Assessment in Basic Science Instruction: Directions for Practice and Research

In this essay, we discuss assessment of students' understanding of the basic biomedical sciences during the basic science component of medical education. Because we strongly believe that assessment should follow from and be congruent with course and curricular goals, the first section discusses recent trends in basic science education: where it's been and where it appears to be headed. The second section discusses considerations in the design of an assessment system that reflects curricular goals and encourages students to achieve them; it also identifies some research issues that we think merit attention. In the last section, we outline some of the special assessment issues and problems that arise in the context of problem-based learning (PBL) and discuss the merits of some of these novel assessment approaches, as well as the use of more traditional methods in PBL curricula.This revised version was published online in September 2005 with corrections to the Cover Date.     

Medical and health care needs of families providing in-home care for relatives with developmental disabilities

The purpose of this investigation was to attempt to describe the health care needs of families providing in-home care to members with developmental disabilities as well as the characteristics and demographics of families providing in-home care. The survey included 761 families who participated in a federal demonstration project in rural southern Georgia. The results indicated that impoverished families need increased assistance to provide adequate medical and health care when providing in-home care to relatives experiencing developmental disabilities. Implications for administration of programs and development of policies are discussed.     

A theorem about Hamiltonian systems

A simple theorem in Hamiltonian mechanics is pointed out. One consequence is a generalization of the classical result that symmetries are generated by Poisson brackets of conserved functionals. General applications are discussed. Special emphasis is given to the Kadomtsev-Petviashvili equation.     

Changes in the proportions of peripheral blood lymphocytes in patients with worn implants

We compared the peripheral blood and periprosthetic tissues of 53 patients at revision arthroplasty with those of 30 patients at primary arthroplasty to determine whether there is a systemic difference in lymphocytes in patients with worn hip implants. The absolute number and relative proportion of lymphocytes bearing CD2, CD3, CD4, CD8, CD16, CD19, HLA-DR, kappa and lambda antigens were compared with the levels of IL-1beta, IL-6 and PGE2 in the pseudosynovial membrane as well as with a semiquantitative estimate of metal and polyethylene particles, necrosis and chronic inflammation and the total concentration of metals within the periprosthetic tissues. There was a significant increase in the relative proportion of CD2-positive T-cells and CD16-positive natural killer cells in the peripheral blood at revision arthroplasty compared with primary arthroplasty and an increased proportion of CD8-positive T-cells and a decreased ratio of CD4 to CD8 (helper inducer/suppressor cytotoxic cells). Three control patients, who went on to have revision surgery, had values at primary arthroplasty which were similar to those of patients at the time of revision surgery. These differences did not correlate with the local concentration of metal, plastic or cement or inflammatory response or the type of prosthesis. An inverse correlation was noted between the necrosis in the periprosthetic tissue and both the local production of IL-6 and the absolute numbers of T-cells in peripheral blood. We conclude that there may be several cell-mediated systemic immune responses to aseptic loosening, at least one of which may be directly related to events in the periprosthetic tissues. We cannot exclude the possibility that the changes in the proportion of CD8-positive cells reflected a predisposition, rather than a reaction, to loosening of the implant.     

Incidence of Femoral Vein Occlusion After Catheter Ablation in Children: Evaluation with Magnetic Resonance Angiography

Catheter ablation in children requires placement of multiple large femoral venous sheaths and catheters. Magnetic resonance angiography (MRA) was used to evaluate the effect of indwelling lines on femoral venous blood flow. Between October 1993 and February 1994 a total of 17 patients scheduled for catheter ablation underwent venous MRA. Two-dimensional time-of-flight MRA was performed 12–70 hours after catheterization on all patients. All patients received intravenous heparin during the procedure and had aspirin therapy instituted after ablation. Eighteen catheter ablations and MRA studies were performed on the 17 patients (one patient underwent repeat ablation). There were 7 females and 10 males, with a mean age of 14.8 ± 4.2 years (range 8–21 years). Patients had three venous sheaths inserted in the left femoral vein (5F, 6F, and 7F with external diameters measuring 1.7, 2.0, and 2.3 mm, respectively) and one sheath in the right femoral vein (7F). Four patients (22%) had altered venous flow (two complete obstructions and two partial obstructions) following catheterization. None of these patients experienced symptoms or complications. It was concluded that there is an increased incidence (22%) of venous obstruction following catheter ablation, but there are no related complications. Venous MRA provides a rapid, noninvasive method for evaluating venous flow abnormalities and possibly detects patients at risk for complications.     

Measurement of albumin and low molecular weight proteins in the urine of newborn infants using a cotton wool ball collection method

Objective : The aim of this study was to investigate the inter-relationship between urinary excretion of alpha-1-microglobulin (AIM), retinol-binding protein (RBP) and albumin in term and premature neonates, with urine collected into cotton wool balls and extracted by a novel method. Subjects and methods : Sixty-four infants were studied on the first day of life; 26 had been born at term (37–42 weeks gestation) and 38 prematurely (24–28 weeks n = 16, 29–36 weeks n = 22). Urine collected into cotton wool balls was analysed following a new detergent extraction method, which resulted in a recovery rate of 94–107% for albumin, AIM, RBP and creatinine. Results : Urinary protein excretion, expressed as a ratio to urinary creatinine, decreased significantly with increasing gestational age (24–28 weeks, 29–36 weeks, 37–42 weeks: albuminxreatinine ratio mg/mmol mean 96.9, 31.7, 19.3; AIM: creatinine ratio mg/mmol mean 99.3, 37.0, 7.8; RBP: creatinine ratio mg/mmol mean 16.2, 3.8, and <0.01, below the limit of detection, respectively). When results were corrected for birthweight, this gestation-associated effect was still present for A1M and RBP, but not for albumin. In premature infants there was a significant positive correlation between AIM: creatinine ratio and RBP: creatinine ratio ( r = 0.85), and also between albumin and both AIM and RBP ( r = 0.82 and 0.77). Conclusion : Increased excretion of AIM, RBP and albumin at earlier gestational ages is probably due to proximal tubular immaturity, although tubular damage and also glomerular dysfunction cannot be excluded as possible explanations.     

Dermal, oral, and inhalation pharmacokinetics of methyl tertiary butyl ether (MTBE) in human volunteers.

Methyl tertiary butyl ether (MTBE), a gasoline additive used to increase octane and reduce carbon monoxide emissions and ozone precursors, has contaminated drinking water and can lead to exposure by oral, inhalation, and dermal routes. To determine its dermal, oral, and inhalation kinetics, 14 volunteers were exposed to 51.3 microg/ml MTBE dermally in tap water for 1 h, drank 2.8 mg MTBE in 250 ml Gatorade(R), and inhaled 3.1 ppm. MTBE for 1 h. Blood and exhaled breath samples were then obtained. Blood MTBE peaked between 15 and 30 min following oral exposure, at the end of inhalation exposure, and ~5 min after dermal exposure. Elimination by each route was described well by a three-compartment model (Rsq >0.9). The Akaike Information Criterion for the three-compartment model was smaller than the two-compartment model, supporting it over the two-compartment model. One metabolite, tertiary butyl alcohol (TBA), measured in blood slowly increased and plateaued, but it did not return to the pre-exposure baseline at the 24-h follow-up. TBA is very water-soluble and has a blood:air partition ratio of 462, reducing elimination by exhalation. Oral exposure resulted in a significantly greater MTBE metabolism into TBA than by other routes based on a greater blood TBA:MTBE AUC ratio, implying significant first-pass metabolism. The slower TBA elimination may make it a better biomarker of MTBE exposure, though one must consider the exposure route when estimating MTBE exposure from TBA because of first-pass metabolism. Most subjects had a baseline blood TBA of 1-3 ppb. Because TBA is found in consumer products and can be used as a fuel additive, it is not a definitive marker of MTBE exposure. These data provide the risk assessment process of pharmacokinetic information relevant to the media through which most exposures occur-air and drinking water.     

Targeting the ERAD pathway via inhibition of signal peptide peptidase for antiparasitic therapeutic design

Early secretory and endoplasmic reticulum (ER)-localized proteins that are terminally misfolded or misassembled are degraded by a ubiquitin- and proteasome-mediated process known as ER-associated degradation (ERAD). Protozoan pathogens, including the causative agents of malaria, toxoplasmosis, trypanosomiasis, and leishmaniasis, contain a minimal ERAD network relative to higher eukaryotic cells, and, because of this, we observe that the malaria parasite Plasmodium falciparum is highly sensitive to the inhibition of components of this protein quality control system. Inhibitors that specifically target a putative protease component of ERAD, signal peptide peptidase (SPP), have high selectivity and potency for P. falciparum. By using a variety of methodologies, we validate that SPP inhibitors target P. falciparum SPP in parasites, disrupt the protein’s ability to facilitate degradation of unstable proteins, and inhibit its proteolytic activity. These compounds also show low nanomolar activity against liver-stage malaria parasites and are also equipotent against a panel of pathogenic protozoan parasites. Collectively, these data suggest ER quality control as a vulnerability of protozoan parasites, and that SPP inhibition may represent a suitable transmission blocking antimalarial strategy and potential pan-protozoan drug target.