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1.
Clin Infect Pract ; 16: 100207, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36268055

ABSTRACT

Background and objectives: Remdesivir, an antiviral drug routinely used in the treatment of COVID-19 has not yet received FDA approval for use in patients with advanced kidney disease defined as GFR < 30 mL/min/1.73 m2. There is concern that an excipient in Veklury (Gilead's proprietary name for remdesivir) called sulfobutylether-beta-cyclodextrin (SBECD), which is renally cleared, may accumulate and reach toxic levels in patients with advanced kidney disease. The aim of this study was to summarize characteristics and incidence of adverse events of chronic kidney disease (CKD) patients who received remdesivir during hospitalization.Design, setting, participants, and measurements.We retrospectively studied patients admitted to one of several hospitals of the Mayo Clinic Foundation with the diagnosis of COVID-19 pneumonia and CKD. Laboratory values were also measured when remdesivir was first administered and stopped. All analyses were performed in the overall patient group and three separate subgroups of patients with a GFR ≥ 15, a GFR < 15 and dialysis, and a GFR < 15 and no dialysis. Results: A total of 444 CKD patients who were admitted to the hospital with COVID-19 pneumonia between May 2020 and September 2021 were included. Information was collected on patient characteristics, hospitalization, and adverse events. In the overall cohort, median age was 72 years (Range: 21-100 years), 55.2 % of patients were male, and most (86.5 %) were Caucasian. CKD stage was 3 for 114 patients (25.7 %), 4 for 229 patients (51.6 %), and 5 for 101 patients (22.7 %). A total of 146 patients (32.9 %) were admitted to the ICU, 103 (23.2 %) died in the hospital, and 120 (27.0 %) were on dialysis. The proportion of patients with an adverse event did not differ dramatically between the GFR ≥ 15 (20.9 %), GFR < 15 and dialysis (30.2 %), and GFR < 15 and no dialysis (32.3 %) groups (P = 0.12). Conclusion: Our results suggest that the use of remdesivir in patients with very severe CKD is safe, even in those who are not on renal replacement therapy.

3.
Qual Saf Health Care ; 17(3): 201-8, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18519627

ABSTRACT

OBJECTIVES: Little research has focused on preventing harm from errors that occur in primary care. We studied mitigation of patient harm by analysing error reports from family physicians' offices. METHODS: The data for this analysis come from reports of testing process errors identified by family physicians and their office staff in eight practices in the American Academy of Family Physicians National Research Network. We determined how often reported error events were mitigated, described factors related to mitigation and assessed the effect of mitigation on the outcome of error events. RESULTS: We identified mitigation in 123 (21%) of 597 testing process event reports. Of the identified mitigators, 79% were persons from inside the practice, and 7% were patients or patient's family. Older age was the only patient demographic attribute associated with increased likelihood of mitigation occurring (unadjusted OR 18-44 years compared with 65 years of age or older = 0.27; p = 0.007). Events that included testing implementation errors (11% of the events) had lower odds of mitigation (unadjusted OR = 0.40; p = 0.001), and events containing reporting errors (26% of the events) had higher odds of mitigation (unadjusted OR = 1.63; p = 0.021). As the number of errors reported in an event increased, the odds of that event being mitigated decreased (unadjusted OR = 0.58; p = 0.001). Multivariate logistic regression showed that an event had higher odds of being mitigated if it included an ordering error or if the patient was 65 years of age or older, and lower odds of being mitigated if the patient was between age 18 and 44, or if the event included an implementation error or involved more than one error. Mitigated events had lower odds of patient harm (unadjusted OR = 0.16; p<0.0001) and negative consequences (unadjusted OR = 0.28; p<0.0001). Mitigated events resulted in less severe and fewer detrimental outcomes compared with non-mitigated events. CONCLUSION: Nearly a quarter of testing process errors reported by family physicians and their staff had evidence of mitigation, and mitigated errors resulted in less frequent and less serious harm to patients. Vigilance throughout the testing process is likely to detect and correct errors, thereby preventing or reducing harm.


Subject(s)
Diagnostic Techniques and Procedures/standards , Family Practice/organization & administration , Medical Errors/prevention & control , Outcome Assessment, Health Care/methods , Risk Management/methods , Adult , Clinical Laboratory Techniques/statistics & numerical data , Data Interpretation, Statistical , Humans , Medical Errors/classification , Outcome Assessment, Health Care/trends , Primary Health Care/organization & administration , Primary Health Care/standards , Risk Management/organization & administration
4.
Eur J Neurosci ; 27(2): 294-300, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18190522

ABSTRACT

Administration of VP025 (Vasogen Inc.), a novel drug formulation based on phospholipid nanoparticles incorporating phosphatidylglycerol, has previously been shown to have a neuroprotective effect in the brain. We examined the effect of VP025 in a rat model of Parkinson's disease, the 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle. VP025 or phosphate-buffered saline (PBS) was administered to rats 14 days, 13 days and 1 day before the unilateral 6-OHDA lesion. Functional integrity of nigrostriatal dopaminergic neurons was assessed 7 and 21 days later by amphetamine-induced rotational testing and we observed that rotational counts were significantly less in rats that were pretreated with VP025 compared with PBS-pretreated 6-OHDA-lesioned rats. Neurochemical analysis at 10 and 28 days after lesion revealed that VP025 protected against a 6-OHDA-induced decrease in concentrations of striatal dopamine and its metabolites. Immunocytochemical studies of the ipsilateral substantia nigra showed that VP025 significantly inhibited 6-OHDA-induced loss of dopaminergic neurons. We also observed that increases in immunostaining for activated microglia and for activated p38 in dopaminergic neurons of 6-OHDA-lesioned rats were prevented by VP025. This study shows that VP025 has significant protective effects on the 6-OHDA-lesioned nigrostriatal pathway and may therefore have potential for the treatment of Parkinson's disease.


Subject(s)
Disease Models, Animal , Neuroprotective Agents/therapeutic use , Oxidopamine/toxicity , Parkinson Disease, Secondary/drug therapy , Phosphatidylglycerols/therapeutic use , Phospholipids/therapeutic use , Animals , Male , Neuroprotective Agents/chemistry , Parkinson Disease, Secondary/chemically induced , Parkinson Disease, Secondary/metabolism , Parkinson Disease, Secondary/pathology , Phosphatidylglycerols/chemistry , Phospholipids/chemistry , Rats , Rats, Sprague-Dawley
5.
Exp Biol Med (Maywood) ; 230(8): 558-68, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16118406

ABSTRACT

Increased intake of phytoestrogens may be associated with a lower risk of cancer in the breast and several other sites, although there is controversy surrounding this activity. One of the mechanisms proposed to explain the activity of phytoestrogens is their ability to bind and activate human estrogen receptor alpha (ERalpha) and human estrogen receptor beta (ERbeta). Nine phytoestrogens were tested for their ability to transactivate ERalpha or ERbeta at a range of doses. Mammary adenocarcinoma (MCF-7) cells were co-transfected with either ERalpha or ERbeta, and an estrogen-response element was linked to a luciferase reporter gene. Dose-dependent responses were compared with the endogenous ligand 17beta-estradiol. Purified genistein, daidzein, apigenin, and coumestrol showed differential and robust transactivation of ERalpha- and ERbeta-induced transcription, with an up to 100-fold stronger activation of ERbeta. Equol, naringenin, and kaempferol were weaker agonists. When activity was evaluated against a background of 0.5 nM 17beta-estradiol, the addition of genistein, daidzein, and resveratrol superstimulated the system, while kaempferol and quercetin were antagonists at the highest doses. This transfection assay provides an excellent model to evaluate the activation of ERalpha and ERbeta by different phytoestrogens in a breast cancer context and can be used as a screening bioassay tool to evaluate the estrogenic activity of extracts of herbs and foods.


Subject(s)
Breast Neoplasms/physiopathology , Estrogen Receptor alpha/physiology , Estrogen Receptor beta/physiology , Phytoestrogens/pharmacology , Adenocarcinoma , Cell Line, Tumor , Estradiol/pharmacology , Estrogen Receptor alpha/drug effects , Estrogen Receptor alpha/genetics , Estrogen Receptor beta/drug effects , Estrogen Receptor beta/genetics , Female , Humans , Mutagenesis, Site-Directed , Plasmids , Point Mutation , Recombinant Proteins/drug effects , Recombinant Proteins/metabolism , Transcriptional Activation , Transfection
6.
Diabetes Obes Metab ; 5(5): 317-24, 2003 Sep.
Article in English | MEDLINE | ID: mdl-12940869

ABSTRACT

AIMS: The specific objective of this study was to determine acute and long-term effects of cyclo (his-pro) (CHP) plus zinc and l-histidine (CZH) treatment on glucose metabolism in genetically obese (ob/ob), type 2 diabetic mice. METHODS: Acute effects of 0.3 mg of CHP plus 10 mg of zinc and 0.5 mg of l-histidine/kg body weight (BW) on fed blood glucose concentrations and 3-h average of above fasting blood glucose concentrations (TAFGCs), an index of oral glucose tolerance test, in lean and ob/ob mice were determined. To evaluate long-term effects of CZH on TAFGCs, lean and ob/ob mice were treated with drinking water containing increasing doses of CHP (0, 0.5, 1.0 or 1.5 mg/l) plus 10 mg zinc and 0.5 mg of l-histidine/l for 3 weeks. During the treatment period, fed blood glucose concentrations, BW and food and water intake were determined. At the end of the treatment, fasting blood glucose concentrations, TAFGC and fed plasma insulin concentrations were determined. RESULTS: Blood glucose concentrations significantly decreased when CZH was administered acutely via gastric gavage in food-deprived ob/ob mice. Similarly, 1.0 mg/l CHP treatment of mice with fixed amounts of 10 mg zinc and 0.5 mg l-histidine/l was optimal to decrease fed blood glucose and plasma insulin concentrations during a 3-week treatment period in ob/ob mice. TAFGC values in these mice also improved most significantly with the same combination of CHP, zinc and l-histidine used to test for fed blood glucose and plasma insulin levels. Fasting blood glucose concentrations and BW gains also decreased in ob/ob mice treated with 1.0 mg of CHP/l plus the same amount of zinc and l-histidine used in the above experiments. No effects of CZH treatment in lean mice were observed. CONCLUSIONS: CZH is effective in decreasing blood glucose concentrations in genetically obese (ob/ob), type 2 diabetic mice. These data support our working hypothesis that CZH may be an important anti-hyperglycaemic agent.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus/drug therapy , Hypoglycemic Agents/therapeutic use , Obesity , Peptides, Cyclic/therapeutic use , Piperazines/therapeutic use , Zinc/therapeutic use , Animals , Blood Glucose/metabolism , Diabetes Mellitus/blood , Diabetes Mellitus, Type 2/blood , Drug Therapy, Combination , Male , Mice , Mice, Inbred C57BL , Mice, Obese , Weight Gain/drug effects
7.
Pancreas ; 25(4): 405-10, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12409837

ABSTRACT

INTRODUCTION AND AIMS: Orexins have been demonstrated to have mainly central physiological functions, including regulation of food and water intake, sleep, and arousal. However, little is known about their direct peripheral effects, if any. As a first step toward understanding the role of Orexin in non-neuronal tissues or cells, we initiated studies to examine expression of Orexin receptors (OXR) in an established pancreatic tumor cell line AR42J. Secondly, we wanted to determine whether Orexins, in various molecular forms, are active to stimulate any known pancreatic cell functions in AR42J cells. METHODOLOGY: Reverse transcription-PCR analysis was performed to identify the presence of specific Orexin receptor subtypes. Intracellular calcium mobilization and cAMP levels were measured following stimulation by Orexin A and B peptides, their respective C-terminal decapeptide fragments, and hypocretin-2-gly (glycine-extended Orexin B). Release of alpha-amylase was measured in conditioned media after acute stimulation with the set of Orexin peptides for 30 minutes. Cell proliferation was determined by H-thymidine incorporation after 24 hours following treatment with Orexins under serum-free condition. RESULTS: RT-PCR and sequencing results showed that Orexin receptor subtype 2 (OX2R) was the main form expressed in AR42J cells. Orexins stimulated dose-dependent increases in intracellular calcium mobilization with EC50 0.05 nM for Orexin A and 0.1 nM for Orexin B but were unable to stimulate any significant cAMP accumulation or DNA synthesis even at micromolar concentrations. Both Orexin-A and -B, but not hypocretin-2-gly, also stimulated dose-dependent increases in amylase release in the AR42J cells. Orexin-A and -B carboxyl-terminal decapeptides elicited significant but much lower calcium and amylase responses. CONCLUSION: Our data demonstrate that OX2R mediates Ca -dependent amylase release in AR42J cells, suggesting that Orexins may have secretory functions in pancreatic tumor cells.


Subject(s)
Amylases/metabolism , Carrier Proteins/pharmacology , Intracellular Signaling Peptides and Proteins , Neuropeptides/pharmacology , Pancreas/enzymology , Receptors, Neuropeptide/physiology , Amino Acid Sequence , Animals , Calcium/metabolism , Carrier Proteins/genetics , Cyclic AMP/analysis , Dose-Response Relationship, Drug , Molecular Sequence Data , Neuropeptides/genetics , Orexin Receptors , Orexins , Pancreas/chemistry , Pancreas/drug effects , RNA, Messenger/biosynthesis , Rats , Receptors, G-Protein-Coupled , Receptors, Neuropeptide/genetics , Sequence Alignment , Tumor Cells, Cultured
8.
Diabetes Obes Metab ; 4(2): 124-31, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11940110

ABSTRACT

AIM: The present study is designed to determine whether arachidonic acid (AA) plus zinc improves clinical signs of diabetes in genetically diabetic ob/ob mice. METHODS: In the first study, effects of acute administration of AA plus zinc on glucose disposal were determined in ob/ob and lean mice (n = 6 each). In the second study, ob/ob and lean mice were treated with increasing doses of AA plus zinc for 2 weeks (n = 5 each). Postprandial and fasting blood glucose concentrations, three-hour-area-average above fasting glucose concentration (TAFGC), water and food intake, body weight and plasma insulin concentrations were measured. RESULTS: Acute administration of AA plus zinc significantly increased glucose disposal in ob/ob mice. In the second study, postprandial and fasting blood glucose concentrations, TAFGC, and water and food intake in ob/ob mice treated with AA plus zinc for 2 weeks were significantly decreased compared with those in mice given no AA. Plasma insulin concentrations in both lean and ob/ob mice were not changed by AA treatment in drinking water. CONCLUSIONS: AA plus zinc in drinking water is effective in decreasing blood glucose levels in obese mice. These results indicate that use of these compounds should be considered as a dietary supplement to control hyperglycaemia in patients with type II diabetes.


Subject(s)
Arachidonic Acid/therapeutic use , Blood Glucose/metabolism , Diabetes Mellitus/genetics , Obesity , Zinc/therapeutic use , Animals , Blood Glucose/drug effects , Diabetes Mellitus/blood , Fasting , Glucose Tolerance Test , Male , Mice , Mice, Inbred C57BL , Mice, Obese , Postprandial Period
9.
Rev Sci Tech ; 21(3): 699-710, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12523708

ABSTRACT

An epidemic of foot and mouth disease occurred on an unprecedented scale in Great Britain in 2001. This was characterised by widespread dissemination of disease in sheep due to infection being present but unreported for at least three weeks before the first case was identified. As envisaged by the contingency plans, existing procedures dealt rapidly with disease in many parts of the country where outbreaks were reported. Elsewhere, the scale and speed of disease spread was so great that veterinary resources had to be supplemented on the operational front by a large influx of military and administrative support. At the time of writing (June 2002), the United Kingdom Government has already identified a number of key lessons, and will learn further from this experience and from the findings of inquiries, how a future outbreak of this unprecedented nature and extent could be handled. Lessons identified so far relate to the improvement of contingency plans, the wider impact on rural businesses and communities, reassessing the possible use of emergency vaccination, the availability of serological capacity, better animal identification and movement controls, carcass disposal, communications, data handling and management information. The authors present the initial lessons learned and which formed the basis of official submissions to the inquiries. Further lessons will be learned from the findings of those inquiries.


Subject(s)
Communicable Disease Control/methods , Disease Outbreaks/veterinary , Foot-and-Mouth Disease/epidemiology , Foot-and-Mouth Disease/prevention & control , Animals , Cattle , Communication , Consumer Product Safety , Disease Outbreaks/prevention & control , Goats , Humans , International Cooperation , Risk Assessment , Risk Management , Sheep , Swine , United Kingdom/epidemiology
10.
Metabolism ; 50(1): 53-9, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11172475

ABSTRACT

Previous studies have already shown that prostate extract (PE) has antidiabetic activity when given to animals and humans. In this study, we explore whether this antidiabetic activity is related to the high concentrations of zinc, cyclo (his-pro) (CHP), and the prostaglandin precursor, arachidonic acid (AA), in prostate tissue. When streptozotocin-induced diabetic rats were given drinking water containing 10 mg/L zinc and 100 mg/L PE for 3 weeks, fasting blood glucose levels and glucose clearance rates, but not plasma insulin levels, were significantly lower than at pretreatment. In subsequent experiments, blood glucose levels in rats given PE for 3 weeks were significantly lower than in rats given distilled water or 10 mg/L zinc alone. However, in rats given 100 mg/L CHP with zinc, blood glucose levels were also lower than in rats given PE alone. Time-course studies in diabetic rats given drinking water containing 20 mg/L Zn, 20 mg/L L-histidine, and 10 mg/L CHP showed that blood glucose levels dropped 209 +/- 53 mg/dL in 1 day and stayed low for 2 weeks. When CHP was replaced with 100 mg AA/L, blood glucose levels dropped 230 +/- 64 mg/dL in 5 days, but returned to the original values 11 days later. Growth rate improved and water consumption decreased significantly in CHP- and AA-treated diabetic rats. High intake of L-histidine and testosterone increased blood glucose concentrations in diabetic rats. To determine optimal dosages of CHP and AA, we gave rats drinking water containing 10 mg/L Zn and 0.5 mg/L L-histidine with various concentrations of CHP or AA. The most effective doses for reducing blood glucose levels were 0.32 mg CHP/kg/day and 11 mg AA/kg/day. These data suggest that the active antidiabetic ingredients in the PE are CHP, zinc, and AA or its precursors.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/therapeutic use , Prostate/chemistry , Animals , Antioxidants/therapeutic use , Arachidonic Acid/therapeutic use , Blood Glucose/drug effects , Cell Extracts/therapeutic use , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/metabolism , Disease Models, Animal , Dogs , Drug Synergism , Insulin/physiology , Male , Peptides, Cyclic/therapeutic use , Piperazines/therapeutic use , Rats , Streptozocin , Zinc/therapeutic use
12.
Aust J Adv Nurs ; 16(4): 7-13, 1999.
Article in English | MEDLINE | ID: mdl-10603766

ABSTRACT

The shift in focus from primarily institutionally based care, to community-based care, has highlighted the need for community psychiatric nurses with appropriate skills to care for clients experiencing mental illness within the community. This paper describes the results of a qualitative research project undertaken to examine the skills required by psychiatric nurses in conducting an assessment within the community. In depth interviews were conducted with a sample of six currently practising community psychiatric nurses, with differing levels of experience. The findings identified the main skills as: interpersonal skills; psychiatric nursing knowledge base; the ability to work with a variety of treatment modalities; and, literacy skills. The specific significance of these skills for the educational preparation of community psychiatric nurses is discussed.


Subject(s)
Health Knowledge, Attitudes, Practice , Psychiatric Nursing/methods , Community Health Nursing/methods , Community Mental Health Services , Humans , Nursing Assessment/methods , Nursing Methodology Research
13.
Pancreas ; 19(3): 224-30, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10505752

ABSTRACT

Expression of the long form of the leptin receptor, the isoform that is considered to have full signaling capability, has been reported in the central nervous system and several peripheral cell types. However, only a few cell lines have been shown to express the long form of the receptor. AR42J, a cell line derived from azaserine-treated rat pancreas, is a common model for pancreatic acinar cell secretion. In this study, the presence of leptin-receptor variants and leptin action was evaluated in this cell line. Messenger RNAs for both the long and a short form of the leptin receptor were detected by reverse transcription-polymerase chain reaction (RT-PCR) in AR42J cells, and authenticity of the receptor was confirmed by DNA sequencing. Competitive binding studies demonstrated that binding of radiolabeled leptin was specific and did not cross-react with cholecystokinin (CCK). Biologic effects of leptin on amylase release and intracellular calcium mobilization were further assessed in the presence and the absence of CCK, a known pancreatic secretagogue. Although leptin alone (< or =200 ng/ml) did not affect basal amylase release, it inhibited amylase release stimulated by 1 nM CCK by 48%. Leptin alone had no significant effect on calcium mobilization. However, pretreatment of leptin (10 and 100 ng/ml) enhanced calcium responses stimulated by CCK. These data demonstrate that the rat pancreatic tumor cell line AR42J expresses a functional form of the leptin receptor that modulates the action of CCK in calcium mobilization and amylase release.


Subject(s)
Amylases/metabolism , Cholecystokinin/pharmacology , Leptin/pharmacology , Pancreas/drug effects , Pancreas/metabolism , Receptors, Cell Surface , Amylases/antagonists & inhibitors , Animals , Binding, Competitive/drug effects , Calcium/metabolism , Carrier Proteins/genetics , Cell Line , Cholecystokinin/pharmacokinetics , Dose-Response Relationship, Drug , Gastrointestinal Agents/pharmacology , Intracellular Fluid/metabolism , Leptin/pharmacokinetics , Protein Isoforms/genetics , RNA, Messenger/metabolism , Rats , Receptors, Leptin , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA , Sincalide/pharmacology
14.
Plant Physiol ; 121(2): 609-17, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10517853

ABSTRACT

Type 2A serine/threonine protein phosphatases (PP2A) have been implicated as important mediators of a number of plant growth and developmental processes. In an effort to identify plant PP2A substrates and/or regulators, we performed a yeast two-hybrid screen using an Arabidopsis PP2A catalytic subunit cDNA as bait. All true positives identified by this screen were derived from the same gene, which we have named TAP46 (2A phosphatase associated protein of 46 kD). The TAP46 gene appears to be a single-copy gene and is expressed in all Arabidopsis organs. Transcripts derived from this gene are induced by chilling treatment but not by heat or anaerobic stress. Immunoprecipitation assays using antibodies generated to a peptide spanning amino acids 356 to 366 of TAP46 indicate that TAP46 is associated with a type 2A protein phosphatase in vivo. A search of the database identified TAP46 as a homolog of Saccharomyces cerevisiae TAP42 and mammalian alpha4. These two proteins are known to bind to the catalytic subunit of PP2A and to function in the target-of-rapamycin signaling pathway. Our results identify TAP46 as a plant PP2A-associated protein, with a possible function in the chilling response, and suggest that a target-of-rapamycin-like signaling pathway may exist in plants.


Subject(s)
Arabidopsis Proteins , Arabidopsis/metabolism , Fungal Proteins/metabolism , Phosphoproteins/metabolism , Plant Proteins/metabolism , Protein Tyrosine Phosphatases/metabolism , Saccharomyces cerevisiae Proteins , Saccharomyces cerevisiae/metabolism , Adaptor Proteins, Signal Transducing , Amino Acid Sequence , Animals , Fungal Proteins/chemistry , Macromolecular Substances , Mammals , Molecular Sequence Data , Phosphoproteins/chemistry , Plant Proteins/chemistry , Plant Proteins/genetics , Protein Binding , Protein Phosphatase 2 , Protein Tyrosine Phosphatases/chemistry , Sequence Alignment , Sequence Homology, Amino Acid
15.
Lasers Surg Med ; 25(2): 107-22, 1999.
Article in English | MEDLINE | ID: mdl-10455216

ABSTRACT

BACKGROUND AND OBJECTIVE: Laser resurfacing of eyelids was examined in a series of experiments designed to measure beam parameters, surface temperatures, ablation characteristics, thermal damage, tissue responses and clinical outcomes. These data were collected for the purpose of developing a logical basis for clinical dosimetry. STUDY DESIGN: All experiments were conducted with similar short-pulse CO(2) lasers (TruPulse, Albuquerque, NM) where the beam had been carefully characterized and calibrated. The chronological sequence examined begins with the photophysical laser/tissue interactions during the first few microsec of irradiation and ends with an evaluation of the efficacy of wrinkle reduction nine months after treatment. RESULTS: Eyelid tissue removed by the first and second passes consisted mostly of epidermis with about 38 microm of thermal damage into the papillary dermis. Erythema resolved within four weeks and most patients experienced 70-100% wrinkle reduction by nine months. CONCLUSION: A layer of contracted dermal scar tissue that replaced the thermally challenged zone in the dermis is identified as the substrate for wrinkle reduction. The data support the following dosimetry for periorbital wrinkle reduction: One pass 4-6 J/cm(2) (350-500 mJ into a 3 x 3 mm spot). A second treatment after 9-12 months may be more beneficial than a second pass.


Subject(s)
Blepharoplasty/methods , Laser Therapy , Animals , Carbon Dioxide , Edema/etiology , Erythema/etiology , Humans , Lasers/adverse effects , Mice , Regression Analysis , Rhytidoplasty/methods , Skin/pathology , Skin Aging , Skin Temperature , Treatment Outcome , Wound Healing
16.
Issues Ment Health Nurs ; 20(5): 495-503, 1999.
Article in English | MEDLINE | ID: mdl-10808833

ABSTRACT

This article describes an Australian research project that explored the relevance of hospital-based experience in preparing psychiatric nurses for community-based practice. A qualitative design was selected to obtain in-depth information in an area in which no formal research has been undertaken. In-depth interviews were conducted with 6 psychiatric nurses currently engaged in community-based practice. The interviews were audiotaped, and the transcribed data were analyzed for major themes. The results indicated that the participants did not believe their hospital experience had prepared them to function effectively in the community. In some respects hospital experience was perceived as having hindered their transition into the community environment. This exploratory study indicates the need for further research and the exploration of alternative methods to prepare psychiatric nurses for community-based practice.


Subject(s)
Attitude of Health Personnel , Clinical Competence/standards , Community Health Nursing/education , Education, Nursing, Baccalaureate/methods , Hospitals, Psychiatric , Nursing Staff/education , Nursing Staff/psychology , Psychiatric Nursing/education , Adult , Female , Humans , Male , Middle Aged , Nursing Education Research , Nursing Methodology Research , Surveys and Questionnaires , Victoria
17.
J Immunol Methods ; 212(2): 169-85, 1998 Mar 15.
Article in English | MEDLINE | ID: mdl-9672205

ABSTRACT

A rapid (30 min) whole blood assay for the detection of lipopolysaccharide (LPS) is described. This chemiluminescent (CL) assay utilizes the CR1 and CR3 receptor-induced oxidant production of polymorphonuclear leucocytes as a detection platform. The differential priming of neutrophils in whole blood by LPS-antibody complexes allows the specificity of the assay to be achieved. Oxidant released in response to complement opsonized zymosan results in luminol oxidation and subsequent light emission. This is dependent on heat labile putative complement proteins in the plasma. The assay consists of a control which measures baseline whole blood neutrophil oxidant production. The test assay contains murine monoclonal IgM antibody against the Lipid A epitope of LPS and measures the enhanced chemiluminescent response of the neutrophils in the presence of LPS-antibody complexes. Maximal sensitivity of the CL assay is dependent upon optimal antigen-antibody equivalence and duration of pre-incubation with the whole blood sample. The quantification of LPS is possible by inclusion of a positive control containing a maximally reactive LPS dose (800 pg/ml Escherichia coli 055:B5 LPS at an antibody concentration of 0.8 microg/assay). The CL assay is insensitive to variations in patient neutrophil concentration over a minimum range of 0.5 to 20 x 10(9) cells/l. The CL assay is widely reactive with the LPS of many strains of gram negative bacteria but not with the cell wall products of gram positive bacteria or Candida and Aspergillus. In comparison to acid extraction chromogenic LAL, the CL assay demonstrates superior recovery precision and accuracy in in vitro studies. This was reproducible over a wide range of LPS concentrations (0.017-1.6 EU/ml or 20-2000 pg/ml). This assay may be a clinically useful tool for the diagnosis of infection or endotoxin in patients.


Subject(s)
Antibodies, Bacterial , Biological Assay/methods , Gram-Negative Bacterial Infections/diagnosis , Lipopolysaccharides/blood , Neutrophil Activation , Sepsis/diagnosis , Antibodies, Monoclonal , HL-60 Cells , Humans , Lipopolysaccharides/immunology , Luminescent Measurements , Luminol , Macrophage-1 Antigen , Oxidation-Reduction , Receptors, Complement 3b , Sensitivity and Specificity , Specimen Handling , Time Factors
18.
Hear Res ; 108(1-2): 145-56, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9213128

ABSTRACT

Multi-unit peristimulus time (MU-PST) histograms were recorded in the gerbil inferior colliculus (IC) in response to tone burst stimuli. Histograms were collected every 100 microns as the recording electrode was advanced along the tonotopic axis of the central nucleus of the IC. Space/time maps of neural activity were constructed from these data. In most of our sample the pattern of response changed systematically as the stimulating frequency was increased in octave steps. At low frequencies (< 500 Hz) the pattern of response was broadly distributed spatially and phase-locked to the stimulus frequency. At higher frequencies (> 1 kHz) the pattern of response was more localized and showed no evidence of phase locking. The location of the maximum response to tones from 1 to 32 kHz moved ventrally along the tonotopic axis at an approximate rate of 230 microns/stimulus octave. The patterns of response were localized near stimulus threshold and spread over a larger region as level increased. This method of collecting and displaying multi-unit response maps provides an overview of ensemble activity that allows concurrent observation of spatial and temporal variations in activity patterns. The quantitative analysis of components of MU-PST Maps are consistent with trends illustrated with single-unit tuning and level functions. This perspective of IC activity suggests potential processing mechanisms that are congruent with single-unit reconstructions.


Subject(s)
Inferior Colliculi/physiology , Acoustic Stimulation , Animals , Auditory Cortex/physiology , Auditory Perception/physiology , Brain Mapping/methods , Electrophysiology , Gerbillinae , Inferior Colliculi/anatomy & histology , Nerve Fibers/physiology , Vestibulocochlear Nerve/physiology
19.
Eur J Biochem ; 245(1): 156-63, 1997 Apr 01.
Article in English | MEDLINE | ID: mdl-9128737

ABSTRACT

Numerous plant processes ranging from signal transduction to metabolism appear to be mediated, in part, by type 2A protein serine/threonine phosphatases (PP2A). In an effort to identify factors that control the activity of this enzyme in plants, we have isolated and characterized DNA sequences encoding the B' regulatory subunit of PP2A from Arabidopsis thaliana. Specifically, we used PCR to amplify a segment of Arabidopsis cDNA that encodes a conserved section of the B' polypeptide. This PCR fragment was subsequently used as a probe to screen an Arabidopsis cDNA library and cDNA clones derived from three distinct genes were identified. The AtB' alpha and AtB' beta genes encode highly similar 57-kDa B' regulatory subunits while the third gene, AtB' gamma, encodes a more divergent 59-kDa B' protein. A comparison of the three Arabidopsis B' polypeptides to those of yeast and animals shows the core region of this protein to be the most conserved while the amino and carboxy termini vary both in length and sequence. Genomic Southern blots indicate that at most the Arabidopsis genome contains five genes encoding the B' regulatory subunit. The three genes identified in this study are expressed in all Arabidopsis organs, albeit at varying levels. In addition, mRNAs derived from the three genes accumulate differentially in response to heat shock. Our results indicate that the activity of plant PP2A might be regulated by a B' type regulatory subunit similar to those found in animals and yeast, and suggest possible roles for B'-containing PP2A complexes within plant cells.


Subject(s)
Arabidopsis/enzymology , Gene Expression Regulation , Genes, Plant , Phosphoprotein Phosphatases/genetics , Amino Acid Sequence , Arabidopsis/genetics , DNA, Complementary/isolation & purification , Molecular Sequence Data , Phosphoprotein Phosphatases/chemistry , Protein Conformation , Protein Phosphatase 2 , RNA, Messenger/analysis , RNA, Plant/analysis , Sequence Alignment
20.
Lasers Surg Med ; 21(4): 384-94, 1997.
Article in English | MEDLINE | ID: mdl-9328986

ABSTRACT

BACKGROUND AND OBJECTIVE: Infrared transmission spectra of dentin reveal a broad absorption band between 6.0 and 7.0 microns composed of absorption peaks of water, collagen and carbonated hydroxyapatite. The nearly constant absorption and the existence of absorption peaks of different tissue components were used to investigate ablation as a function of the primary absorber. STUDY DESIGN/MATERIALS AND METHODS: Laser ablation of dentin as a function of fluence was studied in the wavelength range between 6.0 and 7.5 microns using the Vanderbilt Free-Electron Laser (FEL). Depth and volume of the ablation crater were determined with a silicon replica method and subsequent confocal laser topometry. SEM investigations were performed on the irradiated surfaces. For the description of the experimental data an ablation model is developed. RESULTS: At all applied wavelengths we found a linear increase of ablation depth as a function of fluence above a threshold fluence. The lower absorption of dentin at 7.5 microns compared to the absorption at 6.0, 6.5 and 7.0 microns results in a greater ablation threshold. At 6.0, 6.5 and 7.0 microns wavelengths the ablation thresholds are comparable. The experimental data are in good agreement with an ablation model using a mean absorption coefficient of the target material. No thermal cracking is observed after ablation in dentin. The post ablative surface structure at 6.0 and 7.0 microns looks similar whereas at 7.5 microns the surface reveals a greater roughness. CONCLUSION: The ablation efficiency and threshold depend on the mean absorption but do not depend upon the chemical identity of the primary absorber in dentin. Calculations show that heat conduction during the laser pulse leads to a thermal equalization between the heated microstructures and surrounding tissue resulting in an ablation with little dependence on the primary absorber.


Subject(s)
Dentin/surgery , Laser Therapy/methods , Absorption , Dentin/ultrastructure , Humans , Laser Therapy/instrumentation , Least-Squares Analysis , Linear Models , Mathematics , Microscopy, Electron, Scanning , Surface Properties
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