Impaired helix 12 dynamics due to proline 892 substitutions in the androgen receptor are associated with complete androgen insensitivity

Human Molecular Genetics (2006) 15, 921–931;     

Aerobic exercise training fails to lower hypertriglyceridemia levels in persons with advanced HIV-1 infection.

The purpose of this study was to determine whether blood lipid and lipoprotein concentrations varied in 5 men with advanced HIV-1 infection after 12 months of aerobic exercise training. Prior to exercise, the mean baseline cholesterol and high-density lipoprotein cholesterol (HDL-C) serum concentration were each lower, and mean baseline triglyceride concentration was higher compared to a healthy population norm. Consistent exercise training for 12 months failed to significantly (p > .05) alter cholesterol or HDL-C. Triglyceride concentration was significantly (p < .05) elevated above baseline (63 mg/dL) regardless of exercise compliance. The results suggest that long-term exercise training cannot correct lipid profile abnormality, particularly hypertriglyceridemia, common to individuals with advanced HIV-1 infection.     

Statistical analysis of gait patterns of persons with cerebral palsy

Patients at Boston's Children's Hospital diagnosed as having cerebral palsy were filmed walking. These films were digitized and translated into measurements associated with leg motion. In this paper we use the gait measurements of 128 such patients to illustrate that the kth nearest neighbour clustering procedure results in a gait typology for patients with cerebral palsy. The procedure identifies four subpopulations from the sample data; the membership of a patient within this typology is mostly determined by the patient's motor control. The developed typology differs from the present diagnostic system which classifies a cerebral palsy patient as either quadriplegic, diaplegic or hemiplegic.     

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.