The case for teaching history to student nurse anesthetists.
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Curriculum↗
Biomedical subjects
W Wilson
Publications and source records attributed to W Wilson.
Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling.
Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically heterogeneous: 40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease. We proposed that this variability in natural history reflects unrecognized molecular heterogeneity in the tumours. Using DNA microarrays, we have conducted a systematic characterization of gene expression in B-cell malignancies. Here we show that there is diversity in gene expression among the tumours of DLBCL patients, apparently reflecting the variation in tumour proliferation rate, host response and differentiation state of the tumour. We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation. One type expressed genes characteristic of germinal centre B cells ('germinal centre B-like DLBCL'); the second type expressed genes normally induced during in vitro activation of peripheral blood B cells ('activated B-like DLBCL'). Patients with germinal centre B-like DLBCL had a significantly better overall survival than those with activated B-like DLBCL. The molecular classification of tumours on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer.
Adult↗
Population outbreaks in a discrete world.
We present and analyze a simple three-patch host-parasitoid model where population growth is discrete. The model gives solutions that are qualitatively similar to the stable large-amplitude patterns in space found in reaction-diffusion theory. In the context of host-parasitoid interactions, the large-amplitude portions of the solution can be thought of as spatially localized host population outbreaks. Here, we show that the biological requirements for localized population outbreaks in a discrete world are identical to those found in reaction- diffusion theory. Furthermore, the model conveniently allows investigation into the robustness of these population outbreaks under the influence of density-dependent dispersal behavior. We find that localized population outbreaks in space can still occur with modest amounts of pursuit and aggregative behavior by parasitoids. We end by showing that evidence from a real host-parasitoid system is consistent with the predictions of the model.
Animals↗
An A&E nurse's fast-track for potential miscarriage patients.
When women present at A&E with vaginal bleeding, it is possible that they are miscarrying, and very likely that they are distressed physically and psychologically. This paper outlines the development and auditing of a fast-track protocol for these women, in response to the author's being unable to help them in the A&E department as quickly as she would have wished.
Abortion, Spontaneous↗
Brain morphological changes and early marijuana use: a magnetic resonance and positron emission tomography study.
BACKGROUND: The focus of this report is on the possible role that the age of first use of marijuana may play on brain morphology and function. METHODS: Magnetic resonance imaging (MRI) and positron emission tomography (PET) were utilized to study 57 subjects. Brain volume measures (whole brain, gray matter, white matter and lateral ventricle volumes), global cerebral blood flow (CBF) and body size were evaluated. RESULTS: There are three primary findings related to age of first use of marijuana. Subjects who started using marijuana before age 17, compared to those who started later, had smaller whole brain and percent cortical gray matter and larger percent white matter volumes. Functionally, males who started using marijuana before 17 had significantly higher CBF than other males. Both males and females who started younger were physically smaller in height and weight, with the effects being greater in males. CONCLUSIONS: These findings suggest that the age at which exposure to marijuana begins is important. Early adolescence may be a critical period for effects that are not present when exposure begins later. These results are discussed in light of reported effects of marijuana on gonadal and pituitary hormones.
Adolescent↗
The apical ligament: anatomy and functional significance.
OBJECT: The authors conducted a study to describe the detailed anatomy of the apical ligament and to acknowledge or refute its historical description as a functionally significant contributor to craniocervical stability. METHODS: In 20 adult human cadavers measurements of the apical ligament were obtained, and its detailed anatomy was observed. Ranges of motion were also assessed to discern the function of the apical ligament. CONCLUSIONS: Results of the study support the concept that the apical ligament is best described as a vestigial structure that offers no significant added stability to the craniocervical junction. In fact, this ligament was absent in 20% of the specimens examined. These data will aid physicians who frequently view images or manage clinical problems of the craniocervical junction because they may focus on other ligaments of this area and not the apical ligament.
Adult↗
Blood levels of organochlorines before and after chemotherapy among non-Hodgkin's lymphoma patients.
Several small studies suggest a link between environmental exposure to organochlorine compounds and risk of non Hodgkin's lymphoma (NHL). Because NHL is uncommon, studies of the topic often use a population-based case-control design, in which cases generally are enrolled after treatment has begun. If chemotherapy affects blood levels of organochlorines, exposure will be misclassified and findings distorted. To determine whether chemotherapy alters serum levels of organochlorines in NHL cases, we compared serum samples before and after treatment in 22 cases diagnosed with NHL between March 1994 and August 1995 and enrolled in a clinical trial at the United States National Cancer Institute's Clinical Center. The time difference between pretreatment and posttreatment samples ranged from 15 to 27 months with an average of 20 months. Laboratory analyses were conducted in blinded pretreatment and posttreatment pairs of the subjects. Pretreatment and posttreatment organochlorine serum levels were compared using Pearson correlation coefficient (r) and paired t test. The pretreatment and posttreatment serum levels were highly correlated for 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and polychlorinated biphenyls (PCBs) PCB-138, PCB-153, PCB-156, and total PCBs (ranging from 0.78 to 0.93). Serum levels of all of these organochlorines significantly decreased between initiation and completion of chemotherapy, 25% for total PCB (P = 0.0044), 28% for DDE (P = 0.0014), 25% for PCB-138 (P = 0.0053), 27% for PCB-153 (P = 0.0031), and 29% for PCB-156 (P = 0.045). Neither weight change nor lipid change was correlated with changes in chemical levels. There was no association between the length of time between blood draws and changes in chemical levels. Our data raise the possibility that lymphoma treatment depresses serum organochlorine levels.
Adult↗
Assessment of human exposure to ambient particulate matter.
Recent epidemiological studies have consistently shown that the acute mortality effects of high concentrations of ambient particulate matter (PM), documented in historic air pollution episodes, may also be occurring at the low to moderate concentrations of ambient PM found in modern urban areas. In London in December 1952, the unexpected deaths due to PM exposure could be identified and counted as integers by the coroners. In modern times, the PM-related deaths cannot be as readily identified, and they can only be inferred as fractional average daily increases in mortality rates using sophisticated statistical filtering and analyses of the air quality and mortality data. The causality of the relationship between exposure to ambient PM and acute mortality at these lower modern PM concentrations has been questioned because of a perception that there is little significant correlation in time between the ambient PM concentrations and measured personal exposure to PM from all sources (ambient PM plus indoor-generated PM). This article shows that the critical factor supporting the plausibility of a linear PM mortality relationship is the expected high correlation in time of people's exposure to PM of ambient origin with measured ambient PM concentrations, as used in the epidemiological time series studies. The presence of indoor and personal sources of PM masks this underlying relationship, leading to confusion in the scientific literature about the strong underlying temporal relationship between personal exposure to PM of ambient origin and ambient PM concentration. The authors show that the sources of PM of non-ambient origin operate independently of the ambient PM concentrations, so that the mortality effect of non-ambient PM, if any, must be independent of the effects of the ambient PM exposures.
Air Pollutants, Occupational↗
Paclitaxel chemotherapy after autologous stem-cell transplantation and engraftment of hematopoietic cells transduced with a retrovirus containing the multidrug resistance complementary DNA (MDR1) in metastatic breast cancer patients.
The MDR1 multidrug resistance gene confers resistance to natural-product anticancer drugs including paclitaxel. We conducted a clinical gene therapy study to determine whether retroviral-mediated transfer of MDR1 in human hematopoietic cells would result in stable engraftment, and possibly expansion, of cells containing this gene after treatment with myelosuppressive doses of paclitaxel. Patients with metastatic breast cancer who achieved a complete or partial remission after standard chemotherapy were eligible for the study. Hematopoietic stem cells (HSCs) were collected by both peripheral blood apheresis and bone marrow harvest after mobilization with a single dose of cyclophosphamide (4 g/m2) and daily filgrastim therapy (10 microg/kg/day). After enrichment for CD34+ cells, one-third of each collection was incubated ex vivo for 72 h with a replication-incompetent retrovirus containing the MDR1 gene (G1MD) in the presence of stem-cell factor, interleukin 3, and interleukin 6. The remaining CD34+ cells were stored without further manipulation. All of the CD34+ cells were reinfused for hematopoietic rescue after conditioning chemotherapy with ifosfamide, carboplatin, and etoposide regimen. After hematopoietic recovery, patients received six cycles of paclitaxel (175 mg/m2 every 3 weeks). Bone marrow and serial peripheral blood samples were obtained and tested for the presence of the MDR1 transgene using a PCR assay. Six patients were enrolled in the study and four patients received infusion of genetically altered cells. The ex vivo transduction efficiency, estimated by the PCR assay, ranged from 0.1 to 0.5%. Three of the four patients demonstrated engraftment of cells containing the MDR1 transgene. The estimated percentage of granulocytes containing the MDR1 transgene ranged from a maximum of 9% of circulating nucleated cells down to the limit of detection of 0.01%. One patient remained positive for the MDR1 transgene throughout all six cycles of paclitaxel therapy, whereas the other 2 patients showed a decrease in the number of cells containing the transgene to undetectable levels. Despite the low level of engraftment of MDR1-marked cells, a correlation was observed between the relative number of granulocytes containing the MDR1 transgene and the granulocyte nadir after paclitaxel therapy. No adverse reactions to the genetic manipulation procedures were detected. Therefore, engraftment of human HSCs transduced with the MDR1 gene can be achieved. However, the overall transduction efficiency and stable engraftment of gene-modified HSCs must be improved before MDR1 gene therapy and in vivo selection with anticancer drugs can be reliably used to protect cancer patients from drug-related myelosuppression.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Managing pressure ulcers: a multisite CQI challenge.
Think preventing and tracking pressure ulcers is expensive? Treatment may cost more. The Nurse Executive Council of VHA Alabama partnered with KCI USA, Inc., to implement a CQI project to manage pressure ulcer incidence.
Alabama↗
Stage-specific expression of the 14-3-3 gene in Echinococcus multilocularis.
A cDNA expression library representing the metacestode developmental stage of the tapeworm Echinococcus multilocularis was immunoscreened with monospecific antibodies affinity purified following differential immunoblot analysis. Using this procedure, a metacestode-specific clone was isolated representing a 14-3-3 gene of the parasite, which is present as a single copy in the parasite genome. The identity of this clone was demonstrated by cross-reactivity of the recombinant E. multilocularis 14-3-3 protein with antibodies raised against a heterologous 14-3-3 protein from Saccharomyces cerevisiae. In addition, expression of the E. multilocularis 14-3-3 gene in the mutant S. cerevisiae strain, DS9-22, resulted in complementation of the phenotypic deficiency of this strain, thus demonstrating the functionality of the respective gene product. By reverse transcription-polymerase chain reaction (RT-PCR) we showed that the E. multilocularis 14-3-3 protein is about 10-fold overexpressed in the metacestode stage compared with the expression level in the adult stage. Immunolocalization of the 14-3-3 protein in E. multilocularis metacestodes revealed its predominant presence in the germinal layer of the parasite. The results of this study, taken together with the current knowledge on the 14-3-3 protein family, suggest that this parasite molecule may contribute to the promotion of the progressive, potentially unlimited growth behaviour of the E. multilocularis metacestode within the host tissue.
14-3-3 Proteins↗
Genetic polymorphism in MDR-1: a tool for examining allelic expression in normal cells, unselected and drug-selected cell lines, and human tumors.
By using RNase protection analysis, residues 2677 and 2995 of MDR-1 were identified as sites of genetic polymorphism. Through use of oligonucleotide hybridization, the genomic content and expression of individual MDR-1 alleles were examined in normal tissues, unselected and drug selected cell lines, and malignant lymphomas. In normal tissues, unselected cell lines, and untreated malignant lymphoma samples, expression of MDR-1 from both alleles was similar. In contrast, in drug selected cell lines, and in relapsed malignant lymphoma samples, expression of one allele was found in a large percentage of samples. To understand how expression of one allele occurs, two multidrug resistant sublines were isolated by exposing a Burkitt lymphoma cell line to increasing concentrations of vincristine. The resistant sublines expressed only one allele and had a hybrid MDR-1 gene composed of non-MDR-1 sequences proximal to MDR-1. Previous studies showing hybrid MDR-1 genes after rearrangements provided a potential explanation for activation and expression of one MDR-1 allele. We conclude that oligonucleotide hybridization can be used as a sensitive tool to examine relative allelic expression of MDR-1, and can identify abnormal expression from a single allele. Acquired drug resistance in vitro and in patients is often associated with expression of a single MDR-1 allele, and this can be a marker of a hybrid MDR-1 gene.
Alleles↗
Effect of dual-chamber pacing with automatic rate-drop sensing on recurrent neurally mediated syncope.
We tested the hypotheses that a dual-chamber pacemaker that paces when intrinsic rate drops abruptly would reduce the number of syncopal spells and improve the quality of life in patients with highly recurrent neurally mediated syncope. Twelve patients with highly frequent neurally mediated syncope and at least 1 syncopal spell after tilt testing received dual-chamber pacemakers with automatic rate-drop sensing. The pacemakers were implanted 17+/-26 months after tilt testing, and the patients then were followed for 12+/-2 months. We compared the time to the first recurrence of syncope, syncope frequency, and quality of life for the 2 periods between tilt testing and pacemaker implantation, and between implantation and last follow-up. Only 6 of 12 patients fainted after pacemaker insertion. The median time to syncope recurrence before and after pacing was 7 days and 5.3 months, respectively. The geometric mean frequency of faints before and after pacing was 5.0 spells/month (95% confidence interval 2.7 to 9.2) and 0.30 spells/month (95% confidence interval 0.2 to 0.4), p <0.001. After 6 months the mean perception of health on the 100-point EuroQol scale rose from 55 to 82 (p = 0.003), and the general health perception on the SF-36 scale rose from 51 to 72 (p = 0.005). Permanent dual-chamber pacing with automatic rate-drop sensing in patients with highly frequent syncope is associated with a marked reduction in the likelihood of syncope and a marked improvement in quality of life.
Adolescent↗
Detailed alignment of saccharum and sorghum chromosomes: comparative organization of closely related diploid and polyploid genomes.
The complex polyploid genomes of three Saccharum species have been aligned with the compact diploid genome of Sorghum (2n = 2x = 20). A set of 428 DNA probes from different Poaceae (grasses) detected 2460 loci in F1 progeny of the crosses Saccharum officinarum Green German x S. spontaneum IND 81-146, and S. spontaneum PIN 84-1 x S. officinarum Muntok Java. Thirty-one DNA probes detected 226 loci in S. officinarum LA Purple x S. robustum Molokai 5829. Genetic maps of the six Saccharum genotypes, including up to 72 linkage groups, were assembled into "homologous groups" based on parallel arrangements of duplicated loci. About 84% of the loci mapped by 242 common probes were homologous between Saccharum and Sorghum. Only one interchromosomal and two intrachromosomal rearrangements differentiated both S. officinarum and S. spontaneum from Sorghum, but 11 additional cases of chromosome structural polymorphism were found within Saccharum. Diploidization was advanced in S. robustum, incipient in S. officinarum, and absent in S. spontaneum, consistent with biogeographic data suggesting that S. robustum is the ancestor of S. officinarum, but raising new questions about the antiquity of S. spontaneum. The densely mapped Sorghum genome will be a valuable tool in ongoing molecular analysis of the complex Saccharum genome.
DNA, Plant↗
Safety, tolerance, and pharmacokinetics of a small unilamellar liposomal formulation of amphotericin B (AmBisome) in neutropenic patients.
The safety, tolerance, and pharmacokinetics of a small unilamellar liposomal formulation of amphotericin B (AmBisome) administered for empirical antifungal therapy were evaluated for 36 persistently febrile neutropenic adults receiving cancer chemotherapy and bone marrow transplantation. The protocol was an open-label, sequential-dose-escalation, multidose pharmacokinetic study which enrolled a total of 8 to 12 patients in each of the four dosage cohorts. Each cohort received daily doses of either 1.0, 2.5, 5.0, or 7.5 mg of amphotericin B in the form of AmBisome/kg of body weight. The study population consisted of patients between the ages of 13 and 80 years with neutropenia (absolute neutrophil count, <500/mm3) who were eligible to receive empirical antifungal therapy. Patients were monitored for safety and tolerance by frequent laboratory examinations and the monitoring of infusion-related reactions. Efficacy was assessed by monitoring for the development of invasive fungal infection. The pharmacokinetic parameters of AmBisome were measured as those of amphotericin B by high-performance liquid chromatography. Noncompartmental methods were used to calculate pharmacokinetic parameters. AmBisome administered as a 1-h infusion in this population was well tolerated and was seldom associated with infusion-related toxicity. Infusion-related side effects occurred in 15 (5%) of all 331 infusions, and only two patients (5%) required premedication. Serum creatinine, potassium, and magnesium levels were not significantly changed from baseline in any of the dosage cohorts, and there was no net increase in serum transaminase levels. AmBisome followed a nonlinear dosage relationship that was consistent with reticuloendothelial uptake and redistribution. There were no breakthrough fungal infections during empirical therapy with AmBisome. AmBisome administered to febrile neutropenic patients in this study was well tolerated, was seldom associated with infusion-related toxicity, was characterized by nonlinear saturation kinetics, and was effective in preventing breakthrough fungal infections.
Adult↗
Temporally localized contributions to measures of large-scale heart rate variability.
The purpose of this work was to determine the temporal origins of the standard deviation of successive 5-min mean heart period sequences (SDANN) and the power of the ultralow-frequency (ULF) spectral band (< 0.0033 Hz). We hypothesized that SDANN and ULF might have their origins in changes in human activity rather than slow oscillatory rhythms. Heart period sequences were obtained from 24-h Holter electrocardiograms of 10 healthy ambulatory subjects. There was no evidence of any persistent oscillation within the ULF band. Using moving 4-h windows in short-time Fourier transforms, we showed that the amplitude of ULF fluctuated markedly, particularly during times bordering sleep. The local ULF amplitude correlated (r = 0.59 +/- 0.09) with large-scale changes in heart period quantified with 2- and 4-h wavelet transforms. Local SDANN also fluctuated, mainly around times of sleep. Although the 24-h SDANN and ULF values correlated highly, there was little correlation between their temporal distributions (r = 0.10 +/- 0.25). The temporal distributions of measures of long-range heart period variability suggest that they reflect changes in human activity levels.
Adolescent↗
Novel aspects of the regulation of glycogen storage.
The storage polysaccharide glycogen is widely distributed in nature, from bacteria to mammals. Study of its regulated accumulation has resulted in the discovery or elaboration of several important biochemical principles. Many aspects of the control of glycogen storage still remain poorly understood and glycogen metabolism continues to provide interesting models of more general relevance.
Animals↗
Modus operandi of female serial killers.
The modus operandi of female serial killers was examined from a chronology of 58 cases in America and 47 cases in 17 other countries, compiled over 25-year intervals. Female serial killers in other countries accounted for a disproportionately greater number of victims, but those in America managed a longer killing career when associated with a low profile modus operandi.
Chi-Square Distribution↗