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Biomedical subjects

J Miller

Publications and source records attributed to J Miller.

At least 109 records · Page 6Linked to original sources

Approach and issues relating to shield material design to protect astronauts from space radiation.

One major obstacle to human space exploration is the possible limitations imposed by the adverse effects of long-term exposure to the space environment. Even before human spaceflight began, the potentially brief exposure of astronauts to the very intense random solar energetic particle (SEP) events was of great concern. A new challenge appears in deep space exploration from exposure to the low-intensity heavy-ion flux of the galactic cosmic rays (GCR) since the missions are of long duration and the accumulated exposures can be high. Since aluminum (traditionally used in spacecraft to avoid potential radiation risks) leads to prohibitively expensive mission launch costs, alternative materials need to be explored. An overview of the materials related issues and their impact on human space exploration will be given.

Aluminum↗

The role of the dietitian in a multicenter clinical trial of dialysis therapy: the Hemodialysis (HEMO) Study.

The Hemodialysis (HEMO) Study is a randomized multicenter prospective clinical trial, supported by the National Institute of Diabetes, Digestive, and Kidney Diseases of the National Institutes of Health. The trial is designed to assess the effects of a standard versus higher dialysis dose and low versus high dialysis membrane flux on morbidity and mortality of chronic hemodialysis patients. The role of the dietitian in the HEMO Study is to support and maintain the nutritional status of randomized participants. To ensure participant safety, nutritional status is closely monitored by a variety of biochemical and participant-reported parameters. Serum albumin and equilibrated normalized protein catabolic rates are obtained monthly. Appetite assessment and dietary energy and protein intakes using a 2-day diet diary assisted recall are ascertained at baseline and on a yearly basis. Consumption of vitamins, minerals, and nutritional supplements, including oral enterals, tube feedings, and parenteral nutrition, is obtained at least once a year. In addition, anthropometry is performed at baseline and on a yearly basis. Prespecified changes in serum albumin level or body weight trigger action by the dietitian to prevent protein calorie malnutrition. The HEMO Study dietitians play a vital role in carrying out the nutrition program for the trial. The HEMO Study should provide important information about the natural history of the nutritional status of chronic hemodialysis patients and the impact of dialysis dose and dialysis membrane flux on these parameters.

Anthropometry↗

The designability of protein structures.

It has been noted that natural proteins adapt only a limited number of folds. Several researchers have investigated why and how nature has selected this small number of folds. Using simple models of protein folding, we demonstrate systematically that there is a "designability principle" behind nature's selection of protein folds. The designability of a structure (fold) is measured by the number of sequences that can design the structure--that is, sequences that possess the structure as their unique ground state. Structures differ drastically in terms of their designability. A small number of highly designable structures emerge with a number of associated sequences much larger than the average. These highly designable structures possess proteinlike secondary structures, motifs, and even tertiary symmetries. In addition, they are thermodynamically more stable and fold faster than other structures. These results suggest that protein structures are selected in nature because they are readily designed and stable against mutations, and that such a selection simultaneously leads to thermodynamic stability.

Amino Acid Motifs↗

Early development of the serotonergic and dopaminergic nervous system in Spisula solidissima (surf clam) larvae.

We have defined the development of the serotonergic and dopaminergic components of the central nervous system in the early Spisula solidissima (surf clam) embryo using HPLC and immunocytochemistry. HPLC analysis reveals norepinephrine, dopamine, and serotonin are present at 24 h post-fertilization. Immunocytochemistry shows that the serotonergic nervous system emerges during the late trochophore stage with the development of a single serotonergic cell, C/A1, in the cerebral/apical ganglion. After 48 h, a second serotonergic cell forms, C/A2, which is connected to C/A1 by two serotonergic processes, and a single serotonergic cell emerges in the visceral ganglion, V1. At 72 h, a new serotonergic cell body develops in the cerebral/apical ganglion, C/A3. After 96 h, the cerebral/apical ganglion and visceral ganglion are connected by a serotonergic process. Expression of the dopamine receptor, D2, begins by 24 h with a generalized expression in the region of the developing gut. D2 expression in the gut ceases by 48 h. At 48 h, a network of fibers forms dorsolateral to the mouth. By 72 h, D2 expressing projections emerge from this network.

Animals↗

Negotiating risks in context: a perspective on unprotected anal intercourse and barebacking among men who have sex with men--where do we go from here?

Recently, an alarming trend toward unprotected anal intercourse has emerged in men who have sex with men. A highly dangerous form of unprotected anal intercourse, barebacking--the deliberate and conscious choice to engage in anal sex without condoms knowing that there are risks involved--has received much attention in the gay press. This trend poses new challenges for HIV prevention. As the target population changes, prevention interventions must also evolve to remain effective. A review of the scientific literature on risk behaviors and the popular literature and websites devoted to barebacking suggests that many contextual factors influence the decision to engage in unprotected anal intercourse. This review examines the most salient contextual factors affecting risk behavior in gay/bisexual men. It also identifies four main cohorts and predominant contextual factors that appear to motivate unprotected anal intercourse in each. In answering the question "where do we go from here," we conclude that contextual issues must be addressed in hybrid prevention interventions that include harm reduction, motivational interviewing, and traditional approaches.

Anal Canal↗

The use of intravenous tacrolimus and mycophenolate mofetil as induction and maintenance immunosuppression in simultaneous pancreas--kidney recipients with previous transplants.

Clinical trials using quadruple immunosuppression that include the combination of tacrolimus (TAC) and mycophenolate mofetil (MMF) have been shown to reduce the incidence of acute rejection episodes in simultaneous pancreas-kidney (SPK) transplantation. In attempting to obtain a low rejection rate without antibody induction therapy, we proceeded with the combination of TAC intravenous (i.v.), MMF, and steroids as induction therapy and as primary immunosuppression for recipients with previous transplants. In this study, we analyzed 10 patients who received previous transplants, treated with low-dose TAC i.v. as induction therapy. Group A consisted of 6 patients with previous transplants that underwent SPK and group B consisted of four recipients with previous SPK that underwent cadaveric kidney transplants. For group A, the previous transplants were: living related kidney (LRK) followed by islet cell (IC) transplant (n=2), LRK transplant (n=1), cadaver kidney (CAD) and IC transplant (n=1), SPK (n=1), and three previous CAD kidney transplants (n=1). In group A, all six kidneys were lost due to recurrent diabetic nephropathy, IC possibly to rejection, and the pancreas due to thrombosis. In group B with previous SPK transplants, three recipients lost their kidney to chronic rejection and one to long-term use of a nephrotoxic antibiotic. Currently, in all group A and B patients, the kidney and the pancreas are functioning, although 1 patient in group A developed type 2 diabetes (normal fasting C-peptide). Two patients in group A developed three rejection episodes that responded to steroid treatment. The results indicate the TAC i.v. in combination with oral TAC, MMF, and steroids offer effective induction therapy in patients with previous transplants.

Adult↗

Scaling VO(2) peak in obese and non-obese girls.

OBJECTIVE: The conventional ratio method (milliliters O(2) per mass) typically is used to express VO(2) peak. The goal of the current study was to compare VO(2) peak of obese girls with normal-weight girls by ratio and allometric scaling methods. RESEARCH METHODS AND PROCEDURES: We compared VO(2) peak by ratio and allometric methods in 46 obese and 47 normal-weight girls. Indirect calorimetry was used to measure VO(2) peak during either treadmill running or walking. Regression analysis was used to determine coefficients for mass and stature for each group with ANOVA used to compare data between groups. RESULTS: The obese girls were taller and had higher values of body fatness (p < or = 0.05). Absolute VO(2) peak (liters per minute) was similar between groups; however VO(2) peak relative to mass was 50% lower (p < or = 0.05) in the obese girls. When VO(2) peak (milliliters per minute per kilogram) and mass were correlated, r = -0.48 was found in the obese group. Allometric scaling of logarithmic transformed stature and mass reduced this to r = -0.002, thus eliminating the bias associated with the ratio method. Adjusting VO(2) peak allometrically scaled for mass, stature, and the combination of mass and stature reduced the difference between groups from 50% (ratio method) to 10% to 11% (p < or = 0.05) with higher values found in the normal-weight girls. DISCUSSION: These results demonstrate the bias associated with the ratio method when comparing VO(2) peak in obese girls with VO(2) peak in normal-weight girls. Allometric scaling eliminated the bias and thus may reflect a truer comparative response.

Adolescent↗

Atrichia caused by mutations in the vitamin D receptor gene is a phenocopy of generalized atrichia caused by mutations in the hairless gene.

Generalized atrichia with papules is a rare disorder characterized by loss of hair shortly after birth and development of cutaneous cysts. Mutations in the hairless gene (HR) cause this phenotype in both mouse and human. Here we present a case of atrichia with papules in a patient with a normal HAIRLESS gene but with mutations in both alleles of the VITAMIN D RECEPTOR. The patient exhibited vitamin D resistant rickets, which was confirmed by an absent response of her fibroblasts to 1,25-dihydroxyvitamin D3 in vitro. Similar to individuals with HAIRLESS mutations, her skin showed an absence of normal hair follicles and the presence of follicular remnants and cysts. The cyst epithelium contained keratin-15- and keratin-17-positive cells suggesting derivation from the hair follicle bulge and the presence of epithelial stem cells. Although hair loss has been reported in association with hereditary vitamin D resistant rickets, we now characterize this alopecia as clinically and pathologically indistinguishable from generalized atrichia with papules, which was previously thought to be caused only by mutations in HAIRLESS. These findings suggest that VDR and HR, which are both zinc finger proteins, may be in the same genetic pathway that controls postnatal cycling of the hair follicle.

Alopecia↗

Increased endothelin-1 and decreased adrenomedullin gene expression in the stenotic tissue of congenital pelvi-ureteric junction obstruction in children.

OBJECTIVES: To test the hypothesis that the gene expression of endothelin-1 and adrenomedullin may be altered in stenotic tissues of patients with congenital hydronephrosis caused by pelvi-ureteric junction (PUJ) obstruction. MATERIALS AND METHODS: Using real-time reverse transcription-polymerase chain reaction, mRNA of smooth muscle-constricting endothelin-1 and of smooth muscle-relaxing adrenomedullin was quantified in tissue specimens of 20 patients with PUJ obstruction (mean age 5.1 years, SD 7.0) and of 21 controls with normal PUJs (mean age 23.5 years, SD 24.2). RESULTS: The amount of endothelin-1 mRNA in stenotic specimens was higher than in the controls, indicated by significantly lower threshold cycles (Ct values) in real-time PCR for the target gene in the obstructive tissue, with mean (SD) values of 24.9 (1.6) and 26.0 (2.1) (P < 0.05), respectively. The endothelin-1/CD31 ratio was significantly higher in the patients (P < 0.05) than in controls. In addition, adrenomedullin gene expression in the obstructed junctions was significantly lower than in normal junctions, with higher Ct values for the patient group of 26.7 (1.6) vs 25.2 (1.8) (P < 0.05) and lower adrenomedullin mRNA when standardized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (P < 0.05), CD31 (P < 0.01) and smooth muscle alpha-actin mRNA (P < 0.01). The two groups showed no significant differences for GAPDH and CD31 mRNA content, whereas there was about twice as much alpha-actin mRNA in stenotic tissues than in unaffected PUJs, shown by the lower Ct values for the patient group of 16.9 (2.0) vs 17.9 (2.6) (P < 0.05). Furthermore, endothelin-1, adrenomedullin and alpha-actin mRNA amounts were independent of age. CONCLUSION: Taken together these results provide evidence that the production of autocrine/paracrine acting endothelin-1 and adrenomedullin is altered in tissues of patients with genuine PUJ obstruction, and may be involved in the pathogenesis of congenital hydronephrosis.

Adolescent↗

Comparison of DATs using traditional tube agglutination to gel column and affinity column procedures.

BACKGROUND: Detection of immunoglobulin or complement bound to RBCs by using the DAT is valuable in the diagnosis of immune-mediated hemolytic anemia. Traditionally, the DAT has been performed by tube agglutination using anti-IgG or anti-C3d. The purpose of this study was to compare the tube agglutination DAT to gel microcolumn, affinity microcolumn, and flow cytometric DATs on RBCs coated in vitro and on patient RBC samples. STUDY DESIGN AND METHODS: RBCs from 84 patients were assessed by tube agglutination DAT, one gel microcolumn DAT, and two affinity microcolumn DATs. One affinity microcolumn assay was unmodified and one was modified by the addition of polyspecific antiglobulin or anti-IgG as a secondary antibody. RBCs from 15 of the 84 patients underwent analysis by flow cytometry with fluorescence-labeled anti-IgG. The assays were also compared by using D+ RBCs sensitized with serially adjusted concentrations of anti-D. RESULTS: Both tube agglutination and gel microcolumn DATs were positive in 49 patient samples; both assays were negative in 20 samples, and the results were discordant in 15. Gel microcolumn DATs were more likely than were tube agglutination DATs to detect IgG on RBCs. Affinity microcolumn DATs were less likely than gel microcolumn or tube agglutination DATs to detect IgG on RBCs. Flow cytometry results were the same as gel microcolumn results in 12 of 15 patient samples and the same as tube agglutination results in 13 of 15. Tube agglutination and both affinity microcolumn assays reacted with RBCs coated with anti-D that was diluted 1-in-100. The gel microcolumn and flow cytometry assays reacted with RBCs coated with anti-D diluted 1-in-400. There was no correlation between tube agglutination and gel microcolumn DATs in detecting bound C3d. CONCLUSION: Detection of IgG bound to RBCs was not consistent with the methods described. Gel microcolumn DATs were more sensitive than tube agglutination and affinity microcolumn DATs. Given the varied results of these assays, reference laboratories should not rely on a single method for DATs. More comprehensive testing should be performed when the tube agglutination DAT is negative in a patient with suspected immune-mediated hemolytic anemia. Further comparisons are necessary to determine the proficiency of flow cytometric assays.

Agglutination Tests↗

Accredited work-based learning: an approach for collaboration between higher education and practice.

This article discusses the experience of creating a programme of accredited work based learning (AWBL) for emergency nurse practitioners (ENPs) who work in an Accident and Emergency (A&E) Department in the North East of England. The initiative highlighted the challenges of collaboration with purchasers of education and with professional colleagues, other than nurses. Accredited work-based learning was seen to be an appropriate means of supporting ENP role development. Some of the drivers of the development were: the need for a rapid response to wide ranging changes in the health service; the need to ensure rigour in the quality of both education and health care; to enable participants to engage in role development with appropriate skills, confidence and competence; and to ensure that the learning programme had parity in its design with conventional university based learning. The aim was to collaborate in the creation of learning which was relevant to the Trust's drive to improve patient care which accommodated the nurses' common and individual learning needs and offered academically recognized learning opportunities in tune with the post-Dearing ethos in higher education. This aim was reached and included a great deal of learning on the part of the collaborating partners.

Accreditation↗

Correlation of quantitative protein measurements in 8-, 12-, and 24-hour urine samples for the diagnosis of preeclampsia.

OBJECTIVE: The purpose of this study is to determine if a patient's 8- and/or 12-hour urine total protein values correlate with the 24- hour value to confirm the diagnosis of preeclampsia. STUDY DESIGN: The study population included 65 patients with hypertensive disorders of pregnancy. Patients' urine was collected over 24 hours with the first 8 hours, next 4 hours, and remaining 12 hours collected in separate containers. The urine volume, and total protein and creatinine levels were measured in the 8-, 12-, and 24-hour samples. The 8- and 12-hour results were compared to the 24-hour results by use of simple regression analysis. RESULTS: Of the 65 patients, 20 had no proteinuria, 37 had mild proteinuria, and 8 had severe proteinuria. The results of the 8- hour sample correlated with those of the 24-hour sample for patients with mild (P <.001) and severe disease (P =.003). The 12-hour sample correlated with the 24-hour sample for patients with no disease (P <.001), mild proteinuria (P <.001), and severe proteinuria (P =.0003). CONCLUSION: Total protein values for 8- and 12-hour urine samples correlate positively with values for 24-hour samples for patients with proteinuria. The results for 12- and 24-hour samples correlate for patients without proteinuria.

Adult↗

Long-term consequences of severe closed head injury on episodic memory.

This is the first systematic investigation of the very long-term effects of severe closed head injury (CHI) on objective measures of memory, and the first to employ both a normal control group and an 'other injury' control group consisting of spinal cord injury (SCI) patients. The CHI group displayed significantly poorer performance on every memory measure, and the effect sizes were large. This impairment in episodic memory is neither due to pre-injury nor post-injury differences between CHI and normal control subjects because the same differences were found when the CHI group was compared to a group of SCI patients. The findings demonstrate severe impairment in learning and retention many years after sustaining a severe CHI, which is likely in part due to the bilateral hippocampal damage shown in neuropathological studies. This life-long memory impairment needs to be addressed by community service programs.

Adult↗