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2.
Scand J Rheumatol ; 43(3): 217-20, 2014.
Article in English | MEDLINE | ID: mdl-24650305

ABSTRACT

OBJECTIVE: To determine the clinical impact of muscle involvement in a large systemic sclerosis (SSc) cohort. METHOD: Using the Canadian Scleroderma Research Group (CSRG) database, SSc patients with either elevated creatine kinase (CK) or a prior history of myositis/myopathy were identified. Regression and Kaplan-Meier analyses were performed to determine characteristics associated with muscle involvement in SSc and survival outcome. RESULTS: In 1145 patients with SSc, 5.6% had an elevated CK. This subset was more likely to be male (24.5% in elevated CK vs. 12.6% in normal CK, p < 0.013), younger (52 vs. 56 years, p < 0.045), have diffuse cutaneous SSc (dcSSc; 40.4% vs. 37.9%, p < 0.002), tendon friction rubs (30.0% vs. 13.4%, p < 0.001), and forced vital capacity (FVC) < 70% (23.9% vs. 13.1%, p < 0.039), be ribonucleoprotein (RNP) antibody positive (12.0% vs. 5.0%, p < 0.032), topoisomerase1 (topo1)-antibody positive (26.0% vs. 14.4%, p < 0.026), have a higher modified Rodnan skin score (MRSS; 16.14 vs. 9.81, p < 0.001), and a higher Health Assessment Questionnaire (HAQ) score (0.98 vs. 0.79, p < 0.011). Survival was reduced for patients with elevated CK (p < 0.025). Nearly 10% of patients in the CSRG cohort had a prior history of myositis/myopathy. This subset also had findings similar to those with elevated CK and increased mortality (p < 0.003). CONCLUSIONS: Muscle involvement in SSc has a poor prognosis impacting survival, especially in men with early dcSSc with topo1 and RNP autoantibodies and interstitial lung disease (ILD).


Subject(s)
Cause of Death , Creatine Kinase/metabolism , Lung Diseases, Interstitial/epidemiology , Muscular Diseases/epidemiology , Scleroderma, Systemic/epidemiology , Adult , Age Distribution , Aged , Canada/epidemiology , Cohort Studies , Comorbidity , Databases, Factual , Female , Humans , Kaplan-Meier Estimate , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/therapy , Male , Middle Aged , Muscular Diseases/diagnosis , Muscular Diseases/therapy , Prognosis , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Scleroderma, Systemic/diagnosis , Scleroderma, Systemic/therapy , Severity of Illness Index , Sex Distribution , Statistics, Nonparametric , Survival Analysis
3.
Rural Remote Health ; 14(2): 2648, 2014.
Article in English | MEDLINE | ID: mdl-24870953

ABSTRACT

INTRODUCTION: The shortage of nurses willing to work in rural Australian healthcare settings continues to worsen. Australian rural areas have a lower retention rate of nurses than metropolitan counterparts, with more remote communities experiencing an even higher turnover of nursing staff. When retention rates are lower, patient outcomes are known to be poorer. This article reports a study that sought to explore the reasons why registered nurses resign from rural hospitals in the state of New South Wales, Australia. METHODS: Using grounded theory methods, this study explored the reasons why registered nurses resigned from New South Wales rural hospitals. Data were collected from 12 participants using semi-structured interviews; each participant was a registered nurse who had resigned from a rural hospital. Nurses who had resigned due to retirement, relocation or maternity leave were excluded. Interviews were transcribed verbatim and imported into NVivo software. The constant comparative method of data collection and analysis was followed until a core category emerged. RESULTS: Nurses resigned from rural hospitals when their personal value of how nursing should occur conflicted with the hospital's organisational values driving the practice of nursing. These conflicting values led to a change in the degree of value alignment between the nurse and hospital. The degree of value alignment occurred in three dynamic stages that nurses moved through prior to resigning. The first stage, sharing values, was a time when a nurse and a hospital shared similar values. The second stage was conceding values where, due to perceived changes in a hospital's values, a nurse felt that patient care became compromised and this led to a divergence of values. The final stage was resigning, a stage where a nurse 'gave up' as they felt that their professional integrity was severely compromised. The findings revealed that when a nurse and organisational values were not aligned, conflict was created for a nurse about how they could perform nursing that aligned with their internalised professional values and integrity. Resignation occurred when nurses were unable to realign their personal values to changed organisational values - the organisational values changed due to rural area health service restructures, centralisation of budgets and resources, cumbersome hierarchies and management structures that inhibited communication and decision making, out-dated and ineffective operating systems, insufficient and inexperienced staff, bullying, and a lack of connectedness and shared vision. CONCLUSIONS: To fully comprehend rural nurse resignations, this study identified three stages that nurses move through prior to resignation. Effective retention strategies for the nursing workforce should address contributors to a decrease in value alignment and work towards encouraging the coalescence of nurses' and hospitals' values. It is imperative that strategies enable nurses to provide high quality patient care and promote a sense of connectedness and a shared vision between nurse and hospital. Senior managers need to have clear ways to articulate and imbue organisational values and be explicit in how these values accommodate nurses' values. Ward-level nurse managers have a significant responsibility to ensure that a hospital's values (both explicit and implicit) are incorporated into ward culture.


Subject(s)
Nurses/psychology , Nurses/supply & distribution , Personnel Turnover/statistics & numerical data , Rural Health Services , Adult , Female , Grounded Theory , Humans , Job Satisfaction , Male , Middle Aged , New South Wales , Quality of Health Care/organization & administration , Rural Health Services/organization & administration , Workforce
4.
Aust J Prim Health ; 28(4): 330-337, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35331367

ABSTRACT

BACKGROUND: The integration of general practitioners into specialist outpatient clinics is associated with improved access to care; however, little is understood about the organisation-level factors that affect successful implementation. We aimed to identify factors that were facilitators or barriers to the implementation of a General Practitioner with Special Interest (GPwSI) model of care across a range of specialties. METHODS: Semi-structured, in-depth interviews were conducted with 25 stakeholders at 13 GPwSI clinics in operation within a Queensland public health service. A deductive content analysis was conducted using the Consolidated Framework for Implementation Research (CFIR). RESULTS: Stakeholders generally supported the GPwSI model and saw advantages to patients and specialist medical practitioners in terms of waiting lists, workload, and improving clinician self-efficacy and knowledge. A number of factors were identified as being crucial to the success of the program, such as adequate support and planning for the implementation, appropriate funding and advocacy. CONCLUSIONS: Our evaluation indicates that a GPwSI model can be a beneficial resource for improving care to patients and reducing wait lists, dependent upon adequate planning, training, and support.


Subject(s)
General Practitioners , Ambulatory Care Facilities , Humans , Qualitative Research , Queensland , Specialization , Waiting Lists
5.
Braz J Med Biol Res ; 55: e12161, 2022.
Article in English | MEDLINE | ID: mdl-35584454

ABSTRACT

The high burden of kidney disease, global disparities in kidney care, and the poor outcomes of kidney failure place a growing burden on affected individuals and their families, caregivers, and the community at large. Health literacy is the degree to which individuals and organizations have, or equitably enable individuals to have, the ability to find, understand, and use information and services to make informed health-related decisions and actions for themselves and others. Rather than viewing health literacy as a patient deficit, improving health literacy lies primarily with health care providers communicating and educating effectively in codesigned partnership with those with kidney disease. For kidney policy makers, health literacy is a prerequisite for organizations to transition to a culture that places the person at the center of health care. The growing capability of and access to technology provides new opportunities to enhance education and awareness of kidney disease for all stakeholders. Advances in telecommunication, including social media platforms, can be leveraged to enhance persons' and providers' education. The World Kidney Day declares 2022 as the year of "Kidney Health for All" to promote global teamwork in advancing strategies in bridging the gap in kidney health education and literacy. Kidney organizations should work toward shifting the patient-deficit health literacy narrative to that of being the responsibility of health care providers and health policy makers. By engaging in and supporting kidney health-centered policy making, community health planning, and health literacy approaches for all, the kidney communities strive to prevent kidney diseases and enable living well with kidney disease.


Subject(s)
Health Literacy , Renal Insufficiency , Caregivers , Health Education , Humans , Kidney
6.
Lupus ; 20(13): 1345-55, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21951943

ABSTRACT

OBJECTIVE: It is known that age at disease onset has an impact on the clinical course and outcome of systemic lupus erythematosus (SLE); however, the precise differences in the prevalence of SLE manifestations are debated. Our objective was to conduct a systematic literature review and meta-analysis of all studies that directly compare childhood-onset lupus with adult-onset lupus to determine which clinical manifestations vary with age at disease onset. METHODS: A comprehensive literature search of the MEDLINE/PubMed,EMBASE, CINAHL, and SCOPUS databases was conducted to identify relevant articles. Study quality was assessed using the STROBE checklist. Study sample characteristics and clinical manifestation event rates were extracted from each study. Pooled odds ratios (ORs) were calculated using the random effects method, and between-study heterogeneity was quantified using the I (2) statistic. RESULTS: Of the 484 studies identified by the search strategy, 16 were included in this review. The total number of patients was 5993 adults and 905 children with SLE. Study quality was on average 16/32, ranging from 8 to 29. Several statistically significant differences were found: malar rash, ulcers/mucocutaneous involvement, renal involvement, proteinuria, urinary cellular casts, seizures, thrombocytopenia, hemolytic anemia, fever, and lymphadenopathy were more common in childhood-onset SLE with ORs ranging from 1.3 to 3.7; however, Raynaud's, pleuritis, and sicca were more common in adult-onset SLE (twice as common). CONCLUSIONS: The results of this meta-analysis suggest that some clinical manifestations of lupus are different in childhood-onset SLE and adult-onset SLE.


Subject(s)
Lupus Erythematosus, Systemic/epidemiology , Lupus Erythematosus, Systemic/physiopathology , Adolescent , Adult , Age of Onset , Child , Child, Preschool , Databases, Factual , Female , Humans , Lupus Erythematosus, Systemic/pathology , Odds Ratio , Young Adult
7.
Contemp Nurse ; 56(4): 297-308, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32799620

ABSTRACT

Nurses and midwives of Australia now is the time for change! As powerfully placed, Indigenous and non-Indigenous nursing and midwifery professionals, together we can ensure an effective and robust Indigenous curriculum in our nursing and midwifery schools of education. Today, Australia finds itself in a shifting tide of social change, where the voices for better and safer health care ring out loud. Voices for justice, equity and equality reverberate across our cities, our streets, homes, and institutions of learning. It is a call for new songlines of reform. The need to embed meaningful Indigenous health curricula is stronger now than it ever was for Australian nursing and midwifery. It is essential that nursing and midwifery leadership continue to build an authentic collaborative environment for Indigenous curriculum development. Bipartisan alliance is imperative for all academic staff to be confident in their teaching and learning experiences with Indigenous health syllabus. This paper is a call out. Now is the time for Indigenous and non-Indigenous nurses and midwives to make a stand together, for justice and equity in our teaching, learning, and practice. Together we will dismantle systems, policy, and practices in health that oppress. The Black Lives Matter movement provides us with a 'now window' of accepted dialogue to build a better, culturally safe Australian nursing and midwifery workforce, ensuring that Black Lives Matter in all aspects of health care.


Subject(s)
Administrative Personnel/psychology , Black or African American/psychology , Culturally Competent Care/organization & administration , Midwifery/education , Nursing Care/psychology , Nursing Staff, Hospital/psychology , Racism/prevention & control , Students, Nursing/psychology , Adult , Australia , Curriculum , Education, Nursing, Baccalaureate , Female , Humans , Leadership , Male , Middle Aged , Nursing Staff, Hospital/education , Pregnancy , Racism/psychology
8.
Rural Remote Health ; 7(4): 842, 2007.
Article in English | MEDLINE | ID: mdl-18069907

ABSTRACT

INTRODUCTION: Like the fictional 'Accidental Tourist', an author who does not plan to write about travel, the accidental mentor is an experienced rural nurse who does not plan to be a mentor, and yet assumes that role with new or novice rural nurses as a result of them encountering a critical incident. Accidental mentoring is a short-term relationship that provides support for the new or novice nurse in managing the incident, while maintaining their level of confidence. This article describes the findings from a constructivist grounded theory study that examined Australian rural nurses' experiences of mentoring, including evidence for a new concept of mentoring - accidental mentoring. METHODS: Constructivist grounded theory is a research methodology that focuses on issues of importance for participants around an area of common interest - in this case Australian rural nurse mentoring. In this study, seven participants were interviewed, generating nine transcripts. These were analysed using a process of concurrent data generation and analysis. In addition, the literature regarding rural nurse workforce and mentoring was incorporated as a source of data, using collective frame analysis. RESULTS: Rural nurses live their work, which predisposes them to developing supportive relationships with new or novice rural nurses. Supportive relationships range from preceptoring, to accidental mentoring, mentoring and deep friendship, depending on the level of trust and engagement that is established between the partners and the amount of time they spend together. Accidental mentoring is a short-term relationship that is prompted by experienced rural nurses observing a new or novice rural nurse experiencing a critical incident. CONCLUSIONS: Findings are presented that illustrate a new concept of accidental mentoring not present in the current literature around nurse mentoring. A series of recommendations are included that suggest strategies for improved rural nurse retention as an outcome of recognising and developing such supportive relationships in the workplace. Strategies include: performance review and development processes that account for all forms of supportive relationships conducted in the workplace; recognising the importance of developing supportive relationships and allocating time for these; and continuing professional development designed to meet local needs for developing a culture of support in the workplace.


Subject(s)
Education, Nursing, Continuing/methods , Mentors/psychology , Rural Health Services , Social Support , Staff Development , Australia , Humans , Interprofessional Relations , Interviews as Topic , Models, Educational , Preceptorship/methods , Rural Health Services/organization & administration , Staff Development/methods , Workforce
9.
Mar Environ Res ; 130: 122-133, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28756908

ABSTRACT

Bait collection is a multibillion dollar worldwide activity that is often managed ineffectively. For managers to understand the impacts on protected inter-tidal mudflats and waders at appropriate spatial scales macrofaunal surveys combined with video recordings of birds and bait collectors were undertaken at two UK sites. Dug sediment constituted approximately 8% of the surveyed area at both sites and is less muddy (lower organic content) than undug sediment. This may have significant implications for turbidity. Differences in the macrofaunal community between dug and undug areas if the same shore height is compared as well as changes in the dispersion of the community occurred at one site. Collection also induces a 'temporary loss of habitat' for some birds as bait collector numbers negatively correlate with wader and gull abundance. Bait collection changes the coherence and ecological structure of inter-tidal mudflats as well as directly affecting wading birds. However, as Ɵ diversity increased we suggest that management at appropriate hectare/site scales could maximise biodiversity/function whilst still supporting collection.


Subject(s)
Biodiversity , Birds , Ecosystem , Animals , Ecology
10.
Rev. bras. pesqui. mƩd. biol ; Braz. j. med. biol. res;55: e12161, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1374705

ABSTRACT

The high burden of kidney disease, global disparities in kidney care, and the poor outcomes of kidney failure place a growing burden on affected individuals and their families, caregivers, and the community at large. Health literacy is the degree to which individuals and organizations have, or equitably enable individuals to have, the ability to find, understand, and use information and services to make informed health-related decisions and actions for themselves and others. Rather than viewing health literacy as a patient deficit, improving health literacy lies primarily with health care providers communicating and educating effectively in codesigned partnership with those with kidney disease. For kidney policy makers, health literacy is a prerequisite for organizations to transition to a culture that places the person at the center of health care. The growing capability of and access to technology provides new opportunities to enhance education and awareness of kidney disease for all stakeholders. Advances in telecommunication, including social media platforms, can be leveraged to enhance persons' and providers' education. The World Kidney Day declares 2022 as the year of "Kidney Health for All" to promote global teamwork in advancing strategies in bridging the gap in kidney health education and literacy. Kidney organizations should work toward shifting the patient-deficit health literacy narrative to that of being the responsibility of health care providers and health policy makers. By engaging in and supporting kidney health-centered policy making, community health planning, and health literacy approaches for all, the kidney communities strive to prevent kidney diseases and enable living well with kidney disease.

11.
J Med Genet ; 40(6): 408-17, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12807961

ABSTRACT

Oligonucleotide array based analysis was conducted to examine the temporal pattern of gene expression across the various stages of lung development to identify regulatory pathways at key developmental time points. Whole embryo total RNA or embryonic lung total RNA was harvested from A/J mice at seven developmental stages. To investigate changes in gene expression during lung development, four samples from each stage were examined using Affymetrix U74Av2 murine oligonucleotide microarrays. From the over 12,000 genes and ESTs represented on the array, 1346 genes and ESTs were identified as having a significant change in expression between at least one time point and the others (p<0.001, Kruskal-Wallis test). Within this group of approximately 1300 genes, four patterns of expression were seen: (1) upregulation during the embryonic period of development (up-down); (2) upregulation during the postnatal period of lung development (down-up) and (3) fluctuating expression, up initially, down for one or more time points, and then up again (up-down-up); and (4) vice versa (down-up-down). Expression patterns of genes previously reported to be involved in pulmonary development were also examined. Using the pathway visualisation tool, GenMapp, at least three regulatory pathways were found to contain clusters of differentially expressed genes: Wnt signalling, cell cycle, and apoptosis. Furthermore, we have shown that many of the genes involved in lung development are either known oncogenes or tumour suppressor genes altered in lung cancer, such as Cyr61, Rassf1a, and Dutt1/Robo1, or putative lung cancer genes. In addition, the genes identified pertinent to early development may also serve as candidate susceptibility genes for various inherited lung cancer disorders as well as for various heritable disorders of lung development. These results will contribute to our understanding of novel aspects of the regulatory machinery for embryonic lung development and of the genes involved in lung tumorigenesis.


Subject(s)
Gene Expression Profiling , Gene Expression Regulation, Developmental/genetics , Gene Expression Regulation, Neoplastic/genetics , Lung Neoplasms/genetics , Lung/embryology , Oligonucleotide Array Sequence Analysis , Animals , Animals, Newborn , Apoptosis/genetics , Female , Gene Expression Profiling/methods , Gene Expression Profiling/statistics & numerical data , Gene Expression Regulation, Developmental/physiology , Genes, Neoplasm/genetics , Genes, Neoplasm/physiology , Lung/growth & development , Lung/metabolism , Lung Neoplasms/metabolism , Mice , Mice, Inbred A , Oligonucleotide Array Sequence Analysis/methods , Oligonucleotide Array Sequence Analysis/statistics & numerical data , Pregnancy , Signal Transduction/genetics , Signal Transduction/physiology , Time Factors
12.
Arch Intern Med ; 136(6): 700-4, 1976 Jun.
Article in English | MEDLINE | ID: mdl-58586

ABSTRACT

In this patient, discharge from the bundle of His either conducted normally, conducted with functional right or functional left bundle-branch block, or blocked entirely (concealed), depending on the preceding cycle length and the coupling interval of the premature His bundle depolarization. The presence of both functional right and left bundle-branch block may have been attributable to differences in effective and functional refractory periods between the two bundle branches. Concealed His bundle extrasystoles mimicked first-degree, and types I and II second-degree AV block, according to the interval between His bundle discharge and the subsequent P wave. Lidocaine eliminated His bundle extrasystoles that blocked entirely (concealed) or conducted with functional left bundle-branch block by improving His-Purkinje conduction and by lengthening the coupling interval of the premature His bundle extrasystole. Lidocaine had no effect on AV nodal conduction time. This patient has been known to have concealed His bundle discharge for at least three years and has not required permanent pacemaker insertion.


Subject(s)
Bundle of His/physiopathology , Cardiac Complexes, Premature/physiopathology , Electrocardiography , Heart Block/physiopathology , Heart Conduction System/physiopathology , Lidocaine/pharmacology , Bundle-Branch Block/etiology , Bundle-Branch Block/physiopathology , Cardiac Catheterization , Cardiac Complexes, Premature/complications , Heart Conduction System/drug effects , Humans , Male , Middle Aged , Pacemaker, Artificial
13.
Arch Intern Med ; 136(3): 347-9, 1976 Mar.
Article in English | MEDLINE | ID: mdl-1259502

ABSTRACT

A patient with the prolapsing mitral valve syndrome demonstrated a most striking early diastolic sound. Noninvasive study with phonocardiograms, external pulse recordings, and echocardiograms lead us to believe that the sound may be related to the initial opening movement of the mitral valve. To our knowledge, such a mechanism for the production of a diastolic sound has not been previously reported.


Subject(s)
Heart Auscultation , Heart Sounds , Mitral Valve Insufficiency/diagnosis , Adult , Amyl Nitrite/pharmacology , Echocardiography , Female , Humans , Methoxamine/pharmacology , Phonocardiography
14.
Am J Cardiol ; 37(3): 427-31, 1976 Mar 04.
Article in English | MEDLINE | ID: mdl-1258774

ABSTRACT

In the presence of atrial fibrillation, the diastolic murmur of mitral stenosis can appear augmented during early systole before the mitral valve closure sound. This phenomenon has previously been thought to be due to increased blood flow velocity across the narrowing mitral valve orifice. We have observed patients in whom the third heart sound (S3) gallop, the diastolic flow murmur of atrial septal defect and mitral insufficiency and the initial muscular component of the first heart sound become more intense during this period with short, critically timed cycle lengths. This phenomenon appears to be neither peculiar to nor indicative of mitral stenosis and is probably a direct result of the initial muscular contraction of an underfilled ventricle. Either the contraction itself or the sudden deceleration of the rapidly moving flow of blood across the atrioventricular orifice may produce the sound.


Subject(s)
Atrial Fibrillation/diagnosis , Heart Block/diagnosis , Heart Septal Defects/diagnosis , Heart Sounds , Humans , Mitral Valve Insufficiency/diagnosis
15.
Chest ; 68(6): 829-32, 1975 Dec.
Article in English | MEDLINE | ID: mdl-1192866

ABSTRACT

An unusual, high-pitched, early diastolic sound coinciding with a prominent, sharp precordial pulse was observed in a patient with a large chronic pericardial effusion. The pulse and sound coincided exactly with the anterior excursion of the heart within the fluid-filled pericardial sac, suggesting that the sound and pulse result from the ballistic effect of the heart striking the anterior pericardium and chest wall. This finding may be specific for large pericardial effusion with a "swinging heart."


Subject(s)
Heart Auscultation , Heart Sounds , Heart/physiopathology , Pericardial Effusion/diagnosis , Pulse , Aged , Echocardiography , Female , Humans , Kinetocardiography , Pericardial Effusion/physiopathology , Phonocardiography
16.
J Am Geriatr Soc ; 46(4): 506-10, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9560077

ABSTRACT

OBJECTIVE: This study was undertaken to review the impact of utilizing geriatric nurse practitioner/physician (GNP/ MD) teams on cost and utilization for a cohort of Medicare HMO enrollees residing in long-term care facilities. The results would be used by the organization for further development of the GNP Program. DESIGN: A 1-year retrospective data analysis on revenues and cost for 1077 HMO enrollees residing in 45 long term-care facilities. SETTING: Proprietary and not-for-profit, licensed long term care facilities in the HMO's service area of central Massachusetts. Facilities in the study had both skilled (Medicare-certified) and custodial beds. MEASUREMENTS: Data were collected retrospectively on overall cost, revenues, emergency department (ED) transfers, hospital, and subacute days. RESULTS: Of 1077 residents, 414 were cared for by GNP/MD teams compared with 663 by physicians alone. Acute care and ED costs were significantly lower for the GNP/MD-covered patients. There was a gain of $72 per resident per month (PRPM) with the GNP/MD-covered patients compared with a loss of $197 PRPM for physicians alone. There were no significant differences in ancillary services or prescriptions. CONCLUSION: The use of GNPs in collaboration with physicians reduced ED and acute care utilization costs as well as overall costs for a cohort of HMO enrollees in long-term care. This encouraged the HMO to support the concept that all long-term care HMO residents should be covered by GNP/MD teams.


Subject(s)
Geriatric Nursing/economics , Long-Term Care/economics , Managed Care Programs/economics , Nurse Practitioners/economics , Aged , Aged, 80 and over , Cohort Studies , Cost-Benefit Analysis , Custodial Care/economics , Female , Geriatric Assessment , Health Maintenance Organizations/economics , Humans , Male , Massachusetts , Medicare/economics , Patient Care Team/economics , United States
17.
Metabolism ; 52(4): 389-96, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12701047

ABSTRACT

Few studies have measured brain protein synthesis in vivo using reliable methods that consider the precursor pool, and there is a paucity of data on the regional sensitivity of this organ to nutritional or toxic substances. We hypothesized that different areas of the brain will exhibit variations in protein synthesis rates, which might also be expected to show different sensitivities to the nutritional toxin, ethanol. To test this, we dosed male Wistar rats with ethanol (75 mmol/kg body weight) and measured rates of protein synthesis (ie, the fractional rate of protein synthesis, defined as the percentage of the protein pool renewed each day; k(s), %/d) in different brain regions 2.5 hours later with the flooding dose method using L-[4-(3)H] phenylalanine. In the event that some regions were refractory to the deleterious effects of ethanol, we also predosed rats with cyanamide, an aldehyde dehydrogenase inhibitor (ie, cyanamide + ethanol), to increase endogenous acetaldehyde, a potent neurotoxic agent. The results indicated the mean fractional rates of protein synthesis in the cortex was 21.1%/d, which was significantly lower than either brain stem (30.2%/d, P <.025), cerebellum (30.1%/d, P <.01), or midbrain (29.8%, P <.025). Ethanol significantly decreased protein synthesis in the cortex (21%, P < 0.01), cerebellum (19%, P <.025), brain stem (44%, P <.025), but not in the midbrain (not significant [NS]). However, significant reductions in protein synthesis in the midbrain occurred in cyanamide + ethanol-dosed rats (60%, P <.0001). Cyanamide + ethanol treatment also reduced k(s) in the brain stem (66%, P <.001), cortex (59%, P <.001), and cerebellum (55%, P <.001). In conclusion, the applicability of the flooding dose technique to measure protein synthesis in the brain in vivo is demonstrated by its ability to measure regional difference. Impaired protein synthesis rates may contribute to or reflect the pathogenesis of alcohol-induced brain damage.


Subject(s)
Brain Chemistry/drug effects , Central Nervous System Depressants/pharmacology , Ethanol/pharmacology , Nerve Tissue Proteins/biosynthesis , Acetaldehyde/metabolism , Aldehyde Dehydrogenase/antagonists & inhibitors , Animals , Cyanamide/pharmacology , Drug Tolerance , Enzyme Inhibitors/pharmacology , Kinetics , Male , Phenylalanine/metabolism , Rats , Rats, Wistar
18.
Clin Chim Acta ; 252(2): 123-35, 1996 Aug 30.
Article in English | MEDLINE | ID: mdl-8853560

ABSTRACT

The urinary catabolites, N2,N2-dimethylguanosine (DMG), pseudouridine (PSU) and 7-methylguanine (m7-Gua) are formed from post-transcriptional methylation of RNA bases and are not reincorporated into RNA upon its degradation. Their quantitative urinary excretion may be used to determine rates of whole body degradation of individual RNA species since DMG occurs exclusively in tRNA, PSU occurs in rRNA and tRNA and m7-Gua occurs in all RNA species. Conventional HPLC analysis has several drawbacks since pre-analytical steps may involve selective losses and, under certain conditions, other urinary analytes may co-elute. In the present paper, we report analysis of these compounds by high-field 1H-nuclear magnetic resonance (1H-NMR) spectroscopy. Urinary concentrations of these metabolites were found to be in agreement with previously published HPLC and ELISA determinations. However, NMR analysis required minimal sample preparation (other than lyophilisation and reconstitution) and was capable of the simultaneous determination of other relevant analytes such as creatinine. This technique was therefore applied to urine samples from patients who had undergone surgical stress and insulin-like growth factor-1 (IGF-I) therapy. Surgical stress increased the excretion of DMG and m7-Gua. Degradation rates for tRNA and mRNA were also higher in surgically stressed subjects when compared with controls but degradation rates of rRNA decreased by approx. 30%. However, injection of IGF-I (40 micrograms/kg s.c.) had no significant effect on the excretion of these nucleosides. These data indicated that IGF-I therapy has no marked effects on RNA turnover following trauma. We suggest that this technique can be applied to study of RNA metabolism in any surgical or medical condition. Furthermore, since only 0.6 ml of urine is required, studies in neonates seem to be feasible.


Subject(s)
RNA/metabolism , Surgical Procedures, Operative/adverse effects , Adult , Aged , Humans , Hydrolysis , Insulin-Like Growth Factor I/therapeutic use , Magnetic Resonance Spectroscopy , Male , Middle Aged , Protons , RNA Processing, Post-Transcriptional , Recombinant Proteins/therapeutic use
19.
J Pharm Pharmacol ; 45(2): 81-5, 1993 Feb.
Article in English | MEDLINE | ID: mdl-7680711

ABSTRACT

An investigation was made into the hypothesis that chronic ethanol ingestion disturbs the metabolism of tryptophan which is reflected by alterations in the urinary excretion of the metabolites 5-hydroxyindoleacetic acid (5-HIAA), anthranilic acid (AA) and indoleacetic acid (IAA). In particular, we investigated whether experimental chronic alcoholism is associated with a decrease in the tryptophan metabolite ratios as suggested in the literature. Male Wistar rats were chronically fed a nutritionally-complete liquid diet in which ethanol comprised 35% of total calories: controls were pair-fed identical amounts of the same diet in which ethanol was replaced by isocaloric glucose. At 6 weeks, 24 h urine samples were collected for the analysis of tryptophan, 5-HIAA, AA and IAA by HPLC. During ethanol-feeding there were reductions in the daily urinary excretion (i.e. mumol/24 h) of tryptophan (-57%, P = 0.026) and concomitant increases in 5-HIAA excretion (62%, P = 0.057). Expression of data in terms of lean tissue mass (i.e. urinary creatinine) revealed identical conclusions. An analysis was performed on the molar ratios of these urinary analytes. The tryptophan: total metabolite ratio was significantly decreased (by -53%), but the AA: total metabolite ratio was not significantly altered (P = 0.102). The ratios 5-HIAA/AA and 5-HIAA/IAA were slightly increased, but they did not attain statistical significance (P > 0.351). It was concluded that chronic ethanol feeding is associated with significant changes in the urinary excretion of tryptophan and its related metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Alcoholism/urine , Ethanol/pharmacology , Tryptophan/urine , Alcoholism/metabolism , Animals , Chromatography, High Pressure Liquid , Diet , Hydroxyindoleacetic Acid/urine , Indoleacetic Acids/urine , Male , Rats , Rats, Wistar , Tryptophan/metabolism , ortho-Aminobenzoates/urine
20.
Alcohol ; 13(6): 581-7, 1996.
Article in English | MEDLINE | ID: mdl-8949953

ABSTRACT

Brain atrophy is a common feature of chronic alcohol misuse, although the pathogenic mechanisms are unknown. We propose that defects in protein synthesis are contributing events. To test this hypothesis the experimental effects of chronic (i.e., 2 and 3 weeks) ethanol feeding on brain nucleic acid composition and rates of protein synthesis in vivo were investigated. These were compared with those of skeletal muscle (represented by the plantaris). Male Wistar rats, used at mean body weights of either 82 g (first study for 2 weeks ) or 93 g (second study for 3 weeks) were fed a nutritionally complete liquid diet in which ethanol comprised a third of the total calories. Control rats were pair-fed identical amounts of the same diet, in which ethanol was substituted by isoenergetic glucose. At 2 weeks there were small reductions (i.e., approximately 5-10%) in the weight of the whole brain, cortex, and brain stem. Ethanol-induced reductions in the total protein content of the brain stem was found at 2 weeks, although these changes did not achieve significance. At 3 weeks the weights of whole brain were significantly reduced compared to a greater reduction in skeletal muscle weights. Total protein contents were reduced at 3 weeks in the whole brain and skeletal muscle. At 2 weeks there were decreases in the RNA contents of the cortex, brain stem, and entire brain. There were also reductions in cerebellum RNA composition only when expressed relative to DNA. The DNA composition of the brain was relatively unaffected by chronic ethanol feeding. At 3 weeks, total RNA and DNA were reduced in the whole brain and muscle. Fractional rates of protein synthesis (i.e., the percentage of tissue protein pool renewed each day) in the brain were unaltered after 3 weeks of ethanol feeding, but were reduced in skeletal muscles, largely as a consequence of reduced RNA composition. In conclusion, only moderate changes in the brain were found in ethanol feeding. These data can be compared to skeletal muscle, which shows that ethanol induces profound reductions in protein, RNA, and protein synthesis rates.


Subject(s)
Alcoholism/metabolism , Brain/metabolism , Muscle Proteins/biosynthesis , Muscle, Skeletal/metabolism , Nerve Tissue Proteins/biosynthesis , Nucleic Acids/metabolism , Animals , Brain/anatomy & histology , Brain/drug effects , Cerebellum/metabolism , DNA/metabolism , Ethanol/administration & dosage , Ethanol/pharmacology , Kinetics , Male , Muscle, Skeletal/drug effects , Organ Size , RNA/metabolism , Rats , Rats, Wistar , Weight Gain
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