RESUMO
Intraoperative proximal femur fractures are a significant concern during noncemented total hip arthroplasty. The current study was performed to investigate the hypothesis that broaching the femur and inserting the stem without using mallet applied impact loads will reduce the risk of intraoperative fracture. Rosette strain gauges were applied to the medial and anteromedial cortex of six human anatomic specimen femurs to compare the strain distribution for broaching and stem insertion. Eight additional femurs were used to compare the strain distribution for stem insertion using impact loading and constant rate stem insertion. For the impact loading stem insertions, the soft tissues surrounding the femur were modeled. Constant rate stem insertions were performed using a mechanical testing machine. The largest strains measured at the medial and anteromedial sites primarily were aligned with the femur hoop axis. The largest strain magnitude, orientation, and sign (tensile or compressive) varied widely among femurs. The stem insertion strains were significantly larger than the broaching strains (two-way analysis of variance with replication). The impact stem insertion strains were not significantly different from the constant rate stem insertion strains. The results indicate that the femur geometry and material properties have a greater influence on the strain distribution than does the implantation technique.
Assuntos
Artroplastia de Quadril/métodos , Fêmur/fisiologia , Análise de Variância , Artroplastia de Quadril/estatística & dados numéricos , Fenômenos Biomecânicos , Cimentos Ósseos , Cadáver , Fraturas do Fêmur/prevenção & controle , Fêmur/cirurgia , Humanos , Complicações Intraoperatórias/prevenção & controleRESUMO
A complete review of the literature disclosed that there were 42 reports of 2025 hips treated by either core decompression (1206 hips) or nonoperative management (819 hips), excluding electrical stimulation, for osteonecrosis of the femoral head. The peer-reviewed published reports included general surveys, prospective studies, and multicenter studies, but excluded case reports. Satisfactory clinical results were reported in 63.5% of hips in 24 studies of core decompression and in 22.7% of hips in 21 studies of nonoperative management. When looking at only precollapse hips, there were 71% versus 34.5% good results, respectively. Recalculation excluding reports by the 4 centers that do the most core decompressions (and report the best results) showed a clinical success rate for core decompression of 53% versus 22.7% for the nonoperatively treated group. Investigators of multiple studies have reported that nonoperative management leads to extremely poor results. Core decompression has been reported to have a notable effect on the natural history and clinical progression in early stages of osteonecrosis of the femoral head. In view of the limitations of this data, further clarification of this effect only can be obtained by large prospective randomized studies.
Assuntos
Necrose da Cabeça do Fêmur/terapia , Necrose da Cabeça do Fêmur/cirurgia , Humanos , Complicações Pós-Operatórias , Resultado do TratamentoRESUMO
Probenecid has been shown to decrease renal and biliary excretion of organic acids. In a randomized crossover study, the effect of coadministered probenecid on nonrenal excretion of ceftriaxone was studied in six functionally anephric patients in whom ceftriaxone is eliminated exclusively by nonrenal or presumably by biliary excretion. Each patient received 0.5 g IV ceftriaxone without and with probenecid (0.5 g at 10 and 2 hours prior to ceftriaxone and 0.5 g q12h X 3 doses post ceftriaxone). Serial blood samples were collected over 48 hours and plasma analyzed for ceftriaxone by high performance liquid chromatography (HPLC). Pharmacokinetic analysis was based on a model-independent approach. Probenecid did not significantly affect the disposition of ceftriaxone in this study, thus suggesting that nonrenal excretion of ceftriaxone is not inhibited by probenecid.
Assuntos
Ceftriaxona/farmacocinética , Falência Renal Crônica/metabolismo , Probenecid/farmacologia , Adulto , Ceftriaxona/administração & dosagem , Ceftriaxona/sangue , Cromatografia Líquida de Alta Pressão , Humanos , Pessoa de Meia-Idade , Distribuição Aleatória , Fatores de TempoRESUMO
We examined the effect of prenatal stress exposure on sensitivity to caffeine using behavioral and physiological measures. Pregnant rats were handled 5 minutes daily from the 14th to 21st day of gestation. Male offspring were tested when 60 days of age in a modified open field apparatus 30 and 90 minutes after injection with caffeine (0, 10, 30 mg/kg). Caffeine increased crossover frequency and duration at the 10 mg/kg dose. Rearing frequency and duration were increased by the 10 mg/kg dose while the 30 mg/kg dose was ineffective. Gnawing was increased by caffeine, especially 90 minutes postinjection. Headpoke activity was decreased by caffeine treatment. Caffeine had no effect on defecation and urination. Gnawing activity was increased by caffeine in prenatally nonstressed animals, but was depressed in prenatally stressed animals. Prenatal stress increased sensitivity to caffeine on corner activity and rearing. The other measures were not affected differentially by prenatal stress exposure. Rectal temperature was depressed 0.75 degrees C in both prenatally stressed and nonstressed animals, by the 30 mg/kg dose of caffeine. Thus, our results indicate that prenatal stress affects sensitivity to caffeine in the adult offspring. However, the long-term effects of prenatal stress exposure are dependent on the measures employed.
Assuntos
Cafeína/farmacologia , Efeitos Tardios da Exposição Pré-Natal , Estresse Psicológico/psicologia , Animais , Temperatura Corporal/efeitos dos fármacos , Cafeína/sangue , Corticosterona/sangue , Defecação/efeitos dos fármacos , Feminino , Masculino , Atividade Motora/efeitos dos fármacos , Gravidez , Ratos , Ratos Endogâmicos , Micção/efeitos dos fármacosRESUMO
We have examined factors that alter the effect of diazepam (DZ) on plasma corticosterone (CS) in rats. DZ had a biphasic effect on plasma CS levels: CS decreased with doses below 5 mg/kg and increased with higher doses. Peak response occurred 90 minutes post injection in both sexes. Plasma DZ levels were significantly higher in females than in males and peak at 10 and 30 minutes post injection in males and females, respectively. There was also a sex difference in the pattern of DZ metabolites. An acute stressor (30 minutes of immobilization) did not affect plasma CS levels in rats injected with a 5 mg/kg dose of DZ. Prenatally stressed animals did not differ in basal CS levels or in their response to 5 mg/kg of DZ compared to prenatally non-stressed animals. These two groups of animals also did not differ in plasma levels of DZ or of its metabolites. By contrast, the 5 mg/kg dose of DZ had no effect on plasma testosterone levels in control animals, but increased it in prenatally stressed animals. Furthermore, compared to non-stressed controls, prenatally stressed animals had lower baseline plasma testosterone levels. These results indicate that the effect of DZ on plasma CS is influenced by endogenous as well as exogenous factors and that these effects vary with the particular biochemical parameter under examination.
Assuntos
Corticosterona/sangue , Diazepam/farmacologia , Estresse Psicológico/sangue , Animais , Ansiolíticos/farmacologia , Temperatura Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Cinética , Masculino , Ratos , Ratos Endogâmicos , Valores de Referência , Restrição Física , Fatores SexuaisRESUMO
The disposition of the new antiarrhythmic agent cibenzoline (CBZ) (racemic 4,5-dihydro-2-(2,2-diphenylcyclopropyl)-1H-imidazole) in three male dogs was investigated after oral administration of 13.8 mg/kg of 14C-CBZ base. Within 6 days, 60.5 +/- 6.0% of the dose was excreted in urine and 19.2 +/- 4.6% in feces. In 0-24-hr urine, unchanged drug was excreted (41.6% of the dose) as well as the unconjugated 4,5-dehydro metabolite (DHCBZ, 3.7%), conjugated p-hydroxybenzophenone (0.8%, only in one dog), and a phenolic metabolite, p-hydroxycibenzoline (HCBZ) in a rearranged form (RHCBZ) at 5.2% of the dose (free plus conjugated). Studies with synthetic HCBZ indicated that unrearranged HCBZ was excreted and that rearrangement occurred during purification. CBZ from dog urine displayed slight optical activity, based on ORD/CD data, corresponding to an optical purity of 15% of the S-(-)-CBZ, indicating a limited extent of stereoselective metabolism of CBZ in dogs. After an oral 50-mg/kg dose of 14C-CBZ succinate, male rats excreted in 3 days 27.0 +/- 2.8% in urine and 41.5 +/- 2.6% of the dose in feces, and in a repeated experiment 32.1 +/- 1.9% in urine and 54.5 +/- 0.7% in feces. CBZ (7.6%) and DHCBZ (0.2%) were determined in 0-24-hr urine, and CBZ (4.2%) and RHCBZ (4.2% of the dose) were determined in 0-24-hr feces. RHCBZ (3.1%), m-methoxy p-hydroxycibenzoline (8.3%), and p-hydroxybenzophenone (5.3% of the dose) were identified as glucuronide/sulfate conjugates in bile from rats. Evidence that p-hydroxybenzophenone arose from an unstable unidentified metabolite is discussed.
Assuntos
Imidazóis/metabolismo , Administração Oral , Animais , Antiarrítmicos/metabolismo , Bile/análise , Biotransformação , Radioisótopos de Carbono , Cromatografia Líquida de Alta Pressão , Cães , Fezes/análise , Imidazóis/administração & dosagem , Imidazóis/análise , Imidazóis/urina , Masculino , Espectrometria de Massas/métodos , Ratos , Ratos EndogâmicosRESUMO
A microsomal metabolite of cibenzoline, 4,5-dihydro-2-(2,2-diphenylcyclopropyl)-1H-imidazole butanedioate, was identified by n.m.r. as the 4,5-dehydro analogue, 2-(2,2-diphenylcyclopropyl)-1H-imidazole. Three dogs dosed orally with 13.8 mg/kg 14C-cibenzoline base excreted 1.8-3.5% of the dose as this metabolite in the urine. Mean plasma concentrations of cibenzoline reached a peak of 1.5 micrograms/ml at 2 h while mean concentrations of the metabolite of 0.4-0.5 micrograms/ml were found between 2 and 7 h. The metabolite was synthesized and found to decrease the frequency of ventricular premature depolarizations in conscious dogs having a two-stage occlusion of the left anterior descending coronary artery performed 48 h before. It did not inhibit ventricular arrhythmia in rats induced by i.v. infusion of aconitine. Thus, in contrast to cibenzoline, the metabolite does not appear to be a true antiarrhythmic agent.
Assuntos
Antiarrítmicos/metabolismo , Imidazóis/metabolismo , Animais , Biotransformação , Cães , Espectroscopia de Ressonância Magnética , Masculino , Espectrometria de Massas , Microssomos Hepáticos/metabolismo , Ratos , Ratos EndogâmicosRESUMO
Clonazepam (CZP) was measured in the plasma of eight subjects for 48 hr after a 0.03-mg/kg oral dose. After pretreatment for 19 days with phenytoin (DPH, 4.3 mg/kg/day), plasma CZP concentrations were determined in the same subjects after another 0.03 mg/kg oral dose of CZP. The same protocol was followed in eight additional subjects using phenobarbital (PB, 1.4 mg/kg/day) instead of DPH. DPH pretreatment lowered mean plasma CZP concentration in 8 of the 12 time points. DPH pretreatment increased CZP clearance by 46% to 58% and decreased CZP half-life (t1/2) by 31%. Both changes were statistically significant. After PB pretreatment the mean plasma CZP concentration was lowered by an average of 11%, but the decrease was statistically significant for only 1 of the 12 time points. PB decreased mean CZP t1/2 by 11% and increased CZP clearance by 19% to 24%, but only the increase in clearance was statistically significant. Both DPH and PB increased CZP clearances and decreased the areas under the plasma concentration-time curves without altering the volumes of distribution. This observation is consistent with induction of CZP metabolism. The overall effect of DPH (4.3 mg/kg/day) was greater than the effect of PB (1.4 mg/kg/day). Neither the DPH or PB had a significant effect on the extent of CZP protein binding.
Assuntos
Benzodiazepinonas/metabolismo , Clonazepam/metabolismo , Fenobarbital/farmacologia , Fenitoína/farmacologia , Adulto , Interações Medicamentosas , Feminino , Meia-Vida , Humanos , Cinética , Masculino , Taxa de Depuração Metabólica/efeitos dos fármacos , Modelos BiológicosRESUMO
A specific radioimmunoassay (RIA) for the determination of the widely used non-narcotic antitussive agent, dextromethorphan (DM) in plasma and urine has been developed using an antiserum to DM which was obtained from rabbits following immunization with an albumin conjugate of (+)-3-methoxymorphinan-17-succinyloxyethyl. Specificity of the RIA was achieved by selective extraction of DM from its known metabolites into hexane at pH 6.5 with 86% recovery. Employing tritium labelled-DM as the radioligand the RIA had a limit of sensitivity of about 4 ng/ml of plasma using a 0.5 ml sample. Following I.V. administration of 2 mg/kg of DM to two dogs, the plasma levels of intact DM declined biexponentially; the terminal exponential phase having a half-life of 2.5-3.9 hr. The volume of distribution of the central compartment ranged from 5-6.4 l/kg while the metabolic clearance rate ranged from 2.5-2.6 1/hr/kg. Oral administration of 10 mg/kg of DM in gelatin capsule resulted in peak plasma levels of 50 and 92 ng/ml at 2 hr post-drug. Following both routes of administration, less than 3.5% of the dose was excreted in the urine as intact DM indicating almost complete biotransformation and/or alternate routes of excretion. In one human subject who received 0.5 mg/kg of DM P.O. in a syrup, the plasma levels were less than 1 ng/ml.