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1.
J Prev Alzheimers Dis ; 8(3): 263-266, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34101782

RESUMO

The current demand for cognitive assessment cannot be met with traditional in-person methods, warranting the need for remote unsupervised options. However, lack of visibility into testing conditions and effort levels limit the utility of existing remote options. This retrospective study analyzed the frequency of and factors associated with environmental distractions during a brief digital assessment taken at home by 1,442 adults aged 23-84. Automated scoring algorithms flagged low data capture. Frequency of environmental distractions were manually counted on a per-frame and per-trial basis. A total of 7.4% of test administrations included distractions. Distractions were more frequent in men (41:350) than women (65:1,092) and the average age of distracted participants (51.7) was lower than undistracted participants (57.8). These results underscore the challenges associated with unsupervised cognitive assessment. Data collection methods that enable review of testing conditions are needed to confirm quality, usability, and actionability.


Assuntos
Algoritmos , Cognição/fisiologia , Meio Ambiente , Testes Neuropsicológicos/estatística & dados numéricos , Telemedicina , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Coleta de Dados/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais
2.
Alzheimers Res Ther ; 13(1): 142, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34425883

RESUMO

BACKGROUND: Varoglutamstat (formerly PQ912) is a small molecule that inhibits the activity of the glutaminyl cyclase to reduce the level of pyroglutamate-A-beta (pGluAB42). Recent studies confirm that pGluAB42 is a particular amyloid form that is highly synaptotoxic and plays a significant role in the development of AD. METHODS: This paper describes the design and methodology behind the phase 2b VIVIAD-trial in AD. The aim of this study is to evaluate varoglutamstat in a state-of-the-art designed, placebo-controlled, double-blind, randomized clinical trial for safety and tolerability, efficacy on cognition, and effects on brain activity and AD biomarkers. In addition to its main purpose, the trial will explore potential associations between novel and established biomarkers and their individual and composite relation to disease characteristics. RESULTS: To be expected early 2023 CONCLUSION: This state of the art phase 2b study will yield important results for the field with respect to trial methodology and for the treatment of AD with a small molecule directed against pyroglutamate-A-beta. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04498650.


Assuntos
Doença de Alzheimer , Aminoaciltransferases , Método Duplo-Cego , Humanos , Resultado do Tratamento
3.
Spinal Cord ; 48(6): 498-503, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20029395

RESUMO

STUDY DESIGN: An end-user response survey and assessments of inter-rater reliability before and after training. OBJECTIVES: Evaluate the spinal cord injury (SCI) application of the international classification of external cause of injury (ICECI) in a mixed group of untrained and trained coders to assess agreement, refine coding and training methodology. SETTING: An interactive coding workshop for an international group of coders with varying previous training. METHODS: Evaluate content validity (qualitative survey) and inter-rater reliability (kappa estimate of agreement) of the ICECI in a variety of injury scenarios presented within a computerized data-entry and training module. The results of this evaluation are compared with an earlier published gold standard. RESULTS: The ICECI is a flexible data coding system that appears to work with reasonable content validity in the regions assessed with English-language coders. Training appeared to narrow the difference between the inexperienced and trained coders. This is reflected in a borderline tendency for lower kappa scores pre-training compared with an earlier examined group of expert coders (P=0.073) but no difference in kappa scores after training (P=0.67). Computer-based training on a face-to-face level with computerized data entry appears an effective tool for training coders to use the ICECI. CONCLUSIONS: This report shows that using electronic data-entry and training assistance, inexperienced coders using the SCI-ICECI computerized system quickly approach the levels of agreement of trained coders in related data systems. The content validity of the training data set is adequate but needs to include more cases representative for use in SCI.


Assuntos
Classificação Internacional de Doenças/classificação , Classificação Internacional de Doenças/normas , Cooperação Internacional , Traumatismos da Medula Espinal/classificação , Traumatismos da Medula Espinal/prevenção & controle , Avaliação da Deficiência , Humanos , Classificação Internacional de Doenças/estatística & dados numéricos , Exame Neurológico , Reprodutibilidade dos Testes , Índice de Gravidade de Doença
4.
Inj Prev ; 15(3): 188-96, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19494099

RESUMO

OBJECTIVE: To assess extent of coder agreement for external causes of injury using ICD-10-AM for injury-related hospitalisations in Australian public hospitals. METHODS: A random sample of 4850 discharges from 2002 to 2004 was obtained from a stratified random sample of 50 hospitals across four states in Australia. On-site medical record reviews were conducted and external cause codes were assigned blinded to the original coded data. Code agreement levels were grouped into the following agreement categories: block level, 3-character level, 4-character level, 5th-character level, and complete code level. RESULTS: At a broad block level, code agreement was found in over 90% of cases for most mechanisms (eg, transport, fall). Percentage disagreement was 26.0% at the 3-character level; agreement for the complete external cause code was 67.6%. For activity codes, the percentage of disagreement at the 3-character level was 7.3% and agreement for the complete activity code was 68.0%. For place of occurrence codes, the percentage of disagreement at the 4-character level was 22.0%; agreement for the complete place code was 75.4%. CONCLUSIONS: With 68% agreement for complete codes and 74% agreement for 3-character codes, as well as variability in agreement levels across different code blocks, place and activity codes, researchers need to be aware of the reliability of their specific data of interest when they wish to undertake trend analyses or case selection for specific causes of interest.


Assuntos
Classificação Internacional de Doenças , Ferimentos e Lesões/classificação , Adulto , Austrália/epidemiologia , Criança , Controle de Formulários e Registros/normas , Registros Hospitalares/normas , Hospitalização/estatística & dados numéricos , Hospitais Públicos , Humanos , Pessoa de Meia-Idade , Controle de Qualidade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/etiologia , Adulto Jovem
5.
Inj Prev ; 15(1): 60-4, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19190279

RESUMO

OBJECTIVE: To appraise the published evidence regarding the accuracy of external cause-of-injury codes in hospital records. DESIGN: Systematic review. DATA SOURCES: Electronic databases searched included PubMed, PubMed Central, Medline, CINAHL, Academic Search Elite, Proquest Health and Medical Complete, and Google Scholar. Snowballing strategies were used by searching the bibliographies of retrieved references to identify relevant associated articles. SELECTION CRITERIA: Studies were included in the review if they assessed the accuracy of external cause-of-injury coding in hospital records via a recoding methodology. METHODS: The papers identified through the search were independently screened by two authors for inclusion. Because of heterogeneity between studies, meta-analysis was not performed. RESULTS: Very limited research on the accuracy of external cause coding for injury-related hospitalisation using medical record review and recoding methodologies has been conducted, with only five studies matching the selection criteria. The accuracy of external cause coding using ICD-9-CM ranged from approximately 64% when exact code agreement was examined to approximately 85% when agreement for broader groups of codes was examined. CONCLUSIONS: Although broad external cause groupings coded in ICD-9-CM can be used with some confidence, researchers should exercise caution for very specific codes until further research is conducted to validate these data. As all previous studies have been conducted using ICD-9-CM, research is needed to quantify the accuracy of coding using ICD-10-AM, and validate the use of these data for injury surveillance purposes.


Assuntos
Controle de Formulários e Registros/normas , Registros Hospitalares/normas , Prontuários Médicos/normas , Ferimentos e Lesões/etiologia , Humanos , Escala de Gravidade do Ferimento , Ferimentos e Lesões/classificação
6.
J Prev Alzheimers Dis ; 5(4): 236-244, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30298182

RESUMO

BACKGROUND: The Neuropsychological Test Battery (NTB) is a combination of widely used clinical neuropsychological tests measuring memory and executive function and was designed to overcome some of the limitations of the traditionally used Alzheimer's disease Assessment Scale - Cognitive subscale (ADAS-Cog). A previously reported account indicated high levels of NTB reliability in patients with mild-to-moderate Alzheimer's disease (AD) and mild cognitive impairment (MCI). OBJECTIVES: We examined capacity of the Neuropsychological Test Battery (NTB) and its component subtests to measure cognitive change over time. Correlations with other cognitive and functional assessments were also determined. Design, Settings, Participants: This was a multicentre, prospective, non-interventional, longitudinal cohort study involving patients with mild-to-moderate AD (n=196), MCI (n=70), or cognitively normal control participants (NC, n=75). INTERVENTION: The NTB, as well as other Clinical Outcome Assessments including, ADAS-Cog, other cognitive measures, functional/behavioral questionnaires, health outcome questionnaires, and resource utilization tools were administered. RESULTS: Mean change from baseline for the NTB composite score and the six individual NTB subtests showed greater reductions in performance over time in the AD and MCI groups, compared with NC group. The ADAS-Cog was found to be more sensitive to change than the NTB in all three populations. CONCLUSIONS: The NTB showed high correlation with the ADAS-Cog and appears to be a sensitive and reliable assessment tool for measuring cognitive decline in patients with mild-to-moderate AD. However, the ADAS-Cog was found to be more sensitive to change over time in both the AD and MCI populations.


Assuntos
Doença de Alzheimer/epidemiologia , Disfunção Cognitiva/epidemiologia , Testes Neuropsicológicos/normas , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Estudos Prospectivos , Psicometria
7.
Br J Pharmacol ; 151(7): 1061-70, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17549048

RESUMO

BACKGROUND AND PURPOSE: Racemic (R,S) AM1241 is a cannabinoid receptor 2 (CB(2))-selective aminoalkylindole with antinociceptive efficacy in animal pain models. The purpose of our studies was to provide a characterization of R,S-AM1241 and its resolved enantiomers in vitro and in vivo. EXPERIMENTAL APPROACH: Competition binding assays were performed using membranes from cell lines expressing recombinant human, rat, and mouse CB(2) receptors. Inhibition of cAMP was assayed using intact CB(2)-expressing cells. A mouse model of visceral pain (para-phenylquinone, PPQ) and a rat model of acute inflammatory pain (carrageenan) were employed to characterize the compounds in vivo. KEY RESULTS: In cAMP inhibition assays, R,S-AM1241 was found to be an agonist at human CB(2), but an inverse agonist at rat and mouse CB(2) receptors. R-AM1241 bound with more than 40-fold higher affinity than S-AM1241, to all three CB(2) receptors and displayed a functional profile similar to that of the racemate. In contrast, S-AM1241 was an agonist at all three CB(2) receptors. In pain models, S-AM1241 was more efficacious than either R-AM1241 or the racemate. Antagonist blockade demonstrated that the in vivo effects of S-AM1241 were mediated by CB(2) receptors. CONCLUSIONS AND IMPLICATIONS: These findings constitute the first in vitro functional assessment of R,S-AM1241 at rodent CB(2) receptors and the first characterization of the AM1241 enantiomers in recombinant cell systems and in vivo. The greater antinociceptive efficacy of S-AM1241, the functional CB(2) agonist enantiomer of AM1241, is consistent with previous observations that CB(2) agonists are effective in relief of pain.


Assuntos
Receptor CB2 de Canabinoide/agonistas , Analgésicos/farmacologia , Animais , Benzoxazinas/farmacologia , Células CHO , Bloqueadores dos Canais de Cálcio/farmacologia , Canfanos/farmacologia , Canabinoides/química , Canabinoides/metabolismo , Canabinoides/farmacologia , Carragenina/toxicidade , Colforsina/farmacologia , Cricetinae , Cricetulus , AMP Cíclico/antagonistas & inibidores , AMP Cíclico/metabolismo , Cicloexanóis/farmacologia , Relação Dose-Resposta a Droga , Humanos , Hiperalgesia/induzido quimicamente , Hiperalgesia/fisiopatologia , Hiperalgesia/prevenção & controle , Indóis/farmacologia , Camundongos , Morfolinas/farmacologia , Naftalenos/farmacologia , Ligação Proteica/efeitos dos fármacos , Pirazóis/farmacologia , Ensaio Radioligante , Ratos , Receptor CB2 de Canabinoide/genética , Receptor CB2 de Canabinoide/metabolismo , Especificidade da Espécie , Estereoisomerismo , Trítio
8.
Mol Cell Biol ; 12(3): 1375-86, 1992 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1545819

RESUMO

Biochemical examination of the Rev-dependent expression of gag mRNAs produced from gag-Rev-responsive element (RRE) expression plasmids showed a large discrepancy between the level of cytoplasmic gag mRNA and the produced Gag protein. Significant levels of the mRNA produced in the absence of Rev were localized in the cytoplasm, while very low levels of Gag protein were produced. In the presence of Rev, the levels of mRNA increased by 4- to 16-fold, while the Gag protein production increased by 800-fold. These findings indicated that in addition to promoting nucleus-to-cytoplasm transport, Rev increased the utilization of cytoplasmic viral mRNA. Poly(A) selection and in vitro translation of cytoplasmic gag mRNA verified that the mRNA produced in the absence of Rev was functional. To analyze the translational defect in the absence of Rev, we examined the association of the cytoplasmic gag mRNA with ribosomes. gag mRNA produced in the absence of Rev was excluded from polysomes, while gag mRNA produced in the presence of Rev was associated with polysomes and produced Gag protein. These observations showed that the presence of Rev was required for efficient loading of gag mRNA onto polysomes. This effect required the presence of the RRE on the mRNA. Analysis of mRNAs produced from a rev-minus proviral clone confirmed that the presence of Rev promoted polysomal loading of both gag/pol and vpu/env mRNAs. The localization of gag mRNA was also examined by in situ hybridization. This analysis showed that in the presence of Rev, most of the gag mRNA was found in the cytoplasm, while in the absence of Rev, most of the gag mRNA was found in the nucleus and in the region surrounding the nucleus. These results suggest that a substantial fraction of the gag mRNA is retained in distinct cytoplasmic compartments in the absence and presence of Rev. These findings indicate that the presence of Rev is required along the entire mRNA transport and utilization pathway for the stabilization, correct localization, and efficient translation of RRE-containing mRNAs.


Assuntos
Produtos do Gene rev/metabolismo , Genes Fúngicos , HIV-1/genética , Biossíntese de Proteínas , Northern Blotting , Linhagem Celular , Clonagem Molecular , Citoplasma/metabolismo , Genes env , Genes gag , Genes pol , Genes vpu , HIV-1/metabolismo , Humanos , Hibridização de Ácido Nucleico , Reação em Cadeia da Polimerase , Polirribossomos/metabolismo , RNA Mensageiro/metabolismo , RNA Viral/metabolismo , Produtos do Gene rev do Vírus da Imunodeficiência Humana
9.
Cochrane Database Syst Rev ; (3): CD003452, 2007 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-17636724

RESUMO

BACKGROUND: Prominent upper front teeth are an important and potentially harmful type of orthodontic problem. This condition develops when the child's permanent teeth erupt and children are often referred to an orthodontist for treatment with dental braces to reduce the prominence of the teeth. If a child is referred at a young age, the orthodontist is faced with the dilemma of whether to treat the patient early or to wait until the child is older and provide treatment in early adolescence. When treatment is provided during adolescence the orthodontist may provide treatment with various orthodontic braces, but there is currently little evidence of the relative effectiveness of the different braces that can be used. OBJECTIVES: To assess the effectiveness of orthodontic treatment for prominent upper front teeth, when this treatment is provided when the child is 7 to 9 years old or when they are in early adolescence or with different dental braces or both. SEARCH STRATEGY: The Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE and EMBASE were searched. The handsearching of the key international orthodontic journals was updated to December 2006. There were no restrictions in respect to language or status of publication. Date of most recent searches: February 2007. SELECTION CRITERIA: Trials were selected if they met the following criteria: design - randomised and controlled clinical trials; participants - children or adolescents (age < 16 years) or both receiving orthodontic treatment to correct prominent upper front teeth; interventions - active: any orthodontic brace or head-brace, control: no or delayed treatment or another active intervention; primary outcomes - prominence of the upper front teeth, relationship between upper and lower jaws; secondary outcomes: self esteem, any injury to the upper front teeth, jaw joint problems, patient satisfaction, number of attendances required to complete treatment. DATA COLLECTION AND ANALYSIS: Information regarding methods, participants, interventions, outcome measures and results were extracted independently and in duplicate by two review authors. The Cochrane Oral Health Group's statistical guidelines were followed and mean differences were calculated using random-effects models. Potential sources of heterogeneity were examined. MAIN RESULTS: The search strategy identified 185 titles and abstracts. From this we obtained 105 full reports for the review. Eight trials, based on data from 592 patients who presented with Class II Division 1 malocclusion, were included in the review.Early treatment comparisons: Three trials, involving 432 participants, compared early treatment with a functional appliance with no treatment. There was a significant difference in final overjet of the treatment group compared with the control group of -4.04 mm (95% CI -7.47 to -0.6, chi squared 117.02, 2 df, P < 0.00001, I(2) = 98.3%). There was a significant difference in ANB (-1.35 mm; 95% CI -2.57 to -0.14, chi squared 9.17, 2 df, P = 0.01, I(2) = 78.2%) and change in ANB (-0.55; 95% CI -0.92 to -0.18, chi squared 5.71, 1 df, P = 0.06, I(2) = 65.0%) between the treatment and control groups. The comparison of the effect of treatment with headgear versus untreated control revealed that there was a small but significant effect of headgear treatment on overjet of -1.07 (95% CI -1.63 to -0.51, chi squared 0.05, 1 df, P = 0.82, I(2) = 0%). Similarly, headgear resulted in a significant reduction in final ANB of -0.72 (95% CI -1.18 to -0.27, chi squared 0.34, 1 df, P = 0.56, I(2) = 0%). No significant differences, with respect to final overjet, ANB, or ANB change, were found between the effects of early treatment with headgear and the functional appliances. Adolescent treatment (Phase II): At the end of all treatment we found that there were no significant differences in overjet, final ANB or PAR score between the children who had a course of early treatment, with headgear or a functional appliance, and those who had not received early treatment. Similarly, there were no significant differences in overjet, final ANB or PAR score between children who had received a course of early treatment with headgear or a functional appliance. One trial found a significant reduction in overjet (-5.22 mm; 95% CI -6.51 to -3.93) and ANB (-2.27 degrees; 95% CI -3.22 to -1.31, chi squared 1.9, 1 df, P = 0.17, I(2) = 47.3%) for adolescents receiving one-phase treatment with a functional appliance versus an untreated control.A statistically significant reduction of ANB (-0.68 degrees; 95% CI -1.32 to -0.04, chi squared 0.56, 1 df, P = 0.46, I(2) = 0%) with the Twin Block appliance when compared to other functional appliances. However, there was no significant effect of the type of appliance on the final overjet. AUTHORS' CONCLUSIONS: The evidence suggests that providing early orthodontic treatment for children with prominent upper front teeth is no more effective than providing one course of orthodontic treatment when the child is in early adolescence.


Assuntos
Má Oclusão Classe II de Angle/terapia , Ortodontia Corretiva/métodos , Adolescente , Fatores Etários , Criança , Humanos , Aparelhos Ortodônticos Funcionais , Contenções Ortodônticas , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
10.
J Nutr Health Aging ; 11(4): 327-9, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17653492

RESUMO

In the following paper the cognitive measures used in clinical trials of drugs for Alzheimer's disease are reviewed. The potential benefits of employing innovative tests that map cognitive domains poorly indexed by traditional measures such as the ADAS-cog are considered. Finally, issues pertaining to the cognitive breadth of any proposed new instrument are discussed, as well as the clinical relevance of cognitive change.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/psicologia , Cognição/efeitos dos fármacos , Nootrópicos/uso terapêutico , Idoso , Doença de Alzheimer/diagnóstico , Cognição/fisiologia , Progressão da Doença , Humanos , Entrevista Psiquiátrica Padronizada , Testes Neuropsicológicos , Índice de Gravidade de Doença , Resultado do Tratamento
11.
J Bone Miner Res ; 5 Suppl 1: S81-5, 1990 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2339641

RESUMO

The effects of fluoride (F) on ectopic bone formation induced in rats by implants of demineralized cortical bone tissue were studied. Test rats received sodium fluoride (NaF), 6 mmol/liter in drinking water, and controls received fluoride-free water. Implant accumulations of tracer hydroxyproline ([3H](OH)P), 45Ca, and stable Ca were determined 24 h after injections of tritiated proline ([3H]P) and 45Ca, to estimate rates of collagen synthesis, mineralization, and net mineral mass, respectively. Conventional histology on undemineralized implant sections was done. Mineralized bone was first observed by implant histology, 2 weeks after implantation and continued to increase up to 8 weeks. A few chondrocytes were observed. Prior to bone formation, dense fibrous tissue was observed within the marrow space of the original implant. The rate of collagen synthesis peaked at 1 week, again at 3 weeks, and then continued at a slower rate up to 8 weeks. The rates of mineralization paralleled the rates of collagen synthesis between 2 and 8 weeks, indicating bone mineralization over this period. During the first 2 weeks after implantation no mineral deposition was observed. The initial peak of collagen synthesis without mineralization (0-2 weeks) indicates fibrous tissue formation and is in agreement with the histological analysis. Fluoride treatment increased rates of collagen synthesis during both the initial period of fibrous tissue formation and later bone formation. The ratio of mineralization rate to collagen synthesis rate (45Ca/[3H](OH)P) was decreased by fluoride throughout the 2-8 week period, but net mineral mass was comparable to control rats by 8 weeks, indicating that fluoride delays, but does not prevent, bone mineralization.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Desenvolvimento Ósseo/efeitos dos fármacos , Fluoreto de Sódio/farmacologia , Animais , Transplante Ósseo/fisiologia , Cálcio/metabolismo , Colágeno/biossíntese , Feminino , Modelos Biológicos , Ratos , Ratos Endogâmicos
12.
J Bone Miner Res ; 5 Suppl 1: S91-4, 1990 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2339643

RESUMO

We have developed a localized noninvasive nuclear magnetic resonance (NMR) method for determining the accumulated bone fluoride content in human index fingers. Using a 27 MHz "split-ring" resonator probe, we measure the total fluoride (F) content within a 6.5 cm length of the distal end of the index finger from a calibrated determination of the intensity of the observed 19F free induction decay (FID) signal. Since fluoride impurities accumulate almost exclusively in bone mineral, the 19F resonance signal is broadened by rigid lattice magnetic dipole-dipole interactions, causing the FID signal to have a relatively short lifetime of approximately 75 microseconds. This short signal lifetime, plus the weakness of the signal strength prevents conventional magnetic resonance imaging equipment from observing the 19F in bone mineral. Nevertheless, we have achieved an in vivo sensitivity of +/- 0.5 mg fluoride in an observation period of 30 min. Assuming an index finger has between 0.25 and 0.5 g of bone calcium, this sensitivity is just sufficient to detect fluorides in the index finger of most adults whose bone fluoride concentration is greater than 2.0 mg fluoride/g calcium (0.8 mg/g ash weight). We are particularly interested in using this new NMR technique to monitor the rate of bone fluoride accumulation in osteoporotic patients receiving therapeutic levels of fluoride in their diets.


Assuntos
Osso e Ossos/metabolismo , Fluoretos/metabolismo , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Masculino
13.
J Bone Miner Res ; 5 Suppl 1: S217-22, 1990 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2339632

RESUMO

The possible effects of fluoride in inducing fractures were studied in 61 patients treated with sodium fluoride (NaF), 40-60 mg daily in combination with calcium and vitamin D. Nine patients developed the fluoride-(F) related lower extremity pain syndrome. Four other patients had stress fractures associated with trauma. Seven of the 61 patients had 10 upper femur fractures of which 5 were stress fractures. The bone mineral mass of the central skeleton including the hips was measured by neutron activation and the results expressed as a calcium bone index (CaBI) which normalizes the results to that of young adults of the same body size (normal range 0.75-1.2). At the time of hip fracture, 4 patients with a minimal increase in bone mass (mean delta CaBI 0.01) had 4 femur fractures and 3 patients with a marked increase (mean delta CaBI 0.24) had 6. The 7 patients with upper femur fractures at 4 years had a significantly higher bone fluoride retention, 30 mg/g Ca compared with 23.9 mg/g Ca for the other 54 (p less than 0.02) and were older, 73.1 versus 64.2 years (p less than 0.01). Using all 61 fluoride-treated patients, femur fractures/patient were significantly correlated to bone fluoride (p less than 0.05) and to age (p less than 0.05). By partial correlation, only the correlation between hip fractures/patient and bone fluoride remained significant after controlling for the effect of age (p less than 0.05). These results suggest that fluoride therapy may be implicated in the pathogenesis of hip fractures which may occur in treated patients despite a rapid, marked increase in bone mass. The lower extremity pain syndrome is not frequently associated with stress fractures in this study.


Assuntos
Fraturas Ósseas/induzido quimicamente , Osteogênese/efeitos dos fármacos , Fluoreto de Sódio/efeitos adversos , Idoso , Quimioterapia Combinada , Feminino , Fraturas do Colo Femoral/induzido quimicamente , Fraturas Ósseas/diagnóstico por imagem , Fraturas de Estresse/induzido quimicamente , Humanos , Perna (Membro) , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/tratamento farmacológico , Dor/induzido quimicamente , Dor/diagnóstico por imagem , Cintilografia , Estudos Retrospectivos , Fluoreto de Sódio/uso terapêutico , Síndrome , Vitamina D/efeitos adversos
14.
J Bone Miner Res ; 5 Suppl 1: S27-35, 1990 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2339633

RESUMO

We report on 61 women with postmenopausal osteoporosis who were treated with either plain sodium fluoride (NaF) capsules or enteric-coated NaF tablets for 4 years, in whom possible therapeutic and toxic effects were monitored. In these patients there was a mean increase in axial bone mineral mass, assessed by neutron activation analysis, of 26.2% +/- 2.4% (SEM) during the 4 years. This corresponds to a decrease in the bone deficit (compared with reference values) of 48.6%. The response was linear over 4 years. The main predictors of the osteogenic response were bone fluoride (r = 0.52, p less than 0.01), serum fluoride (r = 0.50, p less than 0.01), and age (0.39, p less than 0.01). Patients over 65 years of age achieved higher bone fluoride (F) levels and a significantly greater increase in bone mineral than younger patients (32.8 vs. 17.9%, p less than 0.01), associated with an age-related decline in renal function; serum fluoride was significantly and negatively correlated to creatinine clearance (r = -0.52, p less than 0.01). Although the effect of NaF on fracture rate could not be assessed in this uncontrolled study, the major factors associated with the occurrence of new vertebral fractures were the number of vertebral fractures and the bone mineral mass at the beginning of therapy. There was no correlation between vertebral fracture rate and serum or bone fluoride or other parameters of the osteogenic response, but patients who did not experience new vertebral fractures achieved a normal bone mineral content sooner than those who had new fractures during therapy.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Envelhecimento/patologia , Rim/fisiopatologia , Osteoporose Pós-Menopausa/tratamento farmacológico , Fluoreto de Sódio/uso terapêutico , Idoso , Envelhecimento/fisiologia , Densidade Óssea/efeitos dos fármacos , Feminino , Seguimentos , Fraturas Espontâneas/etiologia , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/complicações , Fatores de Risco , Fluoreto de Sódio/efeitos adversos , Traumatismos da Coluna Vertebral/etiologia , Comprimidos com Revestimento Entérico
15.
J Bone Miner Res ; 3(2): 127-32, 1988 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-3213607

RESUMO

Forty-one women with idiopathic postmenopausal osteoporosis have been followed for 2 years after initiation of sodium fluoride at 40-50 mg/day, given together with a daily calcium supplement of 1 gram and vitamin D2, at 50,000 IU weekly. Histological and histomorphometric analyses were done on bone biopsies taken prior to and after 1 year of treatment (mean 1.25 +/- 0.35 years). Thirty patients (74%) developed the histological fluoride effect of hyperosteoidosis, while the remaining 11 patients (26%) had no change from pretreatment biopsies. Hyperosteoidosis was based on increased values for osteoid volume and/or thickened osteoid with greater than 3 lamellar bands. Based on previously reported findings, this histological evidence of hypersoteoidosis within 12-18 months of initiation of therapy provides a useful predictor of ultimate satisfactory fluoride response in terms of bone mineral accretion. No increases in bone mass (measured by neutron activation analysis) were observed at the time of the posttreatment biopsy but, according to this previous work, increases are anticipated over a further 2-3 years of treatment. Factors affecting the development of hyperosteoidosis were analyzed. Hyperosteoidosis was associated with a significantly higher dose of sodium fluoride and a significantly higher level of bone fluoride retention but without significant increase in fasting serum fluoride. Results suggest that fluoride retention depends not only on fluoride dose but also on body size, renal function, and intestinal absorptions of calcium and fluoride. There were no differences in the initial investigations between patients with and without hyperosteoidosis, with respect to age, years of postmenopause, estrogen use, initial biochemistry, or initial bone histology.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Osso e Ossos/patologia , Absorção Intestinal , Osteoporose/tratamento farmacológico , Fluoreto de Sódio/uso terapêutico , Biópsia , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , Osteoporose/fisiopatologia , Fluoreto de Sódio/farmacocinética
16.
Gene ; 144(2): 221-8, 1994 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-8039706

RESUMO

Complementary DNA (cDNA) clones, encoding a fusion protein that was recognised by an antiserum raised against a purified polypeptide fragment of a 180-kDa human leukocyte protein, were isolated from a lambda gt11 expressed library. The clones encoded a unique amino acid (aa) sequence interspersed with heptad repeats that typify coiled-coil proteins, and hybridised to a 5-kb transcript universally expressed in a panel of eight human tissues. Comparatively high levels of RNA expression were seen in testis, ovary and mitogen-activated peripheral blood leukocytes (PBLs). The deduced 1300-aa sequence reveals a protein with a typical signal peptide, a hydrophilic domain containing an N-terminal globular head with a nuclear localization signal sequence, a C-terminal region of coiled-coil structure, a candidate transmembrane domain, and a short 10-aa C-terminal domain. Rabbit polyclonal antisera raised against a truncated lambda gt11 fusion protein recognized a 150-170-kDa protein (non-reduced) in mitogen-activated PBLs. The protein designated here as CG-1 may exist as a homodimer destined for translocation to the nucleus, with a role in leukocyte differentiation and/or effector function.


Assuntos
Proteínas Sanguíneas/genética , Leucócitos/metabolismo , Proteínas de Membrana , Sequências Repetitivas de Ácido Nucleico , Sequência de Aminoácidos , Animais , Sequência de Bases , Proteínas Sanguíneas/química , Células Cultivadas , Clonagem Molecular , Sequência Conservada , DNA , Eletroforese em Gel de Poliacrilamida , Humanos , Soros Imunes , Leucócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Mitógenos/metabolismo , Dados de Sequência Molecular , Filogenia , Conformação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
17.
Am J Clin Nutr ; 30(3): 326-33, 1977 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-842485

RESUMO

Body composition was studied in subjects from the seventh decade of life (13 M, 25F), observations being made on recruitment and at selected points over a 1-year program of endurance training. As at younger ages, the women initially had more subcultaneous fat than the men, particularly over the limbs. In both sexes, excess weights (9.3 kg. M; 8.1 kg, F) and average skinfold radings (16.2 mm, M; 21.1mm, F) were greater than in younger adults. Edurance training (1 hr of supervised exercise, 150-200 kcal persession, nominal four sessions per week) progressively reduced skinfold readings, by an average of 1.6 mm at 7 weeks, by 2.4 dependent upon the intensity and the frequency of exercise undertaken by the individual. Total body potassium (40K determinations) agreed well with previous studies of older subjects. Body fat estimated form 40K showed a fair correlation with skinfold estimates of body fat (r=0.69, M; 0.93, F), but absolute precentages were higher by 40K(36.6%, M; 48.7%, F) than by subcutaneous fat measurements (20%, M;32% F). Body potassium increased by 4% over the year of training, 70% of this change, occurring between the 14th and the 52nd week of conditioning. Small gains were also recorded in arm circumference, grip strenght (R but not L) and knee extension force. Neutron activation data showed that both sexes had lower initial bone calcium counts than sedentary middle-aged adults. The sample as a whole showed no calcium loss over the year of training, but the group taking the least exercise did show a significant loss (P less than 0.05). Modest endurance training of an elderly population seems not only to correct loss of cardiorespiratory condition, but also to induce favorable changes in body fat and lean mass.


Assuntos
Idoso , Composição Corporal , Resistência Física , Antropometria , Peso Corporal , Cálcio/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Educação Física e Treinamento , Potássio/metabolismo , Fatores Sexuais , Dobras Cutâneas
18.
Am J Clin Nutr ; 48(1): 91-4, 1988 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-3389334

RESUMO

Seventeen obese adolescents were treated with the protein-sparing modified fast (PSMF), a high-protein, low-carbohydrate, low-calorie diet, for approximately 3 mo and then followed for a total of 12 mo. The diet provided a mean of 880 kcal.kg-1. d-1 and 2.5 g protein. kg IBW-1. d-1. Body composition was determined using four skinfold measurements, total body potassium (TBK), and total body nitrogen (TBN) at baseline, 3 mo, and 12 mo. Twelve subjects returned for follow-up at 1 y (71%) and 48% had sustained weight loss with the percentage ideal body weight for height decreased from 154 to 125 over the year. Six subjects had TBK and TBN measured and TBK decreased 13.0% and TBN decreased 14.3% over the year. This reflected a change toward normalization of the predicted TBK from 121 to 102% and TBN from 119 to 102%.


Assuntos
Peso Corporal , Proteínas Alimentares/administração & dosagem , Jejum , Nitrogênio/metabolismo , Obesidade/dietoterapia , Potássio/metabolismo , Adolescente , Composição Corporal , Estatura , Criança , Feminino , Seguimentos , Humanos , Masculino , Obesidade/metabolismo , Obesidade/patologia
19.
Am J Clin Nutr ; 32(9): 1955-61, 1979 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-474485

RESUMO

Measurement of nitrogen in the human body gives a measure of total protein in the body. Nitrogen (N) may be measured in vivo by a nuclear technique in which the characteristic nitrogen gamma rays emitted after capture of neutrons are detected and counted. The accuracy (as determined by comparison of the measurement of nitrogen in a pig by nuclear and chemical methods) is better than 10%. The reproducibility is less than 6%. The radiation dose is about 5 millirads. This method had been used with 43 patients and 23 normal volunteers and the results are reported. The data are presented in the from of total N content, percentage N by weight, and as a comparison of N and potassium (K) in the body. It is found that the mean percentage of N in the normal males is 2.5%, giving a value of 1.75 kg in the 70-kg standard man. The mean percentage values are not greatly different between normal volunteers and malnourished patients. Taking all subjects, N/K ratios ranged from 7.5 to 20 g/g. Thus K cannot be used as a predictor of N. Nitrogen content of normals correlates well (r = 0.68) with height squared; for malnourished patients there is again a good correlation (r = 0.81) but the regression line for patients is approximately 34% below that for the volunteers consistent with their depleted state.


Assuntos
Nitrogênio/análise , Proteínas/análise , Animais , Ascite/metabolismo , Feminino , Raios gama , Humanos , Masculino , Métodos , Nêutrons , Isótopos de Nitrogênio , Distúrbios Nutricionais/metabolismo , Obesidade/metabolismo , Doses de Radiação , Suínos
20.
Am J Clin Nutr ; 59(2): 325-30, 1994 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8310981

RESUMO

Bioelectric impedance analysis (BIA) has been widely used for assessment of body composition in healthy subjects but has not been validated in malnourished patients. This study compared calculation of fat-free mass (FFM) by five methods to determine whether the currently used equations for total body water (TBW) as assessed by BIA were applicable to 19 malnourished patients with Crohn's disease. When compared with TBW assessed by H2(18)O dilution, BIA was higher by 5.9 +/- 1.1% (P < 0.005). A stepwise-multiple-regression equation was derived to validate BIA: TBW (kg) = 0.25 (ht2/resistance) + 0.29 (wt) + 3.63 (r = 0.97, SEE = 0.28). Comparison of the hydration of FFM (TBW by 18O dilution/FFM) between methods showed that total body potassium (TBK) gave a significantly higher value when compared with the reference method of body protein, mineral, and 18O analysis. Dual-energy x-ray absorptiometry (DXA) provided a value for TBW/FFM in close agreement with the reference method. We conclude that BIA overestimates TBW, and TBK underestimates FFM in malnourished patients. DXA provides an accurate measurement of body fat in malnutrition.


Assuntos
Composição Corporal , Doença de Crohn/patologia , Impedância Elétrica , Distúrbios Nutricionais/patologia , Absorciometria de Fóton , Tecido Adiposo , Análise de Variância , Antropometria , Estatura , Água Corporal , Densidade Óssea , Doença de Crohn/complicações , Feminino , Humanos , Masculino , Nitrogênio/análise , Distúrbios Nutricionais/etiologia , Potássio/análise , Análise de Regressão
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