Oral delivery of low-molecular-weight heparin using sodium caprate as absorption enhancer reaches therapeutic levels

The primary objective of this study was to evaluate sodium caprate as an oral penetration enhancer for low molecular weight heparin (LMWH), ardeparin. In vitro studies using Caco-2 cell monolayer indicated that 0.0625% of sodium caprate gave approximately 2-fold enhancement of ardeparin compared to negative control with almost 100% cell survival as evaluated by MTT cytotoxicity assay. In vivo studies in rats with ardeparin (1,200 IU/kg) and sodium caprate (100 mg/kg) led to a relative bioavailability of 27% with plasma anti-factor Xa levels within the therapeutic range (>0.2 IU/ml). Moreover, under these conditions, histological examination provided evidence that there was no damage to the gastrointestinal wall. Regional permeability studies using rat intestine indicated the colon as the region of maximum permeation. These results suggest that, at the dose administered, sodium caprate acts as a relatively safe and efficient absorption enhancer in the quest for alternatives for the oral delivery of LMWH.     

Financial implications of a hospital's specialization in rare physiologically complex surgical procedures

BACKGROUND: The authors previously identified a hospital that has a unique role in its region for surgical care. In children aged 0-2 yr, the hospital performed 64% of all physiologically complex procedures statewide (>or= 8 American Society of Anesthesiologists Relative Value Guide basic units). For all age groups combined, 48% of the physiologically complex procedures performed at that hospital were rare, defined as < 1/workday statewide. METHODS: The authors tested the hypothesis that financially important differences can result from performing relatively large numbers of such specialized procedures. Methods were developed to compare contribution margin (revenue from facility and professional fees minus variable costs) per operating room hour (CM/OR hour) between patient groups and different types of surgical procedures. RESULTS: CM/OR hour was significantly larger by a financially important amount (> 250 dollars/OR hour) for pediatric versus geriatric patients (P 相似文献   

Neuropsychotropic activity of dopamine-analog 1,2,3,4-tetrahydro-beta-carbolines. 2. Alteration of activity by substituents]

Dopamine Analogous 1,2,3,4-Tetrahydro-β-carbolines, II: Alteration of Activity by Substituents Structure-activity relationships of doparnine analogous 1,2,3,4-tetrahydro-β-carbolines were elucidated by the synthesis of 10 new compounds and their psychopharmacological evaluation in rats and mice. Substituents on the 2-phenethyl group in the general formula a can be varied widely without gross alteration of activity. Methylation in 9-position of the carboline skeleton retains the neuroleptic activity, while a carbonyl group in 1 -position causes the activity to get lost. Substitution in 6-position by a methoxy group leads to a severe decrease of activity. A compound carrying chloro substituent in this position is nearly equipotent with 1a , while its action lasts slightly longer.     

Acute hydrocortisone administration does not affect subjective responses to d-amphetamine in humans

RATIONALE: Stress and glucocorticoids facilitate and reinstate psychostimulant self-administration in rodents. However, the effects of stress and glucocorticoids on the subjective and behavioral effects of psychostimulants have not been well studied in humans. OBJECTIVES: To examine the effects of acute hydrocortisone pretreatment on the subjective and behavioral effects of d-amphetamine. METHODS: Hydrocortisone (100 mg) and d-amphetamine (20 mg) were administered orally to 16 healthy male and female volunteers in a four-session, placebo-controlled, within-subject, crossover design. To prevent stomach irritation, subjects received rantidine hydrochloride before each experimental session. Dependent measures included self-reported mood and subjective effects (Addiction Research Center inventory, the profile of mood states, and a series of visual analogue scales), vital signs, salivary cortisol, and psychomotor performance. RESULTS: Hydrocortisone elevated salivary cortisol levels, produced modest dysphoria, and reduced subjects' reports of wanting more drug. However, hydrocortisone pretreatment did not affect any of the physiological, behavioral, or subjective effects of d-amphetamine. CONCLUSIONS: In contrast to the effects of glucocorticoids in rodent studies, these results indicate that an acute increase in cortisol does not enhance the psychostimulant effects of d-amphetamine in humans.     

Analysis of 585 burn patients hospitalized over a 6-year period. Part III: Psychosocial data

We have examined the physical and psychosocial aberrations found in a series of 585 hospitalized burn patients. The implications of this data have been discussed as they apply to identifying persons at high risk for burn injury, and as they apply to estimation of the prognosis in severe burn injury. This is a step towards identifying a psychosocial profile for the evaluation of burned patients.     

Thermal properties calculated from measured water content as a function of depth in porcine skin

In order to develop a realistic tissue water boiling routine for a mathematical model of burn development, it was necessary to know the water content and the thermal properties of skin as a function of depth. Split thickness skin samples were obtained from several pigs using an air-powered dermatome. Alternate segments of these skin slices were processed for skin water content determination and for histopathologic measurements of skin thickness. Tissue samples were weighed, dried and subsequently weighed again using standardized methods to determine tissue water content. In some instances the volume of tissue was also determined to allow the calculation of tissue density. Given a table of measured values of water content as a function of skin thickness, a least-squares cubic polynomial was fitted to the data and water content as a function of depth was computed from the following formula: w(T-d) = Tld× (W_T - W_T-d) + W_T-d where T is the total thickness of a skin slice, W_T is the fraction of water computed from the cubic equation, d is the thickness of the skin slice at a depth T-d, and W_T-d is the fraction of water above the thin slice. Stratum corneum hydration was calculated from measured ambient relative humidity based on a relationship previously described by Rushmer et al. (1966). Skin thermal properties as a function of depth were calculated using the formulation of Cooper and Trezek (1971).

Computer simulations incorporating these new thermal properties and the water profile into our previously presented model (Knox et al., 1978 a) show that these changes have resulted in improved predicted burn depths as judged by reduced root mean square (r.m.s.) error. Using this method studies can now be made of the changes in thermal properties which occur during various stages of thermal tissue damage, e.g. oedema, protein coagulation and shrinkage due to desiccation.     

Liquid-propane freeze injury: a case history

Exposure of skin to liquid propane causes a severe freeze injury. This cutaneous injury has the appearance of a partial-thickness thermal injury of indeterminate depth, but the deep tissue damage is greater than is at first apparent. A case history is presented that illustrates the severity of this particular mechanism of injury and the need for adequate safety precautions.     

Clonal cytogenetic abnormalities in Hodgkin's disease

Cytogenetic studies of Hodgkin's disease (HD), in contrast to those of non-Hodgkin's lymphoma (NHL), have been limited to small numbers of cases with infrequently recurring aberrations, underscoring the need for additional studies in establishing a coherent cytogenetic picture of HD. Over a 6 1/2-year period, we received 95 specimens of HD for cytogenetic analysis. Analyzable chromosome preparations were obtained in 70 cases, of which 57 (81%) showed only normal metaphases. In the remaining 13 cases (19%), karyotypic abnormalities were observed that were nonclonal in 3 and clonal in 10. The latter 10 cases included 6 of the nodular sclerosis subtype, 3 mixed cellularity, and 1 lymphocyte-depleted; 8 of the specimens were obtained pretreatment and 2 posttreatment. Two of the cases had a clonal numerical aberration, monosomy 17 in one and trisomy 13 in the other, as their sole abnormality. The remaining 8 cases showed complex karyotypes with multiple structural rearrangements; in 3 of these, the abnormal clone was near-tetraploid. Bands involved more than once included 1p36, 1q21, and 4q35, each in 2 cases. Arms involved more than once included 6q (6q13,6q23), 9p (9p13,9p21), and 5q (5q15,5q35). Three patients had loss of part or all of 6q (del(6)(q13),del(6)(q23),i(6p). Bands 14q32 and 18q21 were not involved in any case, contrary to some previous reports. Our results confirm the frequent occurrence of 1p, 1q, and 6q abnormalities in HD. In addition, we have identified a 5q35 breakpoint, which has recently been shown to be highly specific for Ki-1-positive NHL in a case of typical nodular sclerosis HD. Its presence in HD may represent a cytogenetic link between the two entities, which are immunophenotypically related but clinically and histologically distinct.