Medical education in the public versus the private setting: a qualitative study of medical students' attitudes

Public hospitals serve as primary training sites for medical students. Public patients may therefore bear a disproportionate burden of medical student education. The purpose of this study was to critically examine the ethics of medical education in the public setting. Attitudes of first- and fourth-year students towards the role of public patients in medical education were elicited in focus groups. Inductive qualitative analysis was utilized to organize data into conceptual groups, which were then analyzed within an ethical framework. All patients have an equal obligation to participate in medical education. Students identified modifying factors that could affect a patient's obligation to educate future physicians. Available data highlight a concern that public teaching hospitals may provide a lower quality of care. If true, then the public teaching setting is creating an unfair burden upon that patient population who would then have a weakened obligation to participate in medical education.     

Prevention of contrast-induced nephropathy: a pharmacological overview

The use of contrast media in diagnostic procedures is a potential risk for the development of acute renal failure. To reduce the occurrence of contrast-induced nephropathy, assessment and subsequent minimization of risk factors is important. If risk factors are present, consider discontinuing concomitant nephrotoxic drugs, limiting exposure to contrast media or using an alternative imaging technique. Additionally, adequate intravenous hydration is universally recommended and should be employed in all patients.     

Dysmorphic and anthropometric outcomes in 6-year-old prenatally cocaine-exposed children

Dysmorphologic and anthropometric assessments were performed on 154 6-year-old children prenatally exposed to cocaine (PCE) and 131 high-risk controls (NCE) of similar race and social class. Adjusted mean height z scores demonstrated a dose-response with metahydroxybenzoylecgonine above a threshold of 100 ng/g of meconium and greater cocaine exposure predicted lower weight for height z score. Higher average alcohol exposure throughout pregnancy and 3rd trimester predicted lower head circumference and weight z scores, respectively. Severity of marijuana use also predicted lower height for age but greater weight for height. There was not an increased rate of minor anomalies among the PCE cohort, nor was a consistent phenotype identified. After controlling for covariates, higher average prenatal cigarette exposure predicted higher incidence of cranial facial abnormalities. First trimester alcohol exposure predicted greater rates of ear abnormalities and third trimester marijuana exposure predicted greater rates of chest and head shape abnormalities. These finding indicate that prenatal cocaine exposure has a negative effect on specific growth outcomes including standardized height and weight for height, but not a systematic pattern of structural abnormalities.     

A homology model for human alpha-l-iduronidase: insights into human disease

Genotype-phenotype correlations in genetic diseases for which missense mutations lead to disease remain a challenge. This is particularly true for diseases caused by alterations of proteins for which no three-dimensional structure is available. One such disease is Mucopolysaccharidosis type I, a disorder arising from a lack of activity of the lysosomal enzyme alpha-l-iduronidase (IDUA, EC 3.2.1.76). This deficiency compromises the degradation pathway of glycosaminoglycans such as heparan sulfate and dermatan sulfate, leading to substrate accumulation, which ultimately results in a multisystem disorder. Patients with IDUA deficiency have a wide spectrum of disease ranging from an early onset, rapidly progressive form leading to death in the first decade of life, to an attenuated disease which manifests in adolescence and leads to progressive joint and cardiac disease but is associated with a normal life span. Many patients fit into a disease phenotype intermediate to these extremes. While a number of point mutations have been described as leading to varying degrees of disease severity, a structural basis for these genotype-phenotype correlations has not been available owing to the lack of a three-dimensional structure for IDUA. A homology model for the IDUA enzyme was constructed based on the recently solved crystal structure of the beta-xylosidase from Thermoanaerobacterium saccharolyticum (XyTS, EC 3.2.1.37), both of which belong to the same sequence-related family (CAZY family 39). This model provides insights into why certain point mutations produce severely misfolded proteins and thus lead to severe disease, and why other mutations produce proteins with only minor structural perturbations and therefore the attenuated form of the disease.     

The effect of endogenous dopamine in rotenone-induced toxicity in PC12 cells

Deficiencies in Complex I have been observed in Parkinson's disease (PD) patients. Systemic exposure to rotenone, a Complex I inhibitor, has been shown to lead to selective dopaminergic cell death in vivo and toxicity in many in vitro models, including dopaminergic cell cultures. However, it remains unclear why rotenone seems to affect dopaminergic cells more adversely. Therefore, the role of dopamine (DA) in rotenone-induced PC12 cell toxicity was examined. Rotenone (1.0 muM) caused significant toxicity in differentiated PC12 cells, which was accompanied by decreases in ATP levels, changes in catechol levels, and increased DA oxidation. To determine whether endogenous DA makes PC12 cells more susceptible to rotenone, cells were treated with the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (AMPT) to reduce DA levels prior to rotenone exposure, and then cell viability was measured. No changes in rotenone-induced toxicity were observed with or without AMPT treatment. However, a potentiation of toxicity was observed following coexposure of PC12 cells to rotenone and methamphetamine. To determine whether this effect was due to DA, PC12 cells were depleted of DA prior to methamphetamine and rotenone cotreatment, resulting in a large attenuation in toxicity. These findings suggest that DA plays a role in rotenone-induced toxicity and possibly the vulnerability of DA neurons in PD.     

Cost-effectiveness of enfuvirtide in treatment-experienced patients with advanced HIV disease

OBJECTIVE: Enfuvirtide (ENF) has been shown to improve short-term virologic responses when given to highly treatment-experienced patients with advanced HIV disease. Because of the high cost of ENF compared with other antiretroviral agents, our objectives were to determine the potential long-term clinical impact and cost-effectiveness of ENF in these patients. METHODS: We used a computer simulation model of HIV disease to project life expectancy, quality-adjusted life expectancy, cost, and cost-effectiveness of ENF in treatment-experienced patients. Input data were from the T-20 versus Optimized Regimen Only (TORO) 1 and 2 trials, 2 studies comparing ENF plus an optimized background regimen (OBR) with an OBR alone. RESULTS: ENF plus an OBR increased projected discounted quality-adjusted life expectancy from 45.4 months with an OBR alone to 54.9 months, a difference of 9.5 quality-adjusted life-months. At the current annual ENF cost of US 18,500 dollars per year (in 2001 US dollars), the incremental cost-effectiveness ratio for ENF plus an OBR was US 69,500 dollars per quality-adjusted life-year (QALY) compared with an OBR alone. When 48-week virologic suppression rates for ENF plus an OBR were varied from a 50% reduction to a 250% increase in the suppression rate attributable to ENF, gains in quality-adjusted life expectancy ranged from 4.5 to 25.9 quality-adjusted life-months compared with an OBR alone, with cost-effectiveness ratios ranging from US 97,900 dollars per QALY to US 52,300 dollars per QALY gained. If ENF is continued after the HIV RNA level returns to the pretreatment baseline, the cost-effectiveness ratio increases to US 168,200 dollars per QALY. CONCLUSIONS: In highly treatment-experienced patients, ENF plus an OBR provides substantial gains in quality-adjusted life expectancy compared with an OBR alone. Although ENF plus an OBR is less cost-effective than other commonly used interventions in HIV disease, its use may be justified, given the poor prognosis of these patients and their otherwise limited options for antiretroviral therapy.     

Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients

Tamoxifen (TAM) is widely used for treatment and prevention of breast cancer. TAM is metabolized by cytochrome P450 (CYP450) enzymes, including CYP3A5. Although two genetic polymorphisms in CYP3A5 are known (CYP3A5*3 and CYP3A5*6), the effects of these polymorphisms on TAM metabolism, TAM side effects, and tumor characteristics are unknown. Thus, this work tested the hypothesis that CYP3A5 polymorphisms are associated with differential TAM levels, TAM side effects, and tumor characteristics in breast cancer patients. Postmenopausal women with breast cancer (n=98) were recruited from a single cancer center. Polymorphic status was established using polymerase chain reactions (PCR). The associations between polymorphic status, race, TAM levels, side effects, and tumor characteristics were assessed using t-tests and logistic regression models. The data indicate that 40.7% of the breast cancer patients had the CYP3A5*3 polymorphism, and 9.1% had the CYP3A5*6 polymorphism. In addition, Caucasian women were 26 times more likely to carry the CYP3A5*3 polymorphism than African American (AA) women, whereas AA women were nine times more likely to carry the CYP3A5*6 polymorphism than Caucasian women. No significant differences were seen in TAM or TAM metabolite levels or TAM side effects by polymorphic status. There was a significant difference, however, in mean tumor size in women with the CYP3A5*6 polymorphism (3.6+/-0.98 cm) compared to those without the polymorphism (2.0+/-0.18 cm) (P<0.02). Taken together, these data suggest that racial differences in CYP3A5 polymorphisms exist although the polymorphisms do not appear to be associated with levels of TAM metabolites and side effects.     

Clinical features and diagnosis of primary central nervous system lymphoma

This article reviews the clinical features of primary central nervous system lymphoma (PCNSL) in immunocompetent and immunocompromised patients. Clinical presentation, differential diagnosis, diagnostic testing, and staging evaluation in both immunocompetent and AIDS patients who have PCNSL are discussed. The differing role of biopsy in these two populations also is addressed.