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Biomedical subjects

R May

Publications and source records attributed to R May.

At least 19 recordsLinked to original sources
PubMed2006

Outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation (RISCT) using antilymphocyte antibodies in patients with high-risk acute myeloid leukemia (AML).

Hemopoietic stem cell transplantation (SCT) with fully ablative conditioning is associated with an age-related increase in treatment-related mortality. It is therefore particularly unsuited to older individuals, who are most at risk of developing acute myeloid leukemia (AML). Reduced-intensity SCT (RISCT) may be of value in this group. We report 17 consecutive patients with high-risk AML whose median age was 58 years and who received stem cells from HLA-matched siblings (n=5), or alternative donors (n=12). We used lymphodepleting antibodies as a part of the reduced-intensity conditioning regimen to limit the risk of graft rejection and graft-versus-host disease (GVHD). All patients engrafted. One patient developed severe fatal GVHD, and two patients died of infection. At a median follow-up of 861 days (372-1957 days), seven patients are alive in remission, which includes two patients treated in relapse and five patients who lacked an MHC identical sibling donor. Both progression-free survival and overall survival are 40% (95% CI, 17-64%). Hence, RISCT using lymphodepleting antibodies may be of value for older patients with AML, even in those with active or high-risk disease, and even if they lack an MHC-identical sibling donor.

Acute Disease↗
PubMed2006

Mast cells express IL-13R alpha 1: IL-13 promotes human lung mast cell proliferation and Fc epsilon RI expression.

BACKGROUND: The Th2 cytokine interleukin (IL)-13 is implicated in the development of various allergic diseases including asthma. The IL-13 receptor, IL-13Ralpha1, is expressed on most leukocytes, except T-cells. Evidence to support IL-13Ralpha1 expression on mast cells is limited. METHODS: We investigated: (i) IL-13Ralpha1 expression by human lung mast cells (HLMC); (ii) the number of IL-13Ralpha1+ bronchial submucosal mast cells in subjects with asthma and normal controls and (iii) the effect of IL-13 priming on HLMC expression of high-affinity IgE receptor (FcepsilonRI), stem cell factor receptor (CD117), histamine release, proliferation, and survival. RESULTS: Human lung mast cell expressed IL-13Ralpha1 mRNA. IL-13Ralpha1 was highly expressed on the surface HLMC (82+/-9%). Bronchial submucosal mast cell IL-13Ralpha1 expression was higher in asthmatics (86+/-2%) than normal controls (78+/-2%; P=0.015). IL-13 priming for 30 min did not increase HLMC histamine release, in the presence or absence of SCF or in response to IgE/anti-IgE activation. IL-13 priming for 5 days upregulated HLMC FcepsilonRI expression (22% increase in fluorescent intensity; P=0.003), increased histamine release following IgE/anti-IgE activation by 56% (P=0.03) and increased proliferation by 50% (P=0.003) without affecting cell survival or CD117 expression. The IL-13 specific neutralizing antibody CAT-354 inhibited all IL-13 mediated effects. CONCLUSION: Human lung mast cell express IL-13Ralpha1 and activation by IL-13 for 5 days increased FcepsilonRI expression and proliferation. Histamine release was not affected by short-term priming with IL-13, but was upregulated by priming for 5 days suggesting that this effect was mediated by the increased FcepsilonRI expression. These data support the view that targeting IL-13 may be beneficial in the treatment of asthma.

Cell Proliferation↗
PubMed2006

A comparative biomechanical analysis of implants for the stabilization of proximal humerus fractures.

A new humerus nail (Sirus) has become available for the treatment of fractures of the proximal humerus. The aim of the study was the biomechanical comparison of this implant with established systems. 12 matched pairs of human humeri were employed for testing. Three randomized groups were formed (n = 4 pairs). A bending moment of 7.5 Nm and a torsional moment of 8.3 Nm were applied in a test of five loading cycles to all intact bones. Loading was consistently initiated at the distal epiphysis. The consequent deformation at the distal epiphysis was continuously recorded. Then an osteotomy with a defect of 5 mm was created to simulate an unstable subcapital humerus fracture. For paired comparison, one of each pair was stabilized with the Sirus proximal humerus nail. The other side was fixed with a reference implant. The following groups were created.: Group I: Sirus versus Proximal humerus nail (PHN) with spiral blade. Group II: Sirus versus PHILOS plate. Group III: Sirus versus 4.5 mm AO T-plate. The proximal humerus nail (Sirus) demonstrated significantly higher stiffness values than the reference implants for both bending and torsional load. The following values were recorded at a bending moment of 7.5 Nm: Sirus 14.2 mm, PHN 20.7 mm, PHILOS plate 28.1 mm, 4.5 AO T-plate 29.3 mm p < 0.0012). The values at 8.3 Nm torsional moment were: Sirus 8.5 degrees , PHN 12.3 degrees , PHILOS plate 16.4 degrees , 4.5 AO T-Platte 15.6 degrees (p < 0.002). The intramedullary load carriers were biomechanically superior when compared to the plating systems in the fracture model presented here. Supplementary, the Sirus Nail showed higher stiffness values than the PHN. However, the latter are gaining in importance due to the possibility of minimal invasive implantation. Whether this will be associated with functional advantages requires further clinical investigation.

Biomechanical Phenomena↗
PubMed2005

The temporal variations of (7)Be, (210)Pb and (210)Po in air in England.

We have conducted measurements of naturally occurring radionuclides (7)Be, (210)Pb and (210)Po in air at ground level at Chilton, Oxfordshire, England. The sampling and analysis regime for the latter two isotopes has been optimised to minimise uncertainties in measurement due to decay of (210)Po and in-growth of (210)Pb during the sampling and analysis period. Analysis times were reduced by using Cerenkov counting to assay the (210)Bi daughter of (210)Pb. Monthly data collected over a four-year period are presented and discussed. (7)Be activity concentrations appear to peak in spring. (210)Pb activity concentrations also follow a seasonal trend reflecting different (222)Rn emanation rates from soil during winter and summer. Data for (210)Po show no such trend.

Air Pollutants, Radioactive↗
PubMed2005

CD52 and CD45 monoclonal antibodies for reduced intensity hemopoietic stem cell transplantation from HLA matched and one antigen mismatched unrelated donors.

Allogeneic hemopoietic stem cell transplantation (HSCT) is the only curative option for many patients with hematological malignancies. Since many of these patients lack HLA-identical sibling donors and are older or have comorbidity, a fully ablative HSCT is not feasible and an alternative approach is required. We studied 22 consecutive patients who could not have myeloablative conditioning because of comorbidity or age - 21/22 being over the age of 50 years (median 58 years range 20-70 years). A conditioning regimen consisting of fludarabine, total body radiation 450 cGy and alemtuzumab (CD52 mAb) was used for 15 patients. A second group of seven patients received CD45 monoclonal antibodies in addition. Unrelated donor stem cells were HLA matched (15 patients - 68%) or one locus mismatched (seven patients - 32%). In all, 16 patients had high-risk disease, including 12 with active malignancy at the time of transplant. With a median follow-up of 715 (216-1470) days, nonrelapse mortality, actuarial event-free and overall survival is 27, 45 and 45%, respectively. Hence the outcome of reduced intensity HSCT with lymphodepleting antibodies in older patients with intermediate/high-risk hematological malignancies appears comparable to that obtained with fully ablative transplantation in younger patients, even when these older recipients lack HLA-identical sibling donors.

Adult↗
PubMed2001

Potassium channel openers depolarize hippocampal mitochondria.

We investigated the effect of the potassium channel openers diazoxide and RP66471 on mitochondrial membrane potential and mitochondrial respiration in digitonin-treated rat hippocampal homogenates. Both diazoxide and RP66471 induced a dose-dependent decrease of mitochondrial membrane potential. Concomitant with the depolarization was an increase of mitochondrial respiration. Furthermore, the mitochondrial membrane depolarization induced by diazoxide and RP66471 was significantly larger in the presence of potassium ions than in the presence of sodium ions. The diazoxide-induced (but not RP66471-induced) mitochondrial membrane depolarization was partially inhibited by blockers of the ATP-regulated potassium channel, 5-hydroxydecanoic acid or the antidiabetic sulfonylurea glibenclamide. In addition, the potassium channel openers diazoxide and RP66471 increased mitochondrial matrix volume and induced a release of cytochrome c from hippocampal mitochondria. These results indicate the presence of a mitochondrial ATP-regulated potassium channel in rat hippocampus being a target for potassium channel openers.

Adenosine Triphosphate↗
PubMed2001

Use of antithymocyte globulin for treatment of steroid-refractory acute graft-versus-host disease: an international practice survey.

Antithymocyte globulin (ATG) is accepted as a treatment option for steroid-refractory acute graft-versus-host disease (GVHD). We conducted an international survey to determine how steroid refractoriness is defined and how ATG is used in clinical practice. Responses were received from 153 centers in 36 countries. The most common threshold steroid dose to define steroid refractoriness was 2 mg/kg/day (67% of respondents), and the median duration of treatment before failure was declared varied from 3 to 5.5 days, depending on whether failure was defined as 'progressed', 'not improved' or 'not resolved'. The threshold corticosteroid dose was significantly higher in pediatric centers than in adult or combined programs (P = 0.003). ATG was used routinely for treatment of steroid-refractory GVHD by 67% of the respondents. Horse ATG was used more frequently than rabbit ATG overall (50% vs 24%, P < 0.001), and predominance of horse ATG was most evident in the western hemisphere, in small- to medium-sized centers, and in pediatric centers. A wide variety of dose schedules for both drugs was reported. We conclude that there is some degree of variation in the definition of steroid refractoriness, especially between pediatric and nonpediatric programs, and no consensus has emerged in identifying the optimal ATG dose schedule in this setting.

Acute Disease↗
PubMed2001

Radiation safety systems for accelerator facilities.

The radiation safety system RSS) of an accelerator facility is used to protect people from prompt radiation hazards associated with accelerator operation. The RSS is a fully interlocked, engineered system with a combination of passive and active elements that are reliable, redundant and fail-safe. The RSS consists of the access control system (ACS) and the radiation containment system (RCS). The ACS is to keep people away from the dangerous radiation inside the shielding enclosure. The RCS limits and contains the beam/radiation conditions to protect people from the prompt radiation hazards outside the shielding enclosure in both normal and abnormal operations. The complexity of an RSS depends on the accelerator and its operation. as well as associated hazard conditions. The approaches of RSS among different facilities can be different. This report gives a review of the RSS for accelerator facilities.

Humans↗
PubMed2000

General practice. Hit and miss.

A survey of practices in a primary care group in outer London found many were poorly prepared for implementing clinical governance. More than half consisted of one doctor, and a quarter of practices were not computerised. Only a third had a staff development plan. Only a minority had sought patients' views about new services. Although three-quarters of practices were using guidelines, few had been trained in the use of protocols and guidelines.

Clinical Audit↗
PubMed1999

Unanswered questions in ecology.

This is very much a personal view of what I think are some of the most important unanswered questions in ecology. That is, these are the questions that I expect will be high on the research agenda over the coming century. The list is organized hierarchically, beginning with questions at the level of individual populations, and progressing through interacting populations to entire communities or ecosystems. I will try to guess both at possible advances in basic knowledge and at potential applications. The only thing that is certain about this view of the future is that much of it will surely turn out to be wrong, and many of the most interesting future developments will be quite unforeseen.

Ecology↗
PubMed1999

Growth changes in measurements of upper facial positioning.

Growth changes in the position of the midline upper face are examined for samples of Pan troglodytes, Gorilla gorilla, and modern humans. Horizontal and vertical distances between nasion and the anterior end of the cribriform plate are plotted against stage of dental development. Kendall's nonparametric correlations between facial positioning and stage of dental development are tested for significance. In African apes, the upper face becomes more projecting and positioned higher relative to the anterior cranial base. The extent of this horizontal and vertical separation reflects primarily facial size. In modern humans, the upper face becomes more projecting but is relatively stable in its vertical position. Comparison of Pan and modern human crania in the youngest dental age category indicates that the upper face of modern humans is positioned lower early in postnatal life. The position of the upper face (glabella) relative to the anterior and posterior cranial base is presented for several fossil hominid crania. The fossil crania are similar to Pan and modern humans in facial projection relative to the anterior cranial base. However, glabella is positioned low in the fossil crania. Total facial projection (relative to hormion) for Sts 5 is similar to the mean for Gorilla. Fossil Homo and robust australopithecine crania display very projecting upper faces. We suggest that the upper face of Homo is projecting due to the length of the anterior cranial fossa, while robust australopithecines possess a thick frontal bone.

Animals↗
PubMed1999

Growth changes in internal and craniofacial flexion measurements.

Growth changes in both internal and craniofacial flexion angles are presented for Pan troglodytes, Gorilla gorilla, and modern humans. The internal flexion angle (IFA) was measured from lateral radiographs, and the craniofacial flexion angle (CFA) was calculated from coordinate data. Stage of dental development is used as a baseline for examination of growth changes and nonparametric correlations between flexion angles and dental development stage are tested for significance. In Gorilla, the IFA increases during growth. The IFA is relatively stable in Pan and modern humans. Pan and Gorilla display an increase in the CFA. However, this angle decreases during growth in modern humans. Flexion angles were derived from coordinate data collected for several early hominid crania. Measurements for two robust australopithecine crania indicate strong internal flexion. It has been suggested that cerebellar expansion in this group may relate to derived features of the posterior cranial base. In general, australopithecine crania exhibit craniofacial flexion intermediate between great apes and modern humans. The "archaic" Homo sapiens specimen from Kabwe is most similar to modern humans.

Animals↗
PubMed1999

Cytotoxic T lymphocytes can induce a condemned state and synchronous post-mitotic apoptosis of daughter target cells.

We have used time-lapse video microscopy to study cytotoxic T lymphocyte (CTL)-mediated apoptosis of LDb fibroblast target cells at different phases of the cell cycle. When aphidicolin-synchronized target cells were exposed to the CTL clone F5, apoptosis occurred with similar morphology during G1, S/G2 and M phase, showing that apoptosis and mitosis are not mutually exclusive cellular events. Interestingly, following normal mitosis of target cells that had been previously contacted by CTL, pairs of daughter cells would occasionally undergo apoptosis within minutes of each other. Such synchronous post-mitotic apoptosis was also observed when using mitotically unsynchronized target cells, and also when using d11S T cell hybridomas as alternative Fas- (CD95-) based effector cells, even if these effectors were physically washed away after an initial period of co-incubation with the target cells. Our observations show that cytotoxic cells can induce a condemned state in pre-mitotic target cells, which can be inherited by both daughter cells, leading to their synchronous apoptosis after mitosis.

Animals↗
PubMed1999

Development of a nomogram that predicts the probability of a positive prostate biopsy in men with an abnormal digital rectal examination and a prostate-specific antigen between 0 and 4 ng/mL.

OBJECTIVES: Early detection of prostate cancer traditionally involves both digital rectal examination (DRE) and serum prostate-specific antigen (PSA) determination in an informed patient population. Abnormalities in either of these studies typically lead to additional evaluations, including prostate biopsy. In this study, we analyzed the operational characteristics of serum PSA between 0 and 4 ng/mL as an initial test for prostate cancer. METHODS: From January 1990 through May 1997, transrectal biopsies were obtained from 700 men with a serum PSA level less than 4.0 ng/mL but DRE suspicious for cancer. Patient age, race, and serum PSA level were reviewed for this study. RESULTS: Of the 700 men studied, 445 were white (64%) and 255 were African American (36%). In multivariate analysis of prebiopsy risk factors (age, race, serum PSA), serum PSA was the only independent predictor of a positive prostate biopsy. A nomogram was created that determines the worst-case probability of a positive prostate biopsy in men with PSA between 0 and 4 ng/mL and a DRE suspicious for cancer. The predictions from the nomogram appeared accurate and discriminating, with a bias-corrected area under the receiver operating characteristic curve (i.e., comparison of the predicted probability with the actual outcome) of 0.75. CONCLUSIONS: Although early detection of prostate cancer has traditionally used both PSA measurement and DRE, PSA testing alone could be more easily implemented and may encourage some men to seek consultation who might not otherwise have done so. By providing a nomogram which provides a worse-case scenario (assuming a positive DRE) of the probability of a positive biopsy, the patient and clinician can make an informed decision as to whether additional evaluation is warranted.

Adult↗
PubMed1999

Superhelical DNA studied by solution scattering and computer models.

We present here recent results on the structure of superhelical DNA and its changes with salt concentration between 0.01 and 1.5 M NaCl. Scattering curves of two different superhelical DNAs were determined by static light scattering. The measured radii of gyration do not change significantly with salt concentration. Small-angle neutron scattering, together with calculations from a Monte Carlo model, allows to determine the superhelix diameter. Measured and simulated scattering curves agreed almost quantitatively. Experimentally we find that the diameter decreases from 16.0 +/- 0.9 nm at 10 mM to 9.0 +/- 0.7 nm at 100 mM NaCl. The superhelix diameter from the simulated conformations decreased from 18.0 +/- 1.5 nm at 10 mM to 9.4 +/- 1.5 nm at 100 mM NaCl. At higher salt concentrations up to 1.5 M NaCl, the diameter stays constant at 9 nm.

Computer Simulation↗