RESUMO
BACKGROUND: Patients with both vascular and osteoarticular injuries require multidisciplinary management. Vascular injuries may be function- and/or life-threatening. The lower limbs are predominantly affected. Traffic, domestic, and work-related accidents contribute most of the cases. The primary objective of this study was to describe the management of patients with concomitant vascular and osteo-articular injuries, with special attention to the rates of amputation and fasciotomy. The secondary objective was to suggest a management sequence to optimise our surgical practice. HYPOTHESIS: The management sequence is a crucial consideration in patients with both vascular and osteo-articular injuries. MATERIAL AND METHODS: A 6-year, retrospective, observational study was conducted in patients with concomitant vascular and osteo-articular injuries. RESULTS: The study included 36 patients with a mean age of 40.6±22.1 years. The main sources of injury were traffic accidents (n=19, 52.8%), crush injury (n=8, 22.2%), and falls (n=5, 13.9%). A compound fracture was present in 20 (55.6%) patients. Evidence of ischaemia in 25 (69.4%) patients, and bleeding in 11 (30.6%) patients. Pre-operative imaging, by ultrasonography or computed tomography, was performed in 27 (75.0%) patients. The lower limb was involved in 30 (83.3%) patients, who had osteoarticular injuries to the femur and leg combined with injury to the popliteal artery. Fasciotomy was performed in 11 (30.6%) patients and secondary amputation in 7 (19.4%) patients. The limb salvage rate was 80.6%. Median patient survival was 9.3 [0-74.8] months. DISCUSSION: Coordinated work by two surgical teams is crucial to manage concomitant vascular and osteo-articular injuries. The management sequence must be defined clearly. Computed tomography angiography is the investigation of choice and should be performed at the slightest suspicion of vascular injury. LEVEL OF EVIDENCE: IV, retrospective observational study.
Assuntos
Fraturas Expostas/cirurgia , Articulações/lesões , Traumatismo Múltiplo/cirurgia , Equipe de Assistência ao Paciente/organização & administração , Lesões do Sistema Vascular/cirurgia , Adolescente , Adulto , Idoso , Amputação Cirúrgica , Fasciotomia , Feminino , Fraturas Expostas/complicações , Hemorragia/etiologia , Hemorragia/cirurgia , Humanos , Isquemia/etiologia , Isquemia/cirurgia , Traumatismos da Perna/cirurgia , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo/complicações , Artéria Poplítea/lesões , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Lesões do Sistema Vascular/complicações , Adulto JovemAssuntos
Implante de Prótese Vascular , Doenças das Artérias Carótidas/cirurgia , Artéria Carótida Interna/cirurgia , Procedimentos Endovasculares , Aneurisma Intracraniano/cirurgia , Neurofibromatose 1/complicações , Idoso , Prótese Vascular , Implante de Prótese Vascular/instrumentação , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/etiologia , Artéria Carótida Interna/diagnóstico por imagem , Angiografia Cerebral/métodos , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares/instrumentação , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/etiologia , Ataque Isquêmico Transitório/etiologia , Masculino , Neurofibromatose 1/diagnóstico , Inibidores da Agregação Plaquetária/uso terapêutico , Stents , Resultado do TratamentoRESUMO
Melanopsin (OPN4) is a photoreceptive molecule regulating circadian systems in mammals. Previous studies from our laboratory have shown that co-localized dopamine-melatonin (DA-MEL) neurons in the hypothalamic premammillary nucleus (PMM) are putatively photosensitive and exhibit circadian rhythms in DAergic and MELergic activities. This study investigates turkey OPN4x (tOPN4x) mRNA distribution in the hypothalamus and brainstem, and characterizes its expression in PMM DA-MEL neurons, using in situ hybridization (ISH), immunocytochemistry (ICC), double-label ISH/ICC, and real time-PCR. The mRNA encoding tOPN4x was found in anatomically discrete areas in or near the hypothalamus and the brainstem, including nucleus preopticus medialis (POM), nucleus septalis lateralis (SL), PMM and the pineal gland. Double ICC, using tyrosine hydroxylase (TH, the rate limiting enzyme in DA synthesis)-and OPN4x antibodies, confirmed the existence of OPN4x protein in DA-MEL neurons. Also, tOPN4x mRNA expression was verified with double ISH/ICC using tOPN4x mRNA and TH immunoreactivity. PMM and pineal gland tOPN4x mRNA expression levels were diurnally high during the night and low during the day. A light pulse provided to short day photosensitive hens during the photosensitive phase at night significantly down-regulated tOPN4x expression. The expression level of tOPN4x mRNA in PMM DA-MEL neurons of photorefractory hens was significantly lower as compared with that of short or long day photosensitive hens. The results implicate tOPN4x in hypothalamic PMM DA-MEL neurons as an important component of the photoreceptive system regulating reproductive activity in temperate zone birds.
Assuntos
Dopamina , Hipotálamo/metabolismo , Melatonina , Reprodução/fisiologia , Opsinas de Bastonetes/biossíntese , Estações do Ano , Animais , Aves , Ritmo Circadiano/fisiologia , Dopamina/análise , Feminino , Regulação da Expressão Gênica , Hipotálamo/química , Melatonina/análise , Neurônios/química , Neurônios/metabolismo , Fotoperíodo , Opsinas de Bastonetes/análise , PerusRESUMO
BACKGROUND: Evidence linking home hazards to falls has not been well established. The evidence-based approach to fall-risk assessment in longitudinal studies becomes difficult because of exposures that change during follow-up. We conducted a cohort study to determine the prevalence of hazards and to resolve whether they are linked to the risk of falls among 959 seniors receiving home-care services. METHODS: A home hazards assessment was completed at entry and every six months thereafter using a standardized form. The adjusted (for a number of confounding factors) relationship between home hazards and falls was estimated using a survival model taking into account updated time-varying exposures and multiple events. Falls leading to a medical consultation were examined as a secondary outcome, hypothesized as a measure of severity. FINDINGS: Home environmental hazards were found in 91% of homes, with a mean of 3.3 risks per individual. The bathroom was the most common place for hazards. The presence of hazards was significantly associated with all falls and fall-related medical consultations, and showed relatively constant effects from one fall to another. IMPLICATIONS: The current study is innovative in its approach and useful in its contribution to the understanding of the interaction between home environmental hazards and falls. Our results indicate that inattention to changes in exposure masks the statistical association between home hazards and falls. Each environmental hazard identified in the home increases the risk of falling by about 19%. These findings support the positive findings of trials that demonstrate the effectiveness of this home hazard reduction program, particularly for at-risk people.
Assuntos
Acidentes por Quedas/estatística & dados numéricos , Acidentes Domésticos/estatística & dados numéricos , Avaliação Geriátrica , Serviços de Assistência Domiciliar , Decoração de Interiores e Mobiliário/estatística & dados numéricos , Medição de Risco , Acidentes por Quedas/prevenção & controle , Acidentes Domésticos/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Lista de Checagem , Fatores de Confusão Epidemiológicos , Feminino , Pisos e Cobertura de Pisos/estatística & dados numéricos , Seguimentos , Avaliação Geriátrica/métodos , Serviços de Assistência Domiciliar/estatística & dados numéricos , Humanos , Incidência , Iluminação/estatística & dados numéricos , Modelos Lineares , Masculino , Prevalência , Modelos de Riscos Proporcionais , Quebeque/epidemiologia , Medição de Risco/organização & administração , Fatores de Risco , Gestão da Segurança/estatística & dados numéricos , Estatísticas não ParamétricasRESUMO
The Stylcam 100R, a rotary press simulator, was designed to simulate speed profiles of rotary tablet presses. Such a simulator was qualified by numerous laboratories and, actually, its ability to be used for studying the behaviour of powders under pressure should be examined. Then, the purpose of this work was to investigate the performances of the Stylcam 100R for characterizing the compaction behaviour and the tabletting properties of pharmaceutical powders. The compressibility of three pharmaceutical excipients (microcrystalline cellulose, dicalcium phosphate dihydrate and alpha-lactose monohydrate) was studied. Four compression speeds were used on the compaction simulator. Force-displacement cycles were associated with two energy parameters, the specific total energy (Es(tot)) and the specific expansion energy (Es(exp)). The mean yield pressure was calculated from Heckel's plots obtained with the in-die method. The diametral tensile strength of compacts was measured in order to evaluate mechanical properties. To evaluate the accuracy of all these parameters, a comparative study was carried out on an eccentric instrumented press. The values of energy parameters and tensile strengths of tablets are close between the eccentric press and the compaction simulator, whatever the compression speed on the latter. The mean yield pressure values obtained using the two presses are different. Finally, the Stylcam 100R seems to be a good tool for characterising tabletting properties of powders, except for the Heckel's model probably due to an unadapted equation of deformation and a lack of accuracy of the displacement transducers. Future improvements should allow correcting these two points.
Assuntos
Excipientes/química , Comprimidos , Fosfatos de Cálcio , Celulose , Pós/química , Pressão , Resistência à TraçãoRESUMO
The premammillary nucleus (PMM) has been shown to contain a daily endogenous dual-oscillation in dopamine (DA)/melatonin (MEL) as well as c-fos mRNA expression that is associated with the daily photo-inducible phase of gonad growth in turkeys. In the present study, the expression of clock genes (Bmal1, Clock, Cry1, Cry2, Per2 and Per3) in the PMM was determined under short (8 : 16 h light/dark cycle) and long (16 : 8 h light/dark cycle) photoperiods relative to changes associated with the diurnal rhythm of DA and MEL. Constant darkness (0 : 24 h light/dark cycle) was used to assess the endogenous response of clock genes. In addition, light pulses were given at zeitgeber time (ZT) 8, 14 and 20 to ascertain whether clock gene expression is modulated by light pulse stimulation and therefore has a daily phase-related response. In the PMM, the temporal clock gene expression profiles were similar under short and long photoperiods, except that Per3 gene was phase-delayed by approximately 16 h under long photoperiod. In addition, Cry1 and Per3 genes were light-induced at ZT 14, the photosensitive phase for gonad recrudescence, whereas the Clock gene was repressed. Gene expression in established circadian pacemakers, the visual suprachiasmatic nucleus (vSCN) and the pineal, was also determined. Clock genes in the pineal gland were rhythmic under both photoperiods, and were not altered after light pulses at ZT 14, which suggests that pineal clock genes may not be associated with the photosensitive phase and reproductive activities. In the vSCN, clock gene expression was phase-shifted depending on the photoperiod, with apexes at night under short day length and during the day under long day length. Furthermore, light pulses at ZT 14 induced the Per2 gene, whereas it repressed the Bmal1 gene. Taken together, the changes in clock gene expression observed within the PMM were unique compared to the pineal and vSCN, and were induced by long photoperiod and light during the daily photosensitive phase; stimuli that are also documented to promote reproductive activity. These results show that Cry1 and Per3 are involved in the photic response associated with the PMM neuronal activation and are coincident with an essential circadian mechanism (photosensitive phase) controlling the reproductive neuroendocrine system.
Assuntos
Proteínas Aviárias/metabolismo , Encéfalo/metabolismo , Ritmo Circadiano/fisiologia , Animais , Feminino , Imuno-Histoquímica , Hibridização In Situ , Luz , Microdissecção , Neurônios/metabolismo , Fotoperíodo , Glândula Pineal/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Núcleo Supraquiasmático/metabolismo , Fatores de Tempo , PerusRESUMO
The aim of this study was to better understand the effects of the curing conditions on the resulting drug release patterns from pellets coated with aqueous polymer dispersions. Diltiazem HCl was used as model drug, ethylcellulose as polymer, triethyl citrate (TEC), dibutyl sebacate (DBS), and distilled acetylated monoglycerides (Myvacet) as plasticizers. Interestingly, the effects of the curing conditions strongly depended on the coating level and the type of plasticizer: in the case of TEC, the drug release rate monotonically decreased with increasing harshness of the curing conditions (time, temperature, and relative humidity), irrespective of the coating level. In contrast, in the case of DBS and Myvacet, this type of relationship was only observed at low coating levels (5%). At intermediate coating levels (around 7.5%), the curing conditions had virtually no effect on drug release. At high coating levels (10%), the release rate initially increased and then decreased with increasing harshness of the curing conditions. This more complex behavior might be attributable to the superposition of two competing phenomena: improved film formation and drug migration into the polymeric membrane. Furthermore, it could be shown that the type of plasticizer had a major effect on drug release in not fully coalesced and equilibrated film coatings, whereas the release profiles were similar for all plasticizers in the case of completely formed and equilibrated film coatings. Importantly, the latter systems were stable for long term even during storage under stress conditions.
Assuntos
Composição de Medicamentos/métodos , Plastificantes/farmacocinética , Polímeros/farmacocinética , Celulose/análogos & derivados , Celulose/química , Diltiazem/farmacocinética , Implantes de Medicamento/síntese química , Implantes de Medicamento/química , Implantes de Medicamento/farmacocinética , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Emulsificantes/química , Umidade , Técnicas In Vitro , Plastificantes/química , Polímeros/química , Propriedades de Superfície , Temperatura , Fatores de Tempo , MolhabilidadeRESUMO
Serotonin and catecholamines (dopamine, norepinephrine, epinephrine) have important roles as neurotransmitters in avian reproduction, but their anatomical relationship to the neuroendocrine circuitry that regulates reproduction is poorly understood. Our previous studies have shown that co-localised dopamine-melatonin (DA-MEL) neurones in the avian premammillary nucleus (PMM) are active during periods of photoresponsiveness and, therefore, are potentially photosensitive neurones. Because serotonergic and catecholaminergic neurotransmitters are important regulators of reproductive function in the female turkey, we hypothesised that the serotonergic/catecholaminergic neurones within the brainstem might interact with PMM DA-MEL neurones and constitute an important circuit for reproductive function. To examine this possible interaction, the retrograde fluorescent tract tracer, 1,1'dioctadecyl-3,3,3'3'-tetramethyleindocarbocyanine perchlorate (DiI) was injected into the PMM, and combined with serotonin, tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH) and phenyl N-methyltransferse (PNMT) immunocytochemistry to reveal neuroanatomical connections. Changes in the activities of serotonergic, dopaminergic, adrenergic and noradrenergic neuronal systems projecting to the PMM were measured at different reproductive states with in situ hybridisation (ISH) techniques, using tryptophan hydroxylase 2 (TPH2) and TH mRNA expression, respectively. Cells labelled with DiI were found in anatomically discrete areas in or near the hypothalamus and the brainstem. Double immunocytochemistry confirmed that there were serotonin, DBH and PNMT fibres in close apposition to DA-MEL neurones. TPH2 mRNA expression in serotonin neurones was found in several nuclei, and its most abundant mRNA expression was seen in the nucleus Locus ceruleus of laying and incubating hens. TH mRNA expression levels in the six catecholaminegic areas labelled with DiI was measured across the different reproductive states. In the nucleus tractus solitarius (adrenergic), the highest level of TH mRNA expression was found in photorefractory hens and the lowest level in incubating hens. These observed patterns of serotonin/catecholamine neuronal distribution and their variable interactions with PMM DA-MEL neurones during different reproductive states may offer a significant neuroanatomical basis for understanding the control of avian reproductive seasonality.
Assuntos
Dopamina/metabolismo , Epinefrina/metabolismo , Hipotálamo/metabolismo , Melatonina/metabolismo , Norepinefrina/metabolismo , Serotonina/metabolismo , Perus , Animais , Encéfalo/anatomia & histologia , Encéfalo/metabolismo , Feminino , Hipotálamo/citologia , Isoenzimas/genética , Isoenzimas/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Reprodução/fisiologia , Triptofano Hidroxilase/genética , Triptofano Hidroxilase/metabolismo , Perus/anatomia & histologia , Perus/metabolismoRESUMO
The identification of risk factors for falls in longitudinal studies becomes difficult because of exposures that change during the follow-up and also because individual subjects may experience an event more than once. These issues have been neglected and improper statistical techniques have been used. The typical approaches have been to report the proportion of fallers or the time to first fall. Both avoid the underlying assumption of independence between events and discard pertinent data. We review the existing methods and propose a Cox hazards extension. We exemplify it in the study of potential risk factors associated with all falls in 959 seniors. Finally, we compare the results of the proposed Wei, Lin, & Weissfeld (WLW) method with those of several other techniques. Stable exposure variables measured at baseline and updated time-varying exposures include socio-demographic characteristics, BMI, nutritional risk, alcohol consumption, home hazards, gait and balance, and medications. Results demonstrate that the usual methods of analyzing risk factors for falling are inappropriate, as they produce considerable biases relative to the WLW model using time-dependent covariates. Results also show that modeling for first events may be inefficient, given that the risk of occurrence varies between falls.
Assuntos
Acidentes por Quedas/estatística & dados numéricos , Serviços de Assistência Domiciliar/estatística & dados numéricos , Modelos de Riscos Proporcionais , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Algoritmos , Benzodiazepinas/uso terapêutico , Viés , Índice de Massa Corporal , Estudos de Coortes , Feminino , Seguimentos , Marcha/fisiologia , Habitação , Humanos , Modelos Logísticos , Masculino , Destreza Motora/fisiologia , Estado Nutricional , Equilíbrio Postural/fisiologia , Medicamentos sob Prescrição , Quebeque/epidemiologia , Recidiva , Fatores de Risco , Classe Social , Fatores de Tempo , Tranquilizantes/uso terapêuticoRESUMO
Changes in circulating levels of prolactin (PRL) and tissue content of PRL receptor (PRLR) messenger RNA (mRNA) in the liver, pancreas, kidney, and gonads (testis/ovary) were measured in turkey and chicken embryos from embryonic day (ED) 21 or ED15, respectively, to 1 d after hatch by real-time PCR. There were no differences between the sexes in chickens or turkeys. Both species had very similar patterns of PRL release and expression of PRLR mRNA, and no major differences were observed between turkey or chicken embryos. Plasma levels of PRL increased from low levels during the last week of embryonic development and were at significantly higher levels (about 4-fold) by 1 d after hatch. Similarly, in all tissues the content of PRLR mRNA was minimal at the outset and increased to reach maxima about the time of hatch. In both species, the highest levels of transcript were observed in the kidney followed by the gonad, liver, and pancreas. The tissue content of PRLR was correlated (0.6 to 0.8 dependent on the tissue) to circulating levels of PRL, which suggested that PRL may be associated with an increase in its receptor number around the time of hatch. Because levels of PRL and tissue content of PRLR mRNA increased around the time of hatch, this suggests that these tissues may be targets for PRL and may be involved in the physiologic changes occurring in embryos around the time of hatching.
Assuntos
Embrião de Galinha/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Receptores da Prolactina/genética , Receptores da Prolactina/metabolismo , Perus/embriologia , Perus/metabolismo , Animais , Feminino , Masculino , Prolactina/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Perus/genéticaRESUMO
Changes in levels of PRLR mRNA in the pituitary gland and hypothalamus of chickens and turkeys from embryonic day (ED) 15 and ED21 to 1 day post-hatch, respectively, were measured by real-time PCR. In both species, PRLR mRNA increased from low levels during the last week of ED to reach maxima at the peri-hatch period. Similarly, circulating levels of PRL also increased during this interval and were highly correlated with levels of the PRLR mRNA in both the pituitary gland and hypothalamus. This suggests that PRL was up-regulating its receptor. In support of this, stimulation of the turkey pituitary gland with VIP on ED24 resulted in a 4- and 3-fold increase in PRL and PRLR, respectively. Since VIP had no direct effect on the levels of PRLR transcript in the hypothalamus, it is likely that VIP is acting indirectly through increased PRL to up-regulate the number of receptors.
Assuntos
Galinhas/metabolismo , Hipotálamo/metabolismo , Adeno-Hipófise/metabolismo , RNA Mensageiro/biossíntese , Receptores da Prolactina/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Perus/metabolismo , Animais , Western Blotting/veterinária , Embrião de Galinha , Galinhas/genética , Desenvolvimento Embrionário/fisiologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Hipotálamo/fisiologia , Adeno-Hipófise/fisiologia , Prolactina/sangue , RNA Mensageiro/genética , Receptores da Prolactina/biossíntese , Perus/embriologia , Perus/genética , Peptídeo Intestinal Vasoativo/farmacologiaRESUMO
Three pharmaceutical excipients (microcrystalline cellulose, lactose, anhydrous calcium phosphate) and their binary mixtures were compacted to form compacts of various mean porosities. Some mechanical properties (Young's modulus, tensile strength and Brinell hardness) were studied on these compacts. The mechanical properties of the binary mixtures were not proportional to the mixture composition expressed in mass. More, for all the properties, a negative deviation was always observed from this linear relationship. In reference to a composition percolation phenomenon, critical mass fractions were detected from the graph mechanical property vs. mass composition of a mixture. The results obtained with Brinell hardness differed from the results of the Young's modulus and the tensile strength, i.e. the most plastic material in the binary mixture controlled the mixture behaviour. Secondly, a predictive model based on a statistical approach was proposed for the Young's modulus and the tensile strength. The validity of this model was verified on experimental data, and an interaction parameter used to characterize the affinity of the two compounds was calculated. Finally, the X-ray tomography technique was applied to the compacts of cellulose/phosphate mixtures to obtain cross-sections images of the compacts. The analysis of the cross-sections images allowed explaining the no linear relationship of the different mechanical properties results observed on these binary mixtures.
Assuntos
Química Farmacêutica/métodos , Comprimidos/química , Tecnologia Farmacêutica/métodos , Celulose/química , Composição de Medicamentos , Desenho de Fármacos , Excipientes/química , Modelos Químicos , Modelos Teóricos , Pós , Estresse Mecânico , Resistência à Tração , Tomografia Computadorizada por Raios X/métodos , Raios XRESUMO
The compressibility of three pharmaceutical excipients (microcrystalline cellulose, lactose and anhydrous calcium phosphate) and their binary mixtures was studied. The aim of this work was to observe the impact of the mass composition of the mixture on the compressibility. The single-compound materials and their mixtures were compacted using instrumented presses. It allowed obtaining compression cycles (i.e., force-displacement curves) which were associated with energy measurements (specific compaction energy, Esp cp and specific expansion energy, Esp exp). It was observed that for the mixtures studied, the change of Esp cp with the mass composition could be fitted using a linear relationship (it was not the case with Esp exp). A linear relationship between the porosity of mixture's compacts and the mass composition was also obtained. Heckel's plots were then obtained for the three excipients and the mixtures. The mean yield pressure was calculated with the "in-die-method" and the "out-of-die method". A proportional relationship was not valid for the mean yield pressures. But, a predictive approach was proposed in order to obtain indirectly the mean yield pressure of a binary mixture if the data of the single materials were known. It used the linear mixing rule observed with the porosity. The validity was verified and compared with the experimental values. This comparison showed that it was possible to predict the mean yield pressure of binary mixtures from the accessible data of the single excipients.
Assuntos
Química Farmacêutica/métodos , Tecnologia Farmacêutica/métodos , Fosfatos de Cálcio/química , Celulose/química , Composição de Medicamentos , Estabilidade de Medicamentos , Lactose/química , Modelos Teóricos , Preparações Farmacêuticas/química , Pós , Pressão , Comprimidos , Resistência à TraçãoRESUMO
Physico-chemical properties of a substance including the compaction behaviour are directly connected with the crystalline structure. The aim of this work is to compare the compaction behaviour in a group of excipient and in this first part, to display the influence of lactose structures on the compressibility. alpha-Lactose monohydrate (LalphaM), anhydrous beta-lactose (LbetaA), anhydrous alpha-lactose (LalphaA) and partly amorphous lactose (FF) were compressed using instrumented presses to investigate the densification behaviour under pressure. Force-displacement curves were associated to two energy parameters, specific cycle energy and specific expansion energy. This approach was used to class the four lactose species. It is possible to differentiate three groups with the specific energy cycle, FF, LalphaA/LbetaA and LalphaM in decreasing order of this energy. At the same time, the values of specific expansion energy are relatively low for FF and LalphaA contrary to LalphaM and LbetaA. Then, Heckel's plots were obtained with two compact geometries and the mean yield pressure was calculated from the in-die-method and the out-of-die-method. Two lactoses seem to differ, LalphaM appears to be the most ductile whereas LalphaA is more brittle than the others. Finally, it is concluded, that in the case of lactoses, pseudopolymorphism seems to affect the compressibility more than anomerisation or partial amorphisation.
Assuntos
Lactose/química , Preparações Farmacêuticas/química , Tecnologia Farmacêutica/métodos , Força Compressiva , Cristalização , Cristalografia por Raios X , Lactose/análogos & derivadosRESUMO
OBJECTIVE: To compare the antipyretic efficacy of an initial 30-mg/kg acetaminophen loading dose versus a 15-mg/kg maintenance dose. METHODS: A double-blind, parallel-group, randomized clinical trial was conducted. A total of 121 febrile (rectal temperature between 39 degrees C and 40 degrees C) but otherwise healthy outpatients who were 4 months to 9 years of age and weighed 4 to 26 kg were assigned randomly to 1 of the dose groups: 15 mg/kg (n = 62) and 30 mg/kg (n = 59). RESULTS: In an "intention to treat" analysis, the time to obtain a temperature lower than 38.5 degrees C was significantly shorter in the 30-mg/kg than in the 15-mg/kg group (110 +/- 94 minutes vs 139 +/- 113 minutes). The maximum temperature decrease was significantly higher in the 30-mg/kg than in the 15-mg/kg group (2.3 +/- 0.7 degrees C vs 1.7 +/- 0.6 degrees C). Duration of rectal temperature below 38.5 degrees C was significantly longer in the 30-mg/kg than in the 15-mg/kg group (250 +/- 92 minutes vs 185 +/- 121 minutes, respectively). Adverse events were reported in 6 children in the 30-mg/kg group compared with 5 in the 15-mg/kg group (hyperthermia, hypothermia, vomiting). The difference was not statistically significant. CONCLUSION: An initial 30-mg/kg acetaminophen loading dose seemed to be more effective in reducing fever than a 15-mg/kg maintenance dose. No difference was observed regarding clinical tolerance. These data suggest that acetaminophen treatment of fever may be more efficient in an initial loading dose.
Assuntos
Acetaminofen/uso terapêutico , Analgésicos não Narcóticos/uso terapêutico , Febre/tratamento farmacológico , Acetaminofen/administração & dosagem , Administração Oral , Assistência Ambulatorial , Analgésicos não Narcóticos/administração & dosagem , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Febre/diagnóstico , Humanos , Lactente , Masculino , Resultado do TratamentoRESUMO
Magnetic Resonance Imaging (MRI) was used to study the mixing process of binary mixtures of free flowing sugar beads in a Turbula mixer. In order to make particles MRI-sensitive, some reference beads were doped with an organic oil. Doped and undoped particles were mixed and MRI was used to non-destructively image the particle bed for a given number of mixer rotations (NR), bead diameter ratio (R=d(ref)/d(i)) and rotation speed (V). All the results were quantified on the basis of image analysis to characterise the degree of mixing. Studies showed that for binary mixtures of identical particle size, the mixing was complete after 30 rotations, whereas for beads of different size (R=2.8) a segregated steady state was obtained after nearly 10 rotations. Experiments revealed that segregation appeared as soon as R=0.9. Moreover, the lower the rotation speed, the more segregated the final state was. It appeared that for a filling level greater than 80%, dead regions appeared in the centre of the powder bed. In conclusion, when the particles are non-cohesive, the Turbula blender perfectly mixes identical beads but segregation occurs for beads of different size after just a few rotations.
Assuntos
Carboidratos , Imageamento por Ressonância Magnética , Tecnologia Farmacêutica , Química FarmacêuticaRESUMO
Diffusion of mifepristone in poly [(D,L) lactide-co-glycolide)] films was studied by release experiments. Five 50/50 copolymers of increasing molecular weights were used. The degradation effects were shown by gel permeation chromatography (GPC). Release kinetics show the effect of copolymer molecular weights on diffusion and degradation properties of loaded films. A new theoretical model for drug release from a biodegradable matrix was proposed with two assumptions: correlation of the diffusion coefficient with the polymer molecular weight and existence of a first order degradation kinetic. Higuchi's equation is verified at early time and the diffusion coefficient in the non-degraded polymer can be measured. The degradation constant is determined at long time and is compared with the results of GPC.
Assuntos
Antagonistas de Hormônios/administração & dosagem , Mifepristona/administração & dosagem , Algoritmos , Cromatografia em Gel , Difusão , Excipientes , Antagonistas de Hormônios/farmacocinética , Ácido Láctico , Mifepristona/farmacocinética , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros , SolubilidadeRESUMO
It has been postulated that existing species have been linked in the past in a way that can be described using an additive tree structure. Any such tree structure reflecting species relationships is associated with a matrix of distances between the species considered which is called a distance matrix or a tree metric matrix. A circular order of elements of X corresponds to a circular (clockwise) scanning of the subset X of vertices of a tree drawn on a plane. This paper describes an optimal algorithm using circular orders to compare the topology of two trees given by their distance matrices. This algorithm allows us to compute the Robinson and Foulds topologic distance between two trees. It employs circular order tree reconstruction to compute an ordered bipartition table of the tree edges for both given distance matrices. These bipartition tables are then compared to determine the Robinson and Foulds topologic distance, known to be an important criterion of tree similarity. The described algorithm has optimal time complexity, requiring O(n(2)) time when performed on two n x n distance matrices. It can be generalized to get another optimal algorithm, which enables the strict consensus tree of k unrooted trees, given their distance matrices, to be constructed in O(kn(2)) time.
Assuntos
Algoritmos , Evolução Biológica , Modelos Biológicos , FilogeniaRESUMO
Most of the pharmaceutical processes involved in the manufacturing of so lid dosage forms are connected with powder flow properties, at least for some of the intermediate steps. Powder flow characteristics are commonl y investigated by various measurements, such as handling angles, tap tes ting, shear cell measurements, etc. All these approaches allow the calc ulation of indices characterising powder flowability. Unfortunately, th ese methodologies are highly product consuming, which is a limitation in the first steps of a novel drug development, when only a small amount of product is available. The use of mercury porosimetry to evaluate compre ssibility and flow properties of powders could be a new and alternative approach to obtain insight in the rheological properties of granular med ium by the interpretation of the first part of programs (low pressures) . We have developed such an evaluation and compared the results obtaine d with those given by tap testing and shear cell measurements, applied t o four excipients for direct tabletting and three different drugs. Merc ury porosimetry turned out to be a sensitive technique, able to providequantitative information about powder flow properties, complemen ted by an evaluation of particles micro porosity and size distribution, in a single step. These characterisations are obtained with only approx imately 250mg of bulk powder compared to high quantities ( >100g) needed for other methods.
Assuntos
Reologia , Tecnologia Farmacêutica , PósRESUMO
An exploratory survey was undertaken in the fall 1995 open-water fishing season with nine Bangladeshi and nine Vietnamese-origin sportfishers. Survey methodology and techniques of dietary and fish intake assessment were adapted to the cultural values and second language of each community. A 70-item instrument assessing sportfishing practices and fish consumption habits was administered by dietitians in participants' homes. Two 24-h diet recalls (aided by photographs taken by the participants) and a fish consumption calendar permitted the assessment of fish intake in the overall dietary context. A fish frequency item addressed consumption of locally available fish species (both sport and market fish) as well as imported frozen or dried species. Annually, Bangladeshi fishers consumed 46.8+/-25.6 sportfish meals, and Vietnamese fishers ate 40. 7+/-35.1 meals. In contrast, Bangladeshis reported greater annual consumption of imported, frozen nonsportfish (76.0+/-40.9 meals), and the Vietnamese ate more ocean than freshwater fish (45.1+/-34.4 ocean fish meals). Fish constituted approximately 19% of all protein foods eaten among the Bangladeshi fishers and 10% in the Vietnamese sample. Plasma and erythrocyte eicosapentanoic acid (EPA):arachidonic acid (AA) ratios supported findings from the fish frequency question showing that the two groups of Asian-origin fishers eat differing quantities of different fish species and that Asian-origin sportfishers-particularly the Bangladeshis-eat fish overall more frequently and in greater variety and quantity than francophone Quebecers; species selection appears to be both culturally motivated and influenced by the availability of St. Lawrence sportfish.