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Biomedical subjects

J Light

Publications and source records attributed to J Light.

At least 19 recordsLinked to original sources

Randomized trial of tacrolimus plus mycophenolate mofetil or azathioprine versus cyclosporine oral solution (modified) plus mycophenolate mofetil after cadaveric kidney transplantation: results at 2 years.

BACKGROUND: A previous report described the 1-year results of a prospective, randomized trial designed to investigate the optimal combination of immunosuppressants in kidney transplantation. Recipients of first cadaveric kidney allografts were treated with tacrolimus+mycophenolate mofetil (MMF), cyclosporine oral solution (modified) (CsA)+MMF, or tacrolimus+azathioprine (AZA). Results at 1 year revealed that optimal efficacy and safety were achieved with a regimen containing tacrolimus+MMF. The present report describes results at 2 years. METHODS: Two hundred twenty-three recipients of first cadaveric kidney allografts were randomized to receive tacrolimus+MMF, CsA+MMF, or tacrolimus+AZA. All regimens contained corticosteroids, and antibody induction was used only in patients who experienced delayed graft function. Patients were followed up for 2 years. RESULTS: The results at 2 years corroborate and extend the findings of the previous report. Patients randomized to either treatment arm containing tacrolimus experienced improved kidney function. New-onset insulin dependence remained in four, three, and four patients in the tacrolimus+MMF, CsA+MMF, and tacrolimus+AZA treatment arms, respectively. Furthermore, patients with delayed graft function/acute tubular necrosis who were treated with tacrolimus+MMF experienced a 23% increase in allograft survival compared with patients receiving CsA+MMF (P=0.06). Patients randomized to tacrolimus+MMF received significantly lower doses of MMF compared with those administered CsA+MMF. CONCLUSIONS: All three immunosuppressive regi-mens provided excellent safety and efficacy. How-ever, the best results overall were achieved with tacrolimus+MMF. The combination may provide particular benefit to kidney allograft recipients who develop delayed graft function/acute tubular necrosis. Renal function at 2 years was better in the tacrolimus treatment groups compared with the CsA group.

Administration, Oral↗

Health-related quality of life among patients with facial acne -- assessment of a new acne-specific questionnaire.

The psychosocial effects of facial acne are well accepted but until recently few validated instruments existed which were suitable for use in clinical trials. The aim of this study was to assess measurement characteristics (reproducibility, correlation with acne severity, and sensitivity to detect change after acne therapy) of a new acne-specific quality of life instrument, the Acne-QoL. We found that the Acne-QoL is reliable, valid and able to distinguish differences across severity groups and improvement over 16 weeks of standard therapy. The use of the Acne-QoL should aid physicians in understanding the impact of facial acne on young adults, and may be useful in assessing therapeutic effects in acne clinical trials.

Acne Vulgaris↗

The dental prosthesis used for intraoral muscle therapy in the rehabilitation of the stroke patient. A preliminary research study.

The dentist can maximize the oral rehabilitation of the stroke patient's weak or paralyzed oral musculature, resulting in dysfunctional speech, swallowing and deglutition, with the use of palatal lift and palatal augmentation prostheses. The study described here evaluates functional changes using these prostheses for three post-stroke patients with left hemiparesis. Clinical tests indicated decreased nasal emission and hypernasality, and improved speech articulation. Videofluoroscopy evaluation showed improvement in the oral phase of swallowing. Patient self-assessment indicated improved satisfaction with treatment.

Adult↗

Randomized trial of tacrolimus (Prograf) in combination with azathioprine or mycophenolate mofetil versus cyclosporine (Neoral) with mycophenolate mofetil after cadaveric kidney transplantation.

BACKGROUND: Our clinical trial was designed to investigate the optimal combination of immunosuppressants for renal transplantation. METHODS: A randomized three-arm, parallel group, open label, prospective study was performed at 15 North American centers to compare three immunosuppressive regimens: tacrolimus + azathioprine (AZA) versus cyclosporine (Neoral) + mycophenolate mofetil (MMF) versus tacrolimus + MMF. All patients were first cadaveric kidney transplants receiving the same maintenance corticosteroid regimen. Only patients with delayed graft function (32%) received antilymphocyte induction. A total of 223 patients were randomized, transplanted, and followed for 1 year. RESULTS: There were no significant differences in baseline demography between the three treatment groups. At 1 year the results are as follows: acute rejection 17% (95% confidence interval 9%, 26%) in tacrolimus + AZA; 20% (confidence interval 11%, 29%) in cyclosporine + MMF; and 15% (confidence interval 7%, 24%) in tacrolimus + MMF. The incidence of steroid resistant rejection requiring antilymphocyte therapy was 12% in the tacrolimus + AZA group, 11% in the cyclosporine + MMF group, and 4% in the tacrolimus + MMF group. There were no significant differences in overall patient or graft survival. Tacrolimus-treated patients had a lower incidence of hyperlipidemia through 6 months posttransplant. The incidence of posttransplant diabetes mellitus requiring insulin was 14% in the tacrolimus + AZA group, 7% in the cyclosporine + MMF and 7% in the tacrolimus + MMF groups. CONCLUSIONS: All regimens yielded similar acute rejection rates and graft survival, but the tacrolimus + MMF regimen was associated with the lowest rate of steroid resistant rejection requiring antilymphocyte therapy.

Adult↗

Immunolocalization of 5alpha-reductase isozymes in acne lesions and normal skin.

BACKGROUND: Dihydrotestosterone mediates androgen-dependent diseases, such as acne, hirsutism, and androgenetic alopecia. This hormone is produced from testosterone by the 5alpha-reductase enzyme. There are 2 isozymes of 5alpha-reductase (types 1 and 2) that differ in their localization within the body and even within the skin. Activity of the type 1 isozyme predominates in sebaceous glands, where it may be involved in regulation of sebum production. Since specific inhibition of 5alpha-reductase type 1 may represent a novel therapeutic approach to acne, it is important to define the localization of these isozymes in normal sebaceous follicles and acne lesions. OBSERVATIONS: Skin biopsy specimens were obtained from the backs of 11 subjects: 8 with acne and 3 without acne. Sections of normal follicles, open comedones, closed comedones, and inflammatory lesions were incubated with antibodies to types 1 and 2 5alpha-reductase. In all samples, the type 1 antibody localized specifically to sebaceous glands, and the type 2 antibody localized to the companion layer of the hair follicle (the innermost layer of the outer root sheath) and granular layer of the epidermis. Localization of the type 2 isozyme was also noted within the walls of open and closed comedones and in endothelial cells from sections of inflammatory lesions. CONCLUSIONS: The immunolocalization of 5alpha-reductase isozymes in normal sebaceous follicles and acne follicles is similar to the pattern described in terminal hair follicles and corresponds with the findings of biochemical studies that have demonstrated predominance of type 1 activity in sebaceous glands. The function of type 2 5alpha-reductase in comedones or endothelial cells in inflammatory lesions is unknown.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Backbone dynamics of a short PU.1 ETS domain.

The resonance assignments, secondary structure and backbone dynamics of the ETS domain of the transcription factor PU.1 have been determined for the free protein in solution by NMR spectroscopy. The secondary structure for the free ETS domain is similar to that observed in the crystal structure of the PU.1 protein complexed with DNA, except that helix alpha2 and recognition helix alpha3 are shorter for the free protein in solution. Backbone dynamics of the protein have been examined using amide hydrogen-deuterium exchange and (15)N laboratory-frame spin relaxation measurements. A significant probability of local unfolding of helix alpha2, which precedes the loop-helix-loop DNA recognition domain, is inferred from the very fast hydrogen-deuterium exchange for amide protons in this helix. The (15)N relaxation measurements indicate that the protein is partially oligomerized at a concentration of 2.5 mM, but monomeric at a concentration of 0.3 mM. The (15)N relaxation data for the low concentration sample were interpreted, using the model-free formalism, to provide insight into protein dynamics on picosecond-nanosecond and microsecond-millisecond time scales. High flexibility of the protein backbone is observed for the residues in the loop between alpha2 and alpha3. This loop is variable in length and in structure within the class of winged helix proteins and is partially responsible for binding to DNA. The dynamic properties observed for alpha2, alpha3 and the intervening loop may indicate a correlation between protein plasticity in particular structural elements and recognition of specific DNA sequences.

Amino Acid Motifs↗

Mutation analysis of the Pip interaction domain reveals critical residues for protein-protein interactions.

The PU.1 interaction partner (Pip) is a member of the interferon regulatory factor family that regulates gene expression through heterodimerization with the ETS transcription factor PU.1. Binding of Pip alone to DNA is weak, and usually it is recruited by phosphorylated PU.1 to form a strong ternary complex with specific DNA sequences. An approach combining sequence homology analysis, secondary structure predictions, and a precise mutational strategy has been used to determine critical residues within the Pip heterodimerization domain that contribute to ternary complex formation. We have delimited the Pip interaction domain to residues 245-422 by using deletion analysis. Site-directed mutagenesis of conserved polar amino acids within two predicted alpha-helices contained in this region, and which are highly conserved in the IRF family, confirmed the importance of these residues for Pip-PU.1 interaction with DNA as well as for trans-activation activity. Our results suggest the existence of a functional epitope essential for heterodimerization between Pip and PU.1 and possibly, in general, between interferon regulatory factor family members and their partners.

Amino Acid Sequence↗

Androgen metabolism in sebaceous glands from subjects with and without acne.

OBJECTIVE: To determine if there are differences in the activity of 17beta-hydroxysteroid dehydrogenase and 5alpha-reductase (responsible for the production of testosterone and dihydrotestosterone, respectively) in sebaceous glands obtained from men and women with and without acne. DESIGN: Single-center examination of androgen levels and sebaceous gland enzyme activity in a cohort of volunteers. SETTING: Academic referral center. PATIENTS: Thirty-four subjects, consisting of 8 women with acne, 10 women without acne, 8 men with acne, and 8 men without acne. INTERVENTIONS: Single visit for blood sampling and 2 biopsies of forehead skin. MAIN OUTCOME MEASURES: Serum levels of androgens were determined and compared with the activity of 5alpha-reductase and 17beta-hydroxysteroid dehydrogenase in sebaceous glands microdissected from skin samples. RESULTS: No significant differences in the activity of 5alpha-reductase or 17beta-hydroxysteroid dehydrogenase in sebaceous glands according to the presence of acne were noted in either men or women. The activity of 5alpha-reductase and 17beta-hydroxysteroid dehydrogenase was significantly greater in sebaceous glands from men (n = 16) than women (n = 17). The oxidative activity of 17beta-hydroxysteroid dehydrogenase was 2-fold higher in men than women. Serum levels of dehydroepiandrosterone sulfate, androstenedione, testosterone, and dihydrotestosterone were significantly higher in women with acne than in women without acne. No differences in serum androgen levels were noted in men on the basis of the presence of acne. CONCLUSIONS: Higher serum androgen levels are associated with the presence of acne in women. A role for locally produced androgens in this process, however, cannot be excluded.

17-Hydroxysteroid Dehydrogenases↗

Is laparoscopic donor nephrectomy here to stay?

BACKGROUND: Open live donor nephrectomy is safe and provides kidneys of excellent quality. The complexity of the laparoscopic donor technique has raised considerable concerns. METHOD: Twenty-six laparoscopic live donor nephrectomies were done from October 1997 to October 1998. RESULTS: All kidneys had immediate function. All recipients except 1 had serum creatinines less than 2.0 mg at 2 months posttransplantation. Three complications (wound infection, neuroma, reoperation) occurred. There was no mortality. CONCLUSIONS: Proper surgical training and patient selection can result in a safe donor operation that provides kidneys of excellent quality.

Adult↗

A comparison of digital cameras.

Digital photography is becoming an increasingly popular alternative to traditional 35-mm photography. Clearly, the efficiency and versatility of digital cameras will have a major impact on the future of clinical photodocumentation in facial plastic surgery. However, most physicians who are interested in incorporating digital photography into their clinical practice have limited experience with this new technology. This article reviews the difference between traditional and digital cameras, compares various commercially available products, and discusses several features unique to digital cameras.

Face↗

Readiness of critical care physicians and nurses to handle requests for organ donation.

BACKGROUND: Critical care nurses and physicians usually care for those patients whose condition progresses to brain death and are also often responsible for requesting organ donation from the family of a brain-dead patient. We hypothesized that staff support, knowledge, and training levels would be significantly associated with organ donation rates. OBJECTIVE: To assess the readiness of critical care staff to successfully handle requests for organ donation. METHODS: A total of 1061 critical care staff from 28 hospitals in four separate regions of the United States completed a questionnaire that assessed (1) factual knowledge about organ donation, (2) understanding of brain death, (3) previous training in procedures for requesting donations, and (4) comfort levels with the donation process. RESULTS: Staff training in effective procedures for requesting organ donations was significantly correlated with hospitals' donation rates. Less than a third of respondents, however, had received training in explaining brain death to and requesting organ donation from a grieving family. In hospitals with high rates of organ donation, 52.9% of staff had received training; in hospitals with low rates of organ donation, 23.5% of staff had received training. Levels of factual knowledge about organ donation and brain death were unexpectedly low but were not significantly related to hospitals' rates of organ donation. CONCLUSIONS: Training of critical care nurses and physicians in effective procedures for requesting organ donation is significantly associated with higher rates of organ donation, yet two thirds of critical care staff report no relevant training. Consequently, critical care staff cannot be considered ready to effectively handle requests for organ donation.

Attitude of Health Personnel↗

A vertical curriculum to teach the knowledge, skills, and attitudes of medical informatics.

It is becoming increasingly apparent that medical schools must begin teaching the knowledge, skills and attitudes of information literacy and applied medical informatics as core competencies in undergraduate medical education. The University of Vermont College of Medicine recognized that these core competencies were lacking in its curriculum, and in 1992 it implemented a four year, integrated program to give students the information habits essential to twenty-first century practice. The first graduates of the program are now in residencies and feedback has enabled the College to refine the program to better meet the informatics education needs of the next generation of physicians. The result of these efforts is the Vertical Curriculum in Information Literacy and Applied Medical Informatics; its process of development, the product of the process, and its outcomes are discussed.

Computer Literacy↗

Functional assessment testing for maxillofacial prosthetics.

STATEMENT OF PROBLEM: The health industry is now concerned with treatment outcomes and accountability to patients, payers, and referral sources. PURPOSE: The purpose of this study was to identify the functional tests that are available to maxillofacial prosthodontists and to provide a list of those tests that are applicable in treatment and documentation. METHODS: Functional assessment may be used to justify reimbursement on the basis of payer guidelines, define eligibility for service, and judge quality and effectiveness of care. Currently, most maxillofacial prosthodontists do not use functional assessment. A literature search resulted in a list of 125 available tests. On the basis of that list a questionnaire was submitted to speech-language pathologists and occupational therapists to identify which tests are being used by them. This article discusses a historic overview of assessment testing and the need for functional assessment testing by the maxillofacial prosthodontist. RESULTS: Outcome measurements used by other members of the rehabilitation team are discussed and summarized, and those useful for the maxillofacial prosthodontist are suggested.

Deglutition↗

Breast cancer audit--the Isle of Wight experience.

The United Kingdom has the unwelcome distinction of having the highest incidence of breast cancer in the world (World Health Organisation Statistics Annual 1985). Publication of the Forrest Report in 1986 (Forrest, 1986) stimulated the introduction of the Breast Screening Programme in 1988.

Breast Neoplasms↗

Expression cloning of cDNA by phage display selection.

Expression cloning of a mouse kappa chain fragment has been achieved from a cDNA library by display of expressed proteins on filamentous phage and affinity selection for binding to anti-mouse Fab antibodies. Expressed proteins were anchored to the phage coat by a synthetic, anti-parallel leucine zipper, which had been selected from a semi-randomized zipper library for the ability to connect a test protein to phage. From a library of 4 x 10(6) transformants, two separate clones displaying different size cDNA inserts were recovered after four selection rounds. These results further demonstrate the utility of phage display for cDNA expression cloning.

Amino Acid Sequence↗

Random mutagenesis of staphylococcal nuclease and phage display selection.

Multiple cycles of mutagenesis and phage display selection have been investigated as a method for obtaining enzymes with altered catalytic properties. A library of staphylococcal nuclease mutants displayed on phage was created by error-prone PCR mutagenesis and selected for binding to thymidine- or guanosine-containing substrate analogs. After discarding non-binders, the binding mutants were then subjected to further mutagenesis and selection rounds. After four mutagenesis and selection cycles, the catalytic properties of some of the resulting nucleases were studied and one nuclease with nine accumulated mutations was found to have a two-fold reduction in kcat for DNA hydrolysis, but a two-fold increase in kcat/Km for hydrolysis of a thymidine containing small molecule substrate. The possibility of this technique for in vitro evolution of enzyme properties is discussed.

Amino Acid Sequence↗