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Biomedical subjects

S McClure

Publications and source records attributed to S McClure.

At least 19 recordsLinked to original sources
PubMed2006

"Virtual unwrapping" of a mummified hand.

The purpose of this work is to demonstrate the feasibility of medical virtual reality technologies in the investigation of a mummified hand. The Ulster Museum obtained the mummy hand, which originated from Thebes, without any identifying information. The mummified hand was investigated using conventional X-ray and 3D multi-slice Computed Tomography (CT). Imaging revealed a range of fractures of the wrist, metacarpals and phalanges whilst 3D CT demonstrated internal structures using volume rendering. The absence of any features of bone healing at the fracture sites would imply that they occurred just prior to death or in the mummified state possibly during excavation. Conventional X-ray imaging indicated that the hand, although small, was likely to have originated from an adult. Medical imaging and virtual reality display will enable us to produce a rapid prototyped model using fused deposition technology. Therefore, further paleopathological research can be performed on the replica without the need to handle the original specimen.

Computer Simulation↗
PubMed2001

Segregation of B lymphocytes into stationary apoptotic and migratory proliferating subpopulations in agglomerate cultures with ileal epithelium.

The B lymphocyte-epithelial cell interactions that define the microenvironment of the ileal Peyer's patch, the primary B lymphocyte organ of the fetal lamb, have been replicated in tissue culture. Mixed suspensions of ileal epithelial cells, lymphocytes and fibroblasts from fetuses of 63-103 days of gestation organized into macroscopically visible agglomerates within 72 h. These agglomerates contained translucent spherical cavities and were enclosed within a marginal cell layer and surrounded by an expanding corona of emigrating cells. The lining of the cavities and the marginal layer consisted of well-differentiated, polarized columnar ileal epithelial cells. One population of B lymphocytes in the initial mixed suspension differentiated into two discrete populations reproducing the characteristics of intact fetal ileal Peyer's patches. B cells apposed to follicle-associated epithelium (FAE) within agglomerates underwent apoptosis. The other population of emigrant B cells proliferated and expressed the BAQ44A differentiation marker. Differentiation of ileal epithelial cells into FAE, typical of Peyer's patches, was markedly accelerated. The mutually inductive influences of intestinal epithelial cells and B lymphocytes in these agglomerates replicate normal mid-gestational fetal development of the mucosal immune system and afford new opportunities for its further investigation.

Animals↗
PubMed2001

Supplementation of urban home visitation with a series of group meetings for parents and infants: results of a "real-world" randomized, controlled trial.

OBJECTIVE: Home visitation has been shown to be effective in reducing rates of child maltreatment and in enhancing psychosocial outcomes in children and their parents. Even when available, however, it is underutilized by parents in some urban settings. We tested a supplemental 10-session group intervention for its ability to increase active participation in home visitation, enhance the quality of caregiving behavior of parents, and improve social developmental outcome in children. METHOD: A randomized controlled design was utilized, involving two separate cohorts of parents of 3- to 18-month old infants, totaling 148 parent-child dyads. The intervention focused on practical experience in promoting parent-infant attachment relationships. RESULTS: At 6 months follow-up, there was a substantial increase in the proportion of intervention group parents participating in home visitation, compared to parents in the control group (Fisher's exact p = .008). Parents in the intervention group exhibited a trend for improvement in their capacity to appropriately interpret infants' emotional cues (p = .08), independent of the effects of home visitation itself. Attrition in both the treatment and control groups was inversely associated with income and level of education. CONCLUSIONS: Group meetings may constitute an effective means of engaging stressed urban families in home visitation.

Adult↗
PubMed2001

Do facet joint capsular ligaments contain estrogen receptors? Application to pathogenesis of degenerative spondylolisthesis.

Studies showing that degenerative spondylolisthesis is 4 to 5 times more common in females than in males have suggested that hormonal influences account for this gender difference. Estrogen has been shown to play a role in other instabilities, such as those of the anterior cruciate ligament and the shoulder capsular ligaments, and estrogen receptors have been identified in these tissues. We wanted to assess facet joint capsular ligaments for the presence of such receptors. Accordingly, we collected facet joint capsular ligaments from 14 consecutive patients undergoing lumbar spinal fusion. Tissue sample analysis was performed by immunohistology using prediluted estrogen monoclonal antibody (Vantana) and automated immunostaining on a Vantana instrument. None of the specimens analyzed contained estrogen receptors. We conclude that, though degenerative spondylolisthesis may have hormonal influences, estrogen seems not to play a direct role in its development.

Female↗
PubMed2000

Effects of sympathetic inhibition on exertional dyspnoea, ventilatory and metabolic responses to exercise in normotensive humans.

Augmentation of circulating noradrenaline concentration stimulates ventilation during the initial stages of exercise and this is accompanied by an increased sensation of dyspnoea and exertion. This previous study [Clark, Galloway, MacFarlane, Henderson, Aitchison and McMurray (1997) Eur. Heart J. 18, 1829-1833] suggested a link between dyspnoea, which commonly limits exercise tolerance in heart failure patients, and high circulating noradrenaline concentration in these patients. The present study investigated this relationship further using sympathetic inhibition. Ten healthy normotensive males performed 10 min of submaximal cycling exercise at approx. 70% of maximal oxygen uptake per min (VO2max) on three occasions one week apart. The first of these sessions was a familiarization session and the other two were experimental study days. On each of the study days, subjects attended the laboratory in the morning after an overnight fast and, following a resting blood sample, were administered placebo or moxonidine (0.4 mg) in a double blind cross-over design. After a 90-min absorption period, subjects undertook the exercise task. Blood was drawn, expired gas was analysed breath by breath, blood pressure, heart rate and ratings of perceived dyspnoea and exertion were obtained. Moxonidine treatment significantly reduced plasma noradrenaline concentration (P < 0.01), mean arterial pressure (P < 0.01), and blood glycerol concentration (P < 0.05), but no differences were observed in heart rate, the ventilatory response to exercise or subjective ratings of dyspnoea and exertion. This study indicates that reducing sympathetic activity does not affect ventilation, perceived dyspnoea or perceived exertion in normotensive males. Therefore it can be concluded that reducing sympathetic activity may not be an appropriate strategy to help reduce perceived dyspnoea.

Adult↗
PubMed1999

Phase II trial of menogaril in non-Hodgkin's lymphomas: a Southwest Oncology Group trial.

PURPOSE: To assess the efficacy and toxicity of menogaril against non-Hodgkin's lymphoma (NHL) in a group of previously treated patients. PATIENTS AND METHODS: Sixty-two eligible patients with a histologic diagnosis of NHL were enrolled, 35 of who had intermediate or high-grade histologies and 27 of who had low-grade lymphomas. Patients with intermediate or high-grade lymphomas had received only 1 prior chemotherapy regimen, while patients with low-grade histologies had received 1 or 2 prior chemotherapy regimens. Menogaril was administered at 160 mg/m2 intravenously over 1 hour, once every 28 days. RESULTS: Among the 35 patients with intermediate or high-grade lymphomas who were evaluable for response, 6 of 35 patients achieved a partial response (PR) for a response rate of 17% (95% confidence interval: 7%-34%). Median survival in this group of patients was 13 months. For those patients with low-grade lymphoma, 5 of 26 patients achieved a PR for a response rate of 19% (95% confidence interval: 6%-38%). No complete responses were observed in either patient group. The incidence of serious (grade 3 or 4) toxicity for those with intermediate/high-grade and low-grade lymphomas was 43% and 44%, respectively. Most of these toxic effects consisted of reversible myelosuppression. Menogaril was discontinued in 2 patients due to prolonged neutropenia. Cardiotoxicity was observed in 4 patients, requiring discontinuation of the drug in 1 patient. No treatment-related deaths occurred and the overall toxicity was felt to be acceptable. CONCLUSION: The observed antitumor activity of single agent menogaril against both intermediate/high-grade and low-grade lymphomas was modest. Further exploration of this agent in patients with non-Hodgkin's lymphomas does not seem warranted.

Aged↗
PubMed1997

Removal of endotoxin from recombinant protein preparations.

OBJECTIVES: To develop an effective method to remove endotoxin from large scale E. coli recombinant protein purifications. DESIGN AND METHODS: Triton X-114 phase separation, affinity chromatography utilizing immobilized polymyxin B or immobilized histidine, were used to remove endotoxin from purified preparations of recombinant CK-BB, CK-MB, CK-MM, myoglobin, and cardiac troponin I. Endotoxin levels were measured by a Limulus Amebocyte Lysate gel-clot assay. The immunoactivity of these protein preparations was determined by BIAcore analysis using a panel of in-house generated monoclonal antibodies and by a Stratus Fluorometric Analyzer. In the case of troponin I, the BIAcore was also utilized to measure troponin C interactions. RESULTS: Phase separation with Triton X-114 was the most effective method in reducing the amount of endotoxin present in the protein preparations compared to either polymyxin B or histidine affinity chromatography. With Triton X-114, the reduction in endotoxin levels was greater than 99% and recovery of the proteins after endotoxin removal was greater than 90%. All three procedures for removing endotoxin had no deleterious effects on the immunoactivity of majority proteins when tested with a panel of monoclonal antibodies. Troponin I also retained its ability to bind to troponin C in the presence of Ca2+. Recombinant CK-BB and CK-MM which were expressed in the soluble fraction of E. coli cell lysates, contained significantly higher endotoxin levels than recombinant CK-MB, myoglobin and cardiac troponin I which were expressed in the form of inclusion bodies. CONCLUSION: Of the three methods tested, Triton X-114 phase separation was the most effective way of removing endotoxin from recombinant proteins.

Biochemistry↗
PubMed1996

Successful treatment of intraoperative malignant hyperthermia during renal transplantation.

Malignant hyperthermia is a complication of general anesthesia that is especially problematic if it occurs during renal transplantation because myoglobinemia, shock, and ischemia play a role in injuring the transplanted kidney. In this report, we describe a case of malignant hyperthermia, its clinical course, and the measures taken to successfully treat it and preserve the function of a kidney allograft.

Adult↗
PubMed1995

Adjuvant chemotherapy with 5-FU, adriamycin, and mitomycin-C (FAM) versus surgery alone for patients with locally advanced gastric adenocarcinoma: A Southwest Oncology Group study.

PURPOSE: To evaluate FAM [5-FU (5-fluorouracil), doxorubicin, mitomycin C] chemotherapy as adjuvant therapy for patients with resected TNM stage I, II, or III gastric carcinoma. PATIENTS AND METHODS: One hundred ninety-three eligible patients were accrued from 1978 to 1991 in a phase III trial comparing six cycles (1 year) of postoperative FAM chemotherapy with observation only. RESULTS: The median follow-up on this study was 9.5 years. For all patients, no differences (log-rank analysis) in disease-free survival (p = 0.45) and overall survival (p = 0.57) between FAM therapy (93 cases) and surgery (100 cases) were observed. Quality of surgical resection affected survival irrespective of FAM use. Cases with curative resection, defined in a retrospective review of pathology and surgical reports as cases having no evidence of residual disease in the abdomen and tumor-free margins > 1 cm, had superior survival compared to cases not meeting these requirements (p < 0.001). FAM was well tolerated with 6% (five of 90) of cases demonstrating grade IV hematologic toxicity. There were two drug-related fatalities (one cardiomyopathy, one hematolytic uremic syndrome). CONCLUSION: FAM is not effective adjuvant therapy for TNM stage I, II, and III patients with resected gastric cancer. Future adjuvant studies must emphasize prospective surgical quality control to assure enrollment of appropriately staged and resected cases and wide participation to assure adequate case accrual over a reasonable period.

Adenocarcinoma↗
PubMed1992

Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck: a Southwest Oncology Group study.

PURPOSE: The Southwest Oncology Group (SWOG) conducted a randomized comparison of cisplatin plus fluorouracil (5-FU) and carboplatin plus 5-FU versus single-agent methotrexate (MTX) in patients with recurrent and metastatic squamous-cell carcinoma (SCC) of the head and neck. The primary objective was to compare separately the response rates of each combination regimen to standard weekly MTX. PATIENTS AND METHODS: Two hundred seventy-seven patients diagnosed with SCC of the head and neck were randomized to one of three treatments: (1) cisplatin 100 mg/m2 intravenously (IV) on day 1 and 5-FU 1,000 mg/m2 per day for a 96-hour continuous infusion repeated every 21 days; (2) carboplatin 300 mg/m2 IV on day 1 and 5-FU 1,000 mg/m2 per day for a 96-hour continuous infusion repeated every 28 days; and (3) MTX 40 mg/m2 IV given weekly. RESULTS: All three treatment regimens were well tolerated. However, both hematologic and nonhematologic toxicities were significantly greater with cisplatin plus 5-FU compared with MTX (P = .001). Toxicity from carboplatin plus 5-FU was intermediate compared with the other regimens. The complete and partial response rates were 32% for cisplatin plus 5-FU, 21% for carboplatin plus 5-FU, and 10% for MTX. The comparison of cisplatin plus 5-FU to MTX was statistically significant (P less than .001), and the comparison of carboplatin plus 5-FU to MTX was of borderline statistical significance (P = .05). Median response durations and median survival times were similar for all three treatment groups. Logistic regression models showed that only treatment assigned was associated significantly with response (P = .001). Cox proportional hazards models indicated that only performance status was associated significantly with survival (P less than .01). CONCLUSIONS: We conclude that combination chemotherapy resulted in improved response rates but was associated with an increased toxicity and no improvement in overall survival. Therefore, new treatments that may alter the course of disease in recurrent head and neck cancer patients still need to be identified.

Adult↗
PubMed1991

Randomized trial of doxorubicin, bisantrene, and mitoxantrone in advanced breast cancer: a Southwest Oncology Group study.

Four hundred eleven women with metastatic breast cancer were randomly assigned to receive either 60 mg/m2 doxorubicin (130 patients), 320 mg/m2 bisantrene (146 patients), or 14 mg/m2 mitoxantrone (135 patients). The doses were given intravenously every 3 weeks with a cross-over design to determine their relative efficacy and toxicity. To be eligible, patients must have had one previous chemotherapy regimen, and patients who were estrogen receptor positive must have failed endocrine therapy. There were 365 patients assessable for response and 399 assessable for toxic effects. The median age was 57 years; 18% were premenopausal or perimenopausal. Visceral dominant disease was present in 66% of the patients. Ninety-seven percent of the patients had a disease-free interval from diagnosis to first recurrence of less than 1 year. The response rate was 28% with doxorubicin, 13% with bisantrene, and 14% with mitoxantrone (P = .004). Median time to treatment failure was 133 days with doxorubicin, 66 days with bisantrene, and 68 days with mitoxantrone (logrank P = .06). The median survival was 315 days for doxorubicin, 290 days for bisantrene, and 177 days for mitoxantrone (logrank P = .04), although survival at 2 years was similar for all three agents. There were five responses in the 66 patients crossed over to doxorubicin and one response each for patients crossed over to bisantrene (39 patients) or mitoxantrone (63 patients). Toxicity leading to discontinuance of therapy was more common with doxorubicin, and discontinuance of therapy was due primarily to patient's request or cardiotoxicity. The major dose-limiting toxic effect for all three agents was leukopenia. Nausea and vomiting, mucositis, and alopecia were more severe with doxorubicin. Congestive heart failure developed in nine patients treated with doxorubicin, zero patients treated with bisantrene, and two patients treated with mitoxantrone. A decrease in the left ventricular ejection fraction, as defined by moderate to severe Alexander grade changes, was more common in patients treated with doxorubicin (doxorubicin-treated patients = 20%, bisantrene-treated patients = 5%, and mitoxantrone-treated patients = 10%). This study demonstrates that bisantrene and mitoxantrone have only modest activity in metastatic breast carcinoma. The activity of doxorubicin is greater than that of the other two agents, but at a cost of increased toxicity.

Adenocarcinoma↗
PubMed1991

The intestinal habitat for organized lymphoid tissues in ruminants; comparative aspects of structure, function and development.

Unlike the Peyer's patches of rats and mice, which are considered to be secondary lymphoid organs, the ileal Peyer's patch of sheep is thought to be responsible for the primary generation of B cells, like the bursa of Fabricius of birds. The ileal Peyer's patch of sheep shows prenatal maturation, antigen-independent lymphopoiesis, a rate of lymphocyte production larger than that of the thymus, and involution at a young age. Follicles contain few T cells and have an IgM+, relatively immature B lymphocyte population, as judged by B-cell differentiation markers. The follicle-associated epithelium of the ileal Peyer's patch is of a special type that sheds carbonic anhydrase-rich, 50-nanometer membrane-bounded particles (carbonic anhydrase-reactive particles; CAP) into the intercellular spaces. The CAP filter into the follicle centre and are taken up by lymphocytes. They represent the epithelial (bursa-like) element in an otherwise mesenchymal stroma of reticular cells embedding the follicle lymphocytes. Transepithelial transport of macromolecules, with the formation of multivesicular body-like cytoplasmic vacuoles, appears to be the basis for CAP formation. The jejunal Peyer's patches are devoid of CAP, persist in the adult animal, contain M cells with clusters of B cells in the follicle-associated epithelium, and have many CD4+ lymphocytes in the follicles and in the interfollicular areas. Aggregates of lymphoid follicles in the large intestine resemble the jejunal Peyer's patches with respect to their lymphocyte population and the ileal Peyer's patch with respect to their follicle-associated epithelium.

Animals↗
PubMed1991

Computer-assisted morphometric analysis of absorptive and follicle-associated epithelia of Peyer's patches in sheep foetuses and lambs indicates the presence of distinct T- and B-cell components.

The phenotypes of lymphocytes infiltrating the epithelium of the jejunal and ileal Peyer's patches in foetal sheep at about 130 days gestation and 2-month-old lambs were examined using indirect immunoperoxidase histochemistry, a panel of monoclonal antibodies and enzyme histochemistry. Computer-assisted morphometric analysis enabled the relative size of reactive areas within epithelia to be estimated. The comparison of the intraepithelial lymphocyte populations associated with structurally developed Peyer's patches of foetal sheep and those of lambs allowed assessment of the impact of extrinsic factors from which the sheep foetus is shielded. The study confirmed the postnatal expansion in the villous intraepithelial lymphocyte population and showed that this expansion involved the CD8 and gamma delta phenotypes. CD4 lymphocytes did not appear in the follicle-associated epithelium until after birth. Unlike the villous epithelium, the follicle-associated epithelium had a high frequency of IgM+ and MHC II+ cells, which was dramatically reduced after birth. This postnatal reduction was particularly prominant in the follicle-associated epithelium of the jejunal Peyer's patch, where the frequency of IgM+ cells fell from 12.4% in foetal sheep to 0.7% in lambs. Double staining for alkaline phosphatase in the jejunal Peyer's patch suggested that clusters of IgM+ cells were associated with M cells.

Animals↗
PubMed1990

Distribution of lymphocyte subsets in the large intestinal lymphoid follicles of lambs.

The phenotypes of lymphocytes in the large intestinal patches (LIP) of lambs were examined by flow cytometry and immunohistology, using a panel of monoclonal antibodies (mAb), and compared to those found in the jejunal (JPP) and ileal Peyer's patches (IPP). T-cell markers were detected on 25% of the LIP and JPP lymphocytes by cytofluorometry, and nearly all T cells expressed the CD4 molecule. In contrast, T cells were scarce in the IPP (less than 1%). The B-cell marker p220 was expressed by 74% of the LIP lymphocytes, whereas surface immunoglobulin-positive cells comprised 50-60% of the lymphocyte population. The adhesion molecule CD2 was expressed by a larger proportion of cells from the LIP and JPP than from the IPP, whereas the adhesion molecule CD44 was detected on more IPP lymphocytes. Major histocompatibility complex (MHC) class I antigens were expressed by nearly all lymphocytes from the LIP, JPP and IPP. The LIP contained 70-80% cells with MHC class II expression, whereas the majority of IPP cells (greater than 95%) were MHC class II positive. Immunohistology showed many CD4+ T lymphocytes in the follicles of the LIP and JPP, but none in the IPP follicles. CD8+ lymphocytes were found in the interfollicular areas and were absent from the follicles. The interfollicular areas of the rectal patch contained about 15% tau delta T cells. In contrast, the JPP, IPP and the colon patch at the beginning of spiral colon contained less than 3% tau delta T cells.

Animals↗
PubMed1989

Postmortem cerebrospinal fluid pleocytosis.

We show that postmortem cerebrospinal fluid (CSF) pleocytosis is a common event. Postmortem cerebrospinal or ventricular fluid was obtained from children and adults. The cells were counted and morphologically characterized using several histochemical markers. Infants exhibit a brisk postmortem CSF pleocytosis. Sudden infant death cases have relatively high CSF counts. Typeable cells are mononuclear and consist of approximately 60%-70% lymphocytes and 20%-40% macrophages. When postmortem duration is greater than 12 h, the cells become vacuolated and cannot be identified. The etiology of these findings requires further study.

Adolescent↗