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Biomedical subjects

K L Miller

Publications and source records attributed to K L Miller.

At least 19 recordsLinked to original sources

Leginon: a system for fully automated acquisition of 1000 electron micrographs a day.

We have developed a system to automatically acquire large numbers of acceptable quality images from specimens of negatively stained catalase, a biological protein which forms crystals. In this paper we will describe the details of the system architecture and analyze the performance of the system as compared to a human operator. The ultimate goal of the system if to automate the process of acquiring cryo-electron micrographs.

Automation

Variations in dose to the extremities of vascular/interventional radiologists.

An evaluation was performed to determine the distribution of radiation dose received by vascular/interventional radiologists, hence forth called radiologists, to their hands and arms during interventional radiology procedures. During 87 patient procedures, measurements were made using thermoluminescent dosimeters to determine the distribution of dose to the hands and forearms. Measurements were made on a finger, the palm, wrist, elbow, and the mid-humerus of both hands and arms. Results suggested a non-uniformity of dose with the maximum dose being measured on the left hypothenar (fleshy side of the palm). The left hand receives a higher dose than the right hand due to positioning of the radiologist with respect to the patient.

Arm

Interleukin-6 production by human neutrophils after Fc-receptor cross-linking or exposure to granulocyte colony-stimulating factor.

Polymorphonuclear neutrophils (PMNs) are essential effector cells in host defense and tissue inflammatory responses. These responses may be initiated after cross-linking of cell surface Fc receptors that bind the constant portion of IgG (FcgammaR). We evaluated the effect of cross-linking FcgammaRI or FcgammaRII on interleukin-6 (IL-6) production by purified PMNs from normal donors or from patients being treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF). In PMNs from normal donors, IL-6 mRNA was detected by reverse transcriptase-polymerase chain reaction only after FcgammaRI or FcgammaRII cross-linking. We also found that IL-6 mRNA could be detected in PMNs after either in vitro or in vivo rhG-CSF treatment in the absence of FcgammaR cross-linking. IL-6 protein was found to be produced intracellularly and secreted by PMNs after cross-linking FcgammaRI or FcgammaRII or after rhG-CSF stimulation. Cross-linking FcgammaRI or FcgammaRII on PMNs from patients treated with rhG-CSF resulted in a synergistic increase in IL-6 secretion. Upregulation of IL-6 production by PMNs after rhG-CSF treatment may contribute to a clinical engraftment syndrome that occurs during periods of rapid increase in PMN numbers in patients receiving rhG-CSF.

Gene Expression Regulation

Molecular characterization of six variant Fcgamma receptor class I (CD64) transcripts.

In humans, three distinct but closely related classes of receptors that bind the Fc portion of IgG (FcgammaRI, II and III) have been identified. FcgammaRI can bind monomeric IgG with high affinity and has a unique third extracellular domain (EC3). Three very similar genes have been characterized for FcgammaRI (A, B, C). Although the sequences are remarkably similar, a number of coding-region differences discriminate between the genes and amongst their transcripts. Six distinct FcgammaRI transcripts were analysed. Three transcripts, one from each gene, contain all six exons. Only the gene A transcript appears to encode a bona fide high affinity receptor, a three Ig-domain membrane spanning receptor that can bind monomeric IgG. Stop codons in the EC3 domains of the gene B and gene C isoforms would be predicted to generate secreted receptors. Three transcripts are alternatively spliced isoforms, one from gene A and two from gene B. One gene B transcript encodes a two Ig-domain transmembrane receptor which has structural characteristics of a low affinity FcgammaR.

Animals

Contrast venography in young haemophiliacs with implantable central venous access devices.

To assess the risk of deep vein thrombosis in haemophiliacs with long-term central venous catheters, we studied haemophiliacs followed at our centre with implantable venous access devices (ports) in place for > 6 months. Medical records were reviewed for a history of catheter-related complications. Each patient was examined for physical stigmata of thrombosis. Patency of the vessels was evaluated by contrast venography. Of 21 males with ports, 19 had factor VIII deficiency and two factor IX deficiency. Nineteen ports were evaluable (i.e. were in place for > 6 months). Seventeen patients have their original ports in place; two ports were replaced for mechanical dysfunction (1) and recurrent infection (1). Difficulty withdrawing or infusing occurred with three ports, two of which were cleared with urokinase. Physical examination was normal on all 19 patients. Venograms were performed in 13 of 19 patients. Parents of the remaining six patients refused venography because of the need for peripheral venipuncture. One patient had a small nonocclusive thrombus on the same side as his functioning catheter, and another had minimal narrowing of the subclavian vein at the site of a prior catheter. The overall prevalence of clinically relevant upper venous system thrombosis identifiable by contrast venography was zero (95% CI, 0-23%). We conclude that haemophiliacs do not have as high a risk of thrombosis as other populations of patients with central venous catheters. The theoretical risk of thrombosis should not preclude use of central venous catheters in patients with haemophilia.

Adolescent

Diagnosis and radioablation treatment of toxic multinodular goiter in a hemodialysis patient.

Toxic multinodular goiter is rare in hemodialysis patients. In addition, establishing the diagnosis of hyperthyroidism in the elderly patient with renal failure is difficult because abnormal thyroid function tests can erroneously be attributed to euthyroid sick syndrome. Treatment of hyperthyroidism in dialysis patients by radioiodine ablation involves careful calculation of 131I dose, determination of interval between 131I administration and its removal by hemodialysis, and minimization of radiation hazards during dialytic removal of 131I. We described the clinical presentation of an elderly dialysis patient with toxic multinodular goiter and discussed our diagnostic and therapeutic approaches. The patient's recovery after 131I ablation was complete and uneventful.

Aged

Chloroform-induced olfactory mucosal degeneration and osseous ethmoid hyperplasia are not associated with olfactory deficits in Fischer 344 rats.

Adult female F-344 rats were trained (avoidance rate > 70%) over four days with a coupled tone- (n = 10 rats/dose) or 2 ppm acetaldehyde-cued (n = 6 rats/dose) foot shock paradigm. Rats were gavaged with chloroform dissolved in corn oil for 5 days/week for 3 week at 0 or 400 (tone-cued) or 0, 34, 100, or 400 (odor-cued) mg/kg body weight/day. Tone-cued response was reevaluated 6, 16, and 38 days after the first chloroform dose (day 1). Olfaction was assessed on days 6-7, 20-21, and 41-42 using 2 or 0.0002 ppm acetaldehyde. Nasal histopathology (n = 4-5 rats/dose) was assessed on days 6, 20, and 42. Significantly decreased body weights were observed following a single 100 or 400 mg/kg chloroform dose. Body weights in the 400 mg/kg/day chloroform group remained depressed for 17 days. Histopathology revealed degenerative changes in olfactory mucosa and underlying ethmoid turbinate bones that were essentially identical in nature and severity, including dose-response and progression, to those reported previously for chloroform gavage (Larson et al., Food Chem. Toxicol., 1995;33:443 456). At all dose level and sacrifice timepoints, however, regions of morphologically normal olfactory mucosa were present, especially in dorsal medial and ventral lateral regions of the nose. Neither odor- nor tone-cued avoidance behaviors were affected, indicating that even fairly severe and extensive chloroform-induced olfactory mucosal degeneration is not associated with a detectable olfactory deficit in rats.

Animals

Pelvic floor electrical stimulation for the treatment of urge and mixed urinary incontinence in women.

OBJECTIVES: To determine the efficacy of daily or every-other-day electrical stimulation in treating detrusor instability (urge) or urge plus genuine stress (mixed) urinary incontinence in women. METHODS: A multicenter, prospective, nonrandomized study enrolled subjects with urge and mixed urinary incontinence assigned to daily or every-other-day treatments (15 minutes twice daily) using pelvic floor stimulation. Outcome measures assessed were (1) leakage episodes, nocturnal episodes, voiding frequency, total voids, and pad count, and (2) patient subjective assessment and quality of life. RESULTS: Seventy-two subjects were enrolled. Sixty-eight subjects completed the 20-week protocol: 33 treated daily and 35 treated every other day. The entire study group (n = 68) experienced a significant decrease in total leaks (P < 0.001), nocturnal episodes (P = 0.001), pad count (P = 0.002), and total voids (P = 0.003) and on visual analog scales. Sixty-nine percent (n = 46) of subjects with urge or mixed incontinence were cured or improved by at least 50%, with 28% (n = 19) being cured. There were no significant differences between daily and every-other-day users. Nonresponse was correlated with number of previous therapies (P < 0.001) and number of vaginal deliveries (P = 0.007). Overall, subjects were 93% compliant with device use, and 72% (n = 47) were satisfied with the therapy. CONCLUSIONS: Twenty weeks of pelvic floor electrical stimulation therapy is effective in treating urge and mixed urinary incontinence, regardless of daily or every-other-day treatments.

Adult

Symptom management outcomes. Do they reflect variations in care delivery systems?

OBJECTIVES: Symptom management is increasingly recognized as a critical element of patient care, particularly in managing chronic illness. However, research on outcomes related to symptom management is in its infancy, except for the symptom of pain. This symptom was therefore chosen as a prototype to review the state of the science regarding relations between organizational variables and symptom management outcomes and to illustrate the issues regardless of the symptom managed. This article discusses pain outcome measures appropriate for acute and cancer pain, proposes attributes of the care delivery system that may affect outcome measures, and identifies challenges associated with this type of research. METHODS: Review of quality assurance studies raises issues concerning the adequacy of currently used outcomes for pain and satisfaction with pain management. Although considerable effort has been expended in developing pain measurement in adults and children, critical issues for examining pain management outcomes include deciding what perspectives should be used as the most valid indicator of the pain outcome and when the measures should be obtained. RESULTS: Critical concerns are raised about the measure of satisfaction with pain management and its appropriateness as the end-result outcome. A key issue is whether respondents actually disentangle satisfaction with pain management from satisfaction with other aspects of care, including caring dispositions of health-care providers. Finally, the question is raised: Are pain outcomes affected by organizational context? CONCLUSIONS: Although the answer to this question is unknown, a few research studies suggest that organizational context is likely to influence pain outcomes. It is clear, however, from ongoing work that until several conceptual, methodological, and analytic challenges are resolved, research is unlikely to capture the influence of variations in care delivery systems on symptom management outcomes.

Adult

Operating on the elderly woman--what are her special needs?

Current studies verify the safety of surgery in the elderly. Delirium is a costly complication, but its incidence and severity can be reduced by pre- and postoperative interventions. Avoidance of even mild hypothermia has now been shown to reduce cardiovascular morbidity. New information available on the cardiovascular response of elderly patients to laparoscopic surgery highlights the importance of avoiding preoperative dehydration. Proper pain management minimizes complications and promotes recovery.

Aged

A novel role for the Fc receptor gamma subunit: enhancement of Fc gamma R ligand affinity.

The Fc receptors (FcR), which belong to the immunoglobulin (Ig) superfamily, bind to specific Ig isotypes with varying affinities triggering complex immune defense responses. Several of the FcR that lack signaling motifs in their cytoplasmic domains rely on associated subunits to transmit signals. Two classes of FcR that bind the Fc portion of IgG, Fc gamma RI, and Fc gamma RIIIa associate with a subunit shared among several FcR, the gamma chain, which is involved in receptor expression and signal transduction. In this report, we propose that a novel role for gamma chain is to enhance the affinity of Fc gamma R for ligand. Our findings demonstrate that Fc gamma RI requires gamma -chain association to attain high affinity binding for monomeric IgG, and suggest that the intermediate binding affinity of the Fc gamma RIIIa isoform results from its association with gamma chain. The affinity increase conferred by gamma chain appears to be mediated through the transmembrane domain of the Fc gamma R, with no requirement for the cytoplasmic domain of the receptor.

3T3 Cells

Pelvic floor electrical stimulation: a comparison of daily and every-other-day therapy for genuine stress incontinence.

OBJECTIVES: To compare the effectiveness of daily and every-other-day electrical stimulation in treating genuine stress incontinence. METHODS: Subjects with genuine stress incontinence were enrolled in a multicenter, prospective, nonrandomized study and underwent daily or every-other-day pelvic floor stimulation treatments for 15 minutes twice a day. Outcome measures assessed were (1) leakage episodes and pad count; (2) leakage amount, and (3) subject subjective assessment and quality of life. Thirteen subjects treated daily and 15 treated every other day completed the 20-week protocol. One-year follow-up data were available for 21 subjects. RESULTS: No significant differences in primary outcome variables were found between the groups. Subjects treated every other day had significant decreases in total leakage episodes (P = 0.04), pad count (P = 0.04), total voids (P = 0.02), and visual analog scale scores, with stress incontinence cured or improved by 50% in 73% (n = 11). Subjects treated every day had significant decreases in urge episodes (P = 0.03), pad count (P = 0.05), and visual analog scale scores, with 62% (n = 8) cured or improved by 50%. Compliance was higher for subjects treated every other day (P = 0.05). Satisfaction with therapy was 75% (n = 10) for daily treatment and 77% (n = 12) for every-other-day treatment. At 1 year, 70% (n = 7) of subjects who continued device use maintained their cure or improvement status. CONCLUSIONS: Both daily and every-other-day therapy with pelvic floor electrical stimulation are effective in treating genuine stress incontinence. Subjects who continue device use maintain a higher curve or improvement rate.

Electric Stimulation

Self-perceptions of preschool children with spina bifida.

The purpose of this study was to compare self-perceptions of 21 preschoolers with spina bifida with those of 21 physically able preschoolers. Each child was asked to draw a self-portrait, fill in the most important body parts on an outline of a child, complete the Pictorial Scale of Perceived Competence and Social Acceptance for Young Children, and rate feelings about self, family, peers, and health care professionals. The spina bifida group drew significantly fewer legs, feet, and trunks than physically able children. The preschoolers with spina bifida rated themselves as significantly different on physical and cognitive competence but not on maternal or peer acceptance. Clinical nursing implications of these data are discussed.

Body Image

Hormone replacement therapy in the elderly.

Hormone replacement therapy improves the quality of life and prolongs life for many elderly women, whether it is initiated at menopause or much later. Counseling about hormone replacement therapy should be given to all postmenopausal women. Patients should be advised that estrogen will lower the chances of death and disability from cardiovascular disease and osteoporosis. Those with low bone density or risks for cardiovascular disease, including smoking and hypertension, will benefit more than those without. Older age may predispose a woman to the carcinogenic potential of estrogen. But this should be placed in statistical perspective for the patient, with estrogen's benefit still clearly outweighing the risk. By evaluating her personal history and attitudes, the physician should help the patient decide if the potential benefit is worth either the risk or the inconvenience of side effects. Although the available data bespeak the general advantages of estrogen replacement, optimum dose, type of estrogen, time of initiation, and duration of therapy need further study in the geriatric population.

Aged

Diabetes insipidus.

Diabetes insipidus (DI), an acute or chronic condition, results from either of two situations: An inadequate secretion of antidiuretic hormone (ADH) from the posterior pituitary gland or an insufficient renal response to adequate levels of ADH. Characterized by massive urinary output despite progressive serum hyperosmolality, hypernatremia, and dehydration, DI can be life-threatening if not promptly diagnosed and appropriately managed. Individuals with renal disease, surgical patients, and persons with cerebral trauma are at risk to develop this condition.

Acute Disease

Evaluating a pediatric pain management research utilization program.

Research-based pain assessment and management innovations are not fully utilized in clinical nursing practice. Thus children continue to suffer despite strategies that could eliminate or significantly reduce their pain. An educational program was developed and implemented to integrate state-of-the-art pain assessment and management strategies into the clinical practice of pediatric nurses. This article reports on evaluation of the research utilization process during development and implementation of the program. The program included formal classes, development of instruments for pain assessment and documentation, ongoing consultation on pain management strategies, and designation of a unit-based staff nurse liaison. Findings illuminated the process through which nursing staff on one unit came to learn about new ideas, try those ideas in their clinical practice, re-invent certain strategies to better meet their needs, and, ultimately, to adopt innovations deemed helpful in their work.

Adult