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Biomedical subjects

Robert Lee

Publications and source records attributed to Robert Lee.

At least 19 recordsLinked to original sources

Non-normal path analysis in the presence of measurement error and missing data: a Bayesian analysis of nursing homes' structure and outcomes.

Path analytic models are useful tools in quantitative nursing research. They allow researchers to hypothesize causal inferential paths and test the significance of these paths both directly and indirectly through a mediating variable. A standard statistical method in the path analysis literature is to treat the variables as having a normal distribution and to estimate paths using several least squares regression equations. The parameters corresponding to the direct paths have point and interval estimates based on normal distribution theory. Indirect paths are a product of the direct path from the independent variable to the mediating variable and the direct path of the mediating variable to the dependent variable. However, in the case of non-normal distributions, the point and interval estimates of the indirect path become much more difficult to estimate. We address the issue of calculating indirect point and interval estimates in the case of non-normally distributed data. Our substantive application is a nursing home research problem in which the variables in the path analysis of interest involve variables with normal, Bernoulli, or Poisson distributions. Additionally, one of the Poisson variables is observed with error. This paper addresses estimating point and interval estimation of indirect paths for variables with non-normal distributions in the presence of missing data and measurement error. We handle these difficulties from a fully Bayesian point of view. We present our substantive path analysis motivated from a nursing home structure, process, and outcomes model. Our results focus on the impact job turnover in the nursing homes has on nursing home outcomes.

Data Interpretation, Statistical↗

A new method of evaluating the quality of radiology reports.

RATIONALE AND OBJECTIVES: The radiology report must provide the ordering physician relevant information in an understandable format. The objectives of this study were to develop and apply a method for the grading of the quality of radiology reports and to evaluate differences based on the reader's experience. This grading method permits evaluation of compliance with the American College of Radiology communication standards. MATERIALS AND METHODS: A total of 240 intensive care unit admission chest radiograph reports were retrieved from our hospital database. These were graded for quality. Our grading system is based on the concept that a radiology report must provide information relevant to the patient's known clinical status and thus is important to the ordering clinician. The best grade for a report is IV and the minimum grade assigned is I. Results were further analyzed based on the experience of the reader. RESULTS: A total of 436 grades from the 240 reports were generated: 374/436 (86%) grades were designated a III or IV, which we deemed as satisfactory reports. The scoring of the radiology reports evaluating the position of endotracheal tubes, catheters, and enteric feeding tubes scored significantly better than definitive diagnosis as the starting point on the clinical spectrum (P < .01). The scores from all other patients starting points on the clinical spectrum, when compared with one another, were nonsignificant. Using a one-way analysis of variance, when comparing reports based on the six different levels of reader experience, first-year residents up to staff radiologists reports showed no significant difference (P = .78). CONCLUSIONS: Ideally, 100% of radiology reports should receive a grade III or IV. Our study showed that only 86% of the reports met this standard.

Analysis of Variance↗

Evaluation of the quality of radiology requisitions for intensive care unit patients.

RATIONALE AND OBJECTIVES: The study aim is to evaluate the quality of radiology requisitions for plain film radiographs on intensive care unit (ICU) patients. MATERIALS AND METHODS: Radiology requisitions for 58 patients in ICU units at our children's hospital and the corresponding original orders for the study, written in patients' charts, were obtained. We reviewed each of the resident's written chart orders for completeness and then directly compared the information on the radiology requisition with the actual order written in the patient's chart by the ward resident physician. RESULTS: In 10% of cases, no "written order" was found in the patient's medical record for the imaging study. Clinical indications for the study were provided by the resident in only 71% (41/58) of cases. The resident's name was missing in the chart in eight of 58 cases (14%). The resident's name was provided in 50 cases, but was legible in only 28 of 50 cases (56%). In 84% of cases, the resident failed to provide his or her pager number. For one patient, the incorrect study was ordered. In only 73% (30/41) of cases did the ward clerk exactly copy the clinical indication that was handwritten in the chart by the resident. In 21% of cases, no resident's name was provided as the ordering resident on the radiology requisition. Inadequate or incomplete clinical information was provided in 24% of cases. CONCLUSION: Our study identifies a large number of problems in the quality of our radiology requisitions. Improving the process has been approved by our hospital as a major quality improvement project for this year.

Clinical Clerkship↗

Chronic antithrombotic therapy in post-myocardial infarction patients.

Recent advances in the acute treatment of myocardial infarction (MI) have allowed more to survive the initial event in coronary artery disease. Increasing importance has been placed on secondary-prevention strategies, with more attention directed toward an optimal therapeutic regimen for post-MI patients. When it comes to the subpopulation of the elderly who have had an MI, however, current practice relies less on population-specific evidence and more on extrapolation of current data. This article reviews the pathogenesis of coronary heart disease and MI, and highlights recent major trials that have explored antiplatelet and anticoagulant medications in the chronic treatment of the post-MI population. Special consideration is given to the geriatric community and its unique challenge regarding chronic antithrombotic therapy.

Aged↗

Is routine prophylactic cervical cerclage associated with significant prolongation of triplet gestation?

OBJECTIVE: The purpose of this study was to determine if routine prophylactic cervical cerclage was associated with a significant prolongation of triplet pregnancy. STUDY DESIGN: A retrospective study of all women carrying triplet pregnancies at a single institution during a four-year period was carried out. Selected maternal characteristics and obstetric outcome measures in women who received prophylactic cerclage (PC) were compared to women who did not receive PC (no cerclage placed and emergency cerclage). Statistical comparison was done using the Mann-Whitney test for continuous variables and Fisher's exact test for categorical variables. RESULTS: Fifty-five women had PC and 40 had no PC. There was no significant difference between these two groups in mean maternal age or weight, nulliparity, history of or current sexually transmitted disease, cigarette smoking, history of cervical insufficiency, prior dilation and curettage, prior cervical surgery, prior preterm labor/prolonged preterm rupture of membranes (PTL/PPROM), medical complications in pregnancy, current PTL/PPROM, gestational age at delivery, delivery prior to 28 weeks, delivery prior to 32 weeks, or delivery of an infant weighing less than 1000 or 1500 grams. Thirteen women in the no PC group (32.5%) required emergency cerclage. CONCLUSION: PC was not associated with significant prolongation of triplet pregnancy.

Adult↗

Evaluation of MRI RF probes utilizing infrared sensors.

The magnetic resonance imaging (MRI) coil's radio frequency (RF) field distribution has a strong effect on image quality as well as specific absorption rate. In this paper, a method of probing a coil's RF field distribution over any unoccupied region of the coil is presented. This technique is based on the use of infrared sensing. The proposed method was implemented and tested on a high field RF volume coil operating at 340 MHz. Very good agreement was achieved between the infrared measurements and numerical data obtained utilizing an in-house three-dimensional finite-difference time-domain package. The results demonstrate that the proposed technique is practical, robust, and efficient in making accurate measurements of the electric field distributions in loaded and unloaded MRI coils.

Equipment Design↗

Synthesis of MFI zeolite films on optical fibers for detection of chemical vapors.

We report the development of a novel zeolite-incorporated optical fiber sensor and demonstrate its capability for in situ detection of chemical vapors. The sensor comprises a polycrystalline silicalite thin film grown upon the cleaved end face of a standard single-mode optical fiber. The sensor device operates by measuring the optical reflectivity of the zeolite crystals, which changes reversibly in response to the amount of chemical vapor adsorbed in its crystalline microporous structure. The sensor has been successfully demonstrated for measuring the concentration of isopropanol vapor in mixtures with nitrogen gas.

2-Propanol↗

Thiamethoxam induced mouse liver tumors and their relevance to humans. Part 1: mode of action studies in the mouse.

Thiamethoxam, a neonicotinoid insecticide, which is not mutagenic either in vitro or in vivo, caused an increased incidence of liver tumors in mice when fed in the diet for 18 months at concentrations in the range 500 to 2500 ppm. A number of dietary studies of up to 50 weeks duration have been conducted in order to identify the mode of action for the development of the liver tumors seen at the end of the cancer bioassay. Both thiamethoxam and its major metabolites have been tested in these studies. Over the duration of a 50-week thiamethoxam dietary feeding study in mice, the earliest change, within one week, is a marked reduction (by up to 40%) in plasma cholesterol. This was followed 10 weeks later by evidence of liver toxicity including single cell necrosis and an increase in apoptosis. After 20 weeks there was a significant increase in hepatic cell replication rates. All of these changes persisted from the time they were first observed until the end of the study at 50 weeks. They occurred in a dose-dependent manner and were only observed at doses (500, 1250, 2500 ppm) where liver tumors were increased in the cancer bioassay. There was a clear no-effect level of 200 ppm. The changes seen in this study are consistent with the development of liver cancer in mice and form the basis of the mode of action. When the major metabolites of thiamethoxam, CGA322704, CGA265307, and CGA330050 were tested in dietary feeding studies of up to 20 weeks duration, only metabolite CGA330050 induced the same changes as those seen in the liver in the thiamethoxam feeding study. It was concluded that thiamethoxam is hepatotoxic and hepatocarcinogenic as a result of its metabolism to CGA330050. Metabolite CGA265307 was also shown to be an inhibitor of inducible nitric oxide synthase and to increase the hepatotoxicity of carbon tetrachloride. It is proposed that CGA265307, through its effects on nitric oxide synthase, exacerbates the toxicity of CGA330050 in thiamethoxam treated mice.

Animals↗

Thiamethoxam induced mouse liver tumors and their relevance to humans. Part 2: species differences in response.

Thiamethoxam is a neonicotinoid insecticide that is not a mutagen, but it did cause a significant increase in liver cancer in mice, but not rats, in chronic dietary feeding studies. Previous studies in mice have characterized a carcinogenicity mode of action that involved depletion of plasma cholesterol, cell death, both as single cell necrosis and as apoptosis, and sustained increases in cell replication rates. In a study reported in this article, female rats have been exposed to thiamethoxam in their diet at concentrations of 0, 1000, and 3000 ppm for 50 weeks, a study design directly comparable to the mouse study in which the mode of action changes were characterized. In rats, thiamethoxam had no adverse effects on either the biochemistry or histopathology of the liver at any time point during the study. Cell replication rates were not increased, in fact they were significantly decreased at several time points. The lack of effect on the rat liver is entirely consistent with the lack of liver tumor formation in the two-year cancer bioassay. Comparisons of the metabolism of thiamethoxam in rats and mice have shown that concentrations of the parent chemical were either similar or higher in rat blood than in mouse blood in both single dose and the dietary studies strongly indicating that thiamethoxam itself is unlikely to play a role in the development of liver tumors. In contrast, the concentrations of the two metabolites, CGA265307 and CGA330050, shown to play a role in the development of liver damage in the mouse, were 140- (CGA265307) and 15- (CGA330050) fold lower in rats than in mice following either a single oral dose, or dietary administration of thiamethoxam for up to 50 weeks. Comparisons of the major metabolic pathways of thiamethoxam in vitro using mouse, rat, and human liver fractions have shown that metabolic rates in humans are lower than those in the rat suggesting that thiamethoxam is unlikely to pose a hazard to humans exposed to this chemical at the low concentrations found in the environment or during its use as an insecticide.

Animals↗

Electromagnetic perspective on the operation of RF coils at 1.5-11.7 Tesla.

In this work experimental and numerical studies of the MR signal were performed at frequencies ranging from 64 MHz to 485 MHz, utilizing three different MRI coils: a single-strut transverse electromagnetic (TEM)-based coil, a TEM resonator, and a high-pass birdcage coil. The experimental analyses were conducted using 1.5 and 8 Tesla whole-body systems and volume RF head coils. The simulation data were obtained utilizing an in-house-developed finite difference time domain (FDTD) model. Pertinent data from the numerical and experimental setups were compared, and a remarkable agreement between the two methods was found that clearly demonstrates the effectiveness of the FDTD method when it is applied rigorously. The numerical and experimental studies demonstrate the complexity of the electromagnetic (EM) fields and their role in the MR signal. These studies also reveal unique similarities and differences between the transmit and receive field distributions at various field strengths. Finally, for ultra high-field operations, it was demonstrated mathematically, numerically, and experimentally that highly asymmetric inhomogeneous images can be acquired even for linear excitation, symmetrical load geometries, and symmetrical load positioning within the coil.

Electromagnetic Fields↗

Quality improvement nursing facilities: a nursing leadership perspective.

The purposes of this study were to characterize the state of quality improvement (QI) in nursing facilities and to identify barriers to improvement from nursing leaders' perspectives. The study employed a non-experimental descriptive design, using closed- and open-ended survey questions in a sample of 51 nursing facilities in a midwestern state. Only two of these facilities had active QI programs. Furthermore, turnover and limited training among these nursing leaders represented major barriers to rapid implementation of such programs. This study is consistent with earlier findings that QI programs are limited in nursing homes.

Aged↗

Preparation of alpha-alumina-supported mesoporous bentonite membranes for reverse osmosis desalination of aqueous solutions.

In this study, mesoporous bentonite clay membranes approximately 2 microm thick were prepared on porous alpha-alumina substrates by a sol-gel method. Nanosized clay particles were obtained from commercial Na-bentonite powders (Wyoming) by a process of sedimentation, washing, and freeze-drying. X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and nitrogen adsorption-desorption were employed for membrane characterization. It was found that the content of solids, concentration of polymer binder, and pH value of the clay colloidal suspension had critical influences on membrane formation during the dip-coating process. The membranes were tested for reverse osmosis separation of a 0.1 M NaCl solution. Both water permeability and Na(+) rejection rate of the supported membranes were comparable to those of the compacted thick membranes reported in the literature. However, due to the drastically reduced membrane thickness, water permeance and flux of the supported membranes were significantly higher than those of the compacted thick membranes. It was also observed that the calcination temperature played a critical role in determining structural stability in water and desalination performance of the clay membrane.

Journal Article↗

Assessing the health risks following environmental exposure to hexachlorobutadiene.

Hexachloro-1,3-butadiene (HCBD) has been reported to be toxic to the rat kidney in a 2 year study at doses higher than 0.2 mg/kg/day. The toxicity is known to be a consequence of the metabolism of HCBD by glutathione conjugation and the renal beta-lyase pathway. Neither toxicity data, nor data on the metabolism of HCBD, are available in humans. In the current work, the potential of HCBD to cause kidney damage in humans environmentally exposed to this chemical has been assessed quantitatively by comparing the key metabolic steps in rats and humans. To that end, the hepatic conjugation of HCBD with glutathione, the metabolism of the cysteine conjugate by renal beta-lyases and N-acetyltransferases, and the metabolism of the N-acetylcysteine conjugate by renal acylases has been compared in vitro in rat and human tissues. Rates for each metabolic step were lower in humans than in rats; 5-fold for glutathione conjugation, 3-fold for beta-lyase and 3.5-fold for N-acetyltransferase. Acylase activity could not be detected in human kidney cytosol. Use of these data in a physiologically based toxicokinetic model to quantify metabolism by the beta-lyase pathway demonstrated that metabolism in humans was an order of magnitude lower than that in rats. At the no effect level for kidney toxicity in the rat the concentration of beta-lyase metabolites was calculated by the model to be 137.7 mg/l. In humans the same concentration would be achieved following exposure to 1.41 ppm HCBD. This is in contrast to the figure of 0.6 ppb which is obtained when it is assumed that the risk is associated with the internal dose of HCBD itself rather than beta-lyase metabolites.

Adult↗

Differential binding of the AP-2 adaptor complex and PSD-95 to the C-terminus of the NMDA receptor subunit NR2B regulates surface expression.

NMDA receptor expression on the plasma membrane and at synaptic sites is tightly regulated. We have recently shown that the NMDA receptor subunit NR2B has an endocytic motif contained within its C-terminus. We now identify this motif as a consensus tyrosine-based motif (YEKL) and demonstrate that this sequence binds directly to the medium chain of the AP-2 adaptor, a protein complex that links internalized proteins to clathrin. Although the AP-2 binding site on NR2B is adjacent to the PSD-95 binding site, it is distinct, as mutation of tyrosine 1472 of the endocytic motif disrupts AP-2 binding but not binding to PSD-95. Internalization assays reveal that like PSD-95, both SAP97 and PSD-93 inhibit NR2B-mediated endocytosis. Furthermore, we find that co-expression of a PSD-95 mutant that is unable to cluster NMDA receptors also inhibits NR2B-mediated endocytosis. Together, these data demonstrate that AP-2 and PSD-95 bind to unique sites on the C-terminus of NR2B and have antagonistic functional consequences that are independent of the ability of the PSD-95 to cluster receptors on the plasma membrane.

Adaptor Protein Complex 2↗

Receptor induction and targeted drug delivery: a new antileukaemia strategy.

Strategic modalities of drug delivery have the potential to greatly improve the therapeutic efficacy of available drugs in acute myelogenous leukaemia (AML). Folate receptor (FR) type beta is selectively expressed on the surface of approximately 70% of AMLs. Increased FR-beta expression in these cells can be induced by all-trans retinoic acid (ATRA) and other retinoid compounds in the absence of terminal differentiation or cell growth inhibition. An apparent post-transcriptional modification prevents FR-beta in normal haematopoietic cells from binding folate, in contrast to AML cells. FR-beta may, therefore, be used as a target for the selective delivery of chemotherapeutic drugs to AML cells; this treatment modality appears to be particularly efficacious when administered in conjunction with retinoid-induction of FR-beta. FR-targeted liposomal drug delivery can also bypass the P-glycoprotein (P-gp)-mediated drug efflux pump commonly associated with multiple drug resistance in AML. The rationale and merits of this novel experimental treatment for AML and the current status of this research are provided.

Animals↗

Improved immunotherapy with a rapid allergen vaccination schedule: a study of 137 patients.

Rapid allergen vaccination (RAV) is the updated term for what was previously called rush immunotherapy and rapid desensitization. RAV offers several advantages over traditional immunotherapy--that is, conventional allergen vaccination (CAV)--in terms of faster efficacy, better compliance, and cost-effectiveness. We used a 3-hour RAV protocol to treat 137 allergy patients. All patients were premedicated with either prednisone or prednisolone and an H1 antihistamine. Following the RAV procedure, all patients resumed a CAV schedule. Only six patients (4.4%) experienced a mild systemic reaction to RAV, and five (3.6%) experienced a mild systemic reaction to CAV 14 to 77 days later. All six patients who reacted to RAV quickly responded to treatment--in most cases, subcutaneous epinephrine and/or nebulized albuterol--and were sent home after a short period of observation. Compliance rates at 3, 6, and 12 months were 96.4, 94.2, and 75.9%, respectively, which is an improvement over rates previously reported for patients undergoing CAV therapy. We conclude that the 3-hour RAV protocol can be safely and successfully administered. Patients who undergo RAV are more compliant with their subsequent CAV regimen than are patients who do not undergo RAV because signs of clinical efficacy manifest almost immediately and because RAV is associated with substantially lower rates of systemic reactions. Moreover, RAV is associated with less morbidity and less expense. Our findings should encourage physicians who treat allergy patients to give further consideration to using RAV.

Adolescent↗

The development of forestomach tumours in the mouse following exposure to 2-butoxyethanol by inhalation: studies on the mode of action and relevance to humans.

2-Butoxyethanol, a forestomach carcinogen in mice exposed by inhalation, has been shown to enter the forestomach as a result of grooming and ingestion of material condensed on the skin and fur during exposure. The material entering the stomach concentrates in the forestomach region and persists for at least 48 h post-exposure. Mice given single oral doses of either 2-butoxyethanol or 2-butoxyacetic acid, daily for 10 days, developed a marked hyperkeratosis in the forestomach. 2-Butoxyacetic acid was more potent than 2-butoxyethanol, the NOEL for the former being 50 mg/kg and for the latter, 150 mg/kg. Although a dose dependent increase in cell replication was also seen with both chemicals, the results were confounded by a high labelling rate in the controls. There was no evidence of significant binding of radiolabelled 2-butoxyethanol to proteins in stomach tissues. 2-Butoxyethanol was metabolised in vitro in both mouse and rat forestomach and glandular stomach fractions by alcohol dehydrogenases forming 2-butoxyacetaldehyde which was rapidly converted by aldehyde dehydrogenases to 2-butoxyacetic acid. There was a marked species difference in alcohol dehydrogenase activity between rats and mice with the maximum rates up to one order of magnitude greater in mouse than rat. The alcohol and aldehyde dehydrogenases were heavily concentrated in the stratified squamous epithelium of the forestomach of both rats and mice whereas in the glandular stomach the distribution was more diffuse. In human stomach both enzymes were evenly distributed throughout the epithelial cells of the mucosa. It is concluded that 2-butoxyethanol is ingested following inhalation exposure and concentrates in the forestomach where it is metabolised to 2-butoxyacetic acid which causes cellular damage, increased cell replication and hyperkeratosis. These changes are believed to lead to the tumours seen in mice exposed to 2-butoxyethanol for a lifetime. Differences in structure and enzyme distribution between the rodent and human stomach suggest that the responses seen in the mouse are unlikely to occur in humans.

Administration, Inhalation↗