salvage cryotherapy is a strong predictor of local failure.

Biopsy↗
PubMed2000

Orthopedic medical malpractice: an attorney's perspective.

Orthopedic surgeons are trained to manage problems involving the musculoskeletal system. It would be helpful to identify certain procedures, anatomic areas, or issues related to the physician-patient relationship that could potentially lead to a malpractice lawsuit. Once the problems are identified, steps toward continuing education and physician awareness could be initiated. In this study, we performed a randomized nationwide survey of medical malpractice attorneys to evoke their opinion on these issues. We found that the lumbar spine was the most common anatomic area involved in orthopedic medical malpractice cases, and a physician appearing rushed and uninterested is most likely to be the subject of a lawsuit where a poor physician-patient relationship was a contributing factor. Educational and professional programs are needed to increase the awareness and knowledge of orthopedic malpractice risks, and also to identify potentially preventable problems leading to malpractice litigation.

Adult↗
PubMed2000

Major surgery to manage definitively severe complications of salvage cryotherapy for prostate cancer.

PURPOSE: Severe complications of salvage cryotherapy may be debilitating and chronic but these complications may be managed by definitive extirpative surgical procedures. We evaluated the effectiveness of the major surgical procedures performed to manage these complications, and assessed patient survival and complications after extirpative surgery. MATERIALS AND METHODS: Between 1992 and 1995 salvage cryotherapy was performed in 150 men with biopsy proved, locally recurrent prostate cancer after radiotherapy and/or systemic therapy. We retrospectively reviewed patient charts to assess the complications managed by extirpative surgery. RESULTS: Extirpative surgery was performed in 6 of the 150 patients for serious complications, including uncontrollable hematuria, osteitis pubis, rectourethral fistula, refractory perineal pain, bladder outlet obstruction and complete urinary incontinence. Cystoprostatectomy was done in 4 patients, of whom 3 also underwent en bloc pubic symphysectomy. In the remaining 2 men salvage prostatectomy was performed with bladder neck closure and continent catheterizable stomal creation. Surgery successfully managed severe cryotherapy complications in all 6 cases. The complications of extirpative surgery included superficial wound infection in 1 patient and 3 incisional hernias in another. Prostate specific antigen was undetectable in 4 of the 6 men at 36, 38, 39 and 42 months, and detectable in 2 at 31 and 41 months, respectively. CONCLUSIONS: Extirpative surgery may successfully alleviate severe salvage cryotherapy complications without major additive morbidity. Long survival duration justifies extirpative surgery in select patients with severe complications of salvage cryotherapy.

Adenocarcinoma↗
PubMed1995

Performance of Americans and israelis with cerebrovascular accident on the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA).

OBJECTIVE: The Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) measures the cognitive performance of persons with cerebrovascular accident (CVA). Although this assessment was developed and standardized in Israel, it is frequently used in the United States. The purpose of this study was to identify whether differences in performance on the LOTCA existed between Americans and Israelis who have had strokes. Additionally, this study was designed to compare the performance of persons with right CVA with the performance of persons with left CVA because the normative data for the LOTCA does not include separate information for these two groups. METHOD: The LOTCA was administered to 25 Americans with CVA (19 right CVA and 6 left CVA) and 56 Israelis with CVA (26 right CVA and 30 left CVA). RESULTS: On the majority of LOTCA subtests, there were no significant differences between American and Israeli subjects. Only one subtest, Orientation to Time, revealed significant differences between Americans and Israeli subjects both for subjects with right CVA and subjects with left CVA. Examination of subjects with right CVA versus subjects with left CVA also indicated few differences. Only one subtest, Pegboard Construction, revealed significant differences between subjects with right CVA and subjects with left CVA for both American and Israeli subjects. CONCLUSION: The LOTCA is an appropriate tool for occupational therapists to use in assessing Americans who have had strokes. In addition, for the most part, the subtests of the LOTCA assess cognitive-perceptual abilities that are not specific to the right or left cerebral hemisphere.

Aged↗
PubMed1990

A bleeding risk index for estimating the probability of major bleeding in hospitalized patients starting anticoagulant therapy.

PURPOSE: To construct and test prospectively a bleeding risk index for estimating the probability of major bleeding in hospitalized patients starting long-term anticoagulant therapy. PATIENTS AND METHODS: In an inception cohort of 617 patients starting long-term anticoagulant therapy in one hospital, data were gathered retrospectively and bleeding was classified using reliable explicit criteria. We constructed a bleeding risk index by identifying and weighting independent predictors of major bleeding using a multivariate proportional-hazards model. The bleeding risk index was tested in 394 other patients prospectively identified in a second hospital. The index was compared to physicians' predictions. RESULTS: Major bleeding developed before discharge in 61 of all 1,011 patients (6%). The bleeding risk index included four independent risk factors for major in-hospital bleeding: the number of specific comorbid conditions; heparin use in patients aged 60 years or older; maximal prothrombin or partial thromboplastin time 2.0 or more times control; liver dysfunction worsening during therapy. In the testing group, the index predicted major bleeding, which occurred in 3% of 235 low-risk patients, 16% of 96 middle-risk patients, and 19% of 63 high-risk patients (p less than 0.001). The bleeding risk index performed as well as physicians' predictions, and integration of the bleeding risk index with physicians' predictions led to a classification system that was more sensitive (p = 0.03) than physicians' predictions alone. In 86% of patients with a high risk of major bleeding, we identified specific ways of improving therapy, e.g., avoiding overanticoagulation and nonsteroidal anti-inflammatory agents. CONCLUSION: The bleeding risk index provides valid estimates of the probability of major bleeding in hospitalized patients starting long-term anticoagulant therapy and complements physicians' predictions. The possibility that bleeding can be prevented in high-risk patients warrants prospective evaluation.

Aged↗
PubMed1990

Clinical findings associated with acute proximal deep vein thrombosis: a basis for quantifying clinical judgment.

PURPOSE: To identify clinical findings useful in estimating the probability of acute proximal deep vein thrombosis (DVT). PATIENTS AND METHODS: The records of 355 symptomatic patients who underwent ascending venography were reviewed. Data on 76 clinical items were collected using standardized forms. Venograms were interpreted according to standard criteria and interobserver agreement was evaluated in a sample of 119 venograms. Independent clinical correlates of proximal DVT were identified using multivariate discriminant analysis in 236 randomly chosen patients; they were tested in the remaining 119 patients. RESULTS: Acute proximal DVT was shown by venogram in 96 patients (27%). Five independent clinical correlates of proximal DVT--swelling above the knee of the affected leg, swelling below the knee, recent immobility, cancer, fever--predicted proximal DVT in the testing group; in patients with none, one, or two or more of these clinical findings, proximal DVT was present in 5%, 15%, and 42%, respectively. If venography had been performed only in patients with one or more of the five factors, 97% of cases of proximal DVT would have been diagnosed and venography would have been avoided in 26% of patients with normal test results. CONCLUSION: These data provide a quantitative basis for estimating the probability of proximal DVT on the basis of clinical findings in symptomatic patients. How these findings can best be integrated with noninvasive testing and venography into diagnostic strategies for DVT remains to be determined.

Adult↗
PubMed1987

Construction of a low pressure reservoir and achievement of continence after "diversion" and in end stage vesical dysfunction.

Creation of a continent low pressure urinary reservoir was attempted in 33 patients: 11 with a supravesical diversion, 6 with a vesicostomy, 9 treated by catheter drainage and 7 with end stage bladder disease. The common problems were poor urine storage associated with bladder fibrosis, defunctionalization and decentralization or spinal cord injury coupled with a poorly functional urethral continence mechanism. The over-all outcome at a mean of 21 months (range 4 months to 11 years) was excellent in terms of upper tract function, reservoir capability and continence.

Adult↗
PubMed1976

The antecubital fossa fistula.

We have reviewed our experience with 19 proximal forearm arteriovenous fistulas used in chronic hemodialysis. Thirteen functioned adequately, and of these 10 were complicated by dislodge needles during dialysis, arm edema or hematomas. Although 3 patients developed symptoms of arterial steal, none required ligation of the fistula. This experience suggests that antecubital fossa fistulas might best be used as a second line angioaccess when distal forearm fistulas have been unsuccessful or are impossible to contruct.

Adolescent↗