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Biomedical subjects

S Webb

Publications and source records attributed to S Webb.

At least 163 records · Page 9Linked to original sources
PubMed1995

Bronchoscopic insufflation of room air for the treatment of lobar atelectasis in mechanically ventilated patients.

Segmental and lobar pulmonary atelectasis is a common occurrence in mechanically ventilated patients. Standard therapy for atelectasis relies on positive pressure ventilation, positive and expiratory pressure (PEEP), tracheobronchial toilet and regular chest physiotherapy. Various adjuncts to physiotherapy such as bronchoscopic clearance of secretions have not proved to be of additional benefit. Bronchoscopic clearance of secretions followed by insufflation of room air at 30 cm H2O into the atelectatic segment was employed on ten occasions in mechanically ventilated patients. Rapid re-expansion of the collapsed segment or lobe occurred in seven out of the ten treatments.

APACHE↗
PubMed1995

The optimization and inherent limitations of 3D conformal radiotherapy treatment plans of the prostate.

This paper describes the applications of an inverse planning optimization algorithm to the real clinical problem of prostate cancer. The algorithm has been designed to compute optimized beam-weights taking full account of three-dimensional spatial information of dose inside the patient. The algorithm is based on fast simulated annealing, utilizing a cost-function containing both linear and quadratic terms. The linear part of the cost function allows for the implementation of "short-cuts" in the cost-function computation, which reduces the calculation time by a factor of about 30. It has been applied to compute optimized beam-weights for a three-field and a seven-field prostate treatment plan. It is shown for the three-field plan that the optimization algorithm can reproduce, and even slightly improve on, the results of an experienced human planner. For the seven-field plan, the human planner experienced difficulty finding beam-weights that gave an acceptable dose distribution. It is shown that the optimization algorithm can achieve good results in this case. The outcome of the optimization of the seven-field plan prompted an investigation into the best results that could be achieved by an "ideal" conformal radiotherapy technique. The results of this investigation are presented and it is shown that the limiting factor for conformal therapy of the prostate is the size of the overlap volume between the planning target volume (PTV) and the rectum. Finally, the efficiency and accuracy of fast simulated annealing is compared with that of classical simulated annealing. The former was found to be at least 10 times faster for the problem studied.

Algorithms↗
PubMed1995

MR magnetization transfer measurements in temporal lobe epilepsy: a preliminary study.

MR magnetization transfer ratio was measured in both hippocampi of three patients with temporal lobe epilepsy, and in two control subjects. The magnetization transfer ratio in each section was significantly lower on the affected side than on the contralateral side and in control subjects. Magnetization transfer ratio measurements are relatively fast and precise, this preliminary study shows that they may provide useful presurgical information.

Adult↗
PubMed1994

Engraftment of human hematopoietic precursor cells with secondary transfer potential in SCID-hu mice.

Human fetal bone fragments implanted subcutaneously in immunodeficient (SCID) mice maintain active human hematopoiesis. In this study, we show that this human hematopoietic microenvironment supports the engraftment and differentiation of HLA-mismatched, CD34+ primitive hematopoietic progenitor cells isolated from fetal and adult human bone marrow (BM). The BM CD34+ cells were depleted of CD2, CD14, CD15, CD16, glycophorin A, and CD19 lineage-committed cells (CD34+Lin-). Donor cell engraftment was manifested by the presence of B (CD19+) and myeloid (CD33+) cells of donor HLA phenotype. Successful engraftment was observed as early as 4 weeks after fetal BM donor cell injection and sustained for at least 12 weeks, with engraftment success rates of 100% (11/11 grafts) and 92% (11/12 grafts) at 8 and 12 weeks, respectively. Mixed BM chimerism of donor and endogenous cells was consistently observed in SCID-hu bones successfully engrafted with HLA-mismatched CD34+Lin- donor cells. Preconditioning of the SCID-hu bone with a single dose of sublethal (350 rad) whole body irradiation (WBI) immediately before cell injection enhanced the repopulation of the bone grafts with donor cells and, in some instances, resulted in complete repopulation. After WBI, as few as 500 fetal bone marrow CD34+Lin- cells injected in the human bone grafts resulted in donor-derived hematopoiesis. Donor progenitor cells recovered from the SCID-hu bone grafts 8 weeks postinjection had the capacity to repopulate secondary groups of HLA-disparate fetal human bones in SCID-hu mice with B and myeloid cells as well as CD34+ cells in some recipients. In addition, these cells repopulated fetal human thymus fragments in SCID mice with donor thymocytes including immature CD4+CD8+ and mature CD4+CD8- as well as CD4-CD8+ subsets. These results indicate that the fetal human bone implants of SCID-hu mice can support the maintenance of a cell population that has both multilineage potential and repopulating potential for periods of time as long as 16 weeks. The SCID-hu bone model consistently supported the engraftment of both fetal and adult CD34+Lin- cells without the administration of exogenous human cytokines to these animals. This model is currently being used to permit the isolation and characterization of candidate human hematopoietic stem cells (HSCs) and provide important information critical for human HSC therapy in humans.

Animals↗
PubMed1994

Human fetal bone marrow early progenitors for T, B, and myeloid cells are found exclusively in the population expressing high levels of CD34.

Experimentation on human stem cells is hampered by the relative paucity of this population and by the lack of assays identifying multilineage differentiation, particularly along the lymphoid lineages. In our current study, phenotypic analysis of low-density fetal bone marrow cells showed two distinct populations of CD34+ cells: those expressing a high density of CD34 antigen on their surface (CD34hi) and those expressing an intermediate level of CD34 antigen (CD34lo). Multiple tissues were used to characterize the in vitro and in vivo potential of these subsets and showed that only CD34hi cells support long-term B lymphopoiesis and myelopoiesis in vitro and mediate T, B, and myeloid repopulation of human tissues implanted into SCID mice. CD34lo cells repeatedly failed to provide long-term hematopoietic activity in vivo or in vitro. These results indicate that a simple fractionation based on well-defined CD34 antigen levels can be used to reproducibly isolate cells highly enriched for in vivo long-term repopulating activity and for multipotent progenitors, including T- and B-cell precursors. Additionally, given the limited variability in the results and the high correlation between in vitro and in vivo hematopoietic potential, we propose that the CD34hi population contains virtually all of the stem cell activity in fetal bone marrow and therefore is the population of choice for future studies in hematopoietic stem cell development and gene therapy.

Animals↗
PubMed1994

Generation of T cells from cytokine-mobilized peripheral blood and adult bone marrow CD34+ cells.

The present study compared the T-cell progenitor content of CD34+ lineage (Lin)- cells isolated from normal adult bone marrow (ABM) and mobilized peripheral blood (MPB). Both cell populations were found to differentiate into T cells when injected into human fetal thymi implanted into severe combined immunodeficient mice. Cytokine-MPB cells were less efficient than ABM cells in engrafting in the fetal human thymus, although both gave rise to thymocytes with identical phenotypes based on the analysis of CD1a, CD3, CD4, and CD8 expression. Thymocytes derived from adult CD34+ Lin- cells were capable of fully differentiating into mature CD3+ T cells expressing either the T-cell receptor (TCR) gamma delta or the TCR alpha beta (the later associated with CD4 or CD8), showing that the T-cell progenies of adult CD34+ cells were polyclonal and functional. Our data indicate that human MPB CD34+ cells are qualitatively identical to their BM counterparts, and demonstrate the existence of T-lymphoid progenitor cell activity in MPB.

Adult↗
PubMed1994

Dr Know.

Explore the source record for details and available documents.

Communication↗
PubMed1994

Stem cell factor enhances the survival of irradiated human bone marrow maintained in SCID mice.

The effect of recombinant human stem cell factor (SCF) on the response of human fetal bone marrow progenitor cells to irradiation was studied using immunodeficient mice with human fetal bone grafts (SCID/Hu mice). SCID/Hu mice were treated with three intraperitoneal injections of 500 micrograms/kg SCF at 20 h before, two h before, and four h after 100 cGy total body irradiation. Fourteen days following irradiation, the fetal bone grafts were harvested and studied. Most of the isolated bone marrow cells were human, as determined by flow cytometry. Colony forming assays were performed on the bone marrow to determine the survival of erythroid (BFU-E) and myeloid (CFU-GM) precursor cells. A statistically significant increase in BFU-E and CFU-GM survival after irradiation was observed for bone marrow maintained in the SCF treated mice when compared to bone marrow from mice not treated with SCF. The enhancement in colony forming unit survival after irradiation ranged from 4.3-fold for BFU-E (p = 0.05) to 13.1-fold for CFU-GM (p = 0.002). These findings suggest that SCF may be of potential clinical value for the prevention of radiation-induced myelosuppression.

Animals↗
PubMed1994

A linkage map of microsatellite markers on the human X chromosome.

The efficiency of mapping and diagnosis of X-linked disorders by linkage depends upon the existence of a high-density genetic map of polymerase chain reaction (PCR)-based markers. DXS1120, DXS1122, DXS1123, DXS1124, DXS1125, DXS1126, and DXS1153 were randomly isolated from a flow-sorted lambda bacteriophage library of the human X chromosome. The CCN (N = A or G) repeat within the androgen receptor was also found to be polymorphic and primers were designed for genotyping the CCN polymorphism in addition to the AGC polymorphism. The above markers, together with microsatellite polymorphisms at DXS237 (GMGX9), 5'DYS-II and 3'DYS MS (within the dystrophin locus), DXS538 (XL27B), PGK1P1, DXS300 (VK29AC), DXS294 (VK17AC), and DXS102 (cX38.1AC), were genotyped in the 40 CEPH reference families. One marker, DXS1153, was found to include cryptic alleles that amplify only in homozygotes and hemizygotes but not heterozygotes. A PCR-based linkage map was constructed using all of the above markers plus PCR-based markers from the CEPH database and those PCR-based markers previously typed in our laboratory: ALAS2, DXS292 (VK14AC), DXS297 (VK23AC), FRAXAC1, and FRAXAC2. The genetic map of the X chromosome incorporates 62 PCR-based marker loci, integrates the Weissenbach markers, and extends from XG near Xpter to DXS52 near Xqter, a distance of 236 cM.

Alleles↗
PubMed1994

A comparison of proton and megavoltage X-ray treatment planning for prostate cancer.

Conformal photon and proton therapy plans for prostate cancer have been compared in an attempt to quantify the potential advantages of using protons. Two X-ray plans (3-field, 6-field) and a 2-field proton plan were made and compared for each of 20 T3 prostate patients with the aid of the 3D planning system VOXELPLAN. Dose distributions were analysed in terms of dose-volume histograms (DVH). Tumour control probability (TCP) and normal tissue complication probability (NTCP) were computed using our own and the Lyman-Kutcher-Burman models, respectively. The study shows that on average the proton technique results in the best dose distribution, giving the lowest rectal complication probability, and also that the 3-field X-ray technique is more effective than the 6-field X-ray technique in sparing the rectum. At 5% rectal NTCP, the predicted proton average TCP for the 20 patients is 2% (in absolute terms) greater than that obtained using 3-field X-ray therapy. For 7 of the patients the gain in TCP is more than 3%. For the same rectal NTCP as the 3-field X-ray plan with a 64 Gy mean target dose, the use of protons increases the TCP by 2% on average, but for 5 of the patients the increases are greater than 4%. The result is in general positive towards the use of protons but a few patients do not benefit from it and this indicates the importance of patient selection for maximum clinical benefit.

Humans↗
PubMed1994

Perceptions and practices of registered nurses regarding pastoral care and the spiritual need of hospital patients.

Reports the findings of a questionnaire survey designed to examine the impact of pastoral care on patient care and job satisfaction of registered nurses (N-280) employed in a metropolitan hospital. Suggests that educational strategies be explored as a way of broadening the perspectives of nurses regarding reasons for consulting pastoral care departments.

Attitude of Health Personnel↗
PubMed1994

Prescribing and referral in general practice: a study of patients' expectations and doctors' actions.

BACKGROUND: What decisions do patients expect the general practitioner to take within the consultation and to what extent are these expectations fulfilled? What factors influence patients' expectations and general practitioners' actions? AIM: This study aimed to examine these questions with reference to prescribing and hospital referral. METHOD: The study covered 1080 consultations with 12 general practitioners in two north London practices. Information was collected by self-administered questionnaires from patients before the consultation and from the general practitioners after the consultation. RESULTS: Fifty one per cent of patients expected and 55% received a prescription; 13% expected hospital referral and 10% were referred. Factors related to their presenting problem were most strongly associated with patients' expectation of receiving a prescription. The actions which the general practitioners took were most strongly associated with patients' expectations. Patients' anxiety about their health problem also appeared to influence their expectations of referral and the doctor's prescribing decision. CONCLUSION: This study suggests that patients' expectation of management and their anxiety associated with the presenting problem may be two of the factors which influence general practitioners' prescribing and referral behaviour and may explain some of the observed variations in behaviour.

Adolescent↗
PubMed1994

Is determination of creatine kinase-2 after electrophoretic separation accurate?

Since 1991, the Ontario Laboratory Proficiency Testing Program has assessed the analytical performance of creatine kinase (CK; EC 2.7.3.2) isoenzyme-2, using fresh human serum supplemented with purified human CK isoenzymes. In Ontario, the 142 laboratories licensed to analyze CK-2 use a variety of methods: electrophoresis-based, immunoinhibition, and mass assays. During a 1992 survey, duplicate CK-2 samples with different total CK activities showed poorer precision when analyzed after electrophoretic separation than by any other method. A 1993 survey designed to validate these observations conclusively showed that electrophoresis-based assays are subject to a bias proportional to the total CK activity. These survey results were confirmed by studies with selected patients' specimens. We therefore conclude that electrophoresis-based assays may not warrant their reputation as the gold standard for CK isoenzyme measurement.

Creatine Kinase↗
PubMed1993

Inheritance of a meiotic abnormality that causes the ovulation of primary oocytes and the production of digynic triploid mice.

Previous studies have demonstrated that the LT/SvKau strain of mice ovulates a high proportion of oocytes as diploid primary oocytes rather than secondary oocytes. These ovulated primary oocytes are arrested at meiotic metaphase I but may be fertilized to produce digynic triploid embryos. In the present study, 40.4% of eggs analysed from LT/SvKau females were ovulated as primary oocytes, compared to 1.2% from control C57BL/Ws strain mothers. These two inbred strains were intercrossed to produce eight sets of F1, F2 and backcross females and the frequency of triploidy was investigated. The results are compatible with segregation of a co-dominant, autosomal gene that has a major influence on the incidence of triploidy. We suggest that the provisional gene symbol Poo (primary oocyte ovulation) be assigned to this gene, with alleles Poo(l) (the 'mutant' allele present in the LT/SvKau strain) and Poo(b) (the normal allele present in C57BL/Ws mice). Poo is incompletely penetrant and has variable expressivity because the proportion of oocytes ovulated as primary oocytes by LT/SvKau mice was variable and, in some cases, nil. In putative Poo(l)/Poo(b) heterozygotes the frequency of ovulated primary oocytes was increased only marginally (from 1.2% to 6.6%) by the presence of one copy of the Poo(l) allele, but this increase was found consistently (in two reciprocal F1 crosses) and was statistically significant. No evidence was found for tight genetic linkage between Poo and two Mendelian loci (brown on chromosome 4 and glucose phosphate isomerase on chromosome 7), that were segregating in the crosses. The Poo(l) mutant in the LT/SvKau strain of mice provides a valuable resource to study the cell and molecular biology of mammalian oocyte maturation and the control of meiosis.

Alleles↗
PubMed1993

The effect on tumour control probability of varying the setting of a multileaf collimator with respect to the planning target volume.

The multileaf collimator (MLC) is being used increasingly to replace Cerrobend blocks when shaping radiation fields. When the MLC has a stepped edge in relation to the planning target volume (PTV) there might be concern that the MLC is not equivalent to the use of a block. This concern is countered by studying the effect on the tumour control probability of varying the distance between the stepped edge of the MLC and the contour of the PTV. It is observed that provided an adequate margin is added to the PTV when using the MLC the TCP is not reduced. The meaning of adequate has been accurately quantitated as being > or = 7 mm when the projected leaf width is 10 mm at the isocentre. This is the margin which when added to the outline of the planning target volume will ensure no reduction in TCP compared with the use of a block.

Humans↗