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Computer Communication Networks↗
Biomedical subjects
P Miller
Publications and source records attributed to P Miller.
Allogeneic peripheral blood stem cell transplantation using normal patient-related pediatric donors.
Successful allogeneic peripheral blood progenitor cell (PBPC) transplantation has recently been reported by several transplant centers. This is a first report describing allogeneic PBPC transplantation in five patients using related pediatric donors between the ages of 4 and 13 years. Donors underwent 3 or 4 days of rhG-CSF treatment (6 micrograms/kg q 12 h) for stem cell peripheralization prior to PBPC collection, which was performed by continuous-flow apheresis on day 4 or 5. Venous access was exclusively by ante-cubital veins. A median of 2.2 times (range 1.4-3.6) the donor's total blood volume (TBV) was processed per procedure. In cases where the donor's TBV was < 2 liters, the blood cell separator was primed with human serum albumin (HSA-5%), and anticoagulation was performed using a combination of heparin (pre-apheresis bolus + continuous infusion (CI)) and/or ACD-A (CI at a reduced rate). The median number of CD34+ cells collected per kg of donor body weight (b.w.) and per liter of donor blood processed during each procedure was 128 x 10(4) (range 58 x 10(4)-314 x 10(4)). Between one and two aphereses were sufficient to collect a safe CD34+ cell engraftment dose of 3 or 4 x 10(6)/kg of recipient b.w. Two PBPC recipients were parents, and three were siblings. After freezing and thawing, the median number of CD34+ cells per kg of recipient b.w. thawed and transfused was 8.5 x 10(6) (range 3.2 x 10(6)-9.7 x 10(6)). The time to PMN > 1000/microliters was between 10 and 16 days (four out of five evaluable patients), and platelets > 20000/microliters were reached between day 13 and 14 post-transplantation (three out of five evaluable patients). Two out of three evaluable patients developed grades one and three acute GVHD, and one out of three developed chronic GVHD. Two patients died of sepsis and VOD at day 10 and 19, respectively. Two adult patients are alive and in cytogenetic and molecular remission of CML at +339 and +227 days post-allotransplantation. One 3-year-old girl with hemophagocytic lymphohistiocytosis is in remission at +304 days post-transplantation. Using pediatric donors for allogeneic PBPC transplantation appears to be safe, yields a sufficient amount of progenitors for prompt engraftment, and results in clinical outcome similar to adult PBPC allotransplantation.
Adult↗
Cannabis use in the community.
BACKGROUND: The illegal use of cannabis has been increasing in many Western countries for the past two decades. Recently, some interest has been shown in modifying legislation and control. The need for general practitioners to be aware of the short- and long-term consequences of cannabis use is increasing, and more information is required about its effects on behaviour, psychological states and the respiratory and cardiovascular systems. The use of general practice populations to study the prevalence of cannabis use and its damaging effects is less represented in the literature than it should be, considering the extent of cannabis consumption. AIM: A study was carried out in 1995 to determine the prevalence of cannabis use in a general practice population and any associated health problems. As a pilot study, samples of cannabis were obtained for forensic analysis. METHOD AND PATIENTS: Two questionnaires were used. One very short enquiry about the use, if any, of the drug, and a longer one about the effects of its use. Data concerning medical effects were included from patients' case notes. Samples of cannabis were obtained for forensic examination. RESULTS: A very high proportion (61%) of patients surveyed indicated some cannabis use (past or present). Thirty-seven per cent had used it in the previous 12 months. Users could be broadly divided into transitory experimenters, regular users and heavy users. Medical problems included those attributed to associated tobacco smoking, other illegal drug use and psychological problems. Benefits perceived by patients recording use were many. Polydrug use and legislation issues were difficult to separate from the effects of cannabis itself. Chest infections, anxiety and depression, and drug dependence were common diagnoses, and 13 of the 32 females in the study group had evidence of cervical smear abnormalities. CONCLUSIONS: Few serious damaging effects from cannabis use itself were identified, although chest infections and anxiety problems were common. Tobacco damage, associated drug use and criminal or legal issues dominated and obscured the important perceived benefits and the scientific understanding of the effects and side effects of the drug. More research into several identified areas is required.
Adolescent↗
Effects of azathioprine withdrawal in kidney recipients with stable function two years after transplant.
To assess the effects of azathioprine withdrawal, renal recipients with grafts > 2 yr function (103 study patients) were tapered off azathioprine over a 1-yr period and compared to 69 patients 2 yr after transplant who were not tapered (controls). Of the 103 study patients, 16 (15%) were living-donor transplants and 87 were cadaveric. Of the 69 control patients, 9 (13%) were living related transplants and 60 were cadaveric. The mean HLA match for those tapered was 3.3 Ag and 3.1 Ag for those remaining on azathioprine. Two study patients restarted azathioprine on their own. Age, sex, and cause of renal failure in both groups was similar. Of the 101 study patients remaining, 9 (8.8%) returned to dialysis due to biopsy proven chronic rejection. There were no acute rejection episodes. Six of the 69 control patients (8.7%) also returned to dialysis for the same reason. Of the 92 patients who have completed the taper, 85 have been off azathioprine for six or more months. There was not a significant difference between the mean 12- and 24-month creatinine levels of the study patients (1.6 mg%, 1.7 mg%) and those of the controls (1.5 mg%, 1.8 mg%). The mean 12- and 24-month hematocritis of patients tapered (41.3%, 40.8%) were comparable with patients not tapered (42.3%, 42.8%). Of interest, the mean hematocritis of both study and control patients rose from 28.9% and 33.5%, respectively, to 41.3% and 42.3% 1 yr following entry into the study. The mean 12- and 24-month white blood counts of those tapered (8.9, 8.7) did not differ significantly from those continued on azathioprine (8.8, 8.8). In stable renal transplant patients on triple drug immunosuppression for at least 2 yr, azathioprine can be discontinued, in a tapered protocol, without an increased risk of graft loss or compromise of renal function.
Azathioprine↗
Structural organization of a Bacillus subtilis operon encoding menaquinone biosynthetic enzymes.
Menaquinone (MK) is a non-protein component of the Bacillus subtilis (Bs) electron transport chain synthesized from chorismate through a series of MK-specific reactions. The genes encoding biosynthesis of the naphthoquinone ring of MK are clustered at 273 degrees on the Bs chromosome. A 3.9-kb region capable of rescuing men mutants blocked in the early stages of MK biosynthesis was sequenced and found to contain three major open reading frames (ORFs). The first ORF (menF) has a predicted size of 51.8 kDa and 34% amino-acid identity with the isochorismate synthases of Escherichia coli (EntC) and Aeromonas hydrophila (AmoA), ORF2 (menD) a predicted size of 60.2 kDa and 21% identity with MenD of E. coli. ORF3 has a predicted size of 21.4 kDa and 29% identity to triacylglycerol lipase of Psychrobacter immobilis. No sequence corresponding to menC was identified. Plasmid integrational studies of the men gene cluster had suggested the presence of promoters secondary to the previously identified p1 men promoter. Sequence analysis revealed a putative promoter region upstream from ORF3.
Bacillus subtilis↗
Allogeneic blood stem cell transplantation: peripheralization and yield of donor-derived primitive hematopoietic progenitor cells (CD34+ Thy-1dim) and lymphoid subsets, and possible predictors of engraftment and graft-versus-host disease.
Apheresis-derived hematopoietic progenitor cells have recently been used for allogeneic transplantation. Forty-one normal donors were studied to assess the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) (12 micrograms/kg/d) on the peripheralization of hematopoietic progenitor cells and lymphoid subsets. The white blood cell, polymorphonuclear cell (PMNC), and lymphocyte concentrations at the peak of rhG-CSF effect in the donor's peripheral blood (PB) exceeded baseline by 6.4-, 8.0-, and 2.2-fold, respectively. Corresponding concentrations of PB CD34+ cells and primitive subsets such as CD34+ Thy-1dim, and CD34+ Thy-1dim CD38- cells increased by 16.3-fold, 24.2-fold, and 23.2-fold, respectively in eight normal donors. The percentage of CD34+ Thy-1dim and CD34+ Thy-1dim CD38- cells among CD34+ cells increased as well, suggesting an additional peripheralization effect of rhG-CSF on primitive CD34+ subsets. The preapheresis PB CD34+ and CD34+ Thy-1dim cell concentrations were predictive of their corresponding apheresis yield per liter of donor blood processed PB lymphoid subsets were not significantly affected by rhG-CSF treatment. The mean apheresis-derived yield of CD34+, CD34+ Thy-1dim, and CD34+ Thy-1dim CD38- cells per kilogram of recipient body weight and per liter of donor blood processed was 48.9 x 10(4) (n = 41), 27.2 x 10(4) (n = 10), and 1.9 x 10(4) (n = 10), respectively. As compared with 43 single bone marrow (BM) harvest, the CD34+ cell yield of peripheral blood progenitor cell allografts of 41 normal donors exceeded that of BM allografts by 3.7-fold and that of lymphoid subsets by 16.1-fold (CD3+), 13.3-fold (CD4+), 27.4-fold (CD8+), 11.0-fold (CD19+), and 19.4-fold (CD56+CD3-). All PBPC allografts were cryopreserved before transplantation. The mean recovery of CD34+ cells after freezing, thawing, and washing out dimethylsulfoxide was 86.6% (n = 31) and the recovery of lymphoid subsets was 115.5% (CD3+), 121.4% (CD4+), 105.6% (CD8+), 118.1% (CD19+), and 102.4% (CD56+CD3-). All donors were related to patients: 39 sibling-to-sibling, 1 parent-to-child, and 1 child-to-parent transplant. Thirty-eight transplants were HLA fully identical, two transplants differed in one and two antigens. Engraftment occurred in 38 recipients; two patients died too early to be evaluated, and one patient did not engraft. The lowest CD34+ cell dose transplanted and resulting in complete and sustained engraftment was 2.5 x 10(6)/kg of recipient body weight. There was no significant correlation between the total number of CD34+ cells transfused and the time to reach PMNC >0.5 x 10(9)/L or platelets > 50 x 10(9)/L posttransplant, nor was there a correlation found between the total number of CD3+, CD4+, and CD8+ cells transfused and the development of acute graft-versus-host disease (GVHD). The actuarial probability of developing acute GVHD in 38 evaluable patients was 48%. In 13 patients followed longer than 100 days posttransplant, the actuarial probability of developing chronic GVHD was 66% (median follow-up, 264 days).
Adolescent↗
Functional characterization of novel IL-2 transcriptional inhibitors.
IL-2-mediated T cell proliferation is a critical early event in the inflammatory process. Formation of the NFAT-1 transcriptional complex on the IL-2 promoter is essential for IL-2 transcription. Using a cell line that is stably transfected with a trimer of the NFAT-1 regulatory element linked to a lac-Z reporter gene, we screened for inhibitors of NFAT-1-mediated beta-galactosidase activity. WIN 61058 and WIN 53071 were identified as microM inhibitors. These compounds also inhibited beta-galactosidase mRNA levels. Similar inhibition of NFAT-1-mediated gene expression was observed in a second cell line, which is stably transfected with NFAT-1 regulatory elements linked to the reporter gene for sCD8. At 10 microM, both compounds inhibited IL-2 mRNA and protein levels in the NFAT-1-linked lac-Z transfectants, and in human lymphocytes. Both compounds inhibited the mixed lymphocyte reaction, and this inhibition was reversed by exogenous IL-2. WIN 53071 inhibited IL-2 production induced in the calcium-dependent PMA and ionomycin pathway. Conversely, calcium-independent anti-CD28 Ab and PMA-induced IL-2 production was resistant. Both compounds altered the NFAT-1 transcriptional complex, causing its retarded mobility on gels. By these functional criteria, we believe we have identified two structurally distinct, novel inhibitors of NFAT-1-mediated transcription.
Base Sequence↗
Structure-function studies of motilin analogues.
Over 100 motilin fragments and analogues, including monosubstituted C-terminal-deleted analogues, conformationally restricted analogues, analogues with peptide bond isoteres (CH2-NH), and N-terminal fragments adjunct to an amphiphilic helix, were synthesized by solid-phase methodology, purified by reverse-phase HPLC, and assayed in vitro in a muscle strip bioassay (rabbit duodenum) and in a radioligand binding assay on crude membrane extracts from smooth muscle (rabbit antrum). The data suggest the existence of three distinct regions involved in the interaction of motilin with its receptor: the N-terminal region (amino acids 1-7) constitutes the minimal basic unit of binding and activity; the transition region (amino acidsa 8-9) links the N-terminal and C-terminal regions; and the C-terminal region (amino acids 10-22) forms an alpha-helix that stabilizes the interaction of the N-terminal residues at the active site.
Amino Acid Sequence↗
The effect of a national control of diarrheal diseases program on mortality: the case of Egypt.
The National Control of Diarrheal Diseases Project (NCDDP) of Egypt began in 1981, became fully operational nation-wide by 1984, and concluded in 1991. The project was designed as a campaign to lower mortality from diarrheal disease in children under five by at least 25% within five years. The principal strategy employed was to improve case-management of diarrhea through rehydration and better feeding: through assured production and distribution of oral rehydration salts, education of families through mass media and health workers through training programs, and creation of rehydration corners throughout the established primary health care and hospital network. A detailed plan for evaluation and research was designed at the start of the project. By its own terms, the NCDDP appears to have succeeded in improving case management; by several local and national mortality surveys, overall infant and childhood mortality fell by at least one-third with the majority proportion in diarrheal deaths. The declines coincided with the peak of NCDDP activities and results in improved case-management. The detailed analyses of this monograph seek to demonstrate that: (a) the mortality decline and the diarrheal mortality decline in particular were actual events; (b) that case-management improved with plausible sufficiency to account for most of the diarrheal mortality reduction; and (c) that changes in other proximate determinants to lowered mortality, such as host resistance or diarrheal incidence, do not plausibly account for the magnitude of the reductions seen. Data are also presented on general socio-economic changes in the decade of the Project. We conclude that improvements in primary care delivery and the use of mass media would have been facilitating factors to NCDDP efforts, while the overall deterioration of economic status would have tended to reduce the benefits. The monograph details the strengths and weaknesses of the available data, and also makes recommendations for sustained efforts in the control of diarrheal diseases.
Causality↗
Remote communication from a mobile terminal: an adjunct for a computerized intensive care unit order management system.
OBJECTIVES: To develop and implement a fully mobile computer terminal that interfaces with our computerized intensive care unit (ICU) local area network and order management system. This system can provide access to the entire network and to order review and entry and during ICU bedside rounds. DESIGN: Descriptive report. SETTING: Surgical ICU in Department of Veterans Affairs Medical Center. SYSTEM CONFIGURATION: A parallel local area network was configured for the remote mobile computer system. A proprietary remote transmission system (Altair II, Motorola) was used. This high-throughput system minimizes interference and errors by using licensed, nonshared, radiofrequency spectra. CONCLUSION: The resulting mobile system is an economical and time-efficient adjunct to an established ICU computerized network and order management system. Clinical working bedside rounds are now routinely conducted with the mobile terminal, providing immediate access to full network resources.
Computer Terminals↗
Batched analysis of genotypes.
Polymorphic microsatellite markers are widely used in molecular analyses. The range of allele sizes and the allele frequencies within a population are important characteristics of the marker. Their determination previously has involved genotyping a large number of individuals. We have developed a technique for defining these characteristics by coamplification of many samples in a DNA pool. Groups of 32 and 42 DNA samples were genotyped and results were compared with those from individual genotype determinations. To improve the accuracy in the estimation of allele frequencies, arithmetic removal of stutter bands was carried out and the consistency of each marker was characterized. This approach was also applied to a group of 94 individuals. All of the work has been done using nonradioactive methods. Potential applications of this technique are in population genetics, high throughput genotyping, and loss of heterozygosity studies.
Alleles↗
Radiology in Rwanda.
This account documents some aspects of military radiology in the aftermath of the Rwandan Civil War of 1994. Following the genocidal conflict of April-July 1994, all radiographic services ceased in Rwanda, a nation of some 7,500,000 people. As part of the United Nations Peacekeeping Force, UNAMIR II, the Australian Medical Support Force established and provided, on an ongoing basis, sophisticated medical, surgical and intensivist care for the sick and wounded United Nations personnel, of whom there were up to 7000 deployed in Rwanda; and, as part of its humanitarian outreach, emergency medical and surgical care for Rwandese civilians. The Australian contingent of 308 service personnel established the Australian Military Hospital (the 'United Nations Hospital') in the former Clinic Wing of the Kigali Central Hospital. From August 1994 the Radiology Department of the Australian Medical Support Force provided the first specialist X-ray services as part of the re-building of the stricken nation and, over the ensuing year, provided a diagnostic service for soldiers and civilians with both chronic and recent war wounds, trauma victims in the aftermath of the Civil War, sick and injured soldiers and Rwandese suffering from any of the full range of medical conditions encountered in tropical Africa.
Australia↗
Alcohol, tobacco, illicit drugs, and sex: an analysis of risky behaviors among young adults.
This paper reexamines data from two previous surveys. It looks at self-reported alcohol, tobacco, and illicit drug use and sexual risk-taking among three subgroups of young adults. All subjects (N = 1,387) were aged 20-30. The samples consisted of nurses in the Lothian Region, and residents in Muirhouse (Edinburgh) and Easterhouse (Glasgow). Factor analysis revealed that risk-taking behavior was neither entirely general nor entirely specific. Although there was some tendency for a risk-taker in one area to be a risk-taker in others, five fairly distinct types of risk-taking could be distinguished. These included sexual risk-taking, illicit use of drugs, and excessive alcohol consumption. The samples differed in the extent to which they indulged in the different types of risk-taking, and various other predictors of these behaviors were found. Different patterns of association emerged in relation to specific subgroups of respondents.
Adolescent↗
The relationship of substance use with sex to the use of condoms among young adults in two urban areas of Scotland.
The relationship of the use of alcohol or drugs in conjunction with sexual activity and the use of condoms and other contraceptives was examined among 1378 respondents in a household survey of two urban areas of Scotland. In bivariate analyses, respondents who reported having had sex under the influence of alcohol or drugs were no less likely than respondents with no such experience to report consistent use of condoms, and having had sex under the influence of substances was positively related to lifetime condom use. Multivariate analyses that included gender and urban area as predictors yielded similar findings. The results suggest that individuals who combine sex with alcohol or drugs are not necessarily more likely to engage in riskier sex.
Adolescent↗
Syphilis in pregnancy: experience from a rural aboriginal community.
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Australia↗
Conditions for electron tomographic data acquisition.
The conventional algorithms employed in electron microscope tomography require that the series of images obtained from different orientations of the specimen each represent a parallel orthographic projection under uniform magnification. Electron microscope optics can produce distortions in images that may affect the accuracy of a tomographic reconstruction. These distortions result in images with differential rotation and magnification of regions of a thick or highly tilted specimen located at different distances with respect to the plane of focus. The distortions increase in magnitude and may significantly affect the accuracy of the tomographic data when images are acquired under current center misalignment or non-eucentric positioning of the specimen. An additional source of error can be introduced if the condenser lenses are adjusted to compensate for the intensity attenuation due to the increased beam path length as the specimen is tilted. The change in beam crossover position due to adjustment of the condensers alters the beam divergence and may introduce systematic changes in magnification over the tilt series. The process of alignment of the tilt series will propagate these errors to more central regions of the image. In most cases, with proper consideration, it is possible to minimize these errors to levels where they will have negligible effects on the resolution of the tomographic reconstruction.
Algorithms↗
Motilin synthetic analogues and motilin receptor antagonists.
While studying the structure-activity characteristics of motilin with motilin synthetic analogues, two compounds, motilin 1-12 [CH2 NH]3-4 and motilin 1-12 [CH2 NH]10-11, showed high affinity for the motilin receptor combined to a weak contractile activity. The following data suggest that motilin 1-12 [CH2 NH]10-11 is a potent motilin receptor antagonist. It showed a high affinity for the motilin receptor present on membranes of rabbit antrum (pIC50: 8.24 +/- 0.08 for the analogue vs 8.96 +/- 0.02 for the native peptide). When tested in vitro on strips of rabbit duodenum, the dose-response curve to motilin 1-22 was displaced to the right with motilin 1-12 [CH2 NH]10-11 (pIC50: 8.91 +/- 0.06 in presence of saline versus 7.19 +/- 0.40 with the analogue). However, when injected i.v. in dogs, motilin 1-12 [CH2 NH]10-11 was undetectable in the peripheral blood, suggesting enzymatic degradation precluding its use in vivo.
Animals↗
Microscopic haematuria. Cystoscopy has little value in children.
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Adult↗