RESUMO
BACKGROUND AND AIM: Acute respiratory failure (ARF) is a condition that must be treated as quickly as possible. Continuous Positive Airway Pressure (CPAP) is a common method used to treat ARF in hospital. The main objective of our study was to investigate the effect of CPAP prior to admission to the emergency room, on the reduction of endotracheal intubation, in-hospital mortality and on the length of stay in hospital (HLOS). METHODS: A prospective, observational (non-randomised) study with a historical control group. Data from 3 groups of patients with ARF, irrespective of cause, was collected: pre-hospital CPAP (PHCPAP) group, i.e., 35 patients treated with a helmet CPAP in the ambulance, by trained nurses (mean age, years 80.1 +/- 7.9 SD; 14 males); hospital CPAP (HCPAP) group, i.e., 46 patients treated with helmet CPAP in the hospital emergency room (mean age 78.6 +/- 6.9 SD; 27 males), and a historical control group of 125 patients treated with medical therapy only (mean age 76.7 +/- 5.5 SD; 52 males). CPAP was delivered via a helmet interface. RESULTS: Compared with standard medical therapy, helmet CPAP (pre and in-hospital) reduced mortality by 77% (p = 0.005), while pre-hospital helmet CPAP reduced it by 94% (p = 0.011), after adjustment for age, sex, severity of clinical conditions at entry and diagnosis upon admission. HLOS was reduced, compared with standard medical therapy, by 63.5% and by 66% (adjusting for age, sex, severity of clinical conditions at entry and diagnosis at admission) with helmet CPAP (pre and in-hospital) and with helmet CPAP in the ambulance, respectively (p < 0.0001). CONCLUSIONS: Treating patients with ARF of any cause, with CPAP by trained nurses, before hospital admission, is safe, reduces mortality and the length of stay needed in hospital.
Assuntos
Pressão Positiva Contínua nas Vias Aéreas/métodos , Serviços Médicos de Emergência , Insuficiência Respiratória/terapia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Dispositivos de Proteção da Cabeça , Mortalidade Hospitalar , Humanos , Intubação Intratraqueal , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/mortalidade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
In this communication, an application of classical thermodynamics to crystalline solid state polymorphism is shown to allow stability p, T domains and stability hierarchy among crystalline phases of a polymorph to be defined by constructing the unary p, T phase diagram. The three topological rules upon which this construction is founded are presented; the first one is a straight consequence of the least vapour pressure criterion by Ostwald. Calculation of triple point co-ordinates and of two-phase equilibrium curves is based upon using both thermodynamic and crystallographic data obtained at ordinary pressure. Clapeyron equation allows the slopes of the straight lines representing equilibria between condensed phases to be calculated and, hence, triple points situated at high or negative pressure to be determined. On the other hand, the hierarchy among the thermodynamic stability degrees of the crystalline varieties may be inferred from the location of the sublimation curves, by merely acknowledging inequalities among vapour pressures at each temperature on the whole T-range. These building-up processes are pointed out by outlining the achievement of a phase diagram related to the tetramorphism of fananserine, an anxiolytic drug. Three out four crystalline forms, namely phases II, III and IV, possess their own stability domain, although those belonging to phases II and III are limited at high pressure by that of phase IV. Conversely, phase I is overall metastable and exhibits a whole monotropic behaviour.
Assuntos
Ansiolíticos/química , Óxidos S-Cíclicos/química , Naftalenos/química , Estabilidade de Medicamentos , Conformação Molecular , Pressão , TermodinâmicaRESUMO
The present work extended previous physico-chemical investigations on the effects of solid dispersion on the solubility, the dissolution rate and the pharmacokinetic profile of carbamazepine. Solubility studies showed a linear increase in carbamazepine solubility with the increase of PEG 6000 concentration. There is no marked difference between physical mixtures and solid dispersions for the enhancement of carbamazepine solubility by PEG 6000. Less than 60% of pure carbamazepine was dissolved in 90 min. Physical mixtures (carbamazepine phase III) and solid dispersions (carbamazepine phase II) dissolution rates were higher in comparison of the parent drug. The dissolution of carbamazepine phase III was more pronounced than that evoked by the phase II. The dissolution profiles indicated that the percentage of the drug dissolved was dependent on the proportion of PEG 6000. In solid dispersions there was a remarkable enhancement in the dissolution rates of the drug in the vicinity of the eutectic composition as compared with those of corresponding physical mixtures. Hence, the optimum value for the solid dispersion was 80.5+/-1.7% of carbamazepine having dissolved within the first 10 min compared to 40+/-1% for the corresponding physical mixtures of the same composition. Statistical analysis of pharmacokinetic parameters confirmed that the carbamazepine:PEG 6000 binary systems displayed higher bioavailability of the drug than the pure carbamazepine. The area under the curve (AUC) values highlighted the evidence that only slight differences in the bioavailability of the drug occur between physical mixtures and solid dispersions prepared at the 80:20 and 50:50 drug:carrier compositions. However, the mean normalized plasma concentrations showed that standard error deviations are rather wide intervals for pure drug and physical mixtures in comparison to solid dispersions. One additional interesting point to consider is the disappearance of the multiple peaks on the individual kinetic curves of the 50:50 solid dispersion composition. Furthermore, our investigations have highlighted the interest of solid dispersions prepared at <
Assuntos
Anticonvulsivantes/química , Carbamazepina/química , Polietilenoglicóis , Administração Oral , Animais , Anticonvulsivantes/farmacocinética , Área Sob a Curva , Disponibilidade Biológica , Carbamazepina/farmacocinética , Química Farmacêutica , Combinação de Medicamentos , Meia-Vida , Coelhos , SoluçõesRESUMO
PURPOSE: Sulfanilamide trimorphism was chosen as a model system for comparison between stability hierarchies obtained from lattice-energy calculations with those deduced from the relative locations of the sublimation curves of polymorphs in the sulfanilamide p, T diagram. METHODS: The atom-atom potential (AAP) method was used for lattice-energy calculations. The p, T diagram was constructed by using crystallographic and thermodynamic data for alpha-, beta-, and gamma-forms, and by assigning the temperatures of the experimentally observed phase transitions to triple points involving the vapour phase. RESULTS: The hierarchy obtained with the AAP method (E alpha > or = E gamma > > E beta) differs only slightly from that deduced from the positions of the sublimation curves (p gamma > p alpha > p beta) in the p, T diagram at room temperature. No stable phase region was found for form alpha. Thus it is really monotropic. CONCLUSIONS: Provided enthalpy and volume changes at the transitions are accurate enough, it is possible to draw a p, T diagram that accounts for the stability hierarchy of polymorphs.
Assuntos
Sulfanilamidas/química , Temperatura , Termodinâmica , Cristalografia , Estabilidade de Medicamentos , Modelos Moleculares , Pressão , Estereoisomerismo , SulfanilamidaRESUMO
PURPOSE: Sulfanilamide was chosen as a model compound in order to gain insights on the stability hierarchy of drug polymorphs from structural and thermodynamic criteria. Despite numerous studies, disagreements remained on the reported enthalpies associated with the mutual interconvertions of the alpha-, beta-, and gamma-forms of sulfanilamide. Therefore, the unambiguous determination of these enthalpies was the purpose of this work. METHODS: Samples, free of solvent inclusions and made of only one form, were prepared, and analyzed combining X-ray powder diffraction and Differential Scanning Calorimetry (DSC). RESULTS: The enthalpy values associated with the alpha- to gamma- and beta- to gamma-transitions were found to be + 10.2 and + 10.9 J g-1, respectively. The calculated enthalpy of the beta- to alpha-transition is consistent with the experimental one (+ 1 J g-1). CONCLUSIONS: The monotropy of the alpha-form was ascertained over the explored temperature range at ordinary pressure.
Assuntos
Sulfanilamidas/química , Varredura Diferencial de Calorimetria , Temperatura Baixa , Cristalização , Termodinâmica , Difração de Raios XRESUMO
In normal subjects, the early human pancreatic polypeptide (hPP) increase induced by food is mainly dependent on vagal activity. Parasympathetic function and plasma hPP response to a standard mixed meal were evaluated in 10 long term insulin-dependent (type I) diabetic patients (group A), 6 age-matched newly diagnosed type I diabetic patients (group B), and 8 normal subjects. The indices of vagal function (beat to beat heart rate variation during deep breathing and the Valsalva maneuver) were uniformly altered in group A, while they were in the normal range in group B, thus excluding in these latter patients the presence of vagal damage. Plasma hPP in response to standard mixed meal was measured at 5, 15, 30, 60, and 120 min. Fasting plasma hPP concentrations (determined by RIA) in groups A and B (mean +/- SEM, 113 +/- 21 and 83 +/- 21 pg/ml, respectively) did not significantly differ from normal (59 +/- 12 pg/ml). In group A, the initial meal-induced hPP increase was significantly lower than normal (5 min, 139 +/- 12; 15 min, 173 +/- 24; 30 min, 137 +/- 17 pg/ml; P less than 0.01 vs. 5 min, 412 +/- 76; 15 min, 446 +/- 57; 30 min, 325 +/- 56 pg/ml). All group B patients had a marked early increase in the peptide, similar to that in the normal subjects. These results suggest that diabetic autonomic neuropathy is associated with dysfunction of hPP secretion, and the evaluation of hPP in response to SMM may be considered a sensitive and nonstressful method for the assessment of parasympathetic impairment in diabetes.
Assuntos
Doenças do Sistema Nervoso Autônomo/sangue , Neuropatias Diabéticas/sangue , Polipeptídeo Pancreático/sangue , Adolescente , Adulto , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Feminino , Alimentos , Humanos , MasculinoRESUMO
Human pancreatic polypeptide is the only hormone so far reported which clearly suppresses somatostatin release, suggesting that this peptide may have a role in controlling somatostatin secretion from the gut and pancreas. In this study endogenous high circulating human pancreatic polypeptide concentrations in patients with chronic renal failure do not decrease somatostatin circulating levels. The reduced clearance rate of somatostatin in chronic renal failure may partially account for the normal circulating levels of somatostatin observed in our patients with respect to controls. Renal insufficiency may, itself, induce an increase in some gastrointestinal peptides capable of stimulating somatostatin secretion.