Validation of a Flow-Through Diffusion Cell for Use in Transdermal Research

A flow-through finite-dose diffusion cell has been designed for use in transdermal drug delivery research. The diffusion cell consists of an upper donor chamber and a lower receiver compartment through which a continuous supply of fresh solvent flows. The flow is directed to an automatic fraction collector. To validate the flow-through cell, its performance was compared directly against that of a conventional single-reservoir Franz cell. Homologous alkyl p-aminobenzoates were diffused through dimethylpolysiloxane membranes, and permeability coefficients increased with increasing chain length, reaching a plateau at the butyrate ester for both types of cells. This behavior suggests a shift from membrane-controlled diffusion to boundary layer control. Permeation of the butyrate and valerate compounds was significantly faster when the flow-through cell was used, suggesting that better mixing is obtained through the flow-through cell design. Considering the advantages offered in terms of time and labor saved through its use, the flow-through cell with automatic fraction collector appears to be a viable alternative to the conventional Franz cell.     

Nurse practitioner and physician assistant practices in three HMOs: implications for future US health manpower needs.

This study empirically examines the practices of non-physician providers (NPPs) within three large competitive health maintenance organizations (HMOs), as well as the physicians' and NPPs' views regarding the ideal role of NPPs. These roles are compared with NPP delegation patterns incorporated in the modeling methodology developed by the Graduate Medical Education National Advisory Committee (GMENAC). GMENAC recommended relatively high levels of delegation by physicians to NPPs. One of the HMO sites made use of NPPs at rates even higher than GMENAC's national ideals, while the rates at the other two were lower. The normative ideals for pediatric NPPs developed at each HMO were consistently higher than their actual roles. Concerns with acceptance and the role of NPPs are clearly no longer issues. Instead, the limits on NPP involvement appear to relate to considerations of costs, availability, and the increasing numbers of physicians competing for similar opportunities.     

Facilitation of discrimination transfers under amphetamine: the relative control by S+ and S− and general transfer effects

Rats were trained in a Y-maze on a two-choice simultaneous black-white discrimination with either black or white as S⁺. Animals were then transferred to one of three discrimination tasks. In task 1 (New S^–), a new stimulus, either vertical or horizontal stripes, was substituted for the original S^–. In task 2 (New S⁺), a new stimulus, either vertical or horizontal stripes as in task 1, was substituted for the original S⁺. In task 3 (New S⁺/S^–) animals were trained on horizontal-vertical discrimination. The pre-trial administration of 1 mg/kg d-amphetamine facilitated the acquisition of the original black-white discrimination with both black as S⁺ and white as S⁺. Likewise, the drug improved performance in all three transfer conditions. However, the course of learning in the three transfer tasks was different in the placebo- and amphetamine-treated animals. Amphetamine-treated animals were disrupted more by a change in S⁺ than by a change in S^–, whereas the opposite pattern was evident in the placebo controls. When both discriminative stimuli were changed, placebo animals exhibited pronounced decrement in performance, whereas amphetamine animals exhibited excellent learning. The implications of these findings for the effects of amphetamine on discrimination learning are discussed.     

Pharmacokinetics of intravenous bepridil in patients with coronary disease

The pharmacokinetics of intravenous bepridil (1-[2-(N-benzylanilino)-1-(isobutoxymethyl)ethyl]pyrrolidine ) were studied in 16 patients undergoing cardiac catheterization for evaluation of coronary disease, all with normal base-line hemodynamic and renal functions. Ten patients received 3 mg/kg and six patients received 4 mg/kg of bepridil infused over a period of 30 min. Plasma bepridil concentrations were measured by HPLC and analyzed by model-dependent and model-independent methods. The mean (+/- SD) maximum plasma bepridil concentrations at the end of the infusion were 2047 +/- 820 ng/mL (3 mg/kg) and 2478 +/- 1426 ng/mL (4 mg/kg). Postinfusion bepridil concentrations were best described by a two-compartment open model. The model-dependent harmonic mean distribution and elimination half-lives were 1.7 h (range: 1.1-2.2 h) and 19.7 h (range: 8.0-61.9 h), respectively. The harmonic mean elimination half-life from model-independent analysis was 14.9 h (range: 7.4-64.0 h). The arithmetic means of other model-independent kinetic parameters were systemic clearance, 0.524 +/- 0.215 L X kg-1 X h-1; Vd, 15.3 +/- 10.9 L/kg; and Vdss, 10.1 +/- 6.0 L/kg. Model-dependent and model-independent estimates of half-life and clearance agreed reasonably well. Bepridil was well tolerated, effecting little or no change in central hemodynamics or EKG intervals. The extensive distribution and relatively slow clearance of bepridil account for its long elimination half-life. Intravenous bepridil appears to be a safe calcium (II) antagonist that is suitable for once-a-day dosing.     

A ‘Weight‐Listing’ Paradox for Candidates of Renal Transplantation?

Research suggests that end-stage renal disease patients with elevated body mass index (BMI) have superior outcomes on dialysis. In contrast, low and high BMI patients represent the highest risk cohorts for kidney transplant recipients. The important question remains concerning how to manage transplant candidates given the potentially incommensurate impact of BMI by treatment modality. We conducted a retrospective analysis of waitlisted and transplanted patients in the United States from 1990 to 2003. We constructed Cox models to evaluate the effect of BMI on mortality of waitlisted candidates and identified risk factors for rapid weight change. We then assessed the impact of weight change during waitlisting on transplant outcomes. Decline in BMI on the waiting list was not protective for posttransplant mortality or graft loss across BMI strata. Substantial weight loss pretransplantation was associated with rapid gain posttransplantation. The highest risk for death was among listed patients with low BMI (13-20 kg/m(2), adjusted hazard ratio = 1.47, p < 0.01). Approximately one-third of candidates had a change in BMI category prior to transplantation. While observed declines in BMI may be volitional or markers of disease processes, there is no evidence that candidates have improved transplant outcomes attributable to weight loss. Prospective trials are needed to evaluate the efficacy of weight loss protocols for candidates of kidney transplantation.     

Interactions of small polypeptides with dimyristoylphosphatidylcholine monolayers: effect of size and hydrophobicity

The effects of size and hydrophobicity of small (molecular weights below 2,000) polypeptides on their predominantly hydrophobic interactions with a neutral phospholipid monolayer were studied. The changes in surface pressure were determined when various concentrations of Gly, Gly-Gly-Gly, -Ala, -Ala- -Ala- -Ala, -Ala-Gly-Gly-Gly-Gly, -Phe- -Leu- -Glu- -Glu- -Leu, adrenocorticotropic hormone fragments 1–10 (ACTH-(1–10)), porcine β-lipotropin, -endorphin and human fibrinopeptide A were injected under dimyristoylphosphatidylcholine (DMPC) monolayers at an initial surface pressure of 10 dyne/cm. In all cases, when peptides with the same number of residues are compared, the concentration needed to increase the surface pressure of the film by 1 dyne/cm was inversely related to its hydrophobicity. A reasonably good correlation was found to exist between the calculated free energy of transfer of a polypeptide from ethanol to water (a measure of its hydrophobicity) and its ability to increase the surface pressure of the DMPC film (a measure of the extent of its interaction with the neutral lipid monolayer).     

Use of pins and plaster in the treatment of unstable pediatric forearm fractures

The treatment of unstable forearm fractures in children remains a challenging and controversial subject. There are times when more rigid fixation is needed to obtain and maintain fracture reduction. Open reduction/internal fixation or intramedullary nailing can be avoided by the use of the technique of pins and plaster. This study reviewed 20 forearm fractures treated between 1978 and 1984. All fractures healed uneventfully in satisfactory alignment. No complications were encountered. We conclude that the method of pins and plaster is a safe and reliable method to treat unstable pediatric forearm fractures.     

Retrospective multicenter analysis of 3i endosseous dental implants placed over a five‐year period

Osseointegrated dental implants have now become an accepted form of treatment for patients with a fully or partially missing dentition. The purpose of this study was to evaluate the performance of 3i threaded and cylindrical implants. During a 5-year period, a total of 1969 3i endosseous implants were placed at 6 centers in the United States and 2 elsewhere in the edentulous and partially edentulous jaws of 653 consecutive patients ranging in age from 18 to 82 years. Of the total number of implants placed, 1341 were commercially pure titanium threaded implants and 628 were titanium plasma-sprayed implants with a cylindrical configuration. A total of 28 patients with 110 implants were lost to follow-up. Implants in these patients were considered neither a success nor a failure. Success was predicated on the osseointegration of each and every implant followed in this analysis rather than the persistence of prosthetic function. Confirmed bone anchorage was considered essential for success. A total of 625 patients with 1871 implants remain in the study with a follow-up period ranging from 6 to 60 months. A total of 93 implants (5.0% of the total implants followed) were considered as failures. A mean implant survival rate was 95.0% for both the threaded and the cylindrical implant was calculated. The success rate of threaded implants was 97.0% in the mandible and 93.8% in the maxilla. The success rate for the 3.3mm cylindrical implants was 96.0% in the mandible and 95.5% in the maxilla, and the success rate of 4.0mm diameter cylindrical implants was 95% in the mandible and 92.0% in the maxilla. Causes of failure consisted of loss of osseointegration 2.3%crestal bone loss requiring periodontal therapy after the first year of function 1.7% and mechanical problems associated with the prosthesis 0.9%. This retrospective analysis of the 3i endosseous implant system is comparable to previous reports on other implant systems in terms of implant survival and prosthesis stability. It is demonstrated that 3i implants are predictable and can provide lasting osseointegration leading to improvement of oral function if the recommended surgical and restorative protocol is followed.