Search PubMed⌕ Search

Biomedical subjects

S Bryant

Publications and source records attributed to S Bryant.

At least 19 recordsLinked to original sources

Rate-dependent electrical, contractile and restitution properties of isolated left ventricular myocytes in guinea-pig hypertrophy.

Left ventricular hypertrophy predisposes to sudden cardiac death (SCD) and studies of human SCD suggest that the antecedent heart rate (HR) is usually < 100 beats min(-1). This is surprising in view of the known association between adrenergic receptor stimulation and SCD which by itself would suggest that it is more likely to occur from high rather than low HR. We therefore hypothesized that there may be electrical or mechanical abnormalities present in myocytes isolated from animals with left ventricular hypertrophy that predispose to SCD at low stimulation frequencies but which may not be present at high HR. Mild left ventricular hypertrophy was induced in guinea-pigs by infra-renal aortic banding. Electrical and mechanical properties of isolated myocytes were studied at different stimulation frequencies between 0.1 and 3 Hz. Action potential duration (APD) is prolonged in hypertrophy at stimulation frequencies < 1 Hz but not at faster rates. Contraction size, time-to-peak contraction (TTPC) and half-relaxation time are greatly enhanced in hypertrophy at all frequencies between 0.1 and 3 Hz. Electrical (50.3 +/- 5.2 ms in hypertrophy and 78.4 +/- 12.1 ms in control, P < 0.03) and mechanical (205 +/- 16 ms for hypertrophy and 266 +/- 24 ms for control cells, P < 0.03) restitution time constants are quicker in hypertrophy. The finding of APD prolongation at low but not at high frequencies is consistent with the finding that SCD arises from low and not high HR. This data supports the role of abnormal repolarization in SCD.

Action Potentials↗

Efficacy of a simple intraoperative transfusion algorithm for nonerythrocyte component utilization after cardiopulmonary bypass.

BACKGROUND: Abnormal bleeding after cardiopulmonary bypass (CPB) is a common complication of cardiac surgery, with important health and economic consequences. Coagulation test-based algorithms may reduce transfusion of non-erythrocyte allogeneic blood in patients with abnormal bleeding. METHODS: The authors performed a randomized prospective trial comparing allogeneic transfusion practices in 92 adult patients with abnormal bleeding after CPB. Patients with abnormal bleeding were randomized to one of two groups: a control group following individual anesthesiologist's transfusion practices and a protocol group using a transfusion algorithm guided by coagulation tests. RESULTS: Among 836 eligible patients having all types of elective cardiac surgery requiring CPB, 92 patients developed abnormal bleeding after CPB (incidence, 11%). The transfusion algorithm group received less allogeneic fresh frozen plasma in the operating room after CPB (median, 0 units; range, 0-7 units) than the control group (median, 3 units; range, 0-10 units) (P = 0.0002). The median number of platelet units transfused in the operating room after CPB was 4 (range, 0-12) in the algorithm group compared with 6 (range, 0-18) in the control group (P = 0.0001). Intensive care unit (ICU) mediastinal blood loss was significantly less in the algorithm group. Multivariate analysis demonstrated that transfusion algorithm use resulted in reduced ICU blood loss. The control group also had a significantly greater incidence of surgical reoperation of the mediastinum for bleeding (11.8% vs. 0%; P = 0.032). CONCLUSIONS: Use of a coagulation test-based transfusion algorithm in cardiac surgery patients with abnormal bleeding after CPB reduced non-erythrocyte allogeneic transfusions in the operating room and ICU blood loss.

Adult↗

Non-myeloablative transplants for malignant disease.

This article discusses changes in the way hematopoietic stem cell allotransplants may be carried out in the future to treat patients with malignant hematological diseases. Specifically, the focus has shifted away from attempts at eradicating underlying diseases through toxic high-dose chemoradiation therapy towards using the stem cell donor's immune cells for that purpose (allogeneic graft-versus-tumor effect). The non-myeloablative transplant approaches hold promise in reducing the morbidity and mortality associated with conventional high-dose chemoradiation therapy, and they allow allogeneic transplants in elderly or medically infirm patients who are at present not candidates for transplantation. In the future, specific graft-versus-tumor responses may become possible by eliciting donor T cell responses to tumor-associated minor histocompatibility antigens. In Section I, Dr. Rainer Storb describes experimental studies in random-bred dogs that rely on non-cytotoxic immunosuppressive agents to establish stable allografts. Powerful postgrafting immunosuppression, traditionally directed at preventing graft-versus-host disease (GVHD), is also used to overcome host-versus-graft (HVG) reactions, thereby dramatically reducing the need for intensive immunosuppressive conditioning programs. Preclinical canine studies have been translated into the clinical setting for treatment of elderly or medically infirm patients with malignant hematological diseases. The pretransplant conditioning has been reduced to a single dose of 2 Gy total body irradiation (TBI) with or without fludarabine. The lack of toxicity makes it possible for transplants to be conducted in the outpatient setting. Multicenter trials have been initiated, and more than 300 patients have been successfully treated with hematopoietic stem cell grafts both from related and unrelated HLA-matched donors. In Section II, Dr. Richard Champlin describes clinical studies with therapeutic strategies that utilize relatively non-toxic, nonmyeloablative disease-specific preparative regimens incorporating fludarabine, together with other chemotherapeutic agents, to achieve disease suppression and engraftment of allogeneic hematopoietic cells and to allow subsequent infusions of donor lymphocytes. Remissions have been seen in patients with acute myelocytic, chronic myelocytic, chronic lymphocytic, leukemias, lymphomas, and myelomas. In Section III, Dr. Stanley Riddell and colleagues describe studies on isolation of T cells reactive with minor histocompatibility (H) antigens and involved both in GVHD and graft-versus-leukemia (GVL) responses. For example, the gene encoding a novel H-Y antigen in humans has been identified and shown to exhibit restricted tissue expression. Acute myelocytic leukemia stem cells were demonstrated to express the H-Y antigen and additional minor H antigens, and engraftment of such cells in NOD/SCID mice could be selectively prevented by minor antigen-specific T-cell clones. An autosomal encoded human minor H antigen associated with chronic GVHD has been demonstrated. A trial evaluating therapy of relapsed acute myelocytic leukemia or acute lymphoblastic leukemia after allogeneic stem cell transplantation with T-cell clones specific for recipient minor H antigens has been initiated.

Aged↗

Cytochrome P450 induction in rat hepatocytes assessed by quantitative real-time reverse-transcription polymerase chain reaction and the RNA invasive cleavage assay.

The acceleration of drug discovery due to combinatorial chemistry and high-throughput screening methods has increased the numbers of candidate pharmaceuticals entering the drug development phase, and the capability to accurately predict whether drug candidates will induce various members of the drug-metabolizing cytochrome P450 (CYP) enzyme superfamily is currently of great interest to the pharmaceutical industry. In the present study, we describe the rapid and reliable analysis of CYP induction in a readily obtained model system (cultured rat hepatocytes) using both real-time quantitative reverse transcription-polymerase chain reaction (real-time RT-PCR) and the RNA invasive cleavage assay. The levels of members in the three primary inducible rat CYP subfamilies (CYP1A1, CYP2B1/2, and CYP3A1) were analyzed in untreated and induced (beta-naphthoflavone, phenobarbital, and hydrocortisone) hepatocyte cultures under various media conditions to screen for optimal CYP induction profiles. The fold inductions measured by real-time RT-PCR and the RNA invasive cleavage assay were also compared with enzyme activity measurements in parallel cultures using liquid chromatography/double mass spectrometry-based assays, and the sensitivity and the specificity of the two RNA analysis methods were compared. Using these techniques, various culture conditions were examined for optimizing induction of the three CYP subfamily members. Both real-time RT-PCR and the RNA invasive cleavage assay prove to be effective methods for determining the effects of drugs on specific CYPs in primary rat hepatocytes.

Animals↗

Predictors of blood transfusions in spinal instrumentation and fusion surgery.

STUDY DESIGN: A retrospective review of 244 adult spine instrumentation and fusion surgery cases (1994-1995) from one institution. OBJECTIVES: To ascertain the predictors of blood transfusions for adult patients undergoing different types of multilevel spine surgery. SUMMARY OF BACKGROUND DATA: Blood loss and transfusion requirements during and after multilevel spine surgeries have always been perceived as great. Identifying the predictors of blood transfusion with this type of surgery may aid in reducing the amount of blood loss and the transfusion requirements. METHODS: The charts of 244 adult patients who underwent multilevel spine surgery from January 1994 to July 1995 were retrospectively reviewed. RESULTS: A large percentage of patients required blood transfusion. The significant determinants for increased amounts of allogeneic red blood cell units transfused on the day of surgery using linear multiple regression modeling were low preoperative hemoglobin concentration, tumor surgery, increased number of posterior levels surgically fused, history of pulmonary disease, decreased amount of autologous blood available, and no use of the Jackson table (R2 = 0. 63). The significant determinants for an increased amount of autologous red blood cell units transfused on the day of surgery using linear multiple regression modeling were increased autologous red blood cells available, low preoperative hemoglobin concentration, and increased number of posterior levels surgically fused (R2 = 0. 60). CONCLUSION: The need for transfusion is associated with multiple factors, suggesting that a multifaceted, integrated approach may be necessary to reduce this risk.

Adult↗

Use of the surgical blood order equation in spinal instrumentation and fusion surgery.

STUDY DESIGN: A retrospective review of 182 cases of adult spine instrumentation and fusion surgery (1994-1995) from one institution. OBJECTIVES: To develop and retrospectively evaluate the use of the surgical blood ordering equation for patients undergoing spinal instrumentation and fusion surgery. SUMMARY OF BACKGROUND DATA: The provision of effective and safe blood and blood products is the primary function of the hospital transfusion service. A quantification of blood bank efficiency is the crossmatch-to-transfusion ratio. The maximal surgical blood order schedule system has been used to improve the efficiency of surgical ordering practices. The current authors have developed a theoretically more efficient system, the surgical blood ordering equation, which incorporates patient factors for ordering red blood cell units for surgical patients. METHODS: The charts of 63 patients with autologous red blood cells available and 119 adult patients with none available, who underwent multilevel spine surgery from January 1994 to July 1995, were reviewed. RESULTS: The surgical blood ordering equation was exactly correct in the ordering for 37 (20.3%) of 182 patients. The maximal surgical blood order schedule was exactly correct in ordering blood for 14 patients (7.6%). Use of the new surgical blood ordering equation to order red blood cells for surgery would result in a lower crossmatch-to-transfusion ratio than with the current system, the maximal surgical blood order schedule, for patients with autologous red blood cells available (1. 0 vs. 1.3) and patients with none available (0.9 vs. 1.2). CONCLUSION: Incorporating patient factors resulted in increased efficiency of blood ordering practices.

Adult↗

Links from genome proteins to known 3-D structures.

We describe a genome annotation service provided by the Entrez browser, http://www.ncbi.nlm.nih.gov/entrez. All protein products identified in fully sequenced microbial genomes have been compared with proteins with known 3-D structure by use of the BLAST sequence comparison algorithm. For the approximately 20% of genome proteins in which unambiguous sequence similarity is detected, Entrez provides a link from the gene product to its predicted structure. The service uses the Cn3D molecular graphics viewer to present a 3-D view of the known structure, together with an alignment display mapping conserved residues from the genome protein onto the known structure. Using an example from Aeropyrum pernix, we illustrate how mapping to a 3-D structure can confirm predictions of biological function.

Algorithms↗

Introduction

Explore the source record for details and available documents.

Journal Article↗

Turnaround times for reports on uncomplicated biopsies in five major anatomical pathology laboratories in NSW, Australia.

This paper reports on the findings of a 1997 survey of the turnaround times (TATs) of small, uncomplicated biopsies performed in five major anatomical pathology (AP) departments in NSW over a period of four weeks. A comparative analysis of the performance of the departments shows that in the majority of cases the standard of two working days between specimen receipt and availability for dispatch after verification (as proposed by the College of American Pathologists) is met. This is within the two working days of the Clinical Indicator of the Australian Council on Healthcare Standards. Notwithstanding the apparent adequacy of this result, there is an emerging-although still a minority-view in which it is suggested that the TAT between specimen accession and verification of reports for uncomplicated cases should be one day. This more stringent benchmark is readily achievable, as is demonstrated in the results obtained. In this study a one day TAT was obtained in 73.4% of cases.

Biopsy↗

Molecular and functional distributions of chloride conductances in rabbit ventricle.

The regulation of cardiac electrical activity is critically dependent on the distribution of ion channels in the heart. For most ion channels, however, the patterns of distribution and what regulates these patterns are not well characterized. The most likely candidates for the genes that encode the cAMP- and swelling-activated chloride conductances in the heart are an alternatively spliced variant of CFTR and ClC-3, respectively. In this study we have 1) measured the density of CFTR and ClC-3 mRNA levels across the left ventricular free wall (LVFW) of the rabbit heart using in situ hybridization and 2) measured the corresponding current density of cAMP- and swelling-activated chloride channels in myocytes isolated from subepicardial, midmyocardial, and subendocardial regions of the LVFW. There was a highly significant gradient in the whole cell slope conductance of cAMP-activated chloride currents; normalized slope conductance at 0 mV was 15.7 +/- 1.8 pS/pF (n = 9) in subepicardial myocytes, 7.8 +/- 1.5 pS/pF (n = 11) in midmyocardial myocytes, and 4.9 +/- 1.1 pS/pF (n = 9) in subendocardial myocytes. The level of CFTR mRNA was closely correlated with the density of cAMP-activated chloride conductances in different regions of the heart, with the level of CFTR mRNA being three times higher in the subepicardium than in the subendocardium. The whole cell slope conductance of swelling-activated chloride channel activity, measured 3-5 min after the commencement of cell swelling, was higher in myocytes isolated from the subepicardium than in myocytes isolated from the midmyocardium or subendocardium. In contrast, there was a uniform expression of ClC-3 mRNA across the LVFW of the rabbit heart. These results suggest that the control of gene expression is an important contributor in regulating the distribution of cAMP-activated chloride channels in the rabbit heart but that it may be less important for the swelling-activated chloride channels.

Animals↗

Comparison of the performance of four files with rounded tips during shaping of simulated root canals.

A total of 160 simulated canals of various angles and positions of curvature were prepared by hand using either Mani Flexile Files, Mani SEC-O Files, Maillefer Flexofiles, or Zipperer Flexicut Files. After orifice enlargement, each file type was used to prepare 40 canals employing a balanced force motion and a modified double-flared technique. Pre- and postoperative images of the canals were taken with a videocamera, and stored and manipulated in a computer with image analysis software. The presence of canal aberrations and the amount of material removed as a result of preparation were determined from composite images of superimposed pre- and postoperative views. Significant differences (p < 0.001) in preparation time were observed, with Flexile Files being quickest and SEC-O Files being slowest. Overall, Flexofiles and Flexicut Files deformed significantly more (p < 0.001) than Flexile and SEC-O Files. The incidence of canal blockage was not influenced by instrument type, but the incidence of apical extrusion was significantly greater (p < 0.001) with SEC-O Files. SEC-O Files created significantly fewer (p < 0.001) and significantly narrower (p < 0.001) zips, with significantly less (p < 0.001) removal of material from the outer aspect of the curve and thus significantly less (p < 0.001) transportation. Flexicut Files created the widest canals apically, with the greatest removal of material from the outer aspect of the curve and the most transportation. Flexofiles created significantly more (p < 0.001) perforations. Under the conditions of this study, obvious differences between instruments were highlighted with SEC-O Files preparing canals more safely and with least destruction. The unique rounded tip of the SEC-O Files may have had an influence on the outcome.

Analysis of Variance↗

A prospective randomized trial of the surgical blood order equation for ordering red cells for total hip arthroplasty patients.

BACKGROUND: The majority of crossmatched blood is for surgical patients, and most of it is never transfused. An alternative system for ordering red cell (RBC) units, called the surgical blood order equation (SBOE), which incorporates specific patient variables for surgical patients, has been developed. STUDY DESIGN AND METHODS: A prospective double-blind randomized trial compared the SBOE with the maximal surgical blood order schedule (MSBOS) system for ordering allogeneic RBC units in 60 patients undergoing total hip arthroplasty. Autologous RBCs were available for none of the patients. RESULTS: There were no differences in patient demographic, surgical, or laboratory variables at any time. The median number (range) of allogeneic RBC units ordered was 2 (2-3) for the MSBOS and 0 (0-3) for the SBOE (p<0.0001). The SBOE ordered the correct number of RBC units for 58 percent of patients, while the MSBOS did so for 7 percent (p<0.0001). The SBOE had a lower crossmatch-to-transfusion ratio than the MSBOS (0.83 vs. 4.12). Costs were also lower with the SBOE. CONCLUSION: Incorporation of patient factors in the use of the SBOE system resulted in increased efficiency of blood-ordering practices for total hip arthroplasty.

Adult↗

Shaping ability of the M4 handpiece and Safety Hedstrom files in simulated root canals.

The aim of this study was to assess the shaping ability of the M4 reciprocating handpiece and Safety Hedstrom files in simulated canals. A total of 40 simulated canals of various angles and positions of curvature were prepared with an M4 handpiece using Safety Hedstrom files oriented with the ground, flattened surface towards the inner aspect of the curve. A standard regimen was adopted throughout. Pre- and post-operative longitudinal images of the canals were taken with a video camera and stored and manipulated in a computer with image analysis software. The presence of canal aberrations and the amount and location of resin material removed as a result of preparation were determined from composite images of superimposed pre- and post-operative views. Preparation time varied significantly (P < 0.001) between the canal types; overall, 20 degrees canals were prepared more quickly than 40 degrees canals. Zips and elbows were observed in 16 out of the 40 canals with most (11) being created in 40 degrees specimens. Ledges were found in 19 canals and perforations in only 1. There were no significant differences between canal shapes for these aberrations. Excessive removal of material from the inner aspect of the canal at the curve to create a danger zone was found in 20 canals, but only in those with 40 degrees curves. Significant differences in total canal width between the canal types were seen at the zips (P < 0.05), elbows (P < 0.05) and danger zones (P < 0.001). Transportation at the danger zones varied significantly (P < 0.001) between canal types. Under the conditions of this study, the M4 handpiece and Safety Hedstrom files created hour-glass preparations in a substantial proportion of canals. In reality, the Safety Hedstrom file with its one flattened surface was ineffective at reducing removal of material along the inner aspect of canal curves in severely curved specimens and clearly has the potential to create strip perforations in teeth.

Analysis of Variance↗

Comparison of two stainless steel files to shape simulated root canals.

The aim of this study was to compare the shaping ability of two stainless steel files using simulated canals. A total of 80 simulated canals of various angles and positions of curvature were prepared by hand using either Mani K-Files or Micro Mega K-Files. Following orifice enlargement each file type was used to prepare 40 canals employing a linear filing motion and an anticurvature stepback technique. Pre- and post-operative longitudinal images of the canals were taken with a video camera and stored and manipulated in a computer with image analysis software. The presence of canal aberrations and the amount of material removed as a result of preparation were determined from composite images of superimposed pre- and post-operative views. Overall, canal preparation with Mani K-Files was significantly quicker (P < 0.005) and was associated with fewer instrument failures. Zips and elbows were observed in 70% of specimens with significantly more (P < 0.05) occurring following preparation with Micro Mega K-Files. Mani K-Files created significantly more (P < 0.01) danger zones. Micro Mega K-Files created significantly wider (P < 0.001) zips with significantly more (P < 0.01) resin removed from the outer aspect of the curves and, thus, significantly more (P < 0.01) transportation. Canal shape had a significant influence on preparation time (P < 0.001), the incidence of zips (P < 0.05) and danger zones (P < 0.005), the width of zips (P < 0.001) and transportation at the zips (P < 0.001). Under the conditions of this study, Mani K-Files were more effective than Micro Mega K-Files and produced canals with better shapes. Original canal shape had a substantial influence on the outcome of shaping procedures.

Analysis of Variance↗

Cutaneous leiomyomas lack estrogen and progesterone receptor immunoreactivity.

Gonadotropin-releasing hormone analog therapy is useful in treating uterine and some extrauterine smooth muscle tumors. These smooth muscle tumors have been demonstrated to have estrogen receptor and progesterone receptor immunoreactivity. The estrogen receptor and progesterone receptor immunoreactivity of smooth muscle tumors of the skin has not been reported. We evaluated 15 examples of cutaneous leiomyomas for estrogen receptor and progesterone receptor with ER-1D5 antibody and PGR-1A6 antibody. None of the 15 cutaneous leiomyomas demonstrated positive staining by this method. The tumorigenesis of cutaneous leiomyomas does not appear to be related to estrogen or progesterone receptor-mediated effects.

Adult↗

Use of reverse transcription-polymerase chain reaction methodology to detect estrogen-regulated gene expression in small breast cancer specimens.

We describe the development and use of a sensitive reverse transcription-PCR (RT-PCR) procedure to detect novel estrogen-regulated gene expression in small clinical breast cancer samples, in which such study would be extremely difficult by any other molecular or immunocytochemical means. Assay optimization for pLIV1, estrogen receptors (ERs), progesterone receptors, and pS2 gene products was carried out on 50 primary breast cancers for which comparative Northern analysis and immunocytochemical data were available. Using 27 amplification cycles and a 0.5 microM primer concentration, varying expressions of the gene products were recorded simultaneously with a constant densitometric signal for a coamplified endogenous control gene (alpha-actin). Good concordances were subsequently observed between pLIV1 status generated by RT-PCR and both Northern analysis (P = 0.002) and ER status by immunocytochemistry (P = 0.0244). Agreement was also noted between ER (P = 0.002), progesterone receptor (P = 0.0005), and pS2 (P = 0. 0023) RT-PCR and immunocytochemical methodologies. The RT-PCR assays were then applied to 10 needle core trucut biopsies in which similar relationships were obtained. Our results justify the future use of this RT-PCR methodology to examine new estrogen-regulated genes in small breast cancer samples, and it is envisaged that this technology will prove invaluable in many future breast cancer studies.

Biomarkers, Tumor↗